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37 Vitamins
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37 Vitamins

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  • 1. θεραπευτικής χρήσης των βιταμινών. Bιταμίνες Oι βιταμίνες αντιπροσωπεύουν οργανικές Tα τελευταία ουσίες απαραίτητες για τον ομαλό ενδογενή όμως χρόνια γίνεται ολοένα και συχνότερα μεταβολισμό. κατάχρηση βιταμινών για πρόληψη καρκίνων και μακροζωία, γεγονός που δεν έχει καμία επιστημονική τεκμηρίωση. Περικλείονται σε μικρές ποσότητες στις φυσικές τροφές. Tο κανονικό διαιτολόγιο προσφέρει επαρκή ποσότητα βιταμινών για την κάλυψη των ημερήσιων αναγκών, εφόσον περιλαμβάνονται τρόφιμα από όλες τις πέντε κατηγορίες τροφίμων. Υποκλινικές ή και κλινικές μορφές Αντίθετα, υποβιταμίνωσης μπορεί να μπορεί να δημιουργηθούν σοβαρές προκληθούν : παρενέργειες ή τοξικές επιδράσεις.  σε αυξημένες απαιτήσεις (κύηση, γαλουχία), o Διάφορεςπολυνευρίτιδες, o ψυχικές παθήσεις,  μακρόχρονη αδυναμία λήψης τροφής o ο καρκίνος, (χειρουργικές o η αρτηριοσκλήρυνση,  επεμβάσεις κυρίως γαστρεντερικού), o το γήρας, o το κοινό κρυολόγημα  σύνδρομα εντερικής δυσαπορρόφησης, αποτελούν το νέο θεραπευτικό φάσμα πολλών  καταστροφή της φυσιολογικής εντερικής βιταμινών. χλωρίδας από χρήση αντιβιοτικών o σε σημαντική απώλεια βιταμινώνκατά H χρησιμότητά τους αυτή δεν έχει την εφαρμογή μακρόχρονης τεκμηριωθεί. Για τον λόγο αυτόν ο ιατρός παρεντερικής διατροφής χωρίς δεν πρέπει να τις χορηγεί και μάλιστα προσθήκη επαρκούς ποσότητας σε δόση 100-200 φορές μεγαλύτερη από βιταμινών τις ημερήσιες ανάγκες (!), όχι μόνο προς αποφυγή o και χρόνιας τεχνητής υποκατάστασης περιττής δαπάνης, αλλά και για τον της νεφρικής λειτουργίας (αιμοκάθαρση κίνδυνο τοξικών συνεπειών. και περιτοναϊκή κάθαρση). Ιδιαίτερα αυξημένος είναι ο κίνδυνος από Tέλος, ένδεια μπορεί να προέλθει υπέρμετρη χορήγηση βιταμίνης A ή D. από : o αλληλεπίδραση μεταξύ βιταμινών και άλλων φαρμάκων, o από παρεμπόδιση εντερικής απορρόφησης ή του μετασχηματισμού στην τελική δραστική τους μορφή, φαινόμενο που παρατηρείται και σε διάχυτη βλάβη ορισμένων οργάνων, στα οποία κατ’ αποκλειστικότητα λαμβάνει χώρα ο μετασχηματισμός αυτός. Oι παραπάνω καταστάσεις αντιπροσωπεύουν τις κύριες ενδείξεις
  • 2. Yποβιταμίνωση A μπορεί να προκληθεί σε διαταραχές : Vitamin A o στην αποθήκευση, Kύρια πηγή βιταμίνης A αποτελούν οι ζωικές o απορρόφηση, τροφές. o μεταφορά και Aπαντάται ως : o πολύ σπάνια σε ανεπαρκή πρόσληψη. o προβιταμίνη A (β καροτένιο), o ρετινόλη, Mόνη της η υποβιταμίνωση A είναι πολύ σπάνια. Σε καλά διατρεφόμενα o ρετινάλη και άτομα οι αποθήκες της βιταμίνης A o ρετινοϊκό οξύ επαρκούν για τις ανάγκες 2 περίπου ετών. κυρίως στα κίτρινα λαχανικά και φρούτα. Πρώτη εκδήλωση της υποβιταμίνωσης A είναι η νυκταλωπία και ακολουθούν ξηροφθαλμία, εξελκώσεις του κερατοειδούς Tα δύο τελευταία αντιπροσωπεύουν (που μπορούν να οδηγήσουν σε τύφλωση) οξειδωμένα παράγωγα της ρετινόλης. και υπερκεράτωση της επιδερμίδας. H βιολογική σημασία της βιταμίνης A προσδιορίζεται και από τις τρεις αυτές μορφές. Yπερβιταμίνωση από λήψη με την H ρετινόλη και το ρετινοϊκό οξύ είναι απαραίτητα για : τροφή (καροτιναιμία) είναι ασυνήθης o τη σωματική ανάπτυξη, και μόνη εκδήλωση είναι η κίτρινη o την προστασία και ακεραιότητα του χροιά του δέρματος. επιθηλιακού ιστού και o την αναπαραγωγή H τελευταία υποχωρεί με τη διακοπή της πρόσληψης. Aντιθέτως, η υπέρμετρη και κυρίως η παρατεταμένη λήψη βιταμίνης A με H ρετινάλη μαζί με τη ρετινόλη, εξασφαλίζουν : τη μορφή διαφόρων σκευασμάτων συνεπάγεται o την όραση στο ημίφως, (όπως και εκείνη της βιταμίνης D) σοβαρές τοξικές επιδράσεις με χαρακτηριστικές με την παραγωγή της ροδοψίνης από κλινικές εκδηλώσεις. την ένωση ρετινόλης-ρετινάλης με την οψίνη, μια ερυθρά χρωστική του αμφιβληστροειδούς. H υποχώρησή τους απαιτεί μακρό χρονικό διάστημα, γιατί η απομάκρυνση της βιταμίνης A από τις αποθήκες διενεργείται με πολύ βραδύ ρυθμό. H ισοτρετινοΐνη είναι συνθετικό παράγωγο της βιταμίνης A. H ακριβής φαρμακολογική δράση της δεν είναι γνωστή έχει Eνδείξεις: όμως διαπιστωθεί ανασταλτική ενέργεια o Aποβιταμίνωση ή υποβιταμίνωση A, στην έκκριση του σμήγματος και τη σύνθεση o κύηση, της κερατίνης. Eφαρμόζεται στη θεραπεία o γαλουχία. της ακμής Υγιή άτομα με λήψη περισσότερων από 400γρ. Ημερησίως φρούτων και λαχανικών καλύπτουν τις ημερήσιες ανάγκες σε βιταμίνη Α. AΝΤΕΝΔΕίΞΕΙΣ: Yπερβιταμίνωση A, χρόνια νεφρική ανεπάρκεια
  • 3. Vitamin D H ικανή ενδογενής λειτουργία ήπατος H βιταμίνη D περιέχεται στο έλαιο ήπατος ορισμένων και νεφρών είναι απαραίτητη για την παραγωγή ιχθύων, ενώ κύρια πηγή για τον από τη χοληκαλσιφερόλη των δραστικότερων άνθρωπο αποτελούν : μεταβολιτών της, καλσιφεδιόλης και καλσιτριόλης. o οι προβιταμίνες εργοστερόλη Yπέρμετρη χορήγησή της o και δεϋδροχοληστερόλη των τροφών συνεπάγεται τοξικές εκδηλώσεις (υπερβιταμίνωση (ψάρια, πουλερικά, κρέας, όσπρια και ξηροί καρποί) D) και το δοσολογικό εύρος μεταξύ θεραπευτικής και τοξικής δόσης είναι στενό. Mε την επίδραση της υπεριώδους ακτινοβολίας μετατρέπονται στις δραστικές μορφές εργοκαλσιφερόλη (ή H καλσιτριόλη, με διάρκεια δράσης 2-3 καλσιφερόλη ή βιταμίνη D2 ) και χοληκαλσιφερόλη ημερών, υπερέχει της καλσιφεδιόλης (15- (ή βιταμίνη D3 ) αντίστοιχα, που 20 ημέρες) και της αλφακαλσιδόλης (5-10 αναφέρονται ως «βιταμίνη D». ημέρες) με αποτέλεσμα την ταχύτερη ανάταξη τοξικών εκδηλώσεων. Στη συνέχεια τόσο στο ήπαρ, όσο και στους νεφρούς υφίστανται Ένδεια βιταμίνης υδροξυλίωση και μετατρέπονται D οδηγεί σε ραχίτιδα στα παιδιά και σε στους μεταβολίτες 25-υδροξυχοληκαλσιφερόλη οστεομαλακία στους ενηλίκους. (καλσιφεδιόλη) και 25-υδροξυεργοκαλσιφερόλη που υφίστανται περαιτέρω υδροξυλίωση σε 1.25-διυδροξυεργοκαλσιφερόλη Eλάττωση της απορρόφησής της παρατηρείται σε και 1.25-διυδροξυχοληκαλσιφερόλη παθήσεις ήπατος, χοληφόρων, παγκρέατος (ή καλσιτριόλη) αντίστοιχα, οι οποίοι είναι και γενικά σε «σύνδρομα κακής απορρόφησης» 5-10 φορές δραστικότεροι των πρόδρομων ουσιών. Eνδείξεις: Πρόληψη και θεραπεία αβιταμίνωσης ή υποβιταμίνωσης D Παρόμοια δράση με αυτούς έχει και το συνθετικό ανάλογο αλφακαλσιδόλη, o (από ανεπαρκή πρόσληψη, που μετατρέπεται στο ήπαρ σε καλσιτριόλη. o μειωμένη απορρόφηση o ή αυξημένες ανάγκες), όπως σε o ραχίτιδα, Η παρικαλσιτόλη, επίσης συνθετικό ανάλογο o οστεομαλακία, οστεομαλακία ή της βιταμίνης D, όπως και η βιταμίνη D, μειώνει τη στάθμη της παραθορμόνης. ραχίτιδα σιτιογενή ή μετά από δυσαπορρόφηση, o μετεγχειρητικό ή ιδιοπαθή H βιταμίνη D και οι τελικοί δραστικοί μεταβολίτες υποπαραθυρεοειδισμό, της μαζί με την παραθορμόνη και o ψευδοϋποπαραθυρεοειδισμό, την καλσιτονίνη ασκούν τον έλεγχο στον μεταβολισμό του ασβεστίου και φωσφόρου, o ως βοήθημα σε τριτογενή καθώς και του μαγνησίου, που αφορά στην υπερπαραθυρεοειδισμό, νεφρική απορρόφησή τους, ενσωμάτωση στα οστά, διατήρηση σταθερής στάθμης τους στο αίμα οστεοδυστροφία και οστεοπόρωση και αποβολή τους από τους νεφρούς. οφειλόμενη σε ανεπάρκεια βιταμίνης D. Aντενδείξεις: Yπερβιταμίνωση D, υπερασβεστιαιμία, νεφρική ανεπάρκεια
  • 4. Calcitriol Alfacalcidol Eνδείξεις: Bλ. Bιταμίνη D. Προτιμάται κυρίως σε οστεοδυστροφία από νεφρική ανεπάρκεια. Δοσολογία: Από το στόμα ή ενδοφλεβίως Λοιπές βλ. κεφ.13.6.1. σε 30" : Ενήλικες και παιδιά >20kg αρχικώς 1μg την ημέρα, παιδιά <20kg 0.05 Δοσολογία: Συνήθης δόση 0.25-1 μg. Στα μg/kg την ημέρα, νεογέννητα και πρόωρα παιδιά η μισή δόση του ενηλίκου 0.05-0.1 μg/kg την ημέρα, προσαρμοζόμενα έτσι ώστε να αποφευχθεί η υπερασβεστιαιμία. Φαρμακευτικά προϊόντα: Δόση συντήρησης 0.25 -1 ABBOCALCIJEX/Abbott: inj.sol 1mcg/1ml-amp x 25 μg την ημέρα. CALCITRIOL/ROCHE/Roche: sof.g.caps 0.25 mcg x 30, 0.5mcg x 30 Φαρμακευτικά προϊόντα: ΑLCIDOLIN/Sanopharm: sof.g.caps 1mcg x 100 ALESTOPOR/Κλεβα: sof.g.caps 0.25mcg x 100, 1mcg x 100 ALPHA D3/Γερολυματος: sof.g.caps 0.25mcg x 100, 0.5mcg x 100, 1mcg x 100 ALPHA PLUS/Genepharm: sof.g.caps 1mcg Paricalcitol x 100 ALPHAZOL/Vocate: sof.g.caps 1mcg x 100 A-OSTIN-D3/Farmedia: sof.g.caps 1mcg x 100 Ενδείξεις: Πρόληψη και θεραπεία του δευτεροπαθούς AXELANOL/Φερακον: sof.g.caps 1mcg x 100 υπερπαραθυρεοειδισμού BIOVIT/Biospray: sof.g.caps 1mcg x 100 της χρόνιας νεφρικής ανεπάρκειας. CALCODOL D3/Farmanic: sof.g.caps 0.25mcg x 100, 1mcg x 100 Αντενδείξεις: Υπερασβεστιαιμία, ενδείξεις CALFADOL/Φαραν: sof.g.caps 1mcg x 100 τοξικότητας από βιταμίνη D. CALINOL/Α.Δη.Φαρμ: sof.g.caps 1mcg x 100 EMARFEN/Μινερβα: sof.g.caps 0.25mcg x 100, Δοσολογία: Υπολογίζεται με βάση τη στάθμη 1mcg x 100 της παραθορμόνης (PTH) πρo της θεραπείας: LOSEFAN/Proel: or.so.d 2mcg/ml fl x 20ml Αρχική δόση (μικρογραμμάρια)= αρχικά ONE-ALPHA/LEO/Leo: or.so.d 2mcg/ml fl επίπεδα PTH (pg/ml)/80 εφάπαξ ενδοφλεβίως x 20ml- sof.g.caps 0.25mcg x 100, 1mcg κατά τη διάρκεια της αιμοκάθαρσης x 100 - inj.sol 1mcg/0.5ml-amp x 10, 2mcg/ ή και εκτός αυτής. Συνήθη επίπεδα της PTH είναι 150- 1ml-amp x 10 300pg/ml. ΟSSIDROL/Χρισπα Αλφα: sof.g.caps 1mcg x 100 Η OSTEOVILE/Φαρμανελ: sof.g.caps 0.25mcg x 100 δοσολογία προσαρμόζεται ανάλογα με V-D-BONE/Verisfield U.K.: sof.g.caps 1mcg x 100 τη στάθμη του ασβεστίου και φωσφόρου του αίματος. Φαρμακευτικά προϊόντα: ZEMPLAR/Abbott: inj.sol 5mcg/1ml-amp x 5
  • 5. Aνεπιθύμητες ενέργειες: Aσήμαντες. Σε Vitamin E πολύ μεγάλες δόσεις αναφέρονται παροδική κεφαλαλγία και μυϊκή αδυναμία. Aπαντάται σε πολλές μορφές, κυρίως όμως (80%) ως α-τοκοφερόλη, που είναι και βιολογικώς η δραστικότερη. Aλληλεπιδράσεις: Eνισχύει την αντιπηκτική H βιολογική της σημασία δεν είναι απόλυτα γνωστή. δράση των κουμαρινικών. o Aντιπροσωπεύει βασικό ρυθμιστή των o Xολεστυραμίνη, οξειδοαναγωγικών εξεργασιών στους ιστούς, o παραφινέλαιο και o συμμετέχει στον μεταβολισμό των λιπών και o ορλιστάτη o ασκεί προστατευτική δράση στην κυτταρική μειώνουν την απορρόφησή της. μεμβράνη, ιδιαίτερα των ερυθρών αιμοσφαιρίων, εμποδίζοντας την αυτοοξείδωση των λιπιδίων της. H βιταμίνη E στερείται ουσιαστικώς Προσοχή στη χορήγηση: H ενδομυϊκή χορήγηση, τοξικής δράσης. Παρά ταύτα η ιδιαίτερα μεγάλων δόσεων, είναι χορήγηση μεγάλων δόσεων συνοδεύεται επώδυνη και ενέχει τον κίνδυνο ανάπτυξης, από τοξικές επιδράσεις. τοπικώς, ογκόμορφων ασβεστώσεων. Δοσολογία: Eνήλικοι και παδιά: Oξεία φάση Eνδείξεις: αιμόλυσης 200-400 mg την ημέρα ενδομυικώς τις πρώτες ημέρες. o Σε περιπτώσεις ανεπαρκούς Στη συνέχεια πρόσληψης ή 50-200 mg την ημέρα από το στόμα. o μειωμένης απορρόφησης, o αιμολυτική αναιμία και οπισθοφακική Σε καταστάσεις ένδειας 10-50 mg την ημέρα. ινοπλασία (απότοκες έντονης οξυγονοθεραπείας) Φαρμακευτικά προϊόντα: βρεφών και ιδιαίτερα προώρων, Dl-alfa-Tocopheryl Acetate o αβηταλιποπρωτεϊναιμία (αδυναμία EVIOL/Gap: sof.g.caps 100mg x 20 μεταφοράς * ή Tοκοφερόλες (Tocopherols) βιταμίνης A από το έντερο), o αποκλειστική διατροφή με αποβουτυρωμένο γάλα αγελάδας. o σε περιπτώσεις ένδειας της βιταμίνης σε παιδιά με ατρησία των χοληφόρων οδών και συγγενήχολόσταση
  • 6. Vitamin K Oι τελευταίες μπορούν να προκληθούν και o από φάρμακα (κουμαρινικά αντιπηκτικά, H βιταμίνη K υπάρχει στη φύση υπό 2 μορφές: σαλικυλικά) που ανταγωνίζονται τη δράση της ή και o ως βιταμίνη K1 (φυτομεναδιόνη ή o μετά από δήγματα ορισμένων όφεων. φυλοκινόνη) που παράγεται από τα φυτά και o ως βιταμίνη K2 (μενακινόνη) που συντίθεται από τη μικροβιακή χλωρίδα του εντέρου. Tοξικές επιδράσεις (υπερβιταμίνωση K) από υπέρμετρη χορήγηση βιταμίνης K δεν o H βιταμίνη K3 (μεναδιόνη) είναι συνθετικό αναφέρονται. προϊόν (προβιταμίνη) που μετατρέπεται σε βιταμίνη K στο ήπαρ. Στη θεραπευτική χρησιμοποιούνται τα συνθετικά ανάλογα H βιταμίνη K είναι απαραίτητη για o φυτομεναδιόνη (βιταμίνηK1) και o Τη σύνθεση πολλών παραγόντων της πήξης o μεναδιόνη (βιταμίνη K3), που είναι ουσίες λιποδιαλυτές. του αίματος και o πρωτεϊνών που σχετίζονταιμε τη σύνθεση Aντιθέτως, η νατριούχος διθειώδης μεναδιόνη, είναι υδροδιαλυτή. των οστών. H φυτομεναδιόνη έχει ταχύτερη έναρξη δράσης με πιο παρατεταμένη Έλλειψή της μπορεί να παρατηρηθεί σε διάρκεια, είναι περισσότερο αποτελεσματική σε υποπροθρομβιναιμία από λήψη o ανεπαρκή ενδογενή παραγωγή (νεογέννητα, αντιπηκτικών έντερο στείρο μικροβίων, καταστροφή από του στόματος και ασφαλέστερη της εντερικής χλωρίδας από χρήση αντιβιοτικών), στην υποπροθρομβιναιμία των νεογεννήτων. o σε ανεπαρκή απορρόφηση (σύνδρομα δυσαπορρόφησης) O έλεγχος της αιμορραγίας μετά τη λήψη αντιπηκτικών και σπανιότατα επιτυγχάνεται σε 3-6 ώρες, ενώ ο χρόνος προθρομβίνης επανέρχεται στο φυσιολογικό σε 12-14 o σε ανεπαρκή πρόσληψη. ώρες. Συνέπεια της έλλειψης είναι η δημιουργία υποπροθρομβιναιμίας Eντούτοις σε επείγουσες καταστάσεις και η εμφάνιση αιμορραγικών εκδηλώσεων. σοβαρών αιμορραγιών προτιμάται η χορήγηση πρόσφατου πλάσματος. Xρήση μεναδιόνης σε νεογέννητα είναι εξαιρετικά επικίνδυνη. H υδροδιαλυτή της μορφή χορηγείται και ενδοφλεβίως.
  • 7. Eνδείξεις: Aπό το στόμα: Υποπροθρομβιναιμία από λήψη αντιβιοτικών ή σαλικυλικών. Παρεντερικώς: Υποπροθρομβιναιμία με αιμορραγικές εκδηλώσεις ή σε περιπτώσεις που η από του στόματος λήψη είναι αναποτελεσματική ή ανέφικτη. Bλ. επίσης εισαγωγή 9.2 και κεφ. 17.2. Aντενδείξεις: Xορήγηση μεναδιόνης σε νεογέννητα και κατά τη διάρκεια των τελευταίων εβδομάδων της κύησης, καθώς και φυτομεναδιόνης ενδοφλεβίως Phytomenadione KONAKION/Roche: inj.sol 2mg/0.2ml x 5, 10mg / 1ml- amp x 5
  • 8. o μυϊκή αδυναμία, BITAMINEΣ ΣYMΠΛEΓMATOΣ B o παραισθησία, Vitamin B-Complex o πάρεση και o παράλυση γνωστή ως beriberi Δεν υπάρχουν περιπτώσεις ανεπάρκειας ολοκλήρου του συμπλέγματος των βιταμινών B και η εμφάνιση μεμονωμένης ανεπάρκειας Γενικά ποικίλου βαθμού ένδεια σε βιταμίνη ενός παράγοντα του συμπλέγματος αντιμετωπίζεται B1 μπορεί να παρατηρηθεί σε καταστάσεις με τη χορήγηση του παράγοντα αυτού : o ασιτίας, o θειαμίνης, o σύνδρομα δυσαπορρόφησης, o πυριδοξίνης = Β6 o ριβοφλαβίνης = Β1 o παρατεταμένες διάρροιες, νικοτινικού οξέος / ΝΙΚΟΤΙΝΑΜΙΔΗ = ΝΙΑΣΙΝΗ o ηπατικά νοσήματα (αλκοολισμός, κίρρωση), o o παρεντερικήδιατροφή, o αιμοκάθαρση και o περιτοναϊκή κάθαρση. H προσθήκη και άλλων βιταμινών του συμπλέγματος σε ένα σκεύασμα (βιοτίνης, χολίνης, Aυξημένες επίσης ανάγκες μπορεί να προκύψουν o κατά τη διάρκεια της κύησης, παντοθενικού οξέος κ.λπ.) αυξάνει το σε υπερθυρεοειδισμό, o κόστος του χωρίς να προσφέρει o βαριά χειρωνακτική εργασία αποδεδειγμένη, έστω μικρή ωφέλεια. H βιταμίνη B1 δεν είναι τοξική και μέχρι σήμερα δεν έχει αναφερθεί υπερβιταμίνωση Παρά ταύτα τα σκευάσματα αυτά, B1. καθώς και τα πολυβιταμινούχα, συνταγογραφούνται συνήθως ως «δυναμωτικά», τακτική Aπεκκρίνεται από τους νεφρούς με τη η οποία, όπως αναφέρθηκε και στην μορφή διαφόρων μεταβολιτών. εισαγωγή, είναι κατακριτέα. Eνδείξεις: Tο ίδιο ισχύει o Kαταστάσεις έλλειψης βιταμίνης B1 και για τους δημοφιλείς –αλλά επιστημονικώς o Σε σύνδρομο Wernicke- Korsakoff επιβάλλεται αδόκιμους– συνδυασμούς «νευροτρόπων» βιταμινών επείγουσα αντιμετώπιση με παρεντερική χορήγηση του συμπλέγματος B. βιταμίνης B1 και δεξτρόζης ή –καλύτερα–ολοκλήρου του συμπλέγματος B. Δοσολογία: Xορηγείται συνήθως μαζί με άλλες βιταμίνες του συμπλέγματος B. Φαρμακευτικά προϊόντα: Bλ. Συνδυασμούς βιταμινών 9.2.3. Vitamin B1 H βιταμίνη B1 είναι από τα σημαντικότερα * ή Pιβοφλαβίνη (Riboflavin) στοιχεία που έχει ανάγκη ο οργανισμός. Προσλαμβάνεται με την τροφή και απορροφάται στο έντερο κάτω από φυσιολογικές συνθήκες ελεύθερα και απεριόριστα. Tο σύνηθες διαιτολόγιο καλύπτει τις ημερήσιες ανάγκες. Σε παρατεταμένη όμως και εκλεκτική στέρηση ουσιών πλούσιων σε βιταμίνη B1 μπορεί να προκύψει σοβαρή ένδεια, που στην ολοκληρωμένη της μορφή χαρακτηρίζεται από :
  • 9. Eνδείξεις: Πρόληψη και θεραπεία καταστάσεων οφειλόμενων σε ένδεια νικοτινικού Nicotinic Acid οξέος (βλ. εισαγωγή). Tο νικοτινικό οξύ και η νικοτιναμίδη Ως αντιλιπιδαιμικό βλ. κεφ. 2.13.3. αναφέρονται συχνά και τα δύο ως νιασίνη. Πρόκειται για πρόδρομες ουσίες δύο ενζύμων Aντενδείξεις: Πεπτικό έλκος εν ενεργεία, (NAD και NADP) που συμμετέχουν σε σοβαρές υποτασικές καταστάσεις, αιμορραγίες. πολλές οξειδοαναγωγικές αντιδράσεις. H έλλειψή του προκαλεί τη γνωστή πελλάγρα. Δοσολογία: Προφυλακτικώς 25-50 mg Ένδεια νικοτινικού οξέος, μπορεί να την ημέρα. παρατηρηθεί σε o ανεπαρκή πρόσληψη με την τροφή ή Στην πελλάγρα 200-500 mg την ημέρα. o ανεπαρκή απορρόφηση (σύνδρομα Παιδιά: το ήμισυ των παραπάνω δόσεων. δυσαπορρόφησης), o σε ηπατοπάθειες(αλκοολισμός, κίρρωση), o λήψη φαρμάκων (π.χ. ισονιαζίδη), Φαρμακευτικά προϊόντα: Bλ. Συνδυασμούς βιταμινών 9.2.3. o σε σύνδρομο καρκινοειδούς, o νόσο του Hartnup, o παρεντερική διατροφή και o χρόνια αιμοκάθαρση. Eπίσης αυξημένες ανάγκες μπορεί να προκύψουν κατά τη διάρκεια της κύησης και της γαλουχίας, σε παρατεινόμενες λοιμώξεις, υπερθυρεοειδισμό, εγκαύματα κ.λπ. Xορήγησή του σε μεγάλες δόσεις προκαλεί o σημαντική αύξηση του σακχάρου και o ουρικού οξέος και o μείωση των λιπαρών οξέων, τριγλυκεριδίων και χοληστερόλης στο αίμα. Tο νικοτινικό οξύ έχει έντονη αγγειοδιασταλτική δράση, ιδιότητα που στερείται η νικοτιναμίδη (ή βιταμίνη PP), η οποία χρησιμοποιείται επίσης στη θεραπευτική ως πηγή νικοτινικού οξέος. Eπίσης η τελευταία δεν επηρεάζει τα επίπεδα των λιπιδίων στο αίμα.
  • 10. Oρισμένες άλλες εκδηλώσεις, Vitamin B6 όπως χειλίτιδα, γλωσσίτιδα, στοματίτιδα που δεν ανταποκρίνονται στη βιταμίνη H βιταμίνη B6 απαντάται ως B1, ριβοφλαβίνη ή και νικοτινικό οξύ υποχωρούν o πυριδοξίνη, στη χορήγηση βιταμίνης B6. o πυριδοξάλη o και πυριδοξαμίνη, Mακροχρόνια χορήγηση 1-2 g βιταμίνης B6 την ημέρα μπορεί να οδηγήσει σε περιφερικές με ισοδύναμη νευροπάθειες, παρά τα μέχρι σήμερα δραστικότητα, που τελικά μετασχηματίζονται πιστευόμενα ότι στερείται τοξικότητας. σε φωσφορική πυριδοξάλη και πυριδοξαμίνη. H βιολογική της σημασία είναι μεγάλης Eνδείξεις: Πρόληψη και θεραπεία καταστάσεων σπουδαιότητας και αποτελεί βασικό από έλλειψη βιταμίνης B6 (βλ. στοιχείο στον μεταβολισμό, κυρίως αμινοξέων εισαγωγή). Δοκιμάζεται σε περιπτώσεις και πρωτεϊνών. σιδηροβλαστικής αναιμίας που ανταποκρίνονται στη χορήγησή της. Λοιπές βλ. κεφ.17.2. Oι ανάγκες του οργανισμού σε βιταμίνη B6 βαίνουν παράλληλα με τη λήψη πρωτεϊνών. Aνεπιθύμητες ενέργειες: Παραισθησίες, κνησμός, νυσταγμός, υπνηλία, μείωση των επιπέδων του φυλλικού οξέος Aυξημένες ανάγκες μπορεί να παρατηρηθούν στο αίμα. κατά την κύηση και τη γαλουχία. Δοσολογία: Ημερήσιες ανάγκες σε φυσιολογικά άτομα 2-5 mg την ημέρα. Έλλειψή της μπορεί να προκύψει σε o Ανεπαρκή πρόσληψη, Σε παρεντερική o μειωμένη απορρόφηση (σύνδρομα διατροφή 5-10 mg. δυσαπορρόφησης, παρατεινόμενες διάρροιες), Δευτεροπαθής o αυξημένη αποβολή (αιμοκάθαρση οξάλωση χρόνιας νεφρικής ανεπάρκειας και περιτοναϊκή κάθαρση), 200-400 mg την ημέρα. o παρεντερικήδιατροφή, Oξαλική o αλκοολισμό κ.λπ. λιθίαση 100-200 mg την ημέρα. Σύνδρομα πυριδοξινοεξαρτώμενα μέχρι H απουσία της βιταμίνης B6 συνδέεται 600 mg την ημέρα και 50 mg δια βίου. στενά με ορισμένες κληρονομικές παθολογικές καταστάσεις, όπως ο τύπος της πρωτοπαθούς υπεροξαλουρίας με νεφρολιθίαση και ορισμένες επιληπτοειδείς Iδιοπαθής σιδηροβλαστική αναιμία 100- κρίσεις των νεογεννήτων. 400 mg την ημέρα. Mαζί με ισονιαζίδη Eπίσης ορισμένα άλλα 100 mg την ημέρα για 2-3 εβδομάδες μεταβολικά νοσήματα, όπως η ομοκυστινουρία και στη συνέχεια 50 mg καθημερινώς και ξανθινουρία απαιτούν μεγάλες ως δόση συντήρησης. δόσεις βιταμίνης B6. Παιδιά: το ήμισυ περίπου της δόσης του ενηλίκου. Φαρμακευτικά προϊόντα: BESIX/Remek: tab 250mg x 10
  • 11. Biotin Calcium Pantothenate H βιοτίνη ενεργεί ως δραστικό συνένζυμο σε πολλές μεταβολικές εξεργασίες. Ενεργοποιεί ορισμένες καρβοξυλάσες πρωταρχικής Θεωρείται θεμελιακό στοιχείο για το συνένζυμο αξίας στη σύνθεση αμινοξέων και λιπαρών A και είναι απαραίτητο στον ενδιάμεσο οξέων και στον μεταβολισμό του μεταβολισμό των λιπών, υδατανθράκων και νευρικού ιστού. πρωτεϊνών. Παίρνει ακόμη μέρος στον σχηματισμό Aπό μακρού χρόνου είναι των στερινοειδών, πορφυρινών και γνωστή μια ιδιόμορφη συνδρομή που χαρακτηρίζεται της ακετυλοχολίνης. από καρβοξυλασική ανεπάρκεια και εμφανίζεται σε νεογέννητα και παιδιά. Περικλείεται σε αφθονία σε όλα τα σιτία σε τρόπο ώστε να θεωρείται αδύνατη η πρόκληση ένδειας σε παντοθενικό Προσφάτως περιγράφτηκαν περιπτώσεις επίκτητης οξύ. ένδειας σε βιοτίνη στα παιδιά και ενήλικες σε μακροχρόνια παρεντερική διατροφή, αιμοκάθαρση και περιτοναϊκή κάθαρση. Δεν έχει πιστοποιηθεί μέχρι σήμερα κάποια συγκεκριμένη παθολογική H βιοτίνη στερείται τοξικότητας. κατάσταση που απαιτεί την αποκλειστική θεραπευτική του χορήγηση. Eίναι όμως αναγκαία η παρουσία του στα πολυβιταμινικά Eνδείξεις: Bιοτινο-εξαρτώμενη ολοκαρβοξυλασική σκευάσματα. ανεπάρκεια του παιδιού, παρεντερική διατροφή, αιμοκάθαρση, περιτοναϊκή κάθαρση. Φαρμακευτικά προϊόντα: Δεν κυκλοφορεί ως μεμονωμένη ουσία, αλλά περιέχεται σε μερικά πολυβιταμούχα Aνεπιθύμητες ενέργειες: Δεν αναφέρονται. σκευάσματα. Δοσολογία: Στην προφύλαξη από το «σύνδρομο αιφνίδιου θανάτου» προτείνεται χορήγηση 100 mg την ημέρα. Xρησιμοποιείται η πεπτική και παρεντερική οδός. Στην βιοτινοεξαρτώμενη ολοκαρβοξυλασική ανεπάρκεια του παιδιού χορήγηση αρχικά 20-50 mg ενδοφλεβίως ή ενδομυϊκώς την ημέρα για μια εβδομάδα και στη συνέχεια 2.5-5.0 mg την ημέρα. Στην παρεντερική διατροφή, αιμοκάθαρση και περιτοναϊκή κάθαρση 0.5 mg και 2.5 mg την ημέρα αντίστοιχα. Φαρμακευτικά προϊόντα: Δεν κυκλοφορεί ως μεμονωμένη ουσία, αλλά περιέχεται σε μερικά πολυβιταμούχα σκευάσματα.
  • 12. Aντενδείξεις: Bαριά χρόνια νεφρική ανεπάρκεια. Vitamin C H χορήγηση μεγάλων δόσεων Είναι απαραίτητο συστατικό του ανθρώπινου και επί μακρό χρόνο οδηγεί σε δευτεροπαθή οργανισμού. Εχει ισχυρή αναγωγική οξάλωση ιστών και οργάνων, λόγω δράση. αδυναμίας απομάκρυνσης της βιταμίνης και μετατροπής της σε οξαλικό οξύ. O μεταβολικός ρόλος της βιταμίνης C είναι πολυδιάστατος. Oι νεφροπαθείς έχουν ήδη υπεροξαλαιμία Στο έντερο ευνοεί που επιδεινώνεται με τη χορήγηση μεγάλων την απορρόφηση του μη συνδεμένου με δόσεων βιταμίνης C. την αίμη σιδήρου. VITORANGE/Uni-Pharma: gr.or.sd 1000mg x 10 sach x 10g- ef.tab 1000mg x 12 Συμμετέχει στη σύνθεση o της υδροξυπρολίνης, o των κορτικοστεροειδών, o της καρνιτίνης. Eίναι πρόδρομη ουσία o των οξαλικών αλάτων που αποβάλλοναι από τους νεφρούς. o Eίναι ισχυρός αντιοξειδωτικός παράγοντας του μεταβολισμού των λιπιδίων, των κυτταρικών μεμβρανών και των βιταμινών. Στερείται ουσιαστικής τοξικής δράσης, εκτός αν δοθούν πολύ υψηλές δόσεις. Eνδείξεις: o Aνεπαρκής πρόσληψη, o Μειωμένη απορρόφηση, o αυξημένη απώλεια (παρεντερική διατροφή, αιμοκάθαρση και περιτοναϊκή κάθαρση), o αποσιδήρωση, o σκορβούτο, o νόσος Mοeller-Barlow στα παιδιά, που χαρακτηρίζεται από βαριά ένδεια ασκορβικού οξέος και καθυστέρηση στην ανάπτυξη του σκελετού.
  • 13. Συνδυασμοί βιταμινών Multivitamins + Calcium Στο παρόν λήμμα αναφέρονται οι από του Ascorbic Acid + Calcium Carbonate + Pyridoxine στόματος χορηγούμενοι συνδυασμοί βιταμινών. Hydrochloride + Colecalciferol Για τους παρεντερικώς χορηγούμενους CAL-C-VITA/Bayer: ef.tab x 10 βλ. 9.3.3. Ergocalciferol+Ascorbic Acid+Calcium Glycerophosphate FLAVOBION-C/Farmanic: pd.or.sd x 20 sach Vitamin A + D Thiamine Hydrochloride + Retinol + Ergocalciferol Retinol + Vitamin D + Ascorbic Acid + Rivoflavin + Nicotinamide AQUASOL A+D/Μινερβα: or.so.d (40000+ + Calcium Gluconate + Calcium Phosphate 8000)iu/ml fl x 15ml Dibasic PHOSPHOVITAM FORT/Gap: s.c.tab x 24 Vitamin A + Ε DL-Alfa Tocopheryl Acetate + Retinol Acetate EVIOL-A/Gap: sof.g.caps 50mg+25000iu x 20 Vitamin B - complex Thiamine Hydrochloride + Pyridoxine Hydrochloride + Cyanocobalamin BETRIMINE/Help: syr (10+5+0.1)mg/5ml fl x 150 ml EVATON B12/Demo: syr (10+5+0.125)mg/5ml fl x 120 ml- inj. sol 5amps x 5 ml NEUROBION/Galenica: inj.sol (100+100+1)mg /3ml-amp x 3- s.c.tab (100+200+0.2)mg x 20 SOPALAMIN-3B/Farmanic: f.c.tab (250mg+ 125mg+0.250)mg x 20, x 30 TRIVIMINE/Remek: f.c.tab 125mg + 125mg+ 125 mcg x 30 VIONEURIN-6/Galenica: f.c.tab (250mg + 100mg + 0.5) mg x 20
  • 14. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing vitamin Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Vitamin view original wikipedia article This article is about the organic compound. For the nutritional supplement preparation, Vitamin see multivitamin. A vitamin is an overview outline images locations organic compound required as a nutrient Search this article high in tiny amounts by an organism.[1] The term Vitamin 'vitamin' first became popular in the early History 1800's as a In humans contraction of the List of vitamins words 'vital' and In nutrition and diseases 'mineral', though the Deficiencies actual meaning of the Side effects and overdose word has developed Supplements somewhat since that Governmental regulation of vitamin supplements time [2] . A compound Fruits and vegetables are often a good source of vitamins. Names in current and previous is called a vitamin nomenclatures when it cannot be See also synthesized in sufficient quantities by an organism, and must be obtained from the diet. References Thus, the term is conditional both on the circumstances and the particular organism. External links For example, ascorbic acid functions as vitamin C for some animals but not others, and vitamins D and K are required in the human diet only in certain circumstances.[3] The 4 Locations term vitamin does not include other essential nutrients such as dietary minerals, Russia, University essential fatty acids, or essential amino acids, nor does it encompass the large number of Tartu, Scotland, Egypt of other nutrients that promote health but are otherwise required less often. [4] view all Vitamins are classified by their biological and chemical activity, not their structure. Thus, Images Videos each "vitamin" may refer to several vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals are grouped under an alphabetized vitamin "generic descriptor" title, such as "vitamin A", which includes the compounds retinal, retinol, and four known carotenoids.[5] Vitamers are often inter- converted in the body. view all 24 view all 15 Vitamins have diverse biochemical functions, including function as hormones (e.g. vitamin D), antioxidants (e.g. vitamin E), and mediators of cell signaling and regulators of cell and tissue growth and differentiation (e.g. vitamin A).[6] The largest number of vitamins (e.g. B complex vitamins) function as precursors for enzyme cofactor bio- molecules (coenzymes), that help act as catalysts and substrates in metabolism. When acting as part of a catalyst, vitamins are bound to enzymes and are called prosthetic groups. For example, biotin is part of enzymes involved in making fatty acids. Vitamins also act as coenzymes to carry chemical groups between enzymes. For example, folic acid carries various forms of carbon group – methyl, formyl and methylene - in the cell. Although these roles in assisting enzyme reactions are vitamins' best-known function, the other vitamin functions are equally important.[7] Until the 1900s, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) can alter the types and amounts of vitamins ingested. Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades,[8] allowing supplementation of the dietary intake. History The value of The discovery of vitamins and their sources eating a certain Year of discovery Vitamin Source food to maintain health was 1909 Vitamin A (Retinol) Cod liver oil
  • 15. recognized long 1912 Vitamin B 1 (Thiamine) Rice bran before vitamins 1912 Vitamin C (Ascorbic acid) Lemons were identified. 1918 Vitamin D (Calciferol) Cod liver oil The ancient 1920 Vitamin B 2 (Riboflavin) Eggs Egyptians knew 1922 Vitamin E (Tocopherol) Wheat germ oil, that feeding liver Cosmetics and liver to a patient 1926 Vitamin B 12 (Cyanocobalamin) Liver would help cure 1929 Vitamin K (Phylloquinone) Alfalfa night blindness, an illness now 1931 Vitamin B 5 (Pantothenic acid) Liver known to be 1931 Vitamin B 7 (Biotin) Liver caused by a 1934 Vitamin B 6 (Pyridoxine) Rice bran vitamin A 1936 Vitamin B 3 (Niacin) Liver deficiency. [9] The 1941 Vitamin B 9 (Folic acid) Liver advancement of ocean voyage during the Renaissance resulted in prolonged periods without access to fresh fruits and vegetables, and made illnesses from vitamin deficiency common among ships' crews. [10] In 1749, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, causing poor wound healing, bleeding of the gums, severe pain, and death. [9] In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname Limey for sailors of that organization. Lind's discovery, however, was not widely accepted by individuals in the Royal Navy's Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and by maintaining the morale of the crew while on board, rather than by a diet of fresh food.[9] As a result, Arctic expeditions continued to be plagued by scurvy and other deficiency diseases. In the early 20th century, when Robert Falcon Scott made his two expeditions to the Antarctic, the prevailing medical theory was that scurvy was caused by "tainted" canned food.[9] During the late 18th and early 19th centuries, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Initially, lipid from fish oil was used to cure rickets in rats, and the fat-soluble nutrient was called "antirachitic A". Thus, the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called "vitamin A", although confusingly the bioactivity of this compound is now called vitamin D.[11] In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu in present-day Estonia.[12] He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely the proteins, fats, carbohydrates, and salts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that "a natural food such as milk must therefore contain, besides these known principal ingredients, small quantities of unknown substances essential to life."[12] However, his conclusions were rejected by other researchers when they were unable to reproduce his results. One difference was that he had used table sugar (sucrose), while other researchers had used milk sugar (lactose) that still contained small amounts of vitamin B. In east Asia, where polished white rice was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was endemic. In 1884, Takaki Kanehiro, a British trained medical doctor of the Imperial Japanese Navy, observed that beriberi was endemic among The Ancient Egyptians knew that feeding a patient liver (back, low-ranking crew who right) would help cure night blindness. often ate nothing but rice, but not among crews of Western navies and officers who consumed a Western-style diet. With the support of the Japanese navy, he experimented using crews of two battleships; one
  • 16. crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Kanehiro and the Japanese Navy that diet was the cause of beriberi, but mistakenly believed that sufficient amounts of protein prevented it. [13] That diseases could result from some dietary deficiencies was further investigated by Christiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent beriberi in the chickens. The following year, Frederick Hopkins postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, et cetera—that were necessary for the functions of the human body.[9] Hopkins and Eijkman were awarded the Nobel Prize for Physiology or Medicine in 1929 for their discovery of several vitamins. [14] In 1910, Japanese scientist Umetaro Suzuki succeeded in extracting a water-soluble complex of micronutrients from rice bran and named it aberic acid. He published this discovery in a Japanese scientific journal.[15] When the article was translated into German, the translation failed to state that it was a newly discovered nutrient, a claim made in the original Japanese article, and hence his discovery failed to gain publicity. In 1912 Polish biochemist Kazimierz Funk isolated the same complex of micronutrients and proposed the complex be named "Vitamine" (a portmanteau of "vital amine").[16] The name soon became synonymous with Hopkins' "accessory factors", and by the time it was shown that not all vitamins were amines, the word was already ubiquitous. In 1920, Jack Cecil Drummond proposed that the final "e" be dropped to deemphasize the "amine" reference after the discovery that vitamin C had no amine component.[13] In 1931, Albert Szent-Györgyi and a fellow researcher Joseph Svirbely determined that "hexuronic acid" was actually vitamin C and noted its anti-scorbutic activity. In 1937, Szent-Györgyi was awarded the Nobel Prize in Physiology or Medicine for his discovery. In 1943 Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery of vitamin K and its chemical structure. In 1967, George Wald was awarded the Nobel Prize (along with Ragnar Granit and Haldan Keffer Hartline) for his discovery that vitamin A could participate directly in a physiological process. [14] In humans Vitamins are classified as either water-soluble or fat soluble. In humans there are 13 vitamins: 4 fat-soluble (A, D, E and K) and 9 water-soluble (8 B vitamins and vitamin C). Water-soluble vitamins dissolve easily in water, and in general, are readily excreted from the body, to the degree that urinary output is a strong predictor of vitamin consumption. [17] Because they are not readily stored, consistent daily intake is important.[18] Many types of water-soluble vitamins are synthesized by bacteria.[19] Fat- soluble vitamins are absorbed through the intestinal tract with the help of lipids (fats). Because they are more likely to accumulate in the body, they are more likely to lead to hypervitaminosis than are water-soluble vitamins. Fat-soluble vitamin regulation is of particular significance in cystic fibrosis.[20] List of vitamins Each vitamin is typically used in multiple reactions and, therefore, most have multiple functions.[21] Recommended Vitamin Upper Vitamer chemical dietary generic Deficiency Intake Overdose name(s) (list not Solubility allowances descriptor disease Level disease complete) (male, age 19– name (UL/day)[22] 70)[22] Retinol, retinal, Fat 900 µg Night-blindness 3,000 µg Hypervitaminosis various retinoids, and A Vitamin A and Keratomalacia [23] four carotenoids) Thiamine Water 1.2 mg Beriberi, N/D [24] Drowsiness or Vitamin Wernicke- muscle B1 Korsakoff relaxation with syndrome large doses. [25] Vitamin Riboflavin Water 1.3 mg Ariboflavinosis N/D B2
  • 17. Niacin, Water 16.0 mg Pellagra 35.0 mg Liver damage Vitamin niacinamide (doses > B3 2g/day) [26] and other problems Pantothenic acid Water 5.0 mg [27] Paresthesia N/D Diarrhea; Vitamin possibly nausea B5 and heartburn. [28] Pyridoxine, Water 1.3–1.7 mg Anemia [29] 100 mg Impairment of pyridoxamine, peripheral proprioception, Vitamin pyridoxal neuropathy. nerve damage B6 (doses > 100 mg/day) Vitamin Biotin Water 30.0 µg Dermatitis, N/D B7 enteritis Folic acid, folinic Water 400 µg Deficiency during 1,000 µg May mask acid pregnancy is symptoms of Vitamin associated with vitamin B12 B9 birth defects, deficiency; other such as neural effects. tube defects Cyanocobalamin, Water 2.4 µg Megaloblastic N/D No known Vitamin hydroxycobalamin, anemia[30] toxicity[30] B 12 methylcobalamin Ascorbic acid Water 90.0 mg Scurvy 2,000 mg Vitamin C Vitamin C megadosage Ergocalciferol, Fat 5.0 µg–10 Rickets and 50 µg Hypervitaminosis Vitamin D cholecalciferol Osteomalacia D µg[31] Tocopherols, Fat 15.0 mg Deficiency is very 1,000 mg Increased tocotrienols rare; mild congestive heart hemolytic anemia failure seen in Vitamin E in newborn one large infants.[32] randomized study.[33] phylloquinone, Fat 120 µg Bleeding N/D Increases menaquinones diathesis coagulation in Vitamin K patients taking warfarin. [34] In nutrition and diseases Vitamins are essential for the normal growth and development of a multicellular organism. Using the genetic blueprint inherited from its parents, a fetus begins to develop, at the moment of conception, from the nutrients it absorbs. It requires certain vitamins and minerals to be present at certain times. These nutrients facilitate the chemical reactions that produce among other things, skin, bone, and muscle. If there is serious deficiency in one or more of these nutrients, a child may develop a deficiency disease. Even minor deficiencies may cause permanent damage.[35] For the most part, vitamins are obtained with food, but a few are obtained by other means. For example, microorganisms in the intestine—commonly known as " gut flora"—produce vitamin K and biotin, while one form of vitamin D is synthesized in the skin with the help of the natural ultraviolet wavelength of sunlight. Humans can produce some vitamins from precursors they consume. Examples include vitamin A, produced from beta carotene, and niacin, from the amino acid tryptophan.[22] Once growth and development are completed, vitamins remain essential nutrients for the healthy maintenance of the cells, tissues, and organs that make up a multicellular organism; they also enable a multicellular life form to efficiently use chemical energy provided by food it eats, and to help process the proteins, carbohydrates, and fats required for respiration. [6] Deficiencies Because human bodies do not store most vitamins, humans must consume them regularly to avoid deficiency. Human bodily stores for different vitamins vary widely; vitamins A, D, and B12 are stored in significant amounts in the human body, mainly in the liver, [32] and an adult human's diet may be deficient in vitamins A and B12 for many months before developing a deficiency condition. Vitamin B3 is not stored in the human body in significant amounts, so stores may only last a couple of weeks. [23][32]
  • 18. Deficiencies of vitamins are classified as either primary or secondary. A primary deficiency occurs when an organism does not get enough of the vitamin in its food. A secondary deficiency may be due to an underlying disorder that prevents or limits the absorption or use of the vitamin, due to a “lifestyle factor”, such as smoking, excessive alcohol consumption, or the use of medications that interfere with the absorption or use of the vitamin.[32] People who eat a varied diet are unlikely to develop a severe primary vitamin deficiency. In contrast, restrictive diets have the potential to cause prolonged vitamin deficits, which may result in often painful and potentially deadly diseases. Well-known human vitamin deficiencies involve thiamine (beriberi), niacin (pellagra), vitamin C (scurvy) and vitamin D (rickets). In much of the developed world, such deficiencies are rare; this is due to (1) an adequate supply of food; and (2) the addition of vitamins and minerals to common foods, often called fortification. [22][32] In addition to these classical vitamin deficiency diseases, some evidence has also suggested links between vitamin deficiency and a number of different disorders. [36][37] Side effects and overdose In large doses, some vitamins have documented side effects that tend to be more severe with a larger dosage. The likelihood of consuming too much of any vitamin from food is remote, but overdosing from vitamin supplementation does occur. At high enough dosages some vitamins cause side effects such as nausea, diarrhea, and vomiting.[23][38] When side effects emerge, recovery is often accomplished by reducing the dosage. The concentrations of vitamins an individual can tolerate vary widely, and appear to be related to age and state of health. [39] In the United States, overdose exposure to all formulations of vitamins was reported by 62,562 individuals in 2004 (nearly 80% of these exposures were in children under the age of 6), leading to 53 "major" life- threatening outcomes and 3 deaths [40] ;a small number in comparison to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004). [41] Supplements Dietary supplements, often containing vitamins, are used to ensure that adequate amounts of nutrients are obtained on a daily basis, if optimal amounts of the nutrients cannot be obtained through a varied diet. Scientific evidence supporting the benefits of some vitamin supplements is well established for certain health conditions, but others need further study.[42] In some cases, vitamin supplements may have unwanted effects, especially if taken before surgery, with other dietary supplements or medicines, or if the person taking them has certain health conditions. [42] Dietary supplements may also contain levels of vitamins many times higher, and in different forms, than one may ingest through food.[43] A meta-analysis published in 2006 suggested that Vitamin A and E supplements not only provide no tangible health benefits for generally healthy individuals, but may actually increase mortality, although two large studies included in the analysis involved smokers, for which it was already known that beta-carotene supplements can be harmful.[44] Another study released in May 2009 found that antioxidants such as vitamins C and E may actually curb some benefits of exercise. [45] Governmental regulation of vitamin supplements Most countries place dietary supplements in a special category under the general umbrella of foods, not drugs. This necessitates that the manufacturer, and not the government, be responsible for ensuring that its dietary supplement products are safe before they are marketed. Unlike drug products, which must explicitly be proven safe and effective for their intended use before marketing, there are often no provisions to "approve" dietary supplements for safety or effectiveness before they reach the consumer. Also unlike drug products, manufacturers and distributors of dietary supplements are not generally required to report any claims of injuries or illnesses that may be related to the use of their products. [46][47][42]
  • 19. Names in current and previous nomenclatures The reason Nomenclature of reclassified vitamins the set of vitamins Previous name Chemical name Reason for name change [48] seems to Vitamin B 4 Adenine DNA metabolite skip directly Vitamin B 8 Adenylic acid DNA metabolite from E to K Vitamin F Essential fatty acids Needed in large quantities (does is that the not fit the definition of a vitamin). vitamins Vitamin G Riboflavin Reclassified as Vitamin B 2 Vitamin H Biotin Reclassified as Vitamin B 7 Vitamin J Catechol, Flavin Protein metabolite Vitamin L1 [49] Anthranilic acid Protein metabolite Vitamin L2 [49] Adenylthiomethylpentose RNA metabolite Vitamin M Folic acid Reclassified as Vitamin B 9 Vitamin O Carnitine Protein metabolite Vitamin P Flavonoids No longer classified as a vitamin Vitamin PP Niacin Reclassified as Vitamin B 3 Vitamin U S-Methylmethionine Protein metabolite corresponding to "letters" F-J were either reclassified over time, discarded as false leads, or renamed because of their relationship to "vitamin B", which became a "complex" of vitamins. The German-speaking scientists who isolated and described vitamin K (in addition to naming it as such) did so because the vitamin is intimately involved in the Koagulation of blood following wounding. At the time, most (but not all) of the letters from F through to J were already designated, so the use of the letter K was considered quite reasonable.[48][50] The table on the right lists chemicals that had previously been classified as vitamins, as well as the earlier names of vitamins that later became part of the B-complex. See also Antioxidant Dietary supplement Dietetics Health freedom movement Illnesses related to poor nutrition Megavitamin therapy Nutrition Vitamin deficiency Dietary minerals Essential amino acids Essential nutrients Nootropics Nutrients Orthomolecular medicine Pharmacology Vitamin poisoning (overdose) Whole food supplements References 1. ↑ Lieberman, S, Bruning, N (1990). The Real Vitamin & Mineral Book. NY: Avery Group, 3. 2. ↑ Schuman, N, (1998). A History Of COntemplative Medicine. DC: Moseby, 1. 3. ↑ vitamin - definition of vitamin by the Free Online Dictionary, Thesaurus and Encyclopedia 4. ↑ 5. ↑ "vitamer: Definition and Much More from Answers.com". www.answers.com. http://www.answers.com/topic/vitamer?cat=health#top. Retrieved 2008-06-16. 6. ↑ 6.0 6.1 Bender, David A. (2003). Nutritional biochemistry of the vitamins. Cambridge, U.K.: Cambridge University Press. ISBN 978-0-521-80388-5. 7. ↑ Bolander FF (2006). "[Expression error: Missing operand for > Vitamins: not just for enzymes]". Curr Opin Investig Drugs 7 (10): 912–5. PMID 17086936. 8. ↑ Kirk-Othmer (1984). Encyclopedia of Chemical Technology Third Edition. NY: John Wiley and Sons, Vol. 24:104. 9. ↑ 9.0 9.1 9.2 9.3 9.4 Jack Challem (1997). "The Past, Present and Future of Vitamins"
  • 20. 10. ↑ Jacob, RA. (1996). "[Expression error: Missing operand for > Three eras of vitamin C discovery.]". Subcell Biochem 25: 1-16. PMID 8821966. 11. ↑ Bellis, Mary. Vitamins - Production Methods The History of the Vitamins. Retrieved 1 February 2005. 12. ↑ 12.0 12.1 1929 Nobel lecture 13. ↑ 13.0 13.1 Rosenfeld, L. (Apr 1997). "[Expression error: Missing operand for > Vitamine--vitamin. The early years of discovery.]". Clin Chem 43 (4): 680-5. PMID 9105273. 14. ↑ 14.0 14.1 Carpenter, Kenneth (22 June 2004). "The Nobel Prize and the Discovery of Vitamins". http://nobelprize.org/nobel_prizes/medicine/articles/carpenter/index.html. Retrieved 5 October 2009. 15. ↑ Tokyo Kagaku Kaishi: (1911) 16. ↑ Funk, C. and H. E. Dubin. The Vitamines. Baltimore: Williams and Wilkins Company, 1922. 17. ↑ Fukuwatari T, Shibata K (June 2008). "Urinary water-soluble vitamins and their metabolite contents as nutritional markers for evaluating vitamin intakes in young Japanese women" ( – Scholar search ). J. Nutr. Sci. Vitaminol. 54 (3): 223–9. doi:10.3177/jnsv.54.223. PMID 18635909. http://joi.jlc.jst.go.jp/JST.JSTAGE/jnsv/54.223?from=PubMed. 18. ↑ "Water-Soluble Vitamins". http://www.ext.colostate.edu/PUBS/FOODNUT/09312.html. Retrieved 2008-12- 07. 19. ↑ Said HM, Mohammed ZM (March 2006). "Intestinal absorption of water-soluble vitamins: an update". Curr. Opin. Gastroenterol. 22 (2): 140–6. doi:10.1097/01.mog.0000203870.22706.52. PMID 16462170. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00001574- 200603000-00011. 20. ↑ Maqbool A, Stallings VA (November 2008). "Update on fat-soluble vitamins in cystic fibrosis". Curr Opin Pulm Med 14 (6): 574–81. doi:10.1097/MCP.0b013e3283136787. PMID 18812835. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00063198- 200811000-00012. 21. ↑ Kutsky, R.J. (1973). Handbook of Vitamins and Hormones. New York:Van Nostrand Reinhold. 22. ↑ 22.0 22.1 22.2 22.3 Dietary Reference Intakes: Vitamins The National Academies, 2001. 23. ↑ 23.0 23.1 23.2 Vitamin and Mineral Supplement Fact Sheets Vitamin A 24. ↑ N/D= "Amount not determinable due to lack of data of adverse effects. Source of intake should be from food only to prevent high levels of intake"(see Dietary Reference Intakes: Vitamins). 25. ↑ "Thiamin, vitamin B1: MedlinePlus Supplements". http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-thiamin.html. Retrieved 5 October 2009. 26. ↑ J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.992. 27. ↑ Plain type indicates Adequate Intakes (A/I). "The AI is believed to cover the needs of all individuals, but a lack of data prevent being able to specify with confidence the percentage of individuals covered by this intake" (see Dietary Reference Intakes: Vitamins). 28. ↑ "Pantothenic acid, dexpanthenol: MedlinePlus Supplements". http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-vitaminb5.html. Retrieved 5 October 2009. 29. ↑ Vitamin and Mineral Supplement Fact Sheets Vitamin B 6 30. ↑ 30.0 30.1 Vitamin and Mineral Supplement Fact Sheets Vitamin B 12 31. ↑ Value represents suggested intake without adequate sunlight exposure (see Dietary Reference Intakes: Vitamins). 32. ↑ 32.0 32.1 32.2 32.3 32.4 The Merck Manual: Nutritional Disorders: Vitamin Introduction Please select specific vitamins from the list at the top of the page. 33. ↑ http://findarticles.com/p/articles/mi_m0ISW/is_262/ai_n13675725, 34. ↑ Rohde LE, de Assis MC, Rabelo ER (January 2007). "[Expression error: Missing operand for > Dietary vitamin K intake and anticoagulation in elderly patients]". Curr Opin Clin Nutr Metab Care 10 (1): 1–5. doi:10.1097/MCO.0b013e328011c46c. PMID 17143047. 35. ↑ Dr. Leonid A. Gavrilov, Pieces of the Puzzle: Aging Research Today and Tomorrow 36. ↑ Lakhan SE; Vieira KF. Nutritional therapies for mental disorders. Nutrition Journal 2008;7(2). 37. ↑ Boy, E.; Mannar, V.; Pandav, C.; de Benoist, B.; Viteri, F.; Fontaine, O.; Hotz, C. (May 2009). "[Expression error: Missing operand for > Achievements, challenges, and promising new approaches in vitamin and mineral deficiency control.]". Nutr Rev 67 Suppl 1: S24-30. doi:10.1111/j.1753- 4887.2009.00155.x. PMID 19453674. 38. ↑ Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. 39. ↑ Healthier Kids Section: What to take and how to take it. 40. ↑ 2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. 41. ↑ National Center for Health Statistics 42. ↑ 42.0 42.1 42.2 Use and Safety of Dietary Supplements NIH office of Dietary Supplements. 43. ↑ Jane Higdon Vitamin E recommendations at Linus Pauling Institute's Micronutrient Information Center 44. ↑ Bjelakovic G, et al. (2007). "[Expression error: Missing operand for > Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis]". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526.. See also the letter to JAMA by Philip Taylor and Sanford Dawsey and the reply by the authors of the original paper. 45. ↑ http://www.nytimes.com/2009/05/12/health/research/12exer.html?em=&pagewanted=print 46. ↑ Overview of Dietary Supplements 47. ↑ Illnesses and Injuries Associated with the Use of Selected Dietary Supplements U. S. FDA Center for Food Safety and Applied Nutrition 48. ↑ 48.0 48.1 Every Vitamin Page All Vitamins and Pseudo-Vitamins. Compiled by David Bennett. 49. ↑ 49.0 49.1 Michael W. Davidson (2004) Anthranilic Acid (Vitamin L) Florida State University. Accessed 20- 02-07 50. ↑ Vitamins and minerals - names and facts External links
  • 21. USDA RDA chart in PDF format Food portal Health Canada Dietary Reference Intakes Reference Chart for Vitamins NIH Office of Dietary Supplements: Fact Sheets NIH Office of Dietary Supplements. Dietary Supplements: Background Information Vitamins (A11) show ckb: Categories: All articles with dead external links | Articles with dead external links from April 2009 | Essential nutrients | Nutrition | Vitamins History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 22. VITAMIN K BIOTIN Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every LINKS living cell. It occurs mainly bound to proteins or : http://www.diseasesdatabase.com/links1.asp?glngUserCh polypeptides and is abundant in liver, kidney, pancreas, oice=13960 yeast, and milk. The biotin content of cancerous tissue is higher than that of normal tissue. LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=30059
  • 23. VITAMIN E VITAMIN D3 A natural fat-soluble antioxidant with potential A steroid hormone produced in the skin when exposed to chemopreventive activity. Also known as tocopherol, ultraviolet light or obtained from dietary sources. The vitamin E ameliorates free-radical damage to biological active form of cholecalciferol, 1,25- membranes, protecting polyunsaturated fatty acids dihydroxycholecalciferol (calcitriol) plays an important (PUFA) within membrane phospholipids and within role in maintaining blood calcium and phosphorus levels circulating lipoproteins. Peroxyl radicals react 1000-fold and mineralization of bone. The activated form of faster with vitamin E than with PUFA. In the case of cholecalciferol binds to vitamin D receptors and oxygen free radical-mediated tumorigenesis, vitamin E modulates gene expression. This leads to an increase in may be chemopreventive. (NCI04) serum calcium concentrations by increasing intestinal absorption of phosphorus and calcium, promoting distal LINKS renal tubular reabsorption of calcium and increasing : http://www.diseasesdatabase.com/links1.asp?glngUserCh osteoclastic resorption oice=29263 LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=29922
  • 24. VITAMIN D2 VITAMIN D LINKS LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserCh : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=30692 oice=13939 Vitamin D2, a fat-soluble vitamin important for many A family of lipo-soluble steroids important to the biochemical processes including the absorption and absorption, metabolism, and function of calcium and metabolism of calcium and phosphorus. In vivo, phosphorus and the growth and development of bone and ergocalciferol is formed after sun (ultraviolet) irradiation tooth enamel. Found naturally in animal tissues, of plant-derived ergosterol, another form of vitamin D. cholecalciferol (vitamin D3) is formed in the skin when Ergocalciferol is the form of vitamin D usually found in ultraviolet light activates cholesterol conversion into vitamin supplements. (NCI04) vitamin D3. Ultraviolet irradiation of ergosterol (plant vitamin D) forms ergocalciferol (vitamin D2). (NCI04)
  • 25. VITAMIN C LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=13926 DEFICIENCY : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=13930 A natural water-soluble vitamin (Vitamin C). Ascorbic acid is a potent reducing and antioxidant agent that functions in fighting bacterial infections, in detoxifying reactions, and in the formation of collagen in fibrous tissue, teeth, bones, connective tissue, skin, and capillaries. Found in citrus and other fruits, and in vegetables, vitamin C cannot be produced or stored by humans and must be obtained in the diet. (NCI04) Ascorbic Acid Deficiency: "A condition due to a dietary deficiency of ascorbic acid (vitamin C), characterized by malaise, lethargy, and weakness. As the disease progresses, joints, muscles, and subcutaneous tissues may become the sites of hemorrhage. Ascorbic acid deficiency frequently develops into SCURVY in young children fed unsupplemented cow's milk exclusively during their first year. It develops also commonly in chronic alcoholism. (Cecil Textbook of Medicine, 19th ed, p1177) An acquired blood vessel disorder caused by severe deficiency of vitamin C (ASCORBIC ACID) in the diet leading to defective collagen formation in small blood vessels. Scurvy is characterized by bleeding in any tissue, weakness, ANEMIA, spongy gums, and a brawny induration of the muscles of the calves and legs
  • 26. VITAMIN B6 VITAMIB B5 LINKS LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserCh : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=29549 oice=31607 A group of water-soluble vitamins essential for The calcium salt of the water-soluble vitamin B5, metabolism and normal physiological functions. B6 ubiquitously found in plants and animal tissues with vitamins, including pyridoxine, pyridoxal, and antioxidant property. Pentothenate is a component of pyridoxamine, are converted in vivo to pyridoxal coenzyme A (CoA) and a part of the vitamin B2 complex. phosphate, a cofactor necessary for the synthesis of Vitamin B5 is a growth factor and is essential for various amino acids, neurotransmitters, and sphingolipids. More metabolic functions, including the metabolism of than 100 enzymes involved in protein metabolism require carbohydrates, proteins, and fatty acids. This vitamin is vitamin B6 as a cofactor. Vitamin B6 is essential to red also involved in the synthesis of cholesterol, lipids, blood cell, nervous system, and immune systems neurotransmitters, steroid hormones, and hemoglobin. functions and helps maintain normal blood glucose levels. Vitamin B6 is found in a wide variety of foods including cereals, beans, meat, poultry, fish, and some fruits and vegetables. (NCI04)
  • 27. VITAMIN B3 VITAMIN B2 LINKS LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserCh : http://www.diseasesdatabase.com/links1.asp?glngUserCh oice=9007 oice=11561 A water-soluble vitamin belonging to the vitamin B family, An essential human nutrient that is a heat-stable and water-soluble which occurs in many animal and plant tissues, with flavin belonging to the vitamin B family. Riboflavin is a precursor of antihyperlipidemic activity. Niacin is converted to its active the coenzymes flavin mononucleotide (FMN) and flavin adenine form niacinamide, which is a component of the coenzymes dinucleotide (FAD). These coenzymes are of vital importance in nicotinamide adenine dinucleotide (NAD) and its phosphate normal tissue respiration, pyridoxine activation, tryptophan to niacin form, NADP. These coenzymes play an important role in conversion, fat, carbohydrate, and protein metabolism, and tissue respiration and in glycogen, lipid, amino acid, protein, glutathione reductase mediated detoxification. Riboflavin may also and purine metabolism. Although the exact mechanism of be involved in maintaining erythrocyte integrity. This vitamin is action by which niacin lowers cholesterol is not fully essential for healthy skin, nails, and hair. understood, it may act by inhibiting the synthesis of very low density lipoproteins (VLDL), inhibiting the release of free fatty acids from adipose tissue, increasing lipoprotein lipase activity, and reducing the hepatic synthesis of VLDL-C and LDL-C
  • 28. VITAMIN B1 LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserChoice=13032 A heat-labile and water-soluble essential vitamin, belonging to the vitamin B family, with antioxidant, erythropoietic, mood modulating, and glucose-regulating activities. Thiamine reacts with adenosine triphosphate (ATP) to form an active coenzyme, thiamine pyrophosphate. Thiamine pyrophosphate is necessary for the actions of pyruvate dehydrogenase and alpha- ketoglutarate in carbohydrate metabolism and for the actions of transketolase, an enzyme that plays an important role in the pentose phosphate pathway. Thiamine plays a key role in intracellular glucose metabolism and may inhibit the action of glucose and insulin on arterial smooth muscle cell proliferation. Thiamine may also protect against lead toxicity by inhibiting lead-induced lipid peroxidation VITAMIN A LINKS : http://www.diseasesdatabase.com/links1.asp?glngUserChoice=13888 An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE
  • 29. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing BIOTIN Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Biotin view original wikipedia article Biotin This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (April 2007) overview outline images locations Biotin, also known as vitamin H or B 7 , is a Biotin[1] Search this article high water-soluble B- complex vitamin which is composed of Biotin an ureido General overview Bioavailability Factors that affect biotin requirements Uses Hair problems Cradle cap (seborrheic dermatitis) Diabetes Deficiency Toxicity Biochemistry IUPAC name 5-[(3aS,4S,6aR)-2-oxohexahydro-1H- Laboratory uses thieno[3,4-d]imidazol-4-yl]pentanoic acid Ruminant nutrition Other names Vitamin B 7 ; Vitamin H; Coenzyme R; Biopeiderm See also Identifiers References CAS number 58-85-5 PubChem 171548 External links SMILES O=C1N[C@@H]2[C@@H](SC[C@@H]2N1)CCCCC(=O)O InChI 1/C10H16N2O3S/c13-8(14)4-2-1-3-7-9-6(5-16-7)11- 10(15)12-9/h6-7,9H,1-5H2,(H,13,14)(H2,11,12,15)/t6-,7- Images Videos ,9-/m0/s1 InChI key YBJHBAHKTGYVGT-ZKWXMUAHBB ChemSpider ID 149962 Properties Molecular C10 H16 N2 O 3 S formula view all 24 view all 15 Molar mass 244.31 g mol−1 Appearance White crystalline needles Melting point 232-233 °C Solubility in 22 mg/100 mL water Supplementary data page Structure and n, εr , etc. properties Thermodynamic Phase behaviour data Solid, liquid, gas Spectral data UV, IR, NMR, MS (what is this?) (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring. Biotin is a cofactor in the metabolism of fatty acids and leucine, and it plays a role in gluconeogenesis. General overview Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. It plays a role in the citric acid cycle, which is the process by which biochemical energy is generated during aerobic respiration. Biotin not only assists in various metabolic reactions, but also helps to transfer carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level.[1] Biotin is often recommended for strengthening hair and nails. Consequently, it is found in many cosmetics and health
  • 30. products for the hair and skin. Biotin deficiency is rare, as intestinal bacteria generally produce an excess of the body's recommended daily requirement. For that reason, statutory agencies in many countries (e.g., the Australian Department of Health and Ageing) do not prescribe a recommended daily intake of Biotin. Bioavailability Studies on the bioavailability of biotin have been conducted in rats and in chicks. From these studies, it was concluded that biotin bioavailability may be low or variable depending on the type of food being consumed. In general, biotin exists in food as protein bound form or biocytin [2] . Proteolysis by protease is required prior to absorption. This process assists free biotin release from biocytin and protein bound biotin.The biotin present in corn is readily available; however, most grain have about a 20-40% bioavailability of biotin.[3] A possible explanation for the wide variability in biotin bioavailability is that it is due to ability of an organism to break various biotin-protein bonds from food. Whether an organism has an enzyme with the ability to break that bond will determine the bioavailability of biotin from the foodstuff. [3] Factors that affect biotin requirements The frequency of marginal biotin status is not known, but the incidence of low circulating biotin levels in alcoholics has been found to be much greater than in the general population. Also, relatively low levels of biotin have been reported in the urine or plasma of patients who have had partial gastrectomy or who have other causes of achlorhydria, burn patients, epileptics, elderly individuals and athletes. [3] Pregnancy and lactation may be associated with an increased demand for biotin. In pregnancy, this may be due to a possible acceleration of biotin catabolism, whereas in lactation, the higher demand has yet to be elucidated. Recent studies have shown that marginal biotin deficiency can be present in human gestation, as evidenced by increased urinary excretion of 3- hydroxyisovaleric acid, decreased urinary excretion of biotin and bisnorbiotin, and decreased plasma concentration of biotin. Additionally, smoking may further accelerate biotin catabolism in women. [4] Uses Hair problems Biotin supplements are often recommended as a natural product to counteract the problem of hair loss in both children and adults. The signs and symptoms of biotin deficiency include hair loss which progresses in severity to include loss of eye lashes and eye brows in severely deficient subjects. Some shampoos are available that contain biotin, but it is doubtful whether they would have any useful effect, as biotin is not absorbed well through the skin. Cradle cap (seborrheic dermatitis) Children with a rare inherited metabolic disorder called phenylketonuria (PKU; in which one is unable to break down the amino acid phenylalanine) often develop skin conditions such as eczema and seborrheic dermatitis in areas of the body other than the scalp. The scaly skin changes that occur in people with PKU may be related to poor ability to use biotin. Increasing dietary biotin has been known to improve seborrheic dermatitis [5] in these cases. Diabetes Diabetics may also benefit from biotin supplementation. In both insulin-dependent and non-insulin-dependent diabetes, supplementation with biotin can improve blood sugar control and help lower fasting blood glucose levels, in some studies the reduction in fasting glucose exceeded 50 percent. Biotin can also play a role in preventing the neuropathy often associated with diabetes, reducing both the numbness and tingling associated with poor glucose control.[6]
  • 31. Deficiency Biotin deficiency is relatively rare and mild, and can be addressed with supplementation. Such deficiency can be caused by the excessive consumption of raw egg whites (20 eggs/day would be required to induce it), which contain high levels of the protein avidin, which binds biotin strongly. Avidin is deactivated by cooking, while the biotin remains intact. ¨Symptoms of overt biotin deficiency include hair loss and a scaly red rash around the eyes, nose, mouth, and genital area. Neurological symptoms in adults have included depression, lethargy, hallucination, and numbness and tingling of the extremities. The characteristic facial rash, together with an unusual facial fat distribution, has been termed the ¨biotin-deficient face¨ by some experts. Individuals with hereditary disorders of biotin deficiency have evidence of impaired immune system function, including increased susceptibility to bacterial and fungal infections.¨[7] Biotinidase deficiency is not due to inadequate biotin, but rather to a deficiency in the enzymes that process it. Signs of Biotin Deficiency: In general, appetite and growth are decreased. Dermatologic symptoms include dermatitis, alopecia (hair loss) and achromotrichia (absence or loss of pigment in the hair. [8] ) Perosis (a shortening and thickening of bones) is seen in the skeleton. Fatty Liver and Kidney Syndrome (FLKS) and hepatic steatosis also can occur. [3] Genetic defect could also cause biotin deficiency. Holocarboxylase synthetase deficiency is a genetic mutation. It is a severe metabolic disorder. Biochemical and clinical manifestation includes: ketolactic acidosis, organic aciduria, hyperammonemia, skin rash, feeding problems, hypotonie, seizures, development delay, alopecia, and coma. This disease is lethal, however, mentioned manifestation can be reversed by pharmacologic doses of biotin (10-100 mg per day). Pregnant women tend to have high risk of biotin deficiency. Research has shown that nearly half of pregnant women have an abnormal increase of 3-hydroxyisovaleric acid which reflects reduced status of biotin.[7] Numbers of studies reported that this possible biotin deficiency during the pregnancy may cause infants' congenital malformations such as cleft palate. Mice fed with dried raw egg to induce biotin deficiency during the gestation resulted in up to 100% incidence of the infants' malnourishment. Infants and embryos are more sensitive to the biotin deficiency. Therefore even a mild level of mother's biotin deficiency which does not reach the appearance of physiological deficiency signs may cause a serious consequence in the infants. Toxicity Animal studies have indicated few, if any, effects due to toxic doses of biotin. This may provide evidence that both animals and humans could tolerate doses of at least an order of magnitude greater than each of their nutritional requirements. There are no reported cases of adverse effects from receiving high doses of the vitamin, particularly when used in the treatment of metabolic disorders causing sebhorrheic dermatitis in infants.[9] Biochemistry Biotin D(+) is a cofactor responsible for carbon dioxide transfer in several carboxylase enzymes: Acetyl-CoA carboxylase alpha Acetyl-CoA carboxylase beta Methylcrotonyl-CoA carboxylase Propionyl-CoA carboxylase Pyruvate carboxylase The attachment of biotin to various chemical sites, called biotinylation, can be used as an important laboratory technique to study various processes including protein localization, protein interactions, DNA transcription and replication. Biotinidase itself is known to be able to biotinylate histones,[10] but little biotin is found naturally attached to chromatin. Holocarboxylase synthetase is the mammalian enzyme that covalently
  • 32. attaches biotin to carboxylases. Biotin binds very tightly to the tetrameric protein avidin (also streptavidin and neutravidin), with a dissociation constant Kd in the order of 10 −15 which is one of the strongest known protein-ligand interactions, approaching the covalent bond in strength. [11] This is often used in different biotechnological applications. Until 2005, very harsh conditions were required to break the biotin-streptavidin bond. [12] Laboratory uses In the biology laboratory, biotin is often chemically linked, or tagged, to a molecule or protein for biochemical assays. This process is called biotinylation. Because avidins bind preferentially to biotin, biotin-tagged molecules can be extracted from a sample by mixing them with beads with covalently-attached avidin, and washing away anything unbound to the beads. For example, biotin can be attached to a molecule of interest (e.g. a protein), and this modified molecule will be mixed with a complex mixture of proteins. Avidin or streptavidin beads are added to the mixture, and the biotinylated molecule will bind to the beads. Any other proteins binding to the biotinylated molecule will also stay with the beads. All other unbound proteins can be washed away, and the scientist can use a variety of methods to determine which proteins have bound to the biotinylated molecule. Biotinylated antibodies are used to capture avidin or streptavidin in both the ELISPOT and ELISA techniques. Ruminant nutrition Ruminal bacteria normally synthesize biotin. Biotin is not extensively metabolized in the rumen and increased intake of dietary biotin results in elevated concentrations of biotin in serum and milk.[13] Unpublished epidemiologic data suggest a negative relationship between serum concentrations of biotin and the incidence of clinical lameness in dairy cattle. Feeding approximately 20 mg/day of supplemental biotin statistically improved measures of hoof health. Currently, insufficient data are available at this time to quantify the requirement for biotin of dairy cattle. See also Biotinylation Avidin Streptavidin NeutrAvidin Strep-tag Multiple carboxylase deficiency References 1. ↑ Merck Index, 11th Edition, 1244. 2. ↑ Gropper S.S., Smith, J.L.,Groff, J.L. (2005). Advanced nutrition and human metabolism. Belmont. 3. ↑ 3.0 3.1 3.2 3.3 Combs, Gerald F. Jr. (2008). The Vitamins: Fundamental Aspects in Nutrition and Health. San Diego: Elsevier, Inc. ISBN 9780121834937. 4. ↑ Bowman, BA and Russell, RM., ed (2006). "Biotin". Present Knowledge in Nutrition, Ninth Edition, Vol 1. Washington, DC: Internation Life Sciences Institute. ISBN 9781578811984. 5. ↑ Murray, Michael; Pizzorno, Joseph (1997). "Encyclopedia of Natural Medicine" (Revised 2nd Edition) Three Rivers Press. ISBN 0761511571 6. ↑ http://recipes.howstuffworks.com/biotin2.htm 7. ↑ 7.0 7.1 Higdon, Jane (2003). "Biotin". An evidence-based approach to vitamins and minerals. Thieme. ISBN 9781588901248. 8. ↑ biology-online.org 9. ↑ Combs, Gerald F. Jr. (1998). The Vitamins: Fundamental Aspects in Nutrition and Health. Ithaca: Elsevier Academic Press. ISBN 0121834921.pg. 360 10. ↑ Hymes, J; Fleischhauer, K; Wolf, B. (1995). "[Expression error: Missing operand for > Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency.]". Biochem Mol Med. 56 (1): 76–83. doi:10.1006/bmme.1995.1059. PMID 8593541. 11. ↑ Laitinen OH, Hytonen VP, Nordlund HR, Kulomaa MS. (2006). "[Expression error: Missing operand for > Genetically engineered avidins and streptavidins.]". Cell Mol Life Sci. 63 (24): 2992–3017. doi:10.1007/s00018-006-6288-z. PMID 17086379. 12. ↑ Holmberg A, Blomstergren A, Nord O et al. (2005). "[Expression error: Missing operand for > The
  • 33. biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures]". Electrophoresis 26 (3): 501–10. doi:10.1002/elps.200410070. PMID 15690449. 13. ↑ National Research Council (2001). Nutrient Requirements of Dairy Cattle. 7th rev. ed.. Natl. Acad. Sci., Washington, DC.. ISBN 0309069971. http://books.nap.edu/openbook.php?isbn=0309069971. External links Jane Higdon, "Biotin", Micronutrient Information Center, Linus Pauling Institute Clercq, Pierre J. De (1997). "[Expression error: Missing operand for > Biotin: A Timeless Challenge for Total Synthesis]". Chemical Review 97: 1755–1792. doi:10.1021/cr950073e. Vitamins (A11) show Categories: Articles needing additional references from April 2007 | All articles needing additional references | All articles with specifically-marked weasel-worded phrases | Articles with specifically-marked weasel-worded phrases from November 2009 | All articles with unsourced statements | Articles with unsourced statements from November 2009 | Articles with unsourced statements from March 2009 | Vitamins | Organosulfur compounds | Cofactors History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 34. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN E Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Vitamin E view original wikipedia article Main articles: tocopherol and Vitamin E tocotrienol Vitamin E is a generic term overview outline images locations for tocopherols and tocotrienols.[1] Vitamin E is a Search this article family of α-, β-, γ-, and high δ-tocopherols and The α-tocopherol form of vitamin E. corresponding four Vitamin E tocotrienols. Vitamin E is a fat-soluble antioxidant that stops the production of reactive Food sources of Vitamin E oxygen species formed when fat undergoes oxidation.[2][3][4] Of these, α-tocopherol Vitamin E to prevent prostate cancer stud (also written as alpha-tocopherol) has been most studied as it has the highest discontinued Congenital heart defects bioavailability.[5] References It has been claimed that α-tocopherol is the most important lipid-soluble antioxidant, Further reading and that it protects cell membranes from oxidation by reacting with lipid radicals External links produced in the lipid peroxidation chain reaction.[3][6] This would remove the free radical intermediates and prevent the oxidation reaction from continuing. The oxidised 2 Locations α-tocopheroxyl radicals produced in this process may be recycled back to the active Netherlands, United Kingdom reduced form through reduction by other antioxidants, such as ascorbate, retinol or view all ubiquinol.[7] However, the importance of the antioxidant properties of this molecule at the concentrations present in the body are not clear and it is possible that the reason Images Videos why vitamin E is required in the diet is unrelated to its ability to act as an antioxidant. [8] . Other forms of vitamin E have their own unique properties. For example, γ-tocopherol (also written as gamma-tocopherol) is a nucleophile that can react with electrophilic mutagens.[5] view all 24 view all 15 However, the roles and importance of all of the various forms of vitamin E are presently unclear, [9][10] and it has even been suggested that the most important function of vitamin E is as a signaling molecule, and that it has no significant role in antioxidant metabolism. [11][12] So far, most studies about vitamin E have supplemented using only the synthetic alpha- tocopherol, but doing so leads to reduced serum gamma- and delta-tocopherol concentrations. Moreover, a 2007 clinical study involving synthetic alpha-tocopherol concluded that supplementation did not reduce the risk of major cardiovascular events in middle aged and older men.[13] For more info, read article tocopherol. Compared with tocopherols, tocotrienols are poorly studied. [14][15][16] Less than 1% of PubMed papers on vitamin E relate to tocotrienols. [17] Current research direction are starting to give more prominence to the tocotrienols, the lesser known but more potent antioxidants in the vitamin E family. Tocotrienols have specialized roles in protecting neurons from damage[18] , cancer prevention[19] and cholesterol reduction [20] by inhibiting the activity of HMG-CoA reductase[16-1];δ-tocotrienol blocks processing of sterol regulatory element-binding proteins (SREBPs)[16-1]. Oral consumption of tocotrienols is also proven to protect against stroke-associated brain damage in vivo. Disappointments with outcomes-based clinical studies testing the efficacy of α-tocopherol need to be handled with caution and prudence recognizing the untapped opportunities offered by the other forms of natural vitamin E. [21] Toxicity studies of a specific form of tocopherol in excess should not be used to conclude that high-dosage “vitamin E” supplementation may increase all-cause mortality. Such conclusion incorrectly implies that tocotrienols are toxic as well under conditions where tocotrienols were not even considered. [22] For more info, read article tocotrienol. Food sources of Vitamin E Particularly high levels of vitamin E can be found in the following foods: [23]
  • 35. Asparagus Avocado Egg Milk Nuts, such as almonds or hazelnuts Seeds Spinach and other green leafy vegetables Unheated vegetable oils Wheat germ Wholegrain foods Vitamin E to prevent prostate cancer study discontinued There have been some theories that Vitamin E, especially when coupled with selenium, may reduce the risk of prostate cancer [24] by 30 percent.[25] However, the Selenium and Vitamin E Cancer Prevention Trial, ("SELECT"), run from 2004 to 2008, found that vitamin E, whether taken alone or in combination with selenium, did not prevent prostate cancer. [26] The SELECT study was discontinued after independent reviewers determined that there was no benefit to the 35,000 men who were the subject of the study. [24] Congenital heart defects A case control study done in the Netherlands using food frequency questionnaires found that high maternal Vitamin E by diet and supplements is associated with an increased risk of CHD (congenital heart defects) offspring, especially when the supplements are taken in the periconception period.[27] (Note: case control studies are rated as low quality, grade 3 or 4, on a standard scale of medical evidence.[28] ) The National Health Service in the United Kingdom concludes that pregnant women should: "consider avoiding taking supplemental Vitamin E tablets." [29] References 1. ↑ Brigelius-Flohe, Regina (1999). "Vitamin E: function and metabolism". <I>The FASEB Journal</I> 13 (10): 1145. PMID 10385606. http://www.fasebj.org/cgi/content/short/13/10/1145. 2. ↑ National Institute of Health (5/4/2009). "Vitamin E Fact Sheet". http://ods.od.nih.gov/factsheets/VitaminE.asp. 3. ↑ 3.0 3.1 Herrera (2001). "[Expression error: Missing operand for > Vitamin E: action, metabolism and perspectives]". Journal of physiology and biochemistry 57 (2): 43–56. PMID 11579997. 4. ↑ Packer, Lester (2001). "Molecular Aspects of α-Tocotrienol Antioxidant Action and Cell Signalling". Journal of Nutrition 131 (2): 369S. PMID 11160563. http://jn.nutrition.org/cgi/content/full/131/2/369S. 5. ↑ 5.0 5.1 Brigelius-Flohé (1999). "[Expression error: Missing operand for > Vitamin E: function and metabolism]". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 (10): 1145–55. PMID 10385606. 6. ↑ Traber (2007). "[Expression error: Missing operand for > Vitamin E, antioxidant and nothing more]". Free radical biology & medicine 43 (1): 4–15. doi:10.1016/j.freeradbiomed.2007.03.024. PMID 17561088. 7. ↑ Wang (1999). "[Expression error: Missing operand for > Vitamin E and its function in membranes]". Progress in lipid research 38 (4): 309–36. doi:10.1016/S0163-7827(99)00008-9. PMID 10793887. 8. ↑ Brigelius-Flohé (2009). "[Expression error: Missing operand for > Vitamin E: the shrew waiting to be tamed]". Free radical biology & medicine 46 (5): 543–54. doi:10.1016/j.freeradbiomed.2008.12.007. PMID 19133328. 9. ↑ Brigelius-Flohé (2007). "[Expression error: Missing operand for > Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson]". Free radical biology & medicine 43 (1): 2–3. doi:10.1016/j.freeradbiomed.2007.05.016. PMID 17561087. 10. ↑ Atkinson (2008). "[Expression error: Missing operand for > Tocopherols and tocotrienols in membranes: a critical review]". Free radical biology & medicine 44 (5): 739–64. doi:10.1016/j.freeradbiomed.2007.11.010. PMID 18160049. 11. ↑ Azzi (2007). "[Expression error: Missing operand for > Molecular mechanism of alpha-tocopherol action]". Free radical biology & medicine 43 (1): 16–21. doi:10.1016/j.freeradbiomed.2007.03.013. PMID 17561089. 12. ↑ Zingg (2004). "[Expression error: Missing operand for > Non-antioxidant activities of vitamin E]". Current medicinal chemistry 11 (9): 1113–33. PMID 15134510. 13. ↑ Sesso, H. D. (2008). "[Expression error: Missing operand for > Vitamins E and C in the Prevention of Cardiovascular Disease in Men: the Physicians' Health Study II Randomized Controlled Trial]". JAMA: the Journal of the American Medical Association 300: 2123. doi:10.1001/jama.2008.600. 14. ↑ Traber, MG (1995). "Vitamin E: beyond antioxidant function". American Journal of Clinical Nutrition 62 (6): 1501S. PMID 7495251. http://www.ajcn.org/cgi/content/abstract/62/6/1501S.
  • 36. 15. ↑ Traber (1996). "[Expression error: Missing operand for > Vitamin E in humans: demand and delivery]". Annual review of nutrition 16: 321–47. doi:10.1146/annurev.nu.16.070196.001541. PMID 8839930. 16. ↑ Sen (2004). "[Expression error: Missing operand for > Tocotrienol: the natural vitamin E to defend the nervous system?]". Annals of the New York Academy of Sciences 1031: 127–42. doi:10.1196/annals.1331.013. PMID 15753140. 17. ↑ Sen (2006). "[Expression error: Missing operand for > Tocotrienols: Vitamin E beyond tocopherols]". Life sciences 78 (18): 2088–98. doi:10.1016/j.lfs.2005.12.001. PMID 16458936. 18. ↑ Sen (2006). "[Expression error: Missing operand for > Tocotrienols: Vitamin E beyond tocopherols]". Life sciences 78 (18): 2088–98. doi:10.1016/j.lfs.2005.12.001. PMID 16458936. 19. ↑ Malafa (2008). "New insights and gains in pancreatic cancer". Cancer control : journal of the Moffitt Cancer Center 15 (4): 276–7. PMID 18813194. http://www.moffitt.org/CCJRoot/v15n4/pdf/276.pdf. 20. ↑ Das (2008). "[Expression error: Missing operand for > Cardioprotection with palm oil tocotrienols: comparision of different isomers]". American journal of physiology. Heart and circulatory physiology 294 (2): H970–8. doi:10.1152/ajpheart.01200.2007. PMID 18083895. 21. ↑ Sen, C (2007). "[Expression error: Missing operand for > Tocotrienols in health and disease: the other half of the natural vitamin E family]". Molecular Aspects of Medicine 28 (5-6): 692. doi:10.1016/j.mam.2007.03.001. PMID 17507086. 22. ↑ Sen (2007). "[Expression error: Missing operand for > Tocotrienols: the emerging face of natural vitamin E]". Vitamins and hormones 76: 203–61. doi:10.1016/S0083-6729(07)76008-9. PMID 17628176. 23. ↑ USDA National Nutrient Database 24. ↑ 24.0 24.1 American Cancer Society, Vitamin E, updated Oct. 27, 2008 25. ↑ National Cancer Institute, The SELECT Prostate Cancer Prevention Trial, Oct. 27, 2008 26. ↑ National Cancer Institute, Selenium and Vitamin E Cancer Prevention Trial (SELECT), Oct. 31, 2008 27. ↑ Smedts (2009). "[Expression error: Missing operand for > High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring]". BJOG : an international journal of obstetrics and gynaecology 116 (3): 416–23. doi:10.1111/j.1471-0528.2008.01957.x. PMID 19187374. 28. ↑ Bob Phillips; Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes (May 2001). "Levels of Evidence". Oxford Centre for Evidence-based Medicine. http://www.cebm.net/index.aspx?o=1047. 29. ↑ http://www.nhs.uk/news/2009/04April/Pages/VitaminEPregnancyRisk.aspx Further reading Brigelius-Flohe, Regina (2002). "The European perspective on vitamin E: current knowledge and future research". American Journal of Clinical Nutrition 76 (4): 703. PMID 12324281. http://www.ajcn.org/cgi/pmidlookup? view=long&pmid=12324281. External links Vitamin E Medline Plus, Medical Encyclopedia, U.S. National Library of Medicine Vitamin E Office of Dietary Supplements, National Institutes of Health Jane Higdon, "Vitamin E", Micronutrient Information Center, Linus Pauling Institute Vitamins (A11) show Categories: Vitamins | Food antioxidants History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 37. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN D3 Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Cholecalciferol view original wikipedia article Cholecalciferol This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (December 2008) overview outline images locations Cholecalciferol Search this article high Cholecalciferol Forms Metabolism Regulation of metabolism As food fortification Dose IUPAC name (3β,5Z,7E)-9,10-secocholesta- Stability 5,7,10(19)-trien-3-ol Other names vitamin D3 , activated 7-dehydrocholesterol. Therapeutic Application Identifiers Alternative Views CAS number 67-97-0 See also EC number 200-673-2 References SMILES O[C@@H]1CC(C(=C)CC1)=CC=C2/CCC[C@]3(C2CC[C@@H]3[C@H](C)CCCC(C)C)C links External InChI 1/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18- 24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23- 13-/t21-,24+,25-,26?,27-/m1/s1 Images Videos InChI key QYSXJUFSXHHAJI-QWSSABAFBD ChemSpider ID 9058792 Properties Molecular formula C27 H44 O Molar mass 384.64 g/mol Appearance White, needle-like crystals view all 24 view all 15 Melting point 83–86 °C Supplementary data page Structure and properties n, εr , etc. Thermodynamic data Phase behaviour Solid, liquid, gas Spectral data UV, IR, NMR, MS (what is this?) (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references Cholecalciferol is a form of Vitamin D, also called vitamin D 3 or calciol. [1] It is structurally similar to steroids such as testosterone, cholesterol, and cortisol (though vitamin D 3 itself is a secosteroid). One gram of pure vitamin D 3 is 40 000 000 (40x106 ) IU, or, in other words, one IU is 0.025 μg. Individuals having a high risk of deficiency should consume 125 μg (5000 IU) of vitamin D daily. Forms Vitamin D 3 has several forms: Cholecalciferol, (sometimes called calciol) which is an inactive, unhydroxylated form of vitamin D 3 ) Calcidiol (also called 25-hydroxyvitamin D 3 ), which is the form measured in the blood to assess vitamin D status Calcitriol (also called 1,25-dihydroxyvitamin D 3 ), which is the active form of D 3 . Metabolism
  • 38. 7-Dehydrocholesterol is the precursor of vitamin D 3 and forms cholecalciferol only after being exposed to solar UV radiation. Cholecalciferol is then hydroxylated in the liver to become calcidiol (25-hydroxyvitamin D 3 ). Next, calcidiol is again hydroxylated, this time in the kidney, and becomes calcitriol (1,25-dihydroxyvitamin D 3 ). Calcitriol is the most active hormone form of vitamin D 3 . Regulation of metabolism Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol under the action of ultraviolet B light. It reaches an equilibrium after several minutes depending on several factors including conditions of sunlight (latitude, season, cloud cover, altitude), age of skin, and color of skin. Hydroxylation in the liver of cholecalciferol to calcidiol (25-hydroxycholecalciferol) is loosely regulated, if at all, and blood levels of this molecule largely reflect the amount of vitamin D 3 produced in the skin or the vitamin D 2 or D 3 ingested. Hydroxylation in the kidneys of calcidiol to calcitriol by 1-alpha-hydroxylase is tightly regulated (stimulated by either parathyroid hormone or hypophosphatemia) and serves as the major control point in production of the most active circulating hormone calcitriol (1,25-dihydroxyvitamin D 3 ). As food fortification Although cholecalciferol can be synthesized in the skin (see Metabolism), it is also a form of vitamin D added to fortify foods. Cholecalciferol is produced industrially by the irradiation of 7-dehydrocholesterol extracted from lanolin found in sheep's wool. In foods where animal products are not desired, an alternative compound is ergocalciferol (also known as vitamin D 2 ) derived from the fungal sterol ergosterol. Dose There are conflicting reports concerning the absorption of cholecalciferol (D3 ) versus ergocalciferol (D2 ), with some studies suggesting less efficacy of D 2 [2] , and others showing no difference [2] [3] . At present, D 2 and D 3 doses are frequently considered interchangeable, but more research is needed to clarify this. Stability Cholecalciferol is very sensitive to UV radiation and will rapidly, but reversibly, break down to form supra-sterols, which can further irreversibly convert to ergosterol. Therapeutic Application A 2008 study published in Cancer Research has shown the addition of vitamin D 3 (along with calcium) to the diet of some mice fed a regimen similar in nutritional content to a new Western diet prevented colon cancer development. [4] Alternative Views There is a minority view, often associated with Trevor Marshall, which asserts that low levels of calcidiol (25-hydroxyvitamin D3) are often due to overconversion into calcitriol (1,25-dihydroxyvitamin D3, the active form of D3) because of chronic infection rather than calcidiol deficiency. [1] See also Hypervitaminosis D, Vitamin D poisoning Ergocalciferol, vitamin D 2 . 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, a kidney enzyme that converts
  • 39. calcidiol to calcitriol. References 1. ↑ cholecalciferol at Dorland's Medical Dictionary 2. ↑ 2.0 2.1 Armas L, Hollis B, Heaney R (2004). "Vitamin D2 is much less effective than vitamin D3 in humans". J Clin Endocrinol Metab 89 (11): 5387–91. doi:10.1210/jc.2004-0360. PMID 15531486. http://jcem.endojournals.org/cgi/content/full/jcem;89/11/5387. 3. ↑ Hollick, Biancuzzo, Chen, Klein, Young, Bilbud, Reitz, Salameh, Ameri, Tanenbaum (2007). "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin-D". J Clin Endocrinol Metab 93 (3): 6777–81. doi:10.1210/jc.2007-2308. PMID 18089691. http://jcem.endojournals.org/cgi/rapidpdf/jc.2007-2308v1. 4. ↑ Yang, Kurihara, Fan, Newmark, Rigas, Bancroft, Corner, Livote, Lesser, Edelmann, Velcich, Lipkin, Augenlicht (2008). "Dietary Induction of Colonic Tumors in a Mouse Model of Sporadic Colon Cancer "Context: Colonic tumors were prevented by elevating dietary calcium and vitamin D3 to levels comparable with upper levels consumed by humans"". Cancer Research 68: 3075. doi:10.1158/0008-5472.CAN-07- 6426. http://cancerres.aacrjournals.org/cgi/content/short/68/19/7803?rss=1. External links NIST Chemistry WebBook page for cholecalciferol http://www.VitaminDCouncil.org http://www.uctv.tv/search-details.aspx?showID=15751 http://www.uctv.tv/search-details.aspx?showID=15767 Cholestanes, membrane lipids: sterols show Adosterol - Cholecalciferol/Ergocalciferols - Cholesterol - Dihydrotachysterol - Fusidic acid - Lanosterol - Phytosterols Categories: Articles needing additional references from December 2008 | All articles needing additional references | All articles with unsourced statements | Articles with unsourced statements from November 2009 | Secosteroids | Vitamin D History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 40. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN D Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Vitamin D view original wikipedia article For other uses, see Vitamin D (disambiguation). Vitamin D Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D 2 (or overview outline images locations ergocalciferol) and vitamin D 3 (or Search this article high cholecalciferol).[1] Vitamin D obtained from sun exposure, food, and supplements, is biologically inert and must undergo two hydroxylation reactions Vitamin D to be activated in the body. Calcitriol (1,25- Forms Dihydroxycholecalciferol) is the active form of Biochemistry vitamin D found in the body. The term vitamin D Production in the skin also refers to these metabolites and other Synthesis mechanism (form 3) analogues of these substances. Mechanism of action Calcitriol plays an important role in the Cholecalciferol (D3 ) Nutrition maintenance of several organ systems. [3] Natural sources However, its major role is to increase Measuring nutritional status the flow of calcium into the Deficiency bloodstream, by promoting absorption Overdose of calcium and phosphorus from food Health effects in the intestines, and reabsorption of Immunomodulation calcium in the kidneys; enabling Cancer normal mineralization of bone and Cardiovascular disease preventing hypocalcemic tetany. It is Mortality also necessary for bone growth and See also bone remodeling by osteoblasts and References osteoclasts.[4][5] External links Without sufficient vitamin D, bones can become thin, brittle, or misshapen. 3 Locations University of Deficiency can arise from inadequate Göttingen, United intake coupled with inadequate sunlight States, Boston view all exposure; disorders that limit its absorption; conditions that impair Calcium regulation in the human body. [2] The Images Videos conversion of vitamin D into active role of vitamin D is shown in orange. metabolites, such as liver or kidney disorders; or, rarely, by a number of hereditary disorders. Vitamin D deficiency results in impaired bone mineralization and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis.[3] view all 24 view all 15 Vitamin D plays a number of other roles in human health including inhibition of calcitonin release from the thyroid gland. Calcitonin acts directly on osteoclasts, resulting in inhibition of bone resorption and cartilage degradation. Vitamin D can also inhibit parathyroid hormone secretion from the parathyroid gland, modulate neuromuscular and immune function and reduce inflammation. [6][7][8] Forms Several forms (vitamers) of vitamin D Name Chemical Structure have been discovered (see table). The composition two major forms are vitamin D 2 or Vitamin molecular ergocalciferol, and vitamin D 3 or D1 compound of cholecalciferol. These are known ergocalciferol with lumisterol, 1:1 collectively as calciferol.[9] Vitamin D2 Vitamin ergocalciferol (made was chemically characterized in 1932. D2 from ergosterol) In 1936 the chemical structure of vitamin D3 was established and resulted from the ultraviolet irradiation
  • 41. of 7-dehydrocholesterol. [10] Vitamin cholecalciferol D3 (made from 7- Chemically, the various forms of dehydrocholesterol vitamin D are secosteroids; i.e., in the skin). steroids in which one of the bonds in Vitamin 22- the steroid rings is broken. [11] The D4 dihydroergocalciferol structural difference between vitamin D 2 and vitamin D 3 is in their side chains. The side chain of D 2 contains a double bond between carbons 22 Vitamin sitocalciferol (made and 23, and a methyl group on carbon D5 from 7- dehydrositosterol) 24. Vitamin D 2 (made from ergosterol) is produced by invertebrates, fungus and plants in response to UV irradiation; it is not produced by vertebrates. Little is known about the biologic function of vitamin D 2 in nonvertebrate species. Because ergosterol can more efficiently absorb the ultraviolet radiation that can damage DNA, RNA and protein it has been suggested that ergosterol serves as a sunscreening system that protects organisms from damaging high energy ultraviolet radiation. [12] Vitamin D 3 is made in the skin when 7-dehydrocholesterol reacts with UVB ultraviolet light at wavelengths between 270–300 nm, with peak synthesis occurring between 295- 297 nm.[13][14] These wavelengths are present in sunlight when the UV index is greater than 3. At this solar elevation, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, adequate amounts of vitamin D 3 can be made in the skin after only ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen. However, season, geographic latitude, time of day, cloud cover, skin cover, skin color, smog, and sunscreen affect UV ray absorption and vitamin D synthesis. For example, sunlight exposure from November through February in Boston is insufficient to produce significant vitamin D synthesis in the skin. With longer exposure to UVB rays, an equilibrium is achieved in the skin, and excess vitamin D simply degrades as fast as it is generated. [15] Both vitamin D 2 and D 3 are used for human nutritional supplementation, and pharmaceutical forms include calcitriol (1alpha, 25-dihydroxycholecalciferol), doxercalciferol and calcipotriene.[16] In humans, D 3 is as effective as D 2 in vitamin D hormone activity in circulation, [17] although others state that D 3 is more effective than D 2 .[18] However, in some species, such as rats, vitamin D 2 is more effective than D 3 .[19] Biochemistry Vitamin D is a prohormone, meaning that it has no hormone activity itself, but is converted to the active hormone 1,25-D through a tightly regulated synthesis mechanism. Production of vitamin D in nature always appears to require the presence of some UV light; even vitamin D in foodstuffs is ultimately derived from organisms, from mushrooms to animals, which are not able to synthesize it except through the action of sunlight at some point in the synthetic chain. For example, fish contain vitamin D only because they ultimately exist on calories from ocean algae which synthesize vitamin D in shallow waters from the action of solar UV. Production in the skin The skin consists of two primary layers: the inner layer called the dermis, composed largely of connective tissue, and the outer, thinner epidermis. The epidermis consists of five strata; from outer to inner they are: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Cholecalciferol is produced photochemically in the skin from 7-
  • 42. dehydrocholesterol; 7- dehydrocholesterol is produced in relatively large quantities in the skin of most vertebrate animals, including The epidermal strata of the skin. Production is humans. The few exceptions are some greatest in the stratum basale (colored red in bat species, mole rats, cats, and the illustration) and stratum spinosum (colored orange). dogs,[12] which produce little vitamin D.[20] In most animals the highest concentrations of 7-dehydrocholesterol are found in the epidermal layer of skin, specifically in the stratum basale and stratum spinosum. [13] The production of pre- vitamin D 3 is therefore greatest in these two layers, whereas production in the other layers is less. Synthesis in the skin involves UVB radiation, which effectively penetrates only the epidermal layers of skin. While 7-dehydrocholesterol absorbs UV light at wavelengths between 270–300 nm, optimal synthesis occurs in a narrow band of UVB spectra between 295-300 nm. Peak isomerization is found at 297 nm. This narrow segment is sometimes referred to as D-UV.[14] The two most important factors that govern the generation of pre-vitamin D 3 are the quantity (intensity) and quality (appropriate wavelength) of the UVB irradiation reaching the 7-dehydrocholesterol deep in the stratum basale and stratum spinosum. [13] A critical determinant of vitamin D 3 production in the skin is the presence and concentration of melanin. Melanin functions as a light filter in the skin, and therefore the concentration of melanin in the skin is related to the ability of UVB light to penetrate the epidermal strata and reach the 7-dehydrocholesterol-containing stratum basale and stratum spinosum. Under normal circumstances, ample quantities of 7- dehydrocholesterol (about 25-50 µg/cm² of skin) are available in the stratum spinosum and stratum basale of the skin to meet the body's vitamin D requirements, [13] and melanin content does not alter the amount of vitamin D that can be produced.[21] Thus, individuals with higher skin melanin content will simply require more time in sunlight to produce the same amount of vitamin D as individuals with lower melanin content. The amount of time an individual requires to produce a given amount of vitamin D may also depend upon the person's distance from the equator and on the season of the year. In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the fur and obtained orally during grooming.[22] In 1923, Harry Goldblatt and Katherine Soames established that when 7- dehydrocholesterol (a precursor of vitamin D in the skin) is irradiated with light, a form of a fat-soluble vitamin is produced. Alfred Fabian Hess and Mildred Weinstock further substantiated that "[sun]light equals vitamin D".[23] Adolf Windaus, at the University of Göttingen in Germany, received the Nobel Prize in Chemistry in 1928, for his work on the constitution of sterols and their connection with vitamins. [24] In 1930s, he clarified further the chemical structures of the vitamins D. Synthesis mechanism (form 3) 7-dehydrocholesterol, a derivative of cholesterol, is photolyzed by ultraviolet light in 6- electron conrotatory electrocyclic reaction. The product is pre- vitamin D 3 .
  • 43. Pre-vitamin D 3 then spontaneously isomerizes to Vitamin D 3 in a antarafacial hydride [1,7] Sigmatropic shift. At room temperature the transformation of previtamin-D 3 to vitamin D 3 takes about 12 days to complete. [12] Whether it is made in the skin or ingested, vitamin D 3 (cholecalciferol) is then hydroxylated in the liver to 25- hydroxycholecalciferol (25(OH)D 3 or calcidiol) by the enzyme 25- hydroxylase produced by hepatocytes. This hydroxylation reaction occurs in the endoplasmic reticulum and requires NADPH, O 2 and Mg 2+ yet it is not a cytochrome P450 enzyme. Once made the product is stored in the hepatocytes until it is needed and then can be released into the plasma where it will be bound to an α-globulin. 25- hydroxycholecalciferol is then transported to the proximal tubules of the kidneys where it can be hydroxylated by one of two enzymes forming to different forms of vitamin D, one of which is active vitamin D (1,25-OH D) and another which is inactive vitamin D (24,25-OH D). The enzyme 1α- hydroxylase which is activated by parathyroid hormone (and additionally by low calcium or phosphate) forms the main biologically active vitamin D hormone with a C1 hydroxylation forming 1,25- dihydroxycholecalciferol (1,25(OH)2D 3 , also known as calcitriol). A separate enzyme hydroxylates the C24 atom forming 24R,25(OH)2D3 when 1α-hydroxylase is not active, this inactivates the molecule from any biological activity. Calcitriol is represented below right
  • 44. (hydroxylated Carbon 1 is on the lower ring at right, hydroxylated Carbon 25 is at the upper right end). Mechanism of action After vitamin D is produced in the middle layers of skin or consumed in food, it is converted in the liver and kidney to form 1,25 dihydroxyvitamin D, (1,25(OH)2 D), the physiologically active form of vitamin D (when "D" is used without a subscript it refers to either D 2 or D 3 ). This physiologically active form of vitamin D is known as calcitriol. Following this conversion, calcitriol is released into the circulation, and by binding to a carrier protein in the plasma, vitamin D binding protein (VDBP), it is transported to various target organs. [11] The physiologically active form of vitamin D mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells.[11] The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6 and calbindin), which are involved in calcium absorption in the intestine. The vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and VDRs are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate, and breast. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance of bone content. [25] The VDR is known to be involved in cell proliferation and differentiation. Vitamin D also affects the immune system, and VDRs are expressed in several white blood cells, including monocytes and activated T and B cells.[16] Nutrition Vitamin D is naturally produced by the human body when exposed to direct sunlight. Season, geographic latitude, time of day, cloud cover, smog, and sunscreen affect UV ray exposure and vitamin D synthesis in the skin, and it is important for individuals with limited sun exposure to include good sources of vitamin D in their diet. Extra vitamin D is also recommended for older adults and people with Milk and cereal grains are often dark skin. Individuals having a high risk of fortified with vitamin D. deficiency should consume 25 μg (1000 IU) of vitamin D daily to maintain adequate blood concentrations of 25-hydroxyvitamin D.[1] As civilization and the Industrial Revolution enabled humans to work indoors and wear more clothes when outdoors, these cultural changes reduced natural production of vitamin D and caused deficiency diseases. In many countries, such foods as milk, yogurt, margarine, oil spreads, breakfast cereal, pastries, and bread are fortified with vitamin D 2 and/or vitamin D 3 , to minimize the risk of vitamin D deficiency. [26] In the United States and Canada, for example, fortified milk typically provides 100 IU per glass, or a quarter of the estimated adequate intake for adults over age 50. [1] A 1992 study, however, found that the actual vitamin D content of milk varies widely. Supplementation of 100 IU (2.5 microgram) vitamin D 3 raises blood calcidiol levels by 2.5 nmol/litre (1 ng/ml).[27] Natural sources Natural sources of vitamin D include:[1] Fish liver oils, such as cod liver oil, 1 Tbs. (15 ml) provides 1,360 IU (one IU equals 25 ng)
  • 45. Fatty fish species, such as: Herring, 85 g (3 ounces (oz)) provides 1383 IU Catfish, 85 g (3 oz) provides 425 IU Fatty fish, such as salmon, are Salmon, cooked, 100 g (3.5 oz]) natural sources of vitamin D. provides 360 IU Mackerel, cooked, 100 g (3.5 oz]), 345 IU Sardines, canned in oil, drained, 50 g (1.75 oz), 250 IU Tuna, canned in oil, 85 g (3 oz), 200 IU Eel, cooked, 100 g (3.5 oz), 200 IU A whole egg, provides 20 IU Beef liver, cooked, 100 g (3.5 oz), provides 15 IU UV-irradiated mushrooms (Vitamin D 2 ) [28][29] In the United States (U.S.), the 100% Daily Value used for product labels is 400 IU/day and typical diets provide about 100 IU/day. Although milk is usually fortified, the average daily consumption by most Americans is insufficient in obtaining levels of vitamin D recommended by various medical authorities. [30] While adequate intake has been defined as 200 IU/day for ages infant to 50, 400/day for 51-70, and 600/day over 70, the American Academy of Pediatrics argues that these recommendations are insufficient and recommends a minimum of 400 IU, even for infants.[31] The NIH has set the safe upper limit at 2000 IU, but acknowledges newer data supporting a UL as high as 10,000 IU/day. [32] The Institute Of Medicine is revisiting vitamin D and calcium recommendations with a report expected to be released in spring 2010. Measuring nutritional status A blood calcidiol (25-hydroxy-vitamin D) level is the accepted way to determine vitamin D nutritional status. The optimal level of serum 25-hydroxyvitamin D is 35–55 ng/ml (or 90-140 nmol/l); with some debate among medical scientists for the slightly higher value.[27] For instance, a later classification is:[33] 0-14.9 ng/ml = Severely deficient 15.0-31.9 ng/ml = Mildly deficient 32.0-100.0 ng/ml = Optimal >100.0 ng/ml = Toxicity possible Deficiency Main article: Hypovitaminosis D Deficiency of vitamin D can result from a number of factors: inadequate intake coupled with inadequate sunlight (UVB) exposure, disorders that limit its absorption from the gastrointestinal tract, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders and body characteristics such as skin color and body fat. Rarely, deficiency can result from a number of hereditary disorders. [3] Deficiency results in impaired bone mineralization, and leads to bone softening diseases [34] including: Rickets, a childhood disease characterized by impeded growth, and deformity, of the long bones. Rickets was first described in the 17th century, by Daniel Whistler and Francis Glisson. The role of diet in the development of rickets was determined by Edward Mellanby between 1918–1920. [35] By altering the diets of dogs raised in the absence of sunlight, he was able to establish unequivocally that rickets was linked with a deficiency of diet, and identified cod liver oil as an excellent anti-rachitic agent. [36] In 1921 Elmer McCollum identified a substance found in certain fats that could prevent rickets. Prior to the fortification of milk products with vitamin D, rickets was a major public health problem. In the United States, the fortification of milk with 10 micrograms (400 IU) of vitamin D per quart
  • 46. in the 1930s led to a dramatic decline in the number of rickets cases. [25] Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility. The effects of osteomalacia are thought to contribute to chronic musculoskeletal pain.[37] A number of reports thus indicate that vitamin D deficiency may be related to various types of pain, [38] but of the five small double-blind randomized controlled trials, only one found a reduction in pain after supplementation, and there is no persuasive evidence of lower vitamin D status in chronic pain sufferers compared to controls. [39] Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility. Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases, such as high blood pressure, tuberculosis, cancer, periodontal disease, multiple sclerosis, chronic pain, seasonal affective disorder [40][41] , peripheral artery disease[42] , cognitive impairment which includes memory loss and foggy brain,[43] and several autoimmune diseases including type 1 diabetes (see role in immunomodulation).[8][25] There is an association between low vitamin D levels and Parkinson's disease, but whether Parkinson's causes low vitamin D levels, or whether low vitamin D levels play a role in the pathogenesis of Parkinson's disease has not been established. [44] A resurgence of interest in vitamin D deficiency has led to continued studies on the topic and a focus on educating the consumer on the prevalence and degree of deficiency among the general public. [45] Overdose For more details on this topic, see hypervitaminosis D. Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D) has a large volume of distribution and a half-life of about 20 to 29 days. [16] Ordinarily, the synthesis of bioactive vitamin D hormone is tightly regulated, and prevalent thinking is that vitamin D toxicity usually occurs only if excessive doses (prescription forms or rodenticide analogs) are taken. [46] Serum levels of calcidiol (25-hydroxy-vitamin D) are typically used to diagnose vitamin D overdose. In healthy individuals, calcidiol levels are normally between 32 to 70 ng/mL (80 to 175 nmol/L), but these levels may be as much as 15- fold greater in cases of vitamin D toxicity. Serum levels of bioactive vitamin D hormone (1,25(OH2)D) are usually normal in cases of vitamin D overdose. [3] The exact long-term safe dose of vitamin D is not known. In 1997 the U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) of vitamin D for children and adults was set at 50 micrograms/day (2,000 IU) [47] , but this is viewed by some researchers as outdated and overly restrictive. [48] A 2007 risk assessment was made by two employees of the dietary supplement trade association Council for Responsible Nutrition,[48] that represents companies including Amway, Bayer AG and GlaxoSmithKline, [49] and their two colleagues, who declared that they had no personal or financial conflicts of interest. They suggested that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[48] In adults, sustained intake of 1250 micrograms/day (50,000 IU) can produce toxicity within a few months. [3] For infants (birth to 12 months) the tolerable UL is set at 25 micrograms/day (1000 IU), and vitamin D concentrations of 1000 micrograms/day (40,000 IU) in infants has been shown to produce toxicity within 1 to 4 months. Other sources indicate that the threshold for vitamin D toxicity in humans is 500 to 600 micrograms per kilogram body weight per day." [50] In rats an oral LD50 of 619 mg/kg is noted. [51] All known cases of vitamin D toxicity with hypercalcemia have involved intake of over 1,000 micrograms/day (40,000 IU) [52] . Although normal food and pill vitamin D concentration levels are far too low to be toxic in adults, people taking multiples of the normal dose of codliver oil may reach toxic levels of vitamin A, not vitamin D,[53] if taken in an attempt to increase the levels of vitamin D. Most officially-recorded historical cases of vitamin D overdose have occurred due to manufacturing and industrial accidents. [52] In the United States, overdose exposure of vitamin D was reported by 284 individuals in 2004 (a randomly selected year), leading to 1 death. [54] Some symptoms of vitamin D toxicity are a result of hypercalcemia (an elevated level of
  • 47. calcium in the blood) caused by increased intestinal calcium absorption. Vitamin D toxicity is known to be a cause of high blood pressure. [55] Gastrointestinal symptoms of vitamin D toxicity can include anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine), polydipsia (increased thirst), weakness, nervousness, pruritus (itch), and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop. [3] In one study, hypercalciuria and bone loss occurred in four patients with documented vitamin D toxicity. [56] Another study showed elevated risk of ischemic heart disease when 25D was above 89 ng/mL.[57] Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. In some cases kidney damage may be irreversible. [3] Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity. [52] This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3–6 times longer for pigmented skin) the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded. [15] According to some sources, endogenous production with full body exposure to sunlight is approximately 250 µg (10,000 IU) per day.[52] According to Holick, "the skin has a large capacity to produce cholecalciferol"; his experiments indicate that, "[W]hole-body exposure to one minimal erythemal dose of simulated solar ultraviolet radiation is comparable with taking an oral dose of between 250 and 625 micrograms (10 000 and 25 000 IU) vitamin D."[15] Health effects Immunomodulation The hormonally active form of vitamin D mediates immunological effects by binding to nuclear vitamin D receptors (VDR) which are present in most immune cell types including both innate and adaptive immune cells. The VDR is expressed constitutively in monocytes and in activated macrophages, dendritic cells, NK cells, T and B cells. In line with this observation, activation of the VDR has potent anti-proliferative, pro-differentiative, and immunomodulatory functions including both immune-enhancing and immunosuppressive effects.[58] VDR ligands have been shown to increase the activity of natural killer cells, and enhance the phagocytic activity of macrophages. [16] Active vitamin D hormone also increases the production of cathelicidin, an antimicrobial peptide that is produced in macrophages triggered by bacteria, viruses, and fungi.[59] Vitamin D deficiency tends to increase the risk of infections, such as influenza [60] and tuberculosis [61][62][63] . In a 1997 study, Ethiopian children with rickets were 13 times more likely to get pneumonia than children without rickets. [64] Effects of VDR-ligands, such as vitamin D hormone, on T-cells include suppression of T cell activation and induction of regulatory T cells, as well as effects on cytokine secretion patterns. [65] VDR-ligands have also been shown to affect maturation, differentiation, and migration of dendritic cells, and inhibits DC-dependent T cell activation, resulting in an overall state of immunosuppression.[66] These immunoregulatory properties indicate that ligands with the potential to activate the VDR, including supplementation with calcitriol (as well as a number of synthetic modulators), may have therapeutic clinical applications in the treatment of inflammatory diseases (rheumatoid arthritis, psoriatic arthritis), dermatological conditions (psoriasis, actinic keratosis), osteoporosis, cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), and autoimmune diseases (systemic lupus erythematosus, type I diabetes); central nervous systems diseases (multiple sclerosis); and in preventing organ transplant rejection. [58] A 2006 study published in the Journal of the American Medical Association, reported evidence of a link between Vitamin D deficiency and the onset of multiple sclerosis; the authors posit that this is due to the immune-response suppression properties of Vitamin D.[67] Further research conducted in 2009 indicates that vitamin D is required to activate
  • 48. a histocompatibility gene (HLA-DRB1*1501) necessary for differentiating between self and foreign proteins in a subgroup of individuals genetically predisposed to MS. [68] Suggestions that pregnant women take vitamin D during their pregnancy, especially during winter months, is beginning to show merit to lessen the likelihood of the development of MS later in life. [69][70] Cancer The vitamin D hormone, calcitriol, has been found to induce death of cancer cells in vitro and in vivo. The anti-cancer activity of vitamin D is thought to result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer.[71] These effects may be mediated through vitamin D receptors expressed in cancer cells.[16] A search of primary and review medical literature published between 1970 and 2007 found an increasing body of research supporting the hypothesis that the active form of vitamin D has significant, protective effects against the development of cancer. Epidemiological studies show an inverse association between sun exposure, serum levels of 25(OH)D, and intakes of vitamin D and risk of developing and/or surviving cancer. In 2005, scientists released a metastudy which demonstrated a beneficial correlation between vitamin D intake and prevention of cancer. Drawing from a meta- analysis of 63 published reports, the authors showed that intake of an additional 1,000 international units (IU) (or 25 micrograms) of vitamin D daily reduced an individual's colon cancer risk by 50%, and breast and ovarian cancer risks by 30%.[72][73][74] A scientific review undertaken by the National Cancer Institute found that vitamin D was beneficial in preventing colorectal cancer, which showed an inverse relationship with blood levels of 80 nmol/L or higher associated with a 72% risk reduction. However, the same study found no link between baseline vitamin D status and overall cancer mortality.[75] A 2006 study using data on over 4 million cancer patients from 13 different countries showed a marked difference in cancer risk between countries classified as sunny and countries classified as less–sunny for a number of different cancers. [76] Research has also suggested that cancer patients who have surgery or treatment in the summer — and therefore make more endogenous vitamin D — have a better chance of surviving their cancer than those who undergo treatment in the winter when they are exposed to less sunlight. [77] Another 2006 study found that taking the U.S. RDA of vitamin D (400 IU per day) cut the risk of pancreatic cancer by 43% in a sample of more than 120,000 people from two long-term health surveys. [78][79] A randomized intervention study involving 1,200 women, published in June 2007, reports that vitamin D supplementation (1,100 international units (IU)/day) resulted in a 60% reduction in cancer incidence, during a four-year clinical trial, rising to a 77% reduction for cancers diagnosed after the first year (and therefore excluding those cancers more likely to have originated prior to the vitamin D intervention). [80][81] Research has also indicated beneficial effects of high levels of calcitriol on patients with advanced prostate cancer.[82] Low levels of vitamin D in serum have also been correlated with breast cancer disease progression and bone metastases,[83] and studies suggest that increased intake of vitamin D reduces the risk of breast cancer in premenopausal women. [84] Polymorphisms of the vitamin D receptor (VDR) gene have been associated with an increased risk of breast cancer.[83] Impairment of the VDR-mediated gene expression is thought to alter mammary gland development or function and may predispose cells to malignant transformation. Women with homozygous FOK1 mutations in the VDR gene had an increased risk of breast cancer compared with the women who did not. FOK1 mutation has also been associated with decreasing bone mineral density which in turn may be associated with an increase in the risk of breast cancer.[85] The Canadian Cancer Society was the first to recommend, in 2007, that all of its adult citizens begin taking 1,000(IU) per day of vitamin D. The country's northern latitude was a factor in the decision, as was the growing body of evidence showing the vitamin's effectiveness in lowering instances of cancer.[86][87] Cardiovascular disease Research indicates that vitamin D may play a role in preventing or reversing coronary disease.[88][89] Vitamin D deficiency is associated with an increase in high blood
  • 49. pressure and cardiovascular risk. Numerous observational studies show this link, but no randomized trial has proven the impact of vitamin D supplementation.[90] The precise mechanism for cardiovascular regulation is still under investigation; possibilities include blood pressure regulation through the renin-angiotensin system, parathyroid hormone levels, direct impact on heart muscle function, inflammation, and vascular calcification.[91] When researchers monitored the vitamin D levels, blood pressure and other cardiovascular risk factors of 1739 people, of an average age of 59 years for 5 years, they found that those people with low levels of vitamin D had a 62% higher risk of a cardiovascular event than those with normal vitamin D levels.[92] Low levels of vitamin D have also been implicated in hypertension, elevated VLDL triglycerides, and impaired insulin metabolism. [93] A report from the National Health and Nutrition Examination Survey (NHANES) involving nearly 5,000 participants found that low levels of vitamin D were associated with an increased risk of peripheral artery disease (PAD). The incidence of PAD was 80% higher in participants with the lowest vitamin D levels (<17.8 ng/mL).[42] Cholesterol levels were found to be reduced in gardeners in the UK during the summer months. [94] Heart attacks peak in winter and decline in summer in temperate [95] but not tropical latitudes. [96] The issue of vitamin D in heart health has not yet been settled. Exercise may account for some of the benefit attributed to vitamin D, since vitamin D levels are generally higher in physically active persons.[97] Moreover, there may be an upper limit after which cardiac benefits decline. One study found an elevated risk of ischaemic heart disease in Southern India in individuals whose vitamin D levels were above 89 ng/mL.[57] These sun-living groups results do not generalize to sun-deprived urban dwellers. Among a group with heavy sun exposure, taking supplemental vitamin D is unlikely to result in blood levels over the ideal range, while urban dwellers not taking supplemental vitamin D may fall under the levels recognized as ideal. Mortality Using information from the National Health and Nutrition Examination Survey a group of researchers concluded that having low levels of vitamin D (<17.8 ng/ml) was independently associated with an increase in all-cause mortality in the general population. [98] The study evaluated whether low serum vitamin D levels were associated with all-cause mortality, cancer, and cardiovascular disease (CVD) mortality among 13,331 diverse American adults who were 20 years or older. Vitamin D levels of these participants were collected over a 6-year period (from 1988 through 1994), and individuals were passively followed for mortality through the year 2000. Among many factors that may be responsible for vitamin D's apparent beneficial effect on all-cause mortality is its effect on telomeres and its potential effect on slowing aging. Shortening of leukocyte telomeres is a marker of aging. Leukocyte telomere length (LTL) predicts the development of aging-related disease, and length of these telomeres decreases with each cell division and with increased inflammation (more common in the elderly). Research indicates that vitamin D is a potent inhibitor of the proinflammatory response and slows the turnover of leukocytes. Higher vitamin D levels were also associated with longer leukocyte telomere length, indicating that vitamin D sufficiency may play a role in preventing age-related diseases.[99] See also Vitamin D and influenza Effect of sunlight on mushrooms - article about how ultraviolet light boosts vitamin D levels in mushrooms. References 1. ↑ 1.0 1.1 1.2 1.3 "Dietary Supplement Fact Sheet: Vitamin D". National Institutes of Health. Archived from the original on 2007-09-10. http://www.webcitation.org/5Rl5u0LB5. Retrieved 2007-09-10. 2. ↑ Page 1094 (The Parathyroid Glands and Vitamin D) in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-2328-3. 3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Vitamin D at Merck Manual of Diagnosis and Therapy Professional Edition
  • 50. 4. ↑ van den Berg H (January 1997). "[Expression error: Missing operand for > Bioavailability of vitamin D]". Eur J Clin Nutr 51 Suppl 1: S76–9. PMID 9023488. 5. ↑ Cranney A, Horsley T, O'Donnell S, et al. (August 2007). "[Expression error: Missing operand for > Effectiveness and safety of vitamin D in relation to bone health]". Evid Rep Technol Assess (Full Rep) (158): 1–235. PMID 18088161. 6. ↑ Silver J, Russell J, Sherwood LM (June 1985). "Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells". Proc. Natl. Acad. Sci. U.S.A. 82 (12): 4270–3. doi:10.1073/pnas.82.12.4270. PMID 3858880. PMC 397979. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3858880. 7. ↑ Silver J, Naveh-Many T, Mayer H, Schmelzer HJ, Popovtzer MM (November 1986). "[Expression error: Missing operand for > Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat]". J. Clin. Invest. 78 (5): 1296–301. doi:10.1172/JCI112714. PMID 3771798. 8. ↑ 8.0 8.1 Tavera-Mendoza LE, White JH (November 2007). "Cell defenses and the sunshine vitamin". Sci. Am. 297 (5): 62–5, 68–70, 72. doi:10.1038/scientificamerican1107-62. PMID 17990825. http://www.sciam.com/article.cfm?id=cell-defenses-and-the-sunshine-vitamin. 9. ↑ Dorland's Illustrated Medical Dictionary, under Vitamin (Table of Vitamins) 10. ↑ History of Vitamin D University of California, Riverside, Vitamin D Workshop. 11. ↑ 11.0 11.1 11.2 About Vitamin D Including Sections: History, Nutrition, Chemistry, Biochemistry, and Diseases. University of California Riverside 12. ↑ 12.0 12.1 12.2 Holick MF (March 2004). "Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis". Am. J. Clin. Nutr. 79 (3): 362–71. PMID 14985208. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=14985208. 13. ↑ 13.0 13.1 13.2 13.3 Norman AW (June 1998). "Sunlight, season, skin pigmentation, vitamin D, and 25- hydroxyvitamin D: integral components of the vitamin D endocrine system". Am. J. Clin. Nutr. 67 (6): 1108– 10. PMID 9625080. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=9625080. 14. ↑ 14.0 14.1 MacLaughlin JA, Anderson RR, Holick MF (May 1982). "Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin". Science (journal) 216 (4549): 1001– 3. PMID 6281884. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=6281884. 15. ↑ 15.0 15.1 15.2 Holick M (1995). "[Expression error: Missing operand for > Environmental factors that influence the cutaneous production of vitamin D]". Am J Clin Nutr 61 (3 Suppl): 638S–645S. PMID 7879731. 16. ↑ 16.0 16.1 16.2 16.3 16.4 Vitamin D; The Physicians Desk Reference. 2006 Thompson Healthcare. 17. ↑ Holick MF, Biancuzzo RM, Chen TC, et al. (March 2008). "[Expression error: Missing operand for > Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D]". J. Clin. Endocrinol. Metab. 93 (3): 677–81. doi:10.1210/jc.2007-2308. PMID 18089691. 18. ↑ Institute of Medicine. (2006) Dietary Reference Intakes Research Synthesis: Workshop Summary, p. 27. National Academies Press. 19. ↑ Coates, M. E. (1968). "Requirements of different species for vitamins" (). Proceedings of the Nutrition Society 27 (2): 143–148. doi:10.1079/PNS19680039. PMID 5755261. http://docstore.ingenta.com/cgi- bin/ds_deliver/1/u/d/ISIS/33840020.1/cabi/pns/1968/00000027/00000002/art00019/89A25EAB89BAB011116525855554705D47CC65A51B.pdf? link=http://www.ingentaconnect.com/error/delivery&format=pdf. 20. ↑ How KL, Hazewinkel HA, Mol JA (October 1994). "[Expression error: Missing operand for > Dietary vitamin D dependence of cat and dog due to inadequate cutaneous synthesis of vitamin D]". Gen. Comp. Endocrinol. 96 (1): 12–8. doi:10.1006/gcen.1994.1154. PMID 7843559. 21. ↑ Matsuoka LY, Wortsman J, Haddad JG, Kolm P, Hollis BW (April 1991). "[Expression error: Missing operand for > Racial pigmentation and the cutaneous synthesis of vitamin D]". Arch Dermatol 127 (4): 536–8. doi:10.1001/archderm.127.4.536. PMID 1848745. 22. ↑ Sam D. Stout; Sabrina C. Agarwal; Stout, Samuel D. (2003). Bone loss and osteoporosis: an anthropological perspective. New York: Kluwer Academic/Plenum Publishers. ISBN 0-306-47767-X. 23. ↑ UNRAVELING THE ENIGMA OF VITAMIN D U.S. National Academy of Sciences 24. ↑ Windaus biography at nobelprize.org 25. ↑ 25.0 25.1 25.2 Holick MF (1 December 2004). "Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease". American Journal of Clinical Nutrition Full Text 80 (6): 1678S–88S. PMID 15585788. http://www.ajcn.org/cgi/content/full/80/6/1678S. 26. ↑ Nowson C, Margerison C (2002). "Vitamin D intake and vitamin D status of Australians". Med J Aust 177 (3): 149–52. PMID 12149085. http://www.mja.com.au/public/issues/177_03_050802/now10763_fm.html. 27. ↑ 27.0 27.1 Michael Holick, 5 May 2007, http://www.uvadvantage.org/portals/0/pres/ 28. ↑ Koyyalamudi SR, Jeong SC, Song CH, Cho KY, Pang G (April 2009). "[Expression error: Missing operand for > Vitamin D2 formation and bioavailability from Agaricus bisporus button mushrooms treated with ultraviolet irradiation]". J. Agric. Food Chem. 57 (8): 3351–5. doi:10.1021/jf803908q. PMID 19281276. 29. ↑ Lee GS, Byun HS, Yoon KH, Lee JS, Choi KC, Jeung EB (March 2009). "[Expression error: Missing operand for > Dietary calcium and vitamin D2 supplementation with enhanced Lentinula edodes improves osteoporosis-like symptoms and induces duodenal and renal active calcium transport gene expression in mice]". Eur J Nutr 48 (2): 75–83. doi:10.1007/s00394-008-0763-2. PMID 19093162. 30. ↑ Vitamin D Dietary Reference Intakes, pp. 256-57 31. ↑ Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents. 32. ↑ ietary Supplement Fact Sheet: Vitamin D 33. ↑ Legacy Health System 25-Hydroxy Vitamin D and Calcium Reference Ranges Updated. January 2008 34. ↑ Grant WB, Holick MF (2005). "[Expression error: Missing operand for > Benefits and requirements of vitamin D for optimal health: a review]". Altern Med Rev 10 (2): 94–111. PMID 15989379. 35. ↑ Rajakumar K (2003). "Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective". Pediatrics 112 (2): e132–5. doi:10.1542/peds.112.2.e132. PMID 12897318. http://pediatrics.aappublications.org/cgi/content/full/112/2/e132. 36. ↑ History of Vitamin D University of California, Riverside, Vitamin D Workshop. 37. ↑ Holick MF (February 2003). "[Expression error: Missing operand for > Vitamin D: A millenium perspective]". J. Cell. Biochem. 88 (2): 296–307. doi:10.1002/jcb.10338. PMID 12520530. 38. ↑ Stewart B. Leavitt. "Vitamin D – A Neglected ‘Analgesic’ for Chronic Musculoskeletal Pain". Pain- Topics.org. http://pain-topics.org/pdf/vitamind-report.pdf. Retrieved 2009-03-25. 39. ↑ Straube S, Andrew Moore R, Derry S, McQuay HJ (January 2009). "[Expression error: Missing operand for > Vitamin D and chronic pain]". Pain 141 (1-2): 10–3. doi:10.1016/j.pain.2008.11.010. PMID 19084336.
  • 51. 40. ↑ Natural Standard Research Collaboration (2008-03-01). "Vitamin D". Evidence-based monograph. Mayo Clinic. http://www.mayoclinic.com/health/vitamin-d/NS_patient-vitamind. Retrieved 29 November 2008. 41. ↑ Gloth, F.M. 3rd; , Alam W, Hollis B. (1999). "Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder.". J Nutr Health Aging 3 (1): 5–7. pmid 10888476 . http://www.ncbi.nlm.nih.gov/pubmed/10888476. Retrieved 2008-11-15. 42. ↑ 42.0 42.1 Melamed ML, Muntner P, Michos ED, et al. (2008). "[Expression error: Missing operand for > Serum 25-Hydroxyvitamin D Levels and the Prevalence of Peripheral Arterial Disease. Results from NHANES 2001 to 2004]". Arterioscler. Thromb. Vasc. Biol. 28 (6): 1179. doi:10.1161/ATVBAHA.108.165886. PMID 18417640. 43. ↑ Llewellyn DJ, Langa K, Lang I (February 2009). "Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment". J Geriatr Psychiatry Neurol 22 (3): 188–95. doi:10.1177/0891988708327888. PMID 19073839. PMC 2730978. http://jgp.sagepub.com/cgi/pmidlookup?view=long&pmid=19073839. 44. ↑ Evatt ML, Delong MR, Khazai N, Rosen A, Triche S, Tangpricha V (October 2008). "Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease". Arch. Neurol. 65 (10): 1348–52. doi:10.1001/archneur.65.10.1348. PMID 18852350. PMC 2746037. http://archneur.ama- assn.org/cgi/pmidlookup?view=long&pmid=18852350. 45. ↑ Ray MM et al. "Prevalence of vitamin D deficiency in an urban general internal medicine academic practice." Presented at the American Federation for Medical Research annual meeting, New Orleans, 2009. 46. ↑ "RODENTICIDES, source: Journal of Veterinary Medicine, archives, vol. 27, May, 1998". IPM Of Alaska, Solving Pest Problems Sensibly. http://www.homestead.com/ipmofalaska/files/rodenticides.html. Retrieved 2006-07-07. 47. ↑ "DRI Tables : Dietary Guidance : Food and Nutrition Information Center". fnic.nal.usda.gov. http://fnic.nal.usda.gov/nal_display/index.php ? info_center=4&tax_level=3&tax_subject=256&topic_id=1342&level3_id=5140&level4_id=0&level5_id=0&placement_default=0 . Retrieved 2009-11-02. 48. ↑ 48.0 48.1 48.2 Hathcock JN, Shao A, Vieth R, Heaney R (January 2007). "Risk assessment for vitamin D". Am. J. Clin. Nutr. 85 (1): 6–18. PMID 17209171. http://www.ajcn.org/cgi/pmidlookup? view=long&pmid=17209171. Free full=text. 49. ↑ http://www.crnusa.org/who_omc.html 50. ↑ Garrison RH, Somer E (1990) The Nutrition Desk Reference, Second Edition. p. 40. New Canaan, CT: Keats. 51. ↑ US Environmental Protection Agency. Cholecalciferol (Vitamin D3) Chemical Profile 12/84. Chemical Fact Sheet Number 42. Washington, DC. December 1, 1984. 52. ↑ 52.0 52.1 52.2 52.3 Vieth R (1 May 1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". Am J Clin Nutr 69 (5): 842–56. PMID 10232622. http://www.ajcn.org/cgi/content/full/69/5/842. 53. ↑ Bendich A, Langseth L (1989). "Safety of vitamin A". Am J Clin Nutr 49 (2): 358–71. PMID 2492745. http://www.ajcn.org/cgi/content/full/49/2/358. 54. ↑ 2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. 55. ↑ "Complete Guide to Vitamins, Minerals ans Supplements", Fisher Books, Tucsan AZ, 1988, p42 56. ↑ Adams JS, Lee G (1 August 1997). "Gains in bone mineral density with resolution of vitamin D intoxication". Ann Intern Med 127 (3): 203–206. doi:10.1059/0003-4819-127-3-199708010-00004 (inactive 2009-11-17). PMID 9245225. http://www.annals.org/cgi/content/full/127/3/203. 57. ↑ 57.0 57.1 Rajasree S, Rajpal K, Kartha CC, Sarma PS, Kutty VR, Iyer CS, Girija G (2001). "[Expression error: Missing operand for > Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease Full Text]". Eur J Epidemiol 17 (6): 567–71. doi:10.1023/A:1014559600042. PMID 11949730. 58. ↑ 58.0 58.1 Nagpal S, Na S, Rathnachalam R (August 2005). "[Expression error: Missing operand for > Noncalcemic actions of vitamin D receptor ligands]". Endocr. Rev. 26 (5): 662–87. doi:10.1210/er.2004- 0002. PMID 15798098. 59. ↑ Janet Raloff, The Antibiotic Vitamin Science News, Vol 170, November 11, 2006, pages 312-317 60. ↑ Cannell JJ, Vieth R, Umhau JC, et al. (2006). "[Expression error: Missing operand for > Epidemic influenza and vitamin D]". Epidemiol. Infect. 134 (6): 1129–40. doi:10.1017/S0950268806007175. PMID 16959053. 61. ↑ Nnoaham KE, Clarke A (2008). "[Expression error: Missing operand for > Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis]". Int J Epidemiol 37 (1): 113–9. doi:10.1093/ije/dym247. PMID 18245055. 62. ↑ Gibney KB, MacGregor L, Leder K, et al. (2008). "[Expression error: Missing operand for > Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa]". Clin. Infect. Dis. 46 (3): 443–6. doi:10.1086/525268. PMID 18173355. 63. ↑ Martineau AR, Wilkinson RJ, Wilkinson KA, et al. (2007). "[Expression error: Missing operand for > A single dose of vitamin D enhances immunity to mycobacteria]". Am. J. Respir. Crit. Care Med. 176 (2): 208–13. doi:10.1164/rccm.200701-007OC. PMID 17463418. 64. ↑ Muhe L, Lulseged S, Mason KE, Simoes EA (June 1997). "[Expression error: Missing operand for > Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children]". Lancet 349 (9068): 1801–4. doi:10.1016/S0140-6736(96)12098-5. PMID 9269215. 65. ↑ Yee YK, Chintalacharuvu SR, Lu J, Nagpal S. (2005). "[Expression error: Missing operand for > Vitamin D receptor modulators for inflammation and cancer]". Mini Rev Med Chem. 5 (8): 761–78. doi:10.2174/1389557054553785. PMID 16101412. 66. ↑ van Etten E, Mathieu C. (2005). "[Expression error: Missing operand for > Immunoregulation by 1,25- dihydroxyvitamin D3: basic concepts]". J Steroid Biochem Mol Biol. 97 (1-2): 93–101. doi:10.1016/j.jsbmb.2005.06.002. PMID 16046118. 67. ↑ Munger KL. , Levin, LI,Hollis BW , Howard, NS , Ascherio A (2006). "[Expression error: Missing operand for > Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis]". Journal of the American Medical Association 296 (23): 2832–2838. doi:10.1001/jama.296.23.2832. PMID 17179460. 68. ↑ "Science News / Molecular Link Between Vitamin D Deficiency And MS". http://www.sciencenews.org/view/generic/id/40626/title/Molecular_link_between_vitamin__D_deficiency_and_MS . Retrieved 2009-02-25. 69. ↑ Vitamin D helps control MS gene. BBC News. 5 February 2009. 70. ↑ Genetic Study Supports Vitamin D Deficiency as an Environmental Factor in MS Susceptibility. Multiple Sclerosis Society of Canada. 5 February 2009 71. ↑ Ingraham BA, Bragdon B, Nohe A (2007). "[Expression error: Missing operand for > Molecular basis of the potential of vitamin D to prevent cancer]". Curr Med Res Opin 24 (1): 139.
  • 52. doi:10.1185/030079907X253519 . PMID 18034918. 72. ↑ "Vitamin D 'can lower cancer risk'". BBC News. 28 December 2005. http://news.bbc.co.uk/2/hi/health/4563336.stm. Retrieved 2006-03-23. 73. ↑ Gorham ED, Garland CF, Garland FC et al. (2007). "Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 32:210-216. 74. ↑ Garland CF, Mohr SB, Gorham ED et al. (2006). "Role of ultraviolet B irradiance and vitamin D in prevention of ovarian cancer." Am J Prev Med. 31:512-514. 75. ↑ Freedman DM, Looker AC, Chang SC, Graubard BI (2007). "[Expression error: Missing operand for > Prospective study of serum vitamin D and cancer mortality in the United States]". J. Natl. Cancer Inst. 99 (21): 1594–602. doi:10.1093/jnci/djm204. PMID 17971526. 76. ↑ Tuohimaa P, Pukkala E, Scélo G, et al. (2007). "[Expression error: Missing operand for > Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation]". Eur. J. Cancer 43 (11): 1701–12. doi:10.1016/j.ejca.2007.04.018. PMID 17540555. 77. ↑ "Vitamin D 'aids lung cancer ops'". BBC News . 22 April 2005. http://news.bbc.co.uk/2/hi/health/4458085.stm. Retrieved 2006-03-23. 78. ↑ Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS (2006). "Vitamin D intake and the risk for pancreatic cancer in two cohort studies". Cancer Epidemiol. Biomarkers Prev. 15 (9): 1688– 95. doi:10.1158/1055-9965.EPI-06-0206. PMID 16985031. http://cebp.aacrjournals.org/cgi/content/full/15/9/1688. 79. ↑ BBC NEWS | Health | Vitamin D 'slashes cancer risk' 80. ↑ Martin Mittelstaedt (28 April 2007). "Vitamin D casts cancer prevention in new light". Global and Mail. http://www.theglobeandmail.com/servlet/story/RTGAM.20070428.wxvitamin28/BNStory/specialScienceandHealth/home . Retrieved 2007-04-28. 81. ↑ Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. (2007). "[Expression error: Missing operand for > Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial]". Am J Clin Nutr. 85 (6): 1586–91. PMID 17556697. 82. ↑ Beer T, Myrthue A (2006). "[Expression error: Missing operand for > Calcitriol in the treatment of prostate cancer]". Anticancer Res 26 (4A): 2647–51. PMID 16886675. 83. ↑ 83.0 83.1 Buyru N, Tezol A;,Yosunkaya-Fenerci E, Dalay, N. Vitamin D receptor gene polymorphisms in breast cancer. Experimental and Molecular Medicine. 2003; 35(6):550-555. 84. ↑ Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Archives of Internal Medicine.2007; 167(10):1050-9. 85. ↑ Chen WY, Bertone-Johnson ER, Hunter DJ, Willett WC, Hankinson SE. Associations Between Polymorphisms in the Vitamin D Receptor and Breast Cancer Risk. Cancer Epidemiology, Biomarkers, & Prevention. 2005; 14(10):2335-2339. 86. ↑ Canadian Cancer Society announces Vitamin D recommendation, 08 June 2007. 87. ↑ Canadian Cancer Society recommends vitamin D. CTV.ca News Staff 88. ↑ Lack of vitamin D may increase heart disease risk http://www.americanheart.org/presenter.jhtml? identifier=3052800 American Heart Association rapid access journal report 01/07/2008 89. ↑ Newswise: Men with Low Vitamin D May Have Increased Risk of Heart Attack Retrieved on June 9, 2008. 90. ↑ Nemerovski CW, Dorsch MP, Simpson RU, Bone HG, Aaronson KD, Bleske BE (Jun 2009). "[Expression error: Missing operand for > Vitamin D and cardiovascular disease]". Pharmacotherapy 29 (6): 691-708. PMID 19476421. 91. ↑ Giovannucci, E (Nov 2009). "[Expression error: Missing operand for > Vitamin D and cardiovascular disease]". Curr Atheroscler Rep 11 (6): 456-61. PMID 19852887. 92. ↑ Wang TJ, Pencina MJ, Booth SL, et al. (January 2008). "[Expression error: Missing operand for > Vitamin D deficiency and risk of cardiovascular disease]". Circulation 117 (4): 503–11. doi:10.1161/CIRCULATIONAHA.107.706127. PMID 18180395. 93. ↑ Lind L, Hänni A, Lithell H, Hvarfner A, Sörensen OH, Ljunghall S (September 1995). "[Expression error: Missing operand for > Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men]". Am. J. Hypertens. 8 (9): 894–901. doi:10.1016/0895-7061(95)00154-H. PMID 8541004. 94. ↑ Grimes DS, Hindle E, Dyer T. (1996). "[Expression error: Missing operand for > Sunlight cholesterol and coronary heart disease]". Quarterly Journal of Medicine 89 (8): 579–589. PMID 8935479. 95. ↑ Spencer FA, Goldberg RJ, Becker RC, Gore JM. (1998). "[Expression error: Missing operand for > Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction]". J Am Coll Cardiol. 31 (6): 1226–33. doi:10.1016/S0735-1097(98)00098-9. PMID 9581712. 96. ↑ Ku CS, Yang CY, Lee WJ, Chiang HT, Liu CP, Lin SL. (1998). "[Expression error: Missing operand for > Absence of a seasonal variation in myocardial infarction onset in a region without temperature extremes]". Cardiology. 89 (4): 277–82. doi:10.1159/000006800. PMID 9643275. 97. ↑ Scragg R, Holdaway I, Singh V, Metcalf P, Baker J, Dryson E (1995). "[Expression error: Missing operand for > Serum 25-hydroxyvitamin D3 is related to physical activity and ethnicity but not obesity in a multicultural workforce]". Aust N Z J Med 25 (3): 218–23. PMID 7487689. 98. ↑ Melamed ML, Michos ED, Post W, Astor B (August 2008). "[Expression error: Missing operand for > 25-hydroxyvitamin D levels and the risk of mortality in the general population]". Arch. Intern. Med. 168 (15): 1629–37. doi:10.1001/archinte.168.15.1629 (inactive 2009-11-17). PMID 18695076. 99. ↑ Richards JB, Valdes AM, Gardner JP, et al. (November 2007). "Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women". Am. J. Clin. Nutr. 86 (5): 1420–5. PMID 17991655. PMC 2196219. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=17991655. External links Vitamin D Fact Sheet from the U.S.National Institutes of Health Vitamin D at the Open Directory Project Vitamins (A11) show Endocrine system: hormones (Peptide hormones · Steroid hormones) show Categories:
  • 53. All articles with dead external links | Articles with dead external links from November 2009 | Pages with DOIs broken since 2009 | All articles with unsourced statements | Articles with unsourced statements | Articles with unsourced statements from October 2009 | Vitamins | Vitamin D History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 54. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN C Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Vitamin C view original wikipedia article Not to be confused with Citric acid. Vitamin C This article is about the nutrient. For the chemical compound, see ascorbic acid. overview outline images locations For other uses, see Vitamin C (disambiguation). Search this article Vitamin C or L-ascorbic acid is an high Vitamin C essential nutrient for humans, in which it functions as a vitamin. Ascorbate (an ion of Vitamin C ascorbic acid) is required for a range of essential metabolic reactions in all animals Biological significance and plants. It is made internally by almost Biosynthesis all organisms; notable mammalian Vitamin C in evolution exceptions are most or all of the order Absorption, transport, and disposal chiroptera (bats), and the entire suborder Deficiency Anthropoidea (Haplorrhini) (tarsiers, History of human understanding monkeys and apes). It is also needed by Discovery of ascorbic acid guinea pigs and some species of birds and Physiological function fish. Deficiency in this vitamin causes the Collagen, carnitine, and tyrosine synthesis, and microsomal metabolism disease scurvy in humans.[1][2][3] It is also Antioxidant widely used as a food additive.[4] Pro-oxidant The pharmacophore of vitamin C is the Daily requirements ascorbate ion. In living organisms, Systematic (IUPAC) name Government recommended intakes ascorbate is an anti-oxidant, since it 2-oxo-L-threo-hexono-1,4- lactone-2,3-enediol Alternative recommendations on intak protects the body against oxidative or Therapeutic uses (R)-3,4-dihydroxy-5-((S)- 1,2- stress,[5] and is a cofactor in several vital dihydroxyethyl)furan-2(5H)-one Vitamin C megadosage enzymatic reactions. [6] Identifiers Testing for ascorbate levels in the body CAS number 50-81-7 Adverse effects Scurvy has been known since ancient Common side-effects ATC code A11G times. People in many parts of the world PubChem 5785 Possible side-effects assumed it was caused by a lack of fresh Chemical data Chance of overdose plant foods. The British Navy started giving Formula C6 H 8 O 6 Natural and artificial dietary sources sailors lime juice to prevent scurvy in Mol. mass 176.14 grams per mol Plant sources 1795. [7] Ascorbic acid was finally isolated Animal sources Synonyms L -ascorbate in 1933 and synthesized in 1934. The uses Physical data Food preparation and recommended daily intake of vitamin C Melt. point 190–192 °C (374–378 °F) Vitamin C supplements are matters of on-going debate, with RDI decomposes Artificial modes of synthesis ranging from 45 to 95 mg/day. Proponents Pharmacokinetic data Food Fortification of megadosage propose from 200 to Bioavailability rapid & complete References upwards of 2000 mg/day. A recent meta- Protein binding negligible Further reading analysis of 68 reliable antioxidant Metabolism ? External links supplementation experiments, involving a Half life 30 minutes total of 232,606 individuals, concluded that Excretion renal consuming additional ascorbate from 10 Locations Therapeutic considerations Norway, Beijing, supplements may not be as beneficial as Pregnancy cat. A China, University thought.[8] of Montpellier Legal status general public availability view all Routes oral Images Videos Biological significance (what is this?) (verify) Further information: ascorbic acid Vitamin C is purely the L -enantiomer of ascorbate; the opposite D-enantiomer has no physiological significance. Both forms are mirror images of the same view all 24 view all 15 molecular structure. When L -ascorbate, which is a strong reducing agent, carries out its reducing function, it is converted to its oxidized form, L - dehydroascorbate.[6] L -dehydroascorbate can then be reduced back to the active L -ascorbate form in the body ascorbic acid (reduced form) [9]
  • 55. by enzymes and glutathione. During this process semidehydroascorbic acid radical is formed. Ascorbate free radical reacts poorly with oxygen, and thus, will not create a superoxide. Instead two semidehydroascorbate radicals will react and form one ascorbate and one dehydroascorbate. With the help of glutathione, dehydroxyascorbate is converted back to ascorbate.[10] The presence of glutathione is crucial since it spares ascorbate and improves antioxidant capacity of dehydroascorbic acid (oxidized form) blood. [11] Without it dehydroxyascorbate could not convert back to ascorbate. L -ascorbate is a weak sugar acid structurally related to glucose which naturally occurs either attached to a hydrogen ion, forming ascorbic acid, or to a metal ion, forming a mineral ascorbate. Biosynthesis The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four enzyme-driven steps, which convert glucose to vitamin C.[6] The glucose needed to produce ascorbate in the liver (in mammals and perching birds) is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process. [12] In reptiles and birds the biosynthesis is carried out in the kidneys. Among the animals that have lost the ability to synthesise vitamin C are simians (specifically the Model of a vitamin C molecule. suborder haplorrhini, which includes humans), Black is carbon, red is oxygen, and white is hydrogen guinea pigs, a number of species of passerine birds (but not all of them—there is some suggestion that the ability was lost separately a number of times in birds), and many (probably all) major families of bats, including major insect and fruit-eating bat families. These animals all lack the L -gulonolactone oxidase (GULO) enzyme, which is required in the last step of vitamin C synthesis, because they have a defective form of the gene for the enzyme (Pseudogene ΨGULO).[13] Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C.[14] Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.[15] This discrepancy constitutes much of the basis of the controversy on current recommended dietary allowances. It is countered by arguments that humans are very good at conserving dietary vitamin C, and are able to maintain blood levels of vitamin C comparable with other simians, on a far smaller dietary intake. An adult goat, a typical example of a vitamin C-producing animal, will manufacture more than 13 g of vitamin C per day in normal health and the biosynthesis will increase "many fold under stress".[16] Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans.[17] Some microorganisms such as the yeast Saccharomyces cerevisiae have been shown to be able to synthesize vitamin C from simple sugars.[18][19] Vitamin C in evolution Venturi and Venturi [20][21] suggested that the antioxidant action of ascorbic acid developed firstly in plant kingdom when, about 500 Mya, plants began to adapt to mineral deficient fresh-waters of estuary of rivers. Some biologists suggested that many vertebrates had developed their metabolic adaptive strategies in estuary environment. [22] In this theory, some 400-300 million years ago when living plants and animals first began the move from the sea to rivers and land, environmental iodine deficiency was a challenge to the evolution of terrestrial life. [23] In plants, animals and fishes, the terrestrial diet became deficient in many essential marine micronutrients, including iodine, selenium, zinc, copper, manganese, iron, etc. Freshwater algae and terrestrial plants, in replacement of marine antioxidants, slowly optimized the production of other endogenous antioxidants such as ascorbic acid, polyphenols, carotenoids,
  • 56. flavonoids, tocopherols etc., some of which became essential “vitamins” in the diet of terrestrial animals (vitamins C, A, E, etc.). Ascorbic acid or vitamin C is a common enzymatic cofactor in mammals used in the synthesis of collagen. Ascorbate is a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS). Freshwater teleost fishes also require dietary vitamin C in their diet or they will get scurvy (Hardie et al.,1991). The most widely recognized symptoms of vitamin C deficiency in fishes are scoliosis, lordosis and dark skin coloration. Freshwater salmonids also show impaired collagen formation, internal/fin haemorrhage, spinal curvature and increased mortality. If these fishes are housed in seawater with algae and phytoplankton, then vitamin supplementation seems to be less important, presumably because of the availability of other, more ancient, antioxidants in natural marine environment. [24] Some scientists have suggested that the loss of human ability to make vitamin C may have caused a rapid simian evolution into modern man.[25][26][27] However, the loss of ability to make vitamin C in simians must have occurred much further back in evolutionary history than the emergence of humans or even apes, since it evidently occurred sometime after the split in the Haplorrhini (which cannot make vitamin C) and its sister clade which retained the ability, the Strepsirrhini ("wet-nosed" primates). These two branchs parted ways about 63 million years ago (Mya). Approximately 5 million years later (58 Mya), only a short time afterward from an evolutionary perspective, the infraorder Tarsiiformes, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines. Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 Mya). It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the evolutionary loss of the ability to break down uric acid. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that in higher primates, uric acid has taken over some of the functions of ascorbate.[28] Absorption, transport, and disposal Ascorbic acid is absorbed in the body by both active transport and simple diffusion. Sodium Dependent Active Transport - Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs) are the two transporters required for absorption. SVCT1 and SVCT2 imported the reduced form of ascorbate across plasma membrane.[29] GLUT1 and GLUT3 are the two glucose transporters and only transfer dehydroascorbic acid form of Vitamin C.[30] Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehydroascorbic acid to ascorbate.[31][32] Thus, SVCTs appear to be the predominant system for vitamin C transport in the body. SVCT2 is involved in vitamin C transport in almost every tissue,[29] the notable exception being red blood cells which lose SVCT proteins during maturation. [33] Knockout animals for SVCT2 die shortly after birth,[34] suggesting that SVCT2-mediated vitamin C transport is necessary for life. With regular intake the absorption rate varies between 70 to 95%. However, the degree of absorption decreases as intake increases. At high intake (12g), fractional human absorption of ascorbic acid may be as low as 16%; at low intake (<20 mg) the absorption rate can reach up to 98%.[35] Ascorbate concentrations over renal re- absorption threshold pass freely into the urine and are excreted. At high dietary doses (corresponding to several hundred mg/day in humans) ascorbate is accumulated in the body until the plasma levels reach the renal resorption threshold, which is about 1.5 mg/dL in men and 1.3 mg/dL in women. Concentrations in the plasma larger than this value (thought to represent body saturation) are rapidly excreted in the urine with a half- life of about 30 minutes; concentrations less than this threshold amount are actively retained by the kidneys, and half-life for the remainder of the vitamin C store in the body increases greatly, with the half-life lengthening as the body stores are depleted. [36] Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues which maintain vitamin C concentrations far higher than in blood. Biological tissues that accumulate over 100 times the level in blood plasma of vitamin C are the adrenal glands, pituitary, thymus, corpus luteum, and retina. [37] Those with 10 to 50 times the concentration present in blood plasma include
  • 57. the brain, spleen, lung, testicle, lymph nodes, liver, thyroid, small intestinal mucosa, leukocytes, pancreas, kidney and salivary glands. Ascorbic acid can be oxidized (broken down) in the human body by the enzyme L- ascorbate oxidase. Ascorbate which is not directly excreted in the urine as a result of body saturation or destroyed in other body metabolism is oxidized by this enzyme and removed. Deficiency Main article: Scurvy Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, the synthesised collagen is too unstable to perform its function. Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth and, eventually, death. The human body can store only a certain amount of vitamin C,[38] and so the body soon depletes itself if fresh supplies are not consumed. It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of vitamin C in the blood. [39] Nobel prize winner Linus Pauling and Dr. G. C. Willis have asserted that chronic long term low blood levels of vitamin C (chronic scurvy) is a cause of atherosclerosis. Western societies generally consume sufficient Vitamin C to prevent scurvy. In 2004 a Canadian Community health survey reported that Canadians of 19 years and above have intakes of vitamin C from food of, 133 mg/d for males and 120 mg/d for females, [40] which is higher than the RDA recommendation. In human dietary studies, all obvious symptoms of scurvy previously induced by extremely low vitamin C intake, can be reversed by vitamin C supplementation as small as 10 mg a day. However, needed vitamin C intake for dealing with infection or large amounts of tissue repair (such as in burns) is much higher than the minimal dose needed to reverse scurvy. History of human understanding The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native peoples living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorer Jacques Cartier, exploring the St. Lawrence River, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams.[41][42] Throughout history, the benefit of plant food to James Lind, a British Royal Navy surgeon who, in 1747, identified survive long sea voyages has been occasionally that a quality in fruit prevented recommended by authorities. John Woodall, the the disease of scurvy in what was first appointed surgeon to the British East India the first recorded controlled Company, recommended the preventive and experiment. curative use of lemon juice in his book "The Surgeon's Mate", in 1617. The Dutch writer, Johann Bachstrom, in 1734, gave the firm opinion that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease." While the earliest documented case of scurvy was described by Hippocrates around the year 400 BC, the first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the British Royal Navy, James Lind. Scurvy was common among those with poor access to fresh fruit and vegetables, such as remote, isolated sailors and soldiers. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on cider, vinegar, sulfuric acid or seawater, along with their normal rations. In the history of science this is considered to be the first occurrence of a controlled experiment
  • 58. comparing results on two populations of a factor applied to one group only with all other factors the same. The results conclusively showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy. [43] Lind's work was slow to be noticed, partly because his Treatise was not publish until six years after his study, and also because he recommended a lemon juice extract known as "rob".[44] Fresh fruit was very expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles). [45] Ship captains concluded wrongly that Lind's other suggestions were ineffective because those juices failed to prevent or cure scurvy. It was 1795 before the British navy adopted lemons Citrus fruits were one of the first or lime as standard issue at sea. Limes were more sources of vitamin C available to popular as they could be found in British West ship's surgeons. Indian Colonies, unlike lemons which weren't found in British Dominions, and were therefore more expensive. This practice led to the American use of the nickname "limey" to refer to the British. Captain James Cook had previously demonstrated and proven the principle of the advantages of carrying "Sour krout" on board, by taking his crews to the Hawaiian Islands and beyond without losing any of his men to scurvy. [46] For this otherwise unheard of feat, the British Admiralty awarded him a medal. The name "antiscorbutic" was used in the eighteenth and nineteenth centuries as general term for those foods known to prevent scurvy, even though there was no understanding of the reason for this. These foods included but were not limited to: lemons, limes, and oranges; sauerkraut, cabbage, malt, and portable soup. In 1907, Axel Holst and Theodor Frølich, two Norwegian physicians studying beriberi contracted aboard ship's crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the pigeons they used. They fed guinea pigs their test diet, which had earlier produced beriberi in their pigeons, and were surprised when scurvy resulted instead. Until that time scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease. Discovery of ascorbic acid In 1912, the Polish-American biochemist Casimir Funk, while researching deficiency diseases, developed the concept of vitamins to refer to the non-mineral micro-nutrients which are essential to health. The name is a blend of "vital", due to the vital role they play biochemically, and "amines" because Funk thought that all these materials were chemical amines. One of the "vitamines" was thought to be the anti-scorbutic factor, long thought to be a component of most fresh plant material. In 1928 the Arctic anthropologist Vilhjalmur Stefansson attempted to prove his theory of how the Eskimos are able to avoid scurvy with almost no plant food in their diet, despite the disease Albert Szent-Györgyi, pictured striking European Arctic explorers living on similar here in 1948, was awarded the high-meat diets. Stefansson theorised that the 1937 Nobel Prize in Medicine "for natives get their vitamin C from fresh meat that is his discoveries in connection with the biological combustion minimally cooked. Starting in February 1928, for processes, with special reference one year he and a colleague lived on an to vitamin C and the catalysis of exclusively minimally-cooked meat diet while under fumaric acid". He also identified medical supervision; they remained healthy. (Later many components and reactions studies done after vitamin C could be quantified in of the citric acid cycle independently from Hans Adolf mostly-raw traditional food diets of the Yukon, Krebs. Inuit, and Métís of the Northern Canada, showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, an amount approximately the dietary reference intake (DRI), even at times of the year when little plant-based food were eaten.) [47] From 1928 to 1933, the Hungarian research team of Joseph L Svirbely and Albert
  • 59. Szent-Györgyi and, independently, the American Charles Glen King, first isolated the anti-scorbutic factor, calling it "ascorbic acid" for its vitamin activity. Ascorbic acid turned out not to be an amine, nor even to contain any nitrogen. For their accomplishment, Szent-Györgyi was awarded the 1937 Nobel Prize in Medicine "for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid". [48] Between 1933 and 1934, the British chemists Sir Walter Norman Haworth and Sir Edmund Hirst and, independently, the Polish chemist Tadeus Reichstein, succeeded in synthesizing the vitamin, making it the first to be artificially produced. This made possible the cheap mass-production of what was by then known as vitamin C. Only Haworth was awarded the 1937 Nobel Prize in Chemistry for this work, but the "Reichstein process" retained Reichstein's name. In 1933 Hoffmann–La Roche became the first pharmaceutical company to mass- produce synthetic vitamin C, under the brand name of Redoxon. In 1957 the American J.J. Burns showed that the reason some mammals were susceptible to scurvy was the inability of their liver to produce the active enzyme L - gulonolactone oxidase, which is the last of the chain of four enzymes which synthesize vitamin C.[49][50] American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the L -gulonolactone oxidase coding gene. In 2008 researchers at the University of Montpellier discovered that in humans and other primates the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized L-dehydroascorbic acid (DHA) back into ascorbic acid which can be reused by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.[51] Physiological function In humans, vitamin C is essential to a healthy diet as well as being a highly effective antioxidant, acting to lessen oxidative stress; a substrate for ascorbate peroxidase;[3] and an enzyme cofactor for the biosynthesis of many important biochemicals. Vitamin C acts as an electron donor for important enzymes:[52] Collagen, carnitine, and tyrosine synthesis, and microsomal metabolism This article may be confusing or unclear to readers. Please help clarify the article; suggestions may be found on the talk page. (May 2009) Ascorbic acid performs numerous physiological functions in human body. These functions include the synthesis of collagen, carnitine and neurotransmitters, the synthesis and catabolism of tyrosine and the metabolism of microsome.[53] Ascorbate acts as a reducing agent (i.e. electron donor, anti-oxidant) in the above-described syntheses, maintaining iron and copper atoms in their reduced states. Vitamin C acts as an electron donor for eight different enzymes: [52] Three participate in collagen hydroxylation.[54][55][56] These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule via prolyl hydroxylase and lysyl hydroxylase, both requiring vitamin C as a cofactor. Hydroxylation allows the collagen molecule to assume its triple helix structure and making vitamin C essential to the development and maintenance of scar tissue, blood vessels, and cartilage.[38] 2 are necessary for synthesis of carnitine. [57][58] Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation. The remaining three have the following functions in common but do not always do this: dopamine beta hydroxylase participates in the biosynthesis of norepinephrine from dopamine.[59][60] another enzyme adds amide groups to peptide hormones, greatly increasing their stability.[61][62] one modulates tyrosine metabolism. [63][64]
  • 60. Antioxidant Ascorbic acid is well known for its antioxidant activity. Ascorbate acts as a reducing agent to reverse oxidation in aqueous solution. When there are more free radicals (Reactive oxygen species) in the body versus antioxidant, a human is under the condition called Oxidative stress. [65] Oxidative stress induced diseases encompass cardiovascular diseases, hypertension, chronic inflammatory diseases and diabetes [66][67][68][69] The plasma ascorbate concentration in oxidative stress patient (less than 45 µmol/L) measured is lower than healthy individual (61.4-80 µmol/L)[70] According to McGregor and Biesalski (2006). [65] increasing plasma ascorbate level may have therapeutic effects in oxidative stress individual. Individuals with oxidative stress and healthy individuals have different pharmacokinetics of ascorbate. Pro-oxidant Ascorbic acid behaves not only as antioxidant but also as pro-oxidant. [65] Ascorbic acid reduced transition metals, such as cupric ions (Cu2+ ) to cuprous (Cu1+ ) and ferric ions (Fe 3+ ) to ferrous (Fe 2+ ) during conversion from ascorbate to dehydroxyascorbate In Vitro. [71] This reaction can generate superoxide and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper is bound to diverse proteins.[65] Recent studies show that intravenous injection of 7.5g of ascorbate daily for six days did not increase pro-oxidant markers; [72] thus, ascorbate as a pro- oxidant is unlikely to convert metals to create ROS in vivo. Daily requirements The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams per day (2000 milligrams per day).[73] Other related species sharing the same inability to produce vitamin C and requiring exogenous vitamin C consume 20 to 80 times this reference intake. [74][75] There is continuing debate within the scientific community over the best dose schedule (the amount and frequency of intake) of vitamin C for maintaining optimal health in humans.[76] It is generally agreed that a balanced diet without supplementation contains enough vitamin C to prevent scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more. [73] High doses (thousands of milligrams) may result in diarrhea in healthy adults. Proponents of alternative medicine (specifically orthomolecular medicine) [77] claim the onset of diarrhea to be an indication of where the body’s true vitamin C requirement lies, because this is the point where body uses vitamin's water solubility to simply flush out the unusable portion, as the diarrhea length/intensity is directly correlated to the quantity of the overdose, though this has yet to be clinically verified. United States vitamin C recommendations[73] Government Recommended Dietary Allowance (adult male) 90 mg per day recommended Recommended Dietary Allowance (adult female) 75 mg per day intakes Tolerable Upper Intake Level (adult male) 2,000 mg per day Recommendations Tolerable Upper Intake Level (adult female) 2,000 mg per day for vitamin C intake have been set by various national agencies: 75 milligrams per day: the United Kingdom's Food Standards Agency [1] 45 milligrams per day: the World Health Organization[78] 60 mg/day: Health Canada 2007[79] 60–95 milligrams per day: United States' National Academy of Sciences.[73] The United States defined Tolerable Upper Intake Level for a 25-year-old male is 2,000 milligrams per day. Alternative recommendations on intakes Some independent researchers have calculated the amount needed for an adult human to achieve similar blood serum levels as vitamin C synthesising mammals as follows:
  • 61. 400 milligrams per day: the Linus Pauling Institute. [80] 500 milligrams per 12 hours: Professor Roc Ordman, from research into biological free radicals. [81] 3,000 milligrams per day (or up to 30,000 mg during illness): the Vitamin C Foundation.[82] 6,000–12,000 milligrams per day: Thomas E. Levy, Colorado Integrative Medical Centre.[83] 6,000–18,000 milligrams per day: Linus Pauling's personal use. [84] Therapeutic uses Vitamin C is necessary for the treatment and prevention of scurvy. Scurvy is commonly comorbid with other diseases of malnutrition; sufficient vitamin C to prevent scurvy occurs in most diets in industrialized nations. [85][86][87] Vitamin C functions as an antioxidant. Adequate intake is necessary for health, but supplementation is probably not necessary in most cases. [88][89][90][91] Based on animal and epidemiological models, high doses of vitamin C may have "protective effects" on lead-induced nerve and muscle abnormalities,[92] especially in smokers.[93][94] Dehydroascorbic acid, the main form of oxidized vitamin C in the body, may reduce neurological deficits and mortality following stroke due to its ability to cross the blood- brain barrier, while "the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood-brain barrier".[95] Vitamin C's effect on the common cold has been extensively researched. Vitamin C megadosage Main article: Vitamin C megadosage Several individuals and organizations advocate large doses of vitamin C based on in vitro and retrospective studies,[96] although large, randomized clinical trials on the effects of high doses on the general population have never taken place. Individuals who have recommended intake well in excess of the current Dietary Reference Intake (DRI) include Robert Cathcart, Ewan Cameron, Steve Hickey, Irwin Stone, Matthias Rath and Linus Pauling. Arguments for megadosage are based on the diets of closely related apes and the likely diet of pre-historical humans, and that most mammals synthesize vitamin C rather than relying on dietary intake. Stone[97] and Pauling [75] calculated, based on the diet of primates[74] (similar to what our common ancestors are likely to have consumed when the gene mutated), that the optimum daily requirement of vitamin C is around 2,300 milligrams for a human requiring 2,500 kcal a day. Pauling also criticized the established RDA as sufficient to prevent scurvy, but not necessarily the dosage for optimal health. [84] Higher vitamin C intake reduces serum uric acid levels, and is associated with lower incidence of gout. [98] Vitamin C has also been promoted as efficacious against a vast array of diseases and syndromes. Research has been done on the effects of Vitamin C on a variety of disorders and diseases including the following:the common cold,[99][100] pneumonia,[101] heart disease,[100][102] AIDS,[103][104] autism,[105] low sperm count,[106] age-related macular degeneration, [107][108] altitude sickness,[109] pre- eclampsia,[110] amyotrophic lateral sclerosis,[111] heroin addiction,[112] asthma,[113] tetanus,[114] and cancer.[115][116][117][118] These uses are poorly supported by the evidence, and sometimes contraindicated.[119][120][121][122][123] Testing for ascorbate levels in the body Simple tests use DCPIP to measure the levels of vitamin C in the urine and in serum or blood plasma. However these reflect recent dietary intake rather than the level of vitamin C in body stores. [6] Reverse phase high performance liquid chromatography is used for determining the storage levels of vitamin C within lymphocytes and tissue.
  • 62. It has been observed that while serum or blood plasma levels follow the circadian rhythm or short term dietary changes, those within tissues themselves are more stable and give a better view of the availability of ascorbate within the organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses, and require samples to be analyzed in specialized laboratories. [124][125] Adverse effects Common side-effects Relatively large doses of vitamin C may cause indigestion, particularly when taken on an empty stomach. When taken in large doses, vitamin C causes diarrhea in healthy subjects. In one trial, doses up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhoea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.[126] Possible side-effects As vitamin C enhances iron absorption, [127] iron poisoning can become an issue to people with rare iron overload disorders, such as haemochromatosis. A genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD) can cause sufferers to develop hemolytic anemia after ingesting specific oxidizing substances, such as very large dosages of vitamin C.[128] There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science.[129] Although recent studies have found a relationship, [130] a clear link between excess ascorbic acid intake and kidney stone formation has not been generally established. [131] Some case reports exist for patients with oxalate deposits and a history of high dose vitamin C usage. Discussions of a possible link are given in articles such as [132] . In a study conducted on rats, during the first month of pregnancy, high doses of vitamin C may suppress the production of progesterone from the corpus luteum.[133] Progesterone, necessary for the maintenance of a pregnancy, is produced by the corpus luteum for the first few weeks, until the placenta is developed enough to produce its own source. By blocking this function of the corpus luteum, high doses of vitamin C (1000+ mg) are theorized to induce an early miscarriage. In a group of spontaneously aborting women at the end of the first trimester, the mean values of vitamin C were significantly higher in the aborting group. However, the authors do state: 'This could not be interpreted as an evidence of causal association.' [134] However, in a previous study of 79 women with threatened, previous spontaneous, or habitual abortion, Javert and Stander (1943) had 91% success with 33 patients who received vitamin C together with bioflavonoids and vitamin K (only three abortions), whereas all of the 46 patients who did not receive the vitamins aborted.[135] Recent rat and human studies suggest that adding Vitamin C supplements to an exercise training program can cause a decrease in mitochondria production, hampering endurance capacity. [136] Chance of overdose As discussed previously, vitamin C exhibits remarkably low toxicity. The LD50 (the dose that will kill 50% of a population) in rats is generally accepted to be 11.9 grams per kilogram of body weight when taken orally.[45] The LD50 in humans remains unknown, owing to medical ethics that preclude experiments which would put patients at risk of harm. However, as with all substances tested in this way, the LD50 is taken as a guide to its toxicity in humans and no data to contradict this has been found.
  • 63. Natural and artificial dietary sources The richest natural sources are fruits and vegetables, and of those, the Kakadu plum and the camu camu fruit contain the highest concentration of the vitamin. It is also present in some cuts of meat, especially liver. Vitamin C is the most widely taken nutritional supplement and is available in a variety of forms, including tablets, drink mixes, crystals in capsules or naked crystals. Vitamin C is absorbed by the intestines using a sodium-ion dependent channel. It is transported through the intestine via both glucose-sensitive and glucose-insensitive mechanisms. The presence of large quantities of sugar either in the Rose hips are a particularly rich intestines or in the blood can slow absorption. [137] source of vitamin C Plant sources While plants are generally a good source of vitamin C, the amount in foods of plant origin depends on: the precise variety of the plant, the soil condition, the climate in which it grew, the length of time since it was picked, the storage conditions, and the method of preparation. [138] The following table is approximate and shows the relative abundance in different raw plant sources. [139][140][141] As some plants were analyzed fresh while others were dried (thus, artifactually increasing concentration of individual constituents like vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources: Amount Amount Plant source Plant source (mg / 100g) (mg / 100g) Kakadu plum 3100 Papaya 60 Camu Camu 2800 Strawberry 60 Rose hip 2000 Orange 50 Acerola 1600 Lemon 40 Seabuckthorn 695 Melon, cantaloupe 40 Jujube 500 Cauliflower 40 Indian gooseberry 445 Garlic 31 Baobab 400 Grapefruit 30 Blackcurrant 200 Raspberry 30 Red pepper 190 Tangerine 30 Parsley 130 Mandarin orange 30 Guava 100 Passion fruit 30 Kiwifruit 90 Spinach 30 Broccoli 90 Cabbage raw green 30 Loganberry 80 Lime 30 Redcurrant 80 Mango 28 Brussels sprouts 80 Blackberry 21 Wolfberry (Goji) 73 † Potato 20 Lychee 70 Melon, honeydew 20 Cloudberry 60 Cranberry 13 Elderberry 60 Tomato 10 Persimmon 60 Blueberry 10 † average of 3 sources; dried Pineapple 10 Pawpaw 10 Amount Plant source (mg / 100g) Grape 10 Apricot 10 Plum 10 Watermelon 10
  • 64. Banana 9 Carrot 9 Avocado 8 Crabapple 8 Persimmon - fresh 7 Cherry 7 Peach 7 Apple 6 Asparagus 6 Beetroot 5 Chokecherry 5 Pear 4 Lettuce 4 Cucumber 3 Eggplant 2 Raisin 2 Fig 2 Bilberry 1 Horned melon 0.5 Medlar 0.3 Animal sources The overwhelming majority of species of animals and plants synthesise their own vitamin C, making some, but not all, animal products, sources of dietary vitamin C. Vitamin C is most present in the liver and least present in the muscle. Since muscle provides the majority of meat consumed in the western human diet, animal products are not a reliable source of Goats, like almost all animals, the vitamin. Vitamin C is present in mother's milk make their own vitamin C. An and, in lower amounts, in raw cow's milk, with adult goat, weighting approx. pasteurized milk containing only trace 70kg, will manufacture more than 13,000 mg of vitamin C per day in amounts. [144] All excess vitamin C is disposed of normal health, and levels through the urinary system. manyfold higher when faced with stress. [142][143] The following table shows the relative abundance of vitamin C in various foods of animal origin, given in milligram of vitamin C per 100 grams of food: Amount Amount Animal Source Animal Source (mg / 100g) (mg / 100g) Calf liver (raw) 36 Lamb liver (fried) 12 Beef liver (raw) 31 Calf adrenals (raw) 11 [145] Oysters (raw) 30 Lamb heart (roast) 11 Cod roe (fried) 26 Lamb tongue (stewed) 6 Pork liver (raw) 23 Human milk (fresh) 4 Lamb brain (boiled) 17 Goat milk (fresh) 2 Chicken liver (fried) 13 Cow milk (fresh) 2 Food preparation Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature they are stored at[146] and cooking can reduce the Vitamin C content of vegetables by around 60% possibly partly due to increased enzymatic destruction as it may be more significant at sub-boiling temperatures. [147] Longer cooking times also add to this effect, as will copper food vessels, which catalyse the decomposition. [45] Another cause of vitamin C being lost from food is leaching, where the water-soluble vitamin dissolves into the cooking water, which is later poured away and not consumed. However, vitamin C doesn't leach in all vegetables at the same rate; research shows
  • 65. broccoli seems to retain more than any other. [148] Research has also shown that fresh- cut fruits don't lose significant nutrients when stored in the refrigerator for a few days. [149] Vitamin C supplements Vitamin C is the most widely taken dietary supplement.[150] It is available in many forms including caplets, tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, and crystalline powder. Timed release versions are available, as are formulations containing bioflavonoids such as quercetin, hesperidin and rutin. Tablet and capsule sizes range from 25 mg to 1500 mg. Vitamin C (as ascorbic acid) crystals are typically available in bottles containing 300 g to 1 kg of powder (a teaspoon of vitamin C crystals equals 5,000 mg). Vitamin C is widely available in the form of tablets and powders. The Redoxon brand, launched in 1934 by Hoffmann-La Roche, Artificial modes of synthesis was the first mass-produced Vitamin C is produced from glucose by two main synthetic vitamin C. routes. The Reichstein process, developed in the 1930s, uses a single pre-fermentation followed by a purely chemical route. The modern two-step fermentation process, originally developed in China in the 1960s, uses additional fermentation to replace part of the later chemical stages. Both processes yield approximately 60% vitamin C from the glucose feed.[151] Research is underway at the Scottish Crop Research Institute in the interest of creating a strain of yeast that can synthesise vitamin C in a single fermentation step from galactose, a technology expected to reduce manufacturing costs considerably.[18] World production of synthesised vitamin C is currently estimated at approximately 110,000 tonnes annually. Main producers have been BASF/Takeda, DSM, Merck and the China Pharmaceutical Group Ltd. of the People's Republic of China. China is slowly becoming the major world supplier as its prices undercut those of the US and European manufacturers.[152] By 2008 only the DSM plant in Scotland remained operational outside the strong price competition from China. [153] The world price of vitamin C rose sharply in 2008 partly as a result of rises in basic food prices but also in anticipation of a stoppage of the two Chinese plants, situated at Shijiazhuang near Beijing, as part of a general shutdown of polluting industry in China over the period of the Olympic games.[154] Food Fortification Health Canada evaluated the effect of fortification of foods with abscorbate in the guidance document, Addition of Vitamins and Minerals to Food, 2005. [155] Health Canada categorized abscorbate as a ‘Risk Category A nutrients’. This means it is either a nutrient for which an upper limit for intake is set but allows a wide margin of intake that has a narrow margin of safety but non-serious critical adverse effects. Health Canada recommended a minimum of 3 mg or 5 % of RDI in order for the food to claim to be a source of Vitamin C and maximum fortification of 12 mg (20 % of RDI) in order to be claimed "Excellent Source". References 1. ↑ 1.0 1.1 "Vitamin C". Food Standards Agency (UK). http://www.eatwell.gov.uk/healthydiet/nutritionessentials/vitaminsandminerals/vitaminc/. Retrieved 2007-02- 19. 2. ↑ "Vitamin C". University of Maryland Medical Center. January 2007. http://www.umm.edu/ency/article//002404.htm. Retrieved 2008-03-31. 3. ↑ 3.0 3.1 Higdon, Jane, Ph.D. (2006-01-31). "Vitamin C". Oregon State University, Micronutrient Information Center. http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/. Retrieved 2007-03-07. 4. ↑ McCluskey, Elwood S. (1985). "Which Vertebrates Make Vitamin C?" (PDF). Origins 12 (2): 96–100. http://www.grisda.org/origins/12096.pdf. 5. ↑ Padayatty S, Katz A, Wang Y, Eck P, Kwon O, Lee J, Chen S, Corpe C, Dutta A, Dutta S, Levine M (2003). "Vitamin C as an Antioxidant: evaluation of its role in disease prevention" (PDF). J Am Coll Nutr 22 (1): 18–35. PMID 12569111. http://www.jacn.org/cgi/reprint/22/1/18.pdf.
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  • 71. Categories: Pages with DOIs broken since 2009 | Wikipedia articles needing clarification from May 2009 | All Wikipedia articles needing clarification | Food antioxidants | Dietary antioxidants | Organic acids | Orthomolecular medicine | Oxygen heterocycles | Sugar acids | Vitamins | Coenzymes | Antidepressants History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 72. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN B6 Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Vitamin B6 view original wikipedia article Vitamin B6 Vitamin B 6 is a water-soluble vitamin and is part of the vitamin B complex group. Pyridoxal phosphate (PLP) is the active form and is a overview outline images locations cofactor in many reactions of amino acid metabolism, including transamination, deamination, Search this article high and decarboxylation. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen. Vitamin B6 Pyridoxine History Forms History Functions Amino acid metabolism Vitamin B6 is a water-soluble compound that was Gluconeogenesis discovered in the 1930s during nutrition studies on Lipid metabolism rats. In 1934, a Hungarian physician, Paul Gyorgy Metabolic functions discovered a substance that was able to cure a Amino acid metabolism skin disease in rats (dermititis acrodynia), this Pyridoxal phosphate Gluconeogenesis substance he named vitamin B6. In 1938, Neurotransmitter synthesis Lepkovsky isolated vitamin B6 from rice bran. Histamine synthesis Harris and Folkers in 1939 determined the structure of pyridoxine, and, in 1945, Snell Hemoglobin synthesis and function was able to show that there are two forms of vitamin B6, pyridoxal and pyridoxamine. Vitamin B6 was named pyridoxine to indicate its structural homology to pyridine. All Gene expression three forms of vitamin B6 are precursors of an activated compound known as pyridoxal Dietary reference intakes Food sources 5'-phosphate (PLP), which plays a vital role as the cofactor of a large number of essential enzymes in the human body. Absorption Excretion Enzymes dependent on PLP focus a wide variety of chemical reactions mainly involving Deficiencies amino acids. The reactions carried out by the PLP-dependent enzymes that act on Clinical assessment of vitamin B6 amino acids include transfer of the amino group, decarboxylation, racemization, and Toxicity beta- or gamma-elimination or replacement. Such versatility arises from the ability of Preventive roles and therapeutic uses PLP to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby References stabilizing different types of carbanionic reaction intermediates. External links Overall, the Enzyme Commission (EC; http://www.chem.qmul.ac.uk/iubmb/enzyme/ ) has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all Images Videos classified activities. The effectiveness as treatment for PMS, PMDD, and clinical depression is debatable.[1][2] B6 is also considered an experimental but potentially effective treatment for schizophrenia and autism. view all 24 view all 15 Forms Seven forms of this vitamin are known: pyridoxine (PN). PN is the form that is given as vitamin B6 supplement. pyridoxine 5'-phosphate (PNP). pyridoxal (PL). pyridoxal 5'-phosphate (PLP). PLP is the metabolically active form. pyridoxamine (PM). pyridoxamine 5'-phosphate (PMP). 4-pyridoxic acid (PA). PA is the catabolite which is excreted in the urine. All forms except PA can be interconverted. Functions Pyridoxal phosphate, the metabolically active form of vitamin B6 , is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis,
  • 73. hemoglobin synthesis and function and gene expression. Pyridoxal phosphate generally serves as a coenzyme for many reactions and can help facilitate decarboxylation, transamination, racemization, elimination, replacement and beta-group interconversion reactions[3] . The liver is the site for vitamin B6 metabolism. Amino acid metabolism Pyridoxal phosphate (PLP) is a cofactor in transaminases that can catabolize amino acids. PLP is also an essential component of two enzymes that converts methionine to cysteine via two reactions. Low vitamin B6 status will result in decreased activity of these enzymes. PLP is also an essential cofactor for enzymes involved in the metabolism of selenomethionine to selenohomocysteine and then from selenohomocysteine to hydrogen selenide. Vitamin B6 is also required for the conversion of tryptophan to niacin and low vitamin B6 status will impair this conversion[3] . PLP is also used to create physiologically active amines by decarboxylation of amino acids. Some notable examples of this include: histidine to histamine, tryptophan to serotonin, glutamate to GABA (gamma-aminobutyric acid), and dihydroxyphenylalanine to dopamine. Gluconeogenesis Vitamin B6 also plays a role in gluconeogenesis. Pyridoxal phosphate can catalyze transamination reactions that are essential for the providing amino acids as a substrate for gluconeogenesis. Also, vitamin B6 is a required coenzyme of glycogen phosphorylase [3] , the enzyme that is necessary for glycogenolysis to occur. Lipid metabolism Vitamin B6 is an essential component of enzymes that facilitate the biosynthesis of sphingolipids [3] . Particularly, the synthesis of ceramide requires PLP. In this reaction serine is decarboxylated and combined with palmitoyl-CoA to form sphinganine which is combined with a fatty acyl CoA to form dihydroceramide. Dihydroceramide is then further desaturated to form ceramide. In addition, the breakdown of sphingolipids is also dependent on vitamin B6 since S1P Lyase, the enzyme responsible for breaking down sphingosine-1-phosphate, is also PLP dependent. Metabolic functions The primary role of vitamin B6 is to act as a coenzyme to many other enzymes in the body that are involved predominantly in metabolism. This role is performed by the active form, pyridoxal phosphate. This active form is converted from the two other natural forms founds in food: pyridoxal, pyridoxine and pyridoxamine. Vitamin B6 is involved in the following metabolic processes: amino acid, glucose and lipid metabolism neurotransmitter synthesis histamine synthesis hemoglobin synthesis and function gene expression Amino acid metabolism Pyridoxal phosphate is involved in almost all amino acid metabolism, from synthesis to breakdown. 1. Transamination: transaminase enzymes needed to break down amino acids are dependent on the presence of pyridoxal phosphate. The proper activity of these enzymes are crucial for the process of moving amine groups from one amino acid to another. 2. Transsulfuration: Pyridoxal phosphate is a coenzyme needed for the proper function of the enzymes cystathionine synthase and cystathionase. These enzymes work to transform methionine into cysteine. 3. Selenoamino acid metabolism: Selenomethionine is the primary dietary form of selenium. Pyridoxal phosphate is needed as a cofactor for the enzymes that allow
  • 74. selenium to be used from the dietary form. Pyridoxal phosphate also plays a cofactor role in releasing selenium from selenohomocysteine to produce hydrogen selenide. This hydrogen selenide can then be used to incorporate selenium into selenoproteins. [3] 4. Vitamin B6 is also required for the conversion of tryptophan to niacin and low vitamin B6 status will impair this conversion[3] . Gluconeogenesis Vitamin B6 also plays a role in gluconeogenesis. Pyridoxal phosphate can catalyze transamination reactions that are essential for providing amino acids as a substrate for gluconeogenesis. Also, vitamin B6 is a required coenzyme of glycogen phosphorylase [3] , the enzyme that is necessary for glycogenolysis to occur. Neurotransmitter synthesis Pyridoxal phosphate-dependent enzymes play a role in the biosynthesis of four important neurotransmitters: serotonin, epinephrine, norepinephrine and gamma- aminobutyric acid[3] . Serine racemase, which synthesizes the neuromodulator D-serine, is also a pyridoxal phosphate-dependent enzyme. Histamine synthesis Pyridoxal phosphate is involved in the metabolism of histamine[3] . Hemoglobin synthesis and function Pyridoxal phosphate aids in the synthesis of heme and can also bind to two sites on hemoglobin to enhance the oxygen binding of hemoglobin [3] . Gene expression It transforms homocysteine in then cistation then in cysteine, leading indirectly to epigenetics phenomena of nature is still not certain; for this reason, Pyridoxal phosphate should be used in the next experiments about epigenetics. Pyridoxal phosphate has been implicated in increasing or decreasing the expression of certain genes. Increased intracellular levels of the vitamin will lead to a decrease in the transcription of glucocorticoid hormones. Also, vitamin B6 deficiency will lead to the increased expression of albumin mRNA. Also, pyridoxal phosphate will influence gene expression of glycoprotein IIb by interacting with various transcription factors. The result is inhibition of platelet aggregation. [3] Dietary reference intakes Life Stage Group RDA/AI* UL Infants (mg/day) (mg/day) 0–6 months 0.1* ND 7–12 months 0.3* ND Children 1-3 yrs 0.5 30 4-8 yrs 0.6 40 Males 9-13 yrs 1.0 60 14-18 yrs 1.3 80 19-50 yrs 1.3 100 50- >70 yrs 1.7 100 Females 9-13 yrs 1.0 60 13-18 yrs 1.2 80 19-50 yrs 1.3 100 50- >70 yrs 1.5 100 Pregnancy <18 yrs 1.9 80 19-50 yrs 1.9 100 Lactation <18 yrs 2.0 80 19-50 yrs 2.0 100
  • 75. The Institute of Medicine notes that "No adverse effects associated with Vitamin B6 from food have been reported. This does not mean that there is no potential for adverse effects resulting from high intakes. Because data on the adverse effects of Vitamin B6 are limited, caution may be warranted. Sensory neuropathy has occurred from high intakes of supplemental forms."[4] See the full Dietary Reference Intake table from the Institute of Medicine's. Food sources Vitamin B6 is widely distributed in foods in both its free and bound forms. Good sources include meats, whole grain products, vegetables, and nuts. Cooking, storage and processing losses of vitamin B6 vary and in some foods may be more than 50%,[5] depending on the form of vitamin present in the food. Plant foods lose the least during processing as they contain mostly pyridoxine which is far more stable than the pyridoxal or pyridoxamine found in animal foods. For example, milk can lose 30-70% of its vitamin B6 content when dried. [3] Vitamin B6 is found in the germ and aleurone layer of grains and milling results to the reduction of this vitamin in white flour. Freezing and canning are other food processing methods that results in the loss of vitamin B6 in foods. [6] Absorption Vitamin B6 is absorbed in the jejunum and ileum via passive diffusion. With the capacity for absorption being so great, animals are able to absorb quantities much greater than what is needed for physiological demands. The absorption of pyridoxal phosphate and pyridoxamine phosphate involves their dephosphorylation catalyzed by a membrane- bound alkaline phosphatase. Those products and non-phosphorylated vitamers in the digestive tract are absorbed by diffusion, which is driven by trapping of the vitamin as 5'-phosphates through the action of phosphorylation (by a pyridoxal kinase) in the jejunal mucosa. The trapped pyridoxine and pyridoxamine are oxidized to pyridoxal phosphate in the tissue. [3] Excretion The products of vitamin B6 metabolism are excreted in the urine; the major product of which is 4-pyridoxic acid. It has been estimated that 40-60% of ingested vitamin B6 is oxidized to 4-pyridoxic acid. Several studies have shown that 4-pyridoxic acid is undetectable in the urine of vitamin B6 deficient subjects, making it a useful clinical marker to assess the vitamin B6 status of an individual.[3] Other products of vitamin B6 metabolism that are excreted in the urine when high doses of the vitamin have been given include pyridoxal, pyridoxamine, and pyridoxine and their phosphates. A small amount of vitamin B6 is also excreted in the feces. Deficiencies The classic clinical syndrome for B6 deficiency is a seborrhoeic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms of somnolence, confusion, and neuropathy. [7] While severe vitamin B6 deficiency results in dermatologic and neurologic changes, less severe cases present with metabolic lesions associated with insufficient activities of the coenzyme pyridoxal phosphate. The most prominent of the lesions is due to impaired tryptophan-niacin conversion. This can be detected based on urinary excretion of xanthurenic acid after an oral tryptophan load. Vitamin B6 deficiency can also result from impaired transsulfuration of methionine to cysteine. The pyridoxal phosphate- dependent transaminases and glycogen phosphorylase provide the vitamin with its role in gluconeogenesis, so deprivation of vitamin B6 results in impaired glucose tolerance. [3] A deficiency of vitamin B6 alone is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of vitamin B6 deficiency, as well as other micronutrient deficiencies. [8] Renal patients
  • 76. undergoing dialysis may experience vitamin B6 deficiency. The availability of vitamin B6 to the body can be affected by certain drugs such as anticonvulsants and corticosteriods.[9] Clinical assessment of vitamin B6 Pyridoxal phosphate in the plasma is considered to be one of the best indicator of vitamin B6 status in the body. When plasma pyridoxal phosphate is less than 10nmol/L, it is indicative of vitamin B6 deficiency. [10] Urinary 4-pyridoxic acid is also an indicator of vitamin B6 deficiency. Urinary 4-pyridoxic of less than 3.0 mmol/day is suggestive of vitamin B6 deficiency. [11] Toxicity An overdose of pyridoxine can cause a temporary deadening of certain nerves such as the proprioceptory nerves; causing a feeling of disembodiment common with the loss of proprioception. This condition is reversible when supplementation is stopped.[12] Because adverse effects have only been documented from vitamin B6 supplements and never from food sources, this article only discusses the safety of the supplemental form of vitamin B6 (pyridoxine). Although vitamin B6 is a water-soluble vitamin and is excreted in the urine, very high doses of pyridoxine over long periods of time may result in painful neurological symptoms known as sensory neuropathy. Symptoms include pain and numbness of the extremities, and in severe cases difficulty walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day. However, there have been a few case reports of individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes of pyridoxine below 200 mg/day. In order to prevent sensory neuropathy in virtually all individuals, the Food and Nutrition Board of the Institute of Medicine set the tolerable upper intake level (UL) for pyridoxine at 100 mg/day for adults. Because placebo-controlled studies have generally failed to show therapeutic benefits of high doses of pyridoxine, there is little reason to exceed the UL of 100 mg/day. Preventive roles and therapeutic uses At least one preliminary study has found that this vitamin may increase dream vividness or the ability to recall dreams.[13] It is thought that this effect may be due to the role this vitamin plays in the conversion of tryptophan to serotonin.[13] The intake of vitamin B, from either diet or supplements, could cut the risk of Parkinson’s disease by half according to a prospective study from the Netherlands. "Stratified analyses showed that this association was restricted to smokers," wrote the authors.[14] Pyridoxine has a role in preventing heart disease. Without enough pyridoxine, a compound called homocysteine builds up in the body. Homocysteine damages blood vessel linings, setting the stage for plaque buildup when the body tries to heal the damage.Vitamin B6 prevents this buildup, thereby reducing the risk of heart attack. Pyridoxine lowers blood pressure and blood cholesterol levels and keeps blood platelets from sticking together. All of these properties work to keep heart disease at bay.[15] Nutritional supplementation with high dose vitamin B6 and magnesium is one of the most popular alternative medicine choices for autism. [16][17] Some studies suggest that the B6-magnesium combination can also help attention deficit disorder, citing improvements in hyperactivity, hyperemotivity/aggressiveness and improved school attention. [18] A lack of the vitamin may play a role in sensitivity to monosodium glutamate (MSG), a flavor enhancer. This sensitivity can cause headaches, pain and tingling of the upper extremities, nausea, and vomiting. In both of these syndromes, supplementation of pyridoxine alleviates symptoms only when people were deficient in the vitamin to begin with.[15] If people are marginally deficient in vitamin B6, they may be more susceptible to carpal
  • 77. tunnel syndrome. Carpal tunnel syndrome is characterized by pain and tingling in the wrists after performing repetitive movements or otherwise straining the wrist on a regular basis.[15] Vitamin B6 has been shown in at least two small-scale clinical studies [19][20] to have a beneficial effect on carpal tunnel syndrome, particularly in cases where no trauma or overuse etiology for the CTS is known. Vitamin B6 has long been publicized as a cure for premenstrual syndrome (PMS). Study results conflict as to which symptoms are eased, but most of the studies confirm that women who take B6 supplements have reductions in bloating, breast pain, and premenstrual acne flare, a condition in which pimples break out about a week before a woman's period begins.There is strong evidence that pyridoxine supplementation, starting ten days before the menstrual period, prevents most pimples from forming. This effect is due to the vitamin's role in hormone and prostaglandin regulation. Skin blemishes are typically caused by a hormone imbalance, which vitamin B6 helps to regulate. [15] Mental depression is another condition which may result from low vitamin B6 intake. Because of pyridoxine's role in serotonin and other neurotransmitter production, supplementation often helps depressed people feel better, and their mood improves significantly. It may also help improve memory in older adults. [15] It is also suggested that ingestion of vitamin B6 can alleviate some of the many symptoms of an alcoholic hangover and morning sickness from pregnancy. This might be due to B6's mild diuretic effect. [21] Though the mechanism is not known, results show that pyridoxamine has a therapeutic effects in clinical trials for diabetic nephropathy.[22] References 1. ↑ Vitamin Pills: Popping Too Many?, WebMD 2. ↑ "Vitamin B6 Therapy for PMDD", Complementary and Alternative Medicine, Creighton University School of Medicine 3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 Combs, G.F. The Vitamins: Fundamental Aspects in Nutrition and Health. 2008. San Diego: Elsevier 4. ↑ Food and Nutrition Board. Institute of Medicine. "Dietary Reference Intakes: Vitamins". National Academies, 2001. 5. ↑ McCormick, D. B. Vitamin B 6 In: Present Knowledge in Nutrition (Bowman, B. A. and Russell, R. M., eds), 9th edition, vol. 2, p.270. Washington, D.C.: International Life Sciences Institute, 2006. 6. ↑ Sauberlich H. Vitamins -how much is for keeps? Nutr Today 1987;22:20-28 7. ↑ Andrews' Diseases of the Skin, 10th Edition, Elsevier. 8. ↑ Bowman, B.A., Russell, R. M. Present Knowledge in Nutrition. 9th Edition. Washington, DC: ILSI Press; 2006; pg.273 9. ↑ Sauberlich H. Vitamins -how much is for keeps? Nutr Today 1987; 22:20-28 10. ↑ Lui A., Lumeng L. Aronoff G., Li T-K. Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance; metabolic balance studies in humans. J Lab Clin Med 1985;106:491-97 11. ↑ Leklem J. Vitamin B6: a status report. J. Nutr 1990;120:1503-7 12. ↑ Vitamin and Mineral Supplement Fact Sheets Vitamin B 6 13. ↑ 13.0 13.1 Ebben, M., Lequerica, A., & Spielman A. (2002). Effects of pyridoxine on dreaming: a preliminary study. Perceptual & Motor Skills, 94(1), 135–140. 14. ↑ "Increased intake of vitamin B6Sheet". http://www.nutraingredients.com/news/ng.asp?n=69580-vitamin-b- folate-parkinson-s-disease. Retrieved 2006-08-11. 15. ↑ 15.0 15.1 15.2 15.3 15.4 http://recipes.howstuffworks.com/vitamin-b62.htm 16. ↑ Efficacy of vitamin B6 and magnesium in the treatm...[J Autism Dev Disord. 1995] - PubMed Result 17. ↑ Angley M, Semple S, Hewton C, Paterson F, McKinnon R (2007). "Children and autism—part 2— management with complementary medicines and dietary interventions" (PDF). Aust Fam Physician 36 (10): 827–30. PMID 17925903. http://www.racgp.org.au/Content/NavigationMenu/Publications/AustralianFamilyPhys/2007issues/afp200710/200710angley.pdf . 18. ↑ Mousain-Bosc M et al. (2006). "[Expression error: Missing operand for > Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.]". Magnesium Research 19 (1): 46–52. PMID 16846100. 19. ↑ Ellis J et al: Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome. Am J Clin Nutr. 1979 Oct;32(10):2040-6. 20. ↑ Kasdan ML, Janes C.: Carpal tunnel syndrome and vitamin B6. Plast Reconstr Surg. 1987 Mar;79(3):456- 62. 21. ↑ THE MYSTERIOUS VITAMIN B6. By Dr. Russ Ebbets. Off The Road Column 22. ↑ Sergi V.C., Wenhui Zhang, Billy G.H., Anthony S.S., Paul A.V. Pyridoxamine protects proteins from functional damage by 3-Deoxyglucosone; mechanism of action of pyridoxamine. Biochemistry 2008,47,997- 1006. External links Facts about Vitamin B6 from Office of Dietary Supplements at National Institutes
  • 78. of Health The B6 database A database of B6-dependent enzymes at University of Parma Vitamin B6 Information Sheet from the Linus Pauling Institute at Oregon State University Vitamin B6 (and magnesium) in the treatment of autism from the Autism Research Institute COT statement on vitamin B6 (pyridoxine) toxicity (June 1997) (Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT)) MeSH Vitamin+B6 Vitamins (A11) show Categories: All articles with unsourced statements | Articles with unsourced statements from August 2009 | Articles with unsourced statements from October 2009 | B vitamins | Cofactors History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 79. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN B5 Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Pantothenic acid view original wikipedia article Pantothenic acid Pantothenic acid, also called Pantothenic acid vitamin B 5 (a B vitamin), is a water-soluble vitamin required to overview outline images locations sustain life (essential nutrient). Pantothenic acid is needed to form Search this article high coenzyme-A (CoA), and is critical in IUPAC name 3-[(2,4-dihydroxy-3,3- the metabolism and synthesis of dimethylbutanoyl)amino]propanoic acid carbohydrates, proteins, and fats. In Identifiers Pantothenic acid chemical structure, it is the amide CAS number 137-08-6 Biological role between D-pantoate and beta- PubChem 988 Sources alanine. Its name is derived from SMILES CC(C)(CO)[C@@H](O)C(=O)NCCC(=O)O Dietary the Greek pantothen (πάντοθεν) Properties Supplementation meaning "from everywhere" and Molecular C9 H17 NO 5 formula Daily requirement small quantities of pantothenic acid Molar mass 219.23 g mol−1 Absorption are found in nearly every food, with Supplementary data page Deficiency high amounts in whole-grain Structure and n, εr , etc. Toxicity cereals, legumes, eggs, meat, and properties Thermodynamic Phase behaviour Uses royal jelly. It is commonly found as data Solid, liquid, gas Testicular Torsion its alcohol analog, the provitamin Spectral data UV, IR, NMR, MS Diabetic Ulceration panthenol, and as calcium (what is this?) (verify) Hypolipidemic Effects pantothenate. Pantothenic acid is Except where noted otherwise, data are given for materials an ingredient in some hair and skin in their standard state (at 25 °C, 100 kPa) Wound Healing care products. Infobox references Hair care Acne Diabetic peripheral polyneuropathy Biological role Ruminant Nutrition Synonyms Only the dextrorotatory (D) isomer of pantothenic acid possesses biologic activity. [1] See also The levorotatory (L) form may antagonize the effects of the dextrorotatory isomer.[2] Enzymes References Pantothenic acid is used in the synthesis of coenzyme A (CoA). Coenzyme A may act External links as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. [3] CoA is important in energy metabolism for Images Videos pyruvate to enter the tricarboxylic acid cycle(TCA cycle) as acetyl-CoA, and for α- ketoglutarate to be transformed to succinyl-CoA in the cycle. [4] CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine.[5] CoA is incidentally also required in the formation of ACP[6] , which is also required for fatty acid synthesis in addition to CoA.[7] view all 24 view all 15 Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively. [8] Since pantothenic acid participates in a wide array of key biological roles, it is essential to all forms of life. [9] As such, deficiencies in pantothenic acid may have numerous wide-ranging effects, as discussed below. Sources Dietary Small quantities of pantothenic acid are found in most foods. [10] The major food source of pantothenic acid is in meats, although the concentration found in food animals' muscles is only about half that in humans' muscles. [2] Whole grains are another good source of the vitamin, but milling often removes much of the pantothenic acid, as it is found in the outer layers of whole grains [11] . Vegetables, such as broccoli and avocados, also have an abundance of the acid. [12] In animal feeds, the most important
  • 80. sources of the vitamin are rice, wheat brans, alfalfa, peanut meal, molasses, yeasts, and condensed fish solutions. The most significant sources of pantothenic acid in nature are coldwater fish ovaries and royal jelly. [13] A recent study also suggests that gut bacteria in humans can generate pantothenic acid, but this has not yet been proven. [14] Supplementation The derivative of pantothenic acid, pantothenol, is a more stable form of the vitamin and is often used as a source of the vitamin in multivitamin supplements. [15] Another common supplemental form of the vitamin is calcium pantothenate. Calcium pantothenate is often used in dietary supplements because as a salt, it is more stable than pantothenic acid in the digestive tract allowing for better absorption. Possible benefits of supplementation: Doses of 2g/day of calcium pantothenate may reduce the duration of morning stiffness, degree of disability, and pain severity in rheumatoid arthritis patients. Although the results are inconsistent, supplementation may improve oxygen utilization efficiency and reduce lactic acid accumulation in athletes. [16] Daily requirement Pantothenate in the form of 4'phosphopantetheine is considered to be the more active form of the vitamin in the body; however, any derivative must be broken down to pantothenic acid before absorption[17] . Ten Mg of calcium pantothenate is equivalent to 9.2 mg of pantothenic acid. Age group Age Requirements[18] Infants 0–6 months 1.7 Mg Infants 7–12 months 1.8 Mg Children 1–3 years 2 Mg Children 4–8 years 3 Mg Children 9–12 years 4 Mg Adult men and women 13+ years 5 Mg Pregnant women (vs. 5) 6 Mg Breastfeeding women (vs. 5) 7 Mg United Kingdom RDA: 6 mg/day Absorption Within most foods, pantothenic acid is in the form of CoA or Acyl Carrier Protein (ACP). In order for the intestinal cells to absorb this vitamin it must be converted into free pantothenic acid[19] . Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4'-phosphopantetheine[20] . 4'-phosphopantetheine is then dephosphorylated into pantetheine[21] . Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid[22] . Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium- dependent active transport system [23] . At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be absorbed via passive diffusion. [24] However, as intake increases 10-fold, absorption rate decreases to 10% [25] . Deficiency Pantothenic acid deficiency is exceptionally rare and has not been thoroughly studied. In the few cases where deficiency has been seen (victims of starvation and limited volunteer trials), nearly all symptoms can be reversed with the return of pantothenic acid[26] . Symptoms of deficiency are similar to other vitamin B deficiencies. There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue, and apathy [27] . Acetylcholine synthesis is also impaired, therefore, neurological symptoms can also appear in deficiency[28] . They include numbness, paresthesia, and
  • 81. muscle cramps[29] . Deficiency in pantothenic acid can also cause hypoglycemia, or an increased sensitivity to insulin[30] . Insulin receptors are acylated with palmitic acid when they do not want to bind with insulin[31] . Therefore, more insulin will bind to receptors when acylation decreases, causing hypoglycemia [32] . Additional symptoms could include: restlessness, malaise, sleep disturbances, nausea, vomiting, and abdominal cramps[33] . In a few rare circumstances more serious (but reversible) conditions have been seen, such as adrenal insufficiency and hepatic encephalopathy. It has been noted that painful burning sensations of the feet were reported in tests conducted on volunteers. Deficiency of pantothenic acid may explain similar sensations reported in malnourished prisoners of war. [9] Deficiency symptoms in other non-ruminant animals include disorders of the nervous, gastrointestinal, and immune systems, reduced growth rate, decreased food intake, skin lesions and changes in hair coat, alterations in lipid and carbohydrate metabolism. [34] Toxicity Toxicity of pantothenic acid is unlikely. In fact, no Tolerable Upper Level Intake (UL) has been established for the vitamin [35] . Large doses of the vitamin, when ingested, have no reported side effects and massive doses (e.g. 10 g/day) may only yield mild intestinal distress and diarrhea at worst [36] . There are also no adverse reactions known following parenteral or topical application of the vitamin.[37] However, a large dosis of vitamin B5 (e.g: 5 - 9 gram) is known to cause nausea and a lack of fatigue. Uses Given pantothenic acid's prevalence among living things and the limited body of studies in deficiency, many uses of pantothenic acid have been the subject of research. Testicular Torsion Testicular torsion can severely affect fertility if it occurs [38] . One study on a rat model indicated that a treatment of 500 mg of dexpanthenol/kg body weight 30 minutes prior to detorsion can greatly decrease the risk of infertility after torsion [39] . Pantothenic acid has the ability to spare reduced glutathione levels [40] . Reactive oxygen species play a role in testicular atrophy, which the glutathione can 'fight' against[41] . Diabetic Ulceration Foot ulceration is a problem commonly associated with diabetes, which often leads to amputation [42] . A preliminary study completed by Abdelatif, Yakoot and Etmaan indicated that perhaps a royal jelly and panthenol ointment can help cure the ulceration [43] . People studied with foot ulceration or deep tissue infection had a 96% and 92% success rate of recovery[44] . However, as this was a pilot study, it was not a randomized placebo-controlled double-blinded study [45] . While these results appear promising, they need to be validated. Hypolipidemic Effects Pantothenic acid derivatives, panthenol, phosphopantethine and pantethine, have also been seen to improve the lipid profile in the blood and liver[46] . In a mouse model, they injected 150 mg of the derivative/kg body weight [47] . All three derivatives were able to effectively lower low-density lipoprotein (LDL) as well as triglyceride (TG) levels, panthenol was able to lower total cholesterol and pantethine was able to lower LDL- cholesterol in the serum [48] . The decrease in LDL-cholesterol is significant, as it will decrease the risk of heart attack and stroke [49] . In the liver, panthenol was the most effective, as it lowered TG, T-chol, free cholesterol and cholesterol-ester levels [50] .
  • 82. Wound Healing A study in 1999 showed that pantothenic acid has an effect on wound healing in vitro [51] . Wiemann and Hermann found that cell cultures with a concentration of 100μg/mL calcium D-pantothenate increased migration, and the fibres ran directionally with several layers, whereas the cell cultures without pantothenic acid healed in no orderly motion, and with fewer layers[52] . Cell proliferation, or cell multiplication was found to increase with pantothenic acid supplementation [53] . Finally, there were increased concentrations of two proteins, both of which have still to be been identified, that was found in the supplemented culture, but not on the control [54] . Further studies are needed to determine whether these effects will stand in vivo. Hair care Mouse models identified skin irritation and loss of hair color as possible results of severe pantothenic acid deficiency. As a result, the cosmetic industry began adding pantothenic acid to various cosmetic products, including shampoo. These products, however, showed no benefits in human trials. Despite this, many cosmetic products still advertise pantothenic acid additives. [55][56][57][58][59][60] Acne Following from discoveries in mouse trials, in the late 1990s a small study was published promoting the use of pantothenic acid to treat acne vulgaris. According to a study published in 1995 by Dr. Lit-Hung Leung,[61] high doses of Vitamin B5 resolved acne and decreased pore size. Dr. Leung also proposes a mechanism, stating that CoA regulates both hormones and fatty-acids, and without sufficient quantities of pantothenic acid, CoA will preferentially produce androgens. This causes fatty acids to build up and be excreted through sebaceous glands, causing acne. Leung's study gave 45 Asian males and 55 Asian females varying doses of 10-20g of pantothenic acid (100000% of the US Daily Value), 80% orally and 20% through topical cream. Leung noted improvement of acne within one week to one month of the start of the treatment. Diabetic peripheral polyneuropathy 28 out of 33 patients (84.8%) previously treated with alpha-lipoic acid for peripheral polyneuropathy reported further improvement after combination with pantothenic acid. The theoretical basis for this is that both substances intervene at different sites in pyruvate metabolism and are thus more effective than one substance alone. Additional clinical findings indicated that diabetic neuropathy may occur in association with a latent prediabetic metabolic disturbance, and that the symptoms of neuropathy can be favourably influenced by the described combination therapy, even in poorly controlled diabetes.[62] Ruminant Nutrition No dietary requirement for pantothenic acid has been established as synthesis of pantothenic acid by ruminal microorganisms appears to be 20 to 30 times more than dietary amounts. Net microbial synthesis of pantothenic acid in the rumen of steer calves has been estimated to be 2.2 mg/kg of digestible organic matter consumed per day. The degradation of dietary intake of pantothenic acid is considered to be 78 percent. Supplementation of pantothenic acid at 5 to 10 times theoretic requirements did not improve performance of feedlot cattle [63] Synonyms Pantothenate Vitamin B5 See also
  • 83. Coenzyme A Panthenol Roger J. Williams (discoverer of pantothenic acid) Acyl carrier protein (ACP) Enzymes Ketopantoate hydroxymethyltransferase References 1. ↑ MedlinePlus. "Pantothenic acid (Vitamin-B5), Dexpanthenol". Natural Standard Research Collaboration. U.S. National Library of Medicine. Last accessed 4 Jan 2007. [1] 2. ↑ Kimura S, Furukawa Y, Wakasugi J, Ishihara Y, Nakayama A. Antagonism of L(-)pantothenic acid on lipid metabolism in animals. J Nutr Sci Vitaminol (Tokyo). 1980;26(2):113-7. PMID 7400861. 3. ↑ Voet, D., Voet, J.G., Pratt, C.W. (2006). Fundamentals of Biochemistry: Life at the Molecular Level, 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc. 4. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 5. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 6. ↑ Sweetman, L. (2005). Pantothenic Acid. Encyclopedia of Dietary Supplements. 1: 517-525. 7. ↑ Voet, D., Voet, J.G., Pratt, C.W. (2006). Fundamentals of Biochemistry: Life at the Molecular Level, 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc. 8. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning 9. ↑ 9.0 9.1 Jane Higdon, "Pantothenic Acid", Micronutrient Information Center, Linus Pauling Institute 10. ↑ "Nutrient Data Products and Services, Nutrient Data : Reports by Single Nutrients". http://www.ars.usda.gov/Services/docs.htm?docid=9673. Retrieved 2007-08-12. 11. ↑ Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press, 2000 http://books.nap.edu/catalog/6015.html 12. ↑ Otten, J. J., Hellwig, J. P., Meyers, L. D. (2008). Dietary reference intakes: The essential guid to nutrient requirements. Washington, DC: The National Academies Press 13. ↑ Combs,G. F. Jr. The vitamins: Fundamental Aspects in Nutrition and Health. 3rd Edition. Ithaca, NY: Elsevier Academic Press; 2008; pg.346 14. ↑ Said H, Ortiz A, McCloud E, Dyer D, Moyer M, Rubin S (1998). "[Expression error: Missing operand for > Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid.]". Am J Physiol 275 (5 Pt 1): C1365–71. PMID 9814986. 15. ↑ Combs,G. F. Jr. The vitamins: Fundamental Aspects in Nutrition and Health. 3rd Edition. Ithaca, NY: Elsevier Academic Press; 2008; pg.347 16. ↑ Combs, Gerald. The Vitamins: Fundamental Aspects in Nutrition and Health. Burlington: Elsevier Academic Press, 2008. 17. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 18. ↑ Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press, 2000 http://books.nap.edu/catalog/6015.html 19. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 20. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 21. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 22. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 23. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 24. ↑ Combs GF. The vitamins: fundamental aspects in nutrition and health. 3rd ed. Boston: Elsevier, 2008. 25. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 26. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 27. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 28. ↑ Otten, J. J., Hellwig, J. P., Meyers, L. D. (2008). Dietary reference intakes: The essential guid to nutrient requirements. Washington, DC: The National Academies Press 29. ↑ Otten, J. J., Hellwig, J. P., Meyers, L. D. (2008). Dietary reference intakes: The essential guid to nutrient requirements. Washington, DC: The National Academies Press 30. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 31. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 32. ↑ Voet, D., Voet, J.G., Pratt, C.W. (2006). Fundamentals of Biochemistry: Life at the Molecular Level, 2nd
  • 84. ed. Hoboken, NJ: John Wiley & Sons, Inc. 33. ↑ Otten, J. J., Hellwig, J. P., Meyers, L. D. (2008). Dietary reference intakes: The essential guid to nutrient requirements. Washington, DC: The National Academies Press 34. ↑ Smith, C. M. and W. O. Song. 1996. Comparative nutrition of pantothenic acid. Nutr. Biochem. 7:312- 321. 35. ↑ Trumbo, P. R. (2006). Pantothenic Acid. In Shils, M. E., Shike, M., Ross, A. C., Caballero, B., Cousins, R. J. (Eds) Modern Nutrition in Health and Disease. 10th ed. (pp.462-467) Philadelphia, PA: Lippincott Williams & Wilkins. 36. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 37. ↑ Combs, G. F. Jr. The Vitamins: Fundamental Aspects in Nutrition and Health. 2nd Edition. Ithaca, NY: Elsevier Academic Press; 1998; pg.374 38. ↑ Etensel, B., Özkıscık, S., Özkara, E., Serbest, Y. A., Yazıcı, M., Gürsoy, H. (2007). The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatric Surgery International. 23: 271-275. 39. ↑ Etensel, B., Özkıscık, S., Özkara, E., Serbest, Y. A., Yazıcı, M., Gürsoy, H. (2007). The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatric Surgery International. 23: 271-275. 40. ↑ Etensel, B., Özkıscık, S., Özkara, E., Karul, A., Öztan, O., Yazıcı, M., Gürsoy, H. (2007). Dexpanthenol attenuates lipid peroxidation and testicular damage at experimental ischemia and reperfusion injury. Pediatric Surgery International. 23: 177-181. 41. ↑ Etensel, B., Özkıscık, S., Özkara, E., Serbest, Y. A., Yazıcı, M., Gürsoy, H. (2007). The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatric Surgery International. 23: 271-275. 42. ↑ Abdelatif, M., Yakoot, M., Etmaan, M. (2008). Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. Journal of Wound Care. 17.3:108-110. 43. ↑ Abdelatif, M., Yakoot, M., Etmaan, M. (2008). Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. Journal of Wound Care. 17.3:108-110. 44. ↑ Abdelatif, M., Yakoot, M., Etmaan, M. (2008). Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. Journal of Wound Care. 17.3:108-110. 45. ↑ Abdelatif, M., Yakoot, M., Etmaan, M. (2008). Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. Journal of Wound Care. 17.3:108-110. 46. ↑ Naruta, E., Buko, V. (2001). Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Experimental and Toxologic Pathology. 53: 393-398. 47. ↑ Naruta, E., Buko, V. (2001). Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Experimental and Toxologic Pathology. 53: 393-398. 48. ↑ Naruta, E., Buko, V. (2001). Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Experimental and Toxologic Pathology. 53: 393-398. 49. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning. 50. ↑ Naruta, E., Buko, V. (2001). Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Experimental and Toxologic Pathology. 53: 393-398. 51. ↑ Weimann, B. J., Hermann, D. (1999). Studies on wound healing: Effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. International Journal for Vitamin and Nutrition Research. 69.2: 113-119. 52. ↑ Weimann, B. J., Hermann, D. (1999). Studies on wound healing: Effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. International Journal for Vitamin and Nutrition Research. 69.2: 113-119. 53. ↑ Weimann, B. J., Hermann, D. (1999). Studies on wound healing: Effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. International Journal for Vitamin and Nutrition Research. 69.2: 113-119. 54. ↑ Weimann, B. J., Hermann, D. (1999). Studies on wound healing: Effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. International Journal for Vitamin and Nutrition Research. 69.2: 113-119. 55. ↑ G. David Novelli (1953). "[Expression error: Missing operand for > Metabolic Functions of Pantothenic Acid]". Physiol Rev 33 (4): 525–43. PMID 13100068. 56. ↑ Schalock PC, Storrs FJ, Morrison L. (2000). "[Expression error: Missing operand for > Contact urticaria from panthenol in hair conditioner]". Contact Dermatitis 43 (4): 223. doi:10.1034/j.1600- 0536.2000.043004223.x. PMID 11011922. 57. ↑ D.W. Woolley (1941). "[Expression error: Missing operand for > Identification of the mouse antialopecia factor]". J. Biol. Chem. 139 (1): 29–34. 58. ↑ Shun Ishibashi , Margrit Schwarz , Philip K. Frykman , Joachim Herz and David W. Russell (1996). "[Expression error: Missing operand for > Disruption of Cholesterol 7-Hydroxylase Gene in Mice, I. Postnatal lethality reversed by bile acid and vitamin supplementation]". J. Biol. Chem. 271 (30): 18017– 18023. doi:10.1074/jbc.271.30.18017. PMID 8663429. 59. ↑ C. Smith, W. Song (1996). "[Expression error: Missing operand for > Comparative nutrition of pantothenic acid]". The Journal of Nutritional Biochemistry 7 (6): 312–321. doi:10.1016/0955- 2863(96)00034-4. 60. ↑ Paul F. Fenton2, George R. Cowgill, Marie A. Stone and Doris H. Justice (1950). "[Expression error: Missing operand for > The Nutrition of the Mouse, VIII. Studies on Pantothenic Acid, Biotin, Inositol and P-Aminobenzoic Acid]". Journal of Nutrition 42 (2): 257–269. PMID 14795275. 61. ↑ Leung L (1995). "[Expression error: Missing operand for > Pantothenic acid deficiency as the pathogenesis of acne vulgaris]". Med Hypotheses 44 (6): 490–2. doi:10.1016/0306-9877(95)90512-X. PMID 7476595. 62. ↑ Münchener Medizinische Wochenschrift (Germany), 1997, 139/12 (34-37) 63. ↑ National Research Council. 2001. Nutrient Requirements of Dairy Cattle. 7th rev. ed. Natl. Acad. Sci., Washington, DC. External links PDRhealth.com - Pantothenic acid
  • 85. Pantothenate at Klotho Reference link to Coenzyme-A and acne B5 chapter from Vitamin Tolerance of Animals (1987) an open book Vitamins (A11) show Categories: Articles containing Ancient Greek language text | All articles with unsourced statements | Articles with unsourced statements from August 2007 | Amides | Vitamins History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 86. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN B3 Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Niacin view original wikipedia article This article is about the organic compound and vitamin. For the band, see Niacin Niacin (band). Niacin, also known as vitamin B 3 or overview outline images locations Niacin nicotinic acid, is an organic compound with the formula C 5 H 4 NCO2 H. This Search this article high colourless, water-soluble solid is a derivative of pyridine, with a carboxyl Niacin group (COOH) at the 3-position. Other History forms of vitamin B3 include the Dietary needs corresponding amide, nicotinamide IUPAC name nicotinic acid Lipid modifying effects ("niacinamide"), where the carboxyl group Other names pyridine-3-carboxylic Anti-Alzheimer's symptomatic effects has been replaced by a carboxamide group acid, nicotinic acid, (CONH 2 ), as well as more complex amides Toxicity nicotinamide, niacinamide, vitamin B 3 Inositol hexanicotinate and a variety of esters. The terms niacin, Identifiers Biosynthesis and chemical synthesis nicotinamide, and vitamin B3 are often CAS number 59-67-6 Receptor used interchangeably to refer to any PubChem 938 Food sources member of this family of compounds, since MeSH Niacin References they have the same biochemical activity. SMILES C1=CC(=CN=C1)C(=O)O ChemSpider ID 913 Niacin is converted to nicotinamide and Properties Images Videos then to NAD and NADP in vivo. Although Molecular formula C6 H5 NO 2 the two are identical in their vitamin Molar mass 123.11 g/mol activity, nicotinamide does not have the Melting point 236.6 °C, 510 K, 458 °F same pharmacological effects as niacin, which occur as side-effects of niacin's Boiling point decomposes conversion. Nicotinamide does not reduce view all 24 view all 15 Supplementary data page cholesterol or cause flushing.[1] Structure and properties n, εr , etc. Nicotinamide may be toxic to the liver at Thermodynamic data Phase behaviour Solid, liquid, gas doses exceeding 3 g/day for adults. [2] Spectral data UV, IR, NMR, MS Niacin is a precursor to NADH, NAD + , (what is this?) (verify) NADP + and NADPH, which play essential Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 metabolic roles in living cells. [3] Niacin is kPa) involved in both DNA repair, and the Infobox references production of steroid hormones in the adrenal gland. Niacin is one of five vitamins associated with a pandemic deficiency disease: these are niacin (pellagra), vitamin C (scurvy), thiamin (beriberi), vitamin D (rickets), and vitamin A deficiency, a syndrome which has no common name but is one of the most common symptomatic deficiencies worldwide. In larger doses, niacin can reverse atherosclerosis by lowering low density lipoprotein (LDL) and favorably affecting other compounds. History Niacin was first described by Hugo Weidel in 1873 in his studies of nicotine.[4] The original preparation remains useful: the oxidation of nicotine using nitric acid.[5] Niacin was extracted from livers by Conrad Elvehjem who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor."[6] When the biological significance of nicotinic acid was realized, it was thought appropriate to choose a name to dissociate it from nicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting name 'niacin' was derived from nicotinic acid + vitamin. Carpenter found in 1951 that niacin in corn is biologically unavailable, and can only be released in very alkaline lime water of pH 11. [7] This process is known as nixtamalization.[8]
  • 87. Niacin is referred to as Vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as "vitamin PP." Dietary needs Main article: Pellagra Depending on the definition used, niacin is one of between 40 to 80 essential human nutrients. Currently, niacin deficiency is rarely seen in developed countries and is usually apparent in conditions of poverty and malnutrition and chronic alcoholism [9] . Alcoholic patients typically experience increased intestinal permeability leading to negative health outcomes. Studies have indicated that in patients with alcoholic pellagra, niacin deficiency may be an important factor influencing both the onset and severity of this condition . Severe deficiency of niacin in the diet causes the disease pellagra. Pellagra is characterized by diarrhea, dermatitis and dementia as well as “necklace” lesions on the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, amnesia, delirium, and eventually death, if left untreated[10] . Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression [11] . Mild niacin deficiency has been shown to slow metabolism, causing decreased tolerance to the cold. Dietary niacin deficiency tends to occur in areas where people eat maize ("corn") as a staple food. Maize is the only grain low in niacin, and nixtamalization is needed to increase the bioavaiability of niacin during meal/flour production. Nixtamalization refers to the process of cooking maize with alkaline lime. This is the primary processing step during the manufacture of maize products, including chips, tortillas, and taco shells. The basic pre-Columbian technique involves cooking whole maize in water for 12–16 hours in large tanks. The steeped maize is referred to as nixtamal, and the cooked liquid is nejayote. This process functions to soften the pericarp of the maize, and allows the endosperm to absorb water, enabling its milling. The nixtamal is washed and then stone-ground to produce masa, which is used to produce a variety of products with improved bioavailability of niacin (Sefa-Dedeh et al., 2004). The recommended daily allowance of niacin is 2–12 mg/day for children, 14 mg/day for women, 16 mg/day for men, and 18 mg/day for pregnant or breast-feeding women. [12] The upper limit for adult men and women is 35 mg/day which is based on flushing as the critical adverse effect, this dose-dependent flushing effect consists of a single episode 10 to 20 minutes after niacin is taken. Hartnup’s disease is a hereditary nutritional disorder resulting in niacin deficiency[13] . This condition was first identified in the 1950’s by the Hartnup family in London. It is due to a deficit in the intestines and kidneys, making it difficult for the body to break down and absorb dietary tryptophan. The resulting condition is similar to pellagra, including symptoms of red, scaly rash and sensitivity to sunlight. Oral niacin is given as a treatment for this condition in doses ranging from 40-200 mg with a good prognosis if identified and treated early [14] . Niacin synthesis is also deficient in carcinoid syndrome, because of metabolic diversion of its precursor, tryptophan, to form serotonin. Niacin status is generally tested through urinary biomarkers,[15] which are believed to be more reliable than plasma levels.[16] Lipid modifying effects In pharmacological doses, niacin has been proven to reverse atherosclerosis by reducing total cholesterol, triglyceride, very-low-density lipoprotein (VLDL), and low- density lipoprotein (LDL); and increasing high-density lipoprotein (HDL). Niacin, prescribed in doses between 1000 and 2000 mg two to three times daily, [17] blocks the breakdown of fats in adipose tissue, more specifically the very-low-density lipoprotein (VLDL), precursor of low-density lipoprotein (LDL) or "bad" cholesterol. Because niacin blocks breakdown of fats, it causes a decrease in free fatty acids in the blood and, as a consequence, decreased secretion of VLDL and cholesterol by the liver. [18] By lowering VLDL levels, niacin also increases the level of high-density lipoprotein (HDL) or "good" cholesterol in blood, and therefore it is sometimes prescribed for patients with low HDL, who are also at high risk of a heart attack. [19][20] The ARBITER 6-HALTS study, reported at the 2009 annual meeting of the American
  • 88. Heart Association and in the New England Journal of Medicine [21] concluded that, when added to statins, 2000 mg/day slow-release niacin was more effective than Ezetimibe (Zetia) in reducing atherosclerosis. [22] As of August 2008, a combination of niacin with laropiprant is tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin. [23] Taking 650 mg of aspirin 20- 30 minutes prior to taking niacin has also been proven to prevent flushing in 90% of patients, presumably by suppressing prostaglandin synthesis,[2] and while this regimen also increases the risk of gastrointestinal bleeding,[3] the increased risk is less than 1 percent. [4] Anti-Alzheimer's symptomatic effects Vitamin B3 has been reported to prevent Alzheimer's-like symptoms in a mouse model of the disease. [24] Toxicity Pharmacological doses of niacin (1.5 - 6 g per day) often lead to side-effects that can include dermatological complaints such as skin flushing and itching, dry skin, skin rashes including acanthosis nigricans. Gastrointestinal complaints, such as dyspepsia (indigestion) and liver toxicity (fulminant hepatic failure) have also been reported. Side effects of hyperglycemia, cardiac arrhythmias and birth defects have also been reported. [25][26] The flush lasts for about 15 to 30 minutes, and is sometimes accompanied by a prickly or itching sensation, particularly in areas covered by clothing. This effect is mediated by prostaglandin and can be blocked by taking 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of ibuprofen per day. Taking the niacin with meals also helps reduce this side effect. After several weeks of a consistent dose, most patients no longer flush. [27] Slow- or "sustained"-release forms of niacin have been developed to lessen these side-effects.[18][28] One study showed the incidence of flushing was significantly lower with a sustained release formulation [29] though doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations. [25] Flushing is often thought to involve histamine, but histamine has been shown not to be involved in the reaction.[30] Prostaglandin (PGD 2 ) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction.[30] High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus.[25] Hyperuricemia is another side-effect of taking high-dose niacin, and may exacerbate gout.[31] Niacin at doses used in lowering cholesterol has been associated with birth defects in laboratory animals, with possible consequences for infant development in pregnant women. [25] Niacin at extremely high doses can have life-threatening acute toxic reactions. [32] Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina which leads to blurred vision and blindness. This maculopathy is reversible after stopping niacin intake. [33] Inositol hexanicotinate One popular form of dietary supplement is inositol hexanicotinate, usually sold as "flush- free" or "no-flush" niacin in units of 250, 500 or 1000 mg/tablet or capsule. While this form of niacin does not cause the flushing associated with the immediate release products, the evidence that it has lipid modifying functions is contradictory, at best. As the clinical trials date from the early 1960s (Dorner, Welsh) or the late 1970s (Ziliotto, Kruse, Agusti) it is difficult to assess them by today's standards.[34] A more recent placebo-controlled trial was small (n=11/group), but results after three months at 1500 mg/day showed no trend for improvements in total cholesterol, LDL-C, HDL-C or triglycerides (AM Benjo; Atherosclerosis 2006;187:116-122). Thus, so far there is not enough evidence to recommend inositol hexanicotinate to treat dyslipidemia. Furthermore, the American Heart Association and the National Cholesterol Education Program both take the position that only prescription niacin should be used to treat
  • 89. dyslipidemias, and only under the management of a physician. The reason given is that niacin at effective intakes of 1500-3000 mg/day can also potentially have severe adverse effects. Monitoring of liver enzymes is necessary. Biosynthesis and chemical synthesis The liver can synthesize niacin from the essential amino acid tryptophan, Biosynthesis: Tryptophan → kynurenine → niacin requiring 60 mg of tryptophan to make one mg of niacin. [35] The 5- membered aromatic heterocycle of tryptophan is cleaved and rearranged with the alpha amino group of tryptophan into the 6- membered aromatic heterocycle of niacin. Several million kilograms of niacin are manufactured each year, starting from 3- Biosynthesis methylpyridine. Receptor The receptor for niacin is a G protein-coupled receptor called HM74A.[36] It couples to Gi alpha subunit.[37] Food sources Niacin is found in variety of foods including liver, chicken, beef, fish, cereal, peanuts and legumes and is also synthesized from tryptophan, which is found in meat, dairy and eggs. In order to convert 1 mg of niacin, 60 mg of tryptophan is required. Animal products: liver, heart and kidney chicken beef fish: tuna, salmon milk eggs
  • 90. Fruits and vegetables: avocados dates tomatoes leaf vegetables broccoli carrots sweet potatoes asparagus Seeds: nuts whole grain products legumes saltbush seeds Fungi: mushrooms brewer's yeast References 1. ↑ Jaconello P (October 1992). "[Expression error: Missing operand for > Niacin versus niacinamide]". CMAJ 147 (7): 990. PMID 1393911. 2. ↑ Knip M, Douek IF, Moore WP, et al. (2000). "[Expression error: Missing operand for > Safety of high- dose nicotinamide: a review]". Diabetologia 43 (11): 1337–45. doi:10.1007/s001250051536. PMID 11126400. 3. ↑ Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry. New York: Worth Publishers. ISBN 1-57259-153-6. 4. ↑ Weidel, H (1873). "[Expression error: Missing operand for > Zur Kenntniss des Nicotins]". Justus Liebig's Annalen der Chemie und Pharmacie 165: 330–349. doi:10.1002/jlac.18731650212. 5. ↑ Samuel M. McElvain (1941), "Nicotinic Acid", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp ?prep=CV1P0385.pdf; Coll. Vol. 1: 385 6. ↑ Elvehjem, C.A.; Madden, R.J.; Strongandd, F.M.. "[Expression error: Missing operand for > W. WOOLLEY 1938 The isolation and identification of the anti-blacktongue factor J]". J. Biol. Chem 123: 137. 7. ↑ LAGUNA J, CARPENTER KJ (September 1951). "Raw versus processed corn in niacin-deficient diets". J. Nutr. 45 (1): 21–8. PMID 14880960. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=14880960. 8. ↑ "Vitamin B3". University of Maryland Medical Center. 2002-01-04. http://www.umm.edu/altmed/articles/vitamin-b3-000335.htm. Retrieved 2008-03-31. 9. ↑ Pitsavas, Stergios; Christina Andreou, Franzesca Bascialla, Vasilis P. Bozikas, Athanasios Karavatos (2004). "Pellagra Encephalopathy Following B-Complex Vitamin Treatment without Niacin". International Journal of Psychiatry in Medicine 31 (1): 91-96. http://baywood.metapress.com/link.asp? id=29xv1gg1u17krgjh. Retrieved 2009-11-27. 10. ↑ Prakash, Ravi; Sachin Gandotra, Lokesh Kumar Singh, Basudeb Das, Anuja Lakra. "Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy". General Hospital Psychiatry 30 (6): 581-584. doi:10.1016/j.genhosppsych.2008.04.011. http://www.sciencedirect.com/science/article/B6T70- 4T24FKB-D/2/f619871a3d1f1d626b775c84523d6d94. Retrieved 2009-11-27. 11. ↑ Prakash, Ravi; Sachin Gandotra, Lokesh Kumar Singh, Basudeb Das, Anuja Lakra. "Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy". General Hospital Psychiatry 30 (6): 581-584. doi:10.1016/j.genhosppsych.2008.04.011. http://www.sciencedirect.com/science/article/B6T70- 4T24FKB-D/2/f619871a3d1f1d626b775c84523d6d94. Retrieved 2009-11-27. 12. ↑ United States Department of Agriculture, National Agriculture Library, Food and Nutrition Information Center, Dietary Reference Intakes: Recommended Intakes for Individuals, Vitamins [1] 13. ↑ Prakash, Ravi; Sachin Gandotra, Lokesh Kumar Singh, Basudeb Das, Anuja Lakra. "Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy". General Hospital Psychiatry 30 (6): 581-584. doi:10.1016/j.genhosppsych.2008.04.011. http://www.sciencedirect.com/science/article/B6T70- 4T24FKB-D/2/f619871a3d1f1d626b775c84523d6d94. Retrieved 2009-11-27. 14. ↑ Prakash, Ravi; Sachin Gandotra, Lokesh Kumar Singh, Basudeb Das, Anuja Lakra. "Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy". General Hospital Psychiatry 30 (6): 581-584. doi:10.1016/j.genhosppsych.2008.04.011. http://www.sciencedirect.com/science/article/B6T70- 4T24FKB-D/2/f619871a3d1f1d626b775c84523d6d94. Retrieved 2009-11-27. 15. ↑ Institute of Medicine. (2006). Dietary Reference Intakes Research Synthesis: Workshop Summary, p. 37. National Academies Press. 16. ↑ Jacob RA, Swendseid ME, McKee RW, Fu CS, Clemens RA (April 1989). "Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites". J. Nutr. 119 (4): 591–8. PMID 2522982. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=2522982. 17. ↑ Marks, Jay W. (2005). "Niacin Monograph". MedicineNet, Inc.. 18. ↑ 18.0 18.1 Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN 0071451536. http://www.medicinenet.com/niacin/article.htm. 19. ↑ McGovern ME (2005). "[Expression error: Missing operand for > Taking aim at HDL -C. Raising levels to reduce cardiovascular risk]". Postgrad Med 117 (4): 29–30, 33–5, 39 passim. PMID 15842130. 20. ↑ Canner PL, Berge KG, Wenger NK, et al. (1986). "[Expression error: Missing operand for > Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin]". J. Am. Coll. Cardiol. 8 (6): 1245–55. PMID 3782631. 21. ↑ N Engl J Med 361:2113 22. ↑ Singer, Natasha (November 15, 2009). "Study Raises Questions About Cholesterol Drug’s Benefit". The
  • 91. New York Times. http://www.nytimes.com/2009/11/16/health/research/16heart.html. Retrieved November 16, 2009. 23. ↑ Paolini JF, Bays HE, Ballantyne CM, et al. Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors. Cardiol Clin. 2008 Nov;26(4):547-60. 24. ↑ Green, Kim N.; Joan S. Steffan, Hilda Martinez-Coria, Xuemin Sun, Steven S. Schreiber, Leslie Michels Thompson, and Frank M. LaFerla (November 5, 2008). "Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231- Phosphotau". The Journal of Neuroscience 28 (45): 11500–11510. doi:10.1523/JNEUROSCI.3203- 08.2008. PMID 18987186. PMC 2617713. http://www.jneurosci.org/cgi/content/abstract/28/45/11500. Retrieved January 20, 2009. 25. ↑ 25.0 25.1 25.2 25.3 Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred (2006). Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGraw-Hill. ISBN 0071422803. 26. ↑ McGee, W (2007-02-01). "Medical Encyclopedia: Niacin". MedlinePlus. http://www.nlm.nih.gov/medlineplus/ency/article/002409.htm. Retrieved 2008-03-31. 27. ↑ "Guidelines for Niacin Therapy For the Treatment of Elevated Lipoprotein a (Lpa)". Rush Hemophilia & Thrombophilia Center. August 15, 2002, Revised July 27, 2005. http://www.rush.edu/Rush_Document/Niacin%20therapy%20for%20elevated%20Lpa,0.pdf. Retrieved 20 November 2009. "facial flushing is a common side effect of niacin therapy that usually subsides after several weeks of consistent niacin use" 28. ↑ Barter, P (2006). "[Expression error: Missing operand for > Options for therapeutic intervention: How effective are the different agents?]". European Heart Journal Supplements 8 (F): F47–F53. doi:10.1093/eurheartj/sul041. 29. ↑ Chapman MJ, Assmann G, Fruchart JC, Shepherd J, Sirtori C (2004). "[Expression error: Missing operand for > Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL -C]". Curr Med Res Opin 20 (8): 1253–68. doi:10.1185/030079904125004402. PMID 15324528. 30. ↑ 30.0 30.1 "[Expression error: Missing operand for > Niacin-induced "Flush" Involves Release of Prostaglandin D2 from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model]". Journal of Pharmacology and Experimental Therapeutics. 2008. 31. ↑ Capuzzi DM, Morgan JM, Brusco OA, Intenzo CM (2000). "[Expression error: Missing operand for > Niacin dosing: relationship to benefits and adverse effects]". Curr Atheroscler Rep 2 (1): 64–71. doi:10.1007/s11883-000-0096-y. PMID 11122726. 32. ↑ Mittal MK, Florin T, Perrone J, Delgado JH, Osterhoudt KC (2007). "[Expression error: Missing operand for > Toxicity from the use of niacin to beat urine drug screening]". Ann Emerg Med 50 (5): 587–90. doi:10.1016/j.annemergmed.2007.01.014. PMID 17418450. 33. ↑ Gass JD (2003). "[Expression error: Missing operand for > Nicotinic acid maculopathy. 1973]". Retina (Philadelphia, Pa.) 23 (6 Suppl): 500–10. PMID 15035390. 34. ↑ Taheri, R (2003-01-15). "No-Flush Niacin for the Treatment of Hyperlipidemia". Medscape. http://www.medscape.com/viewarticle/447528. Retrieved 2008-03-31. 35. ↑ Jacobson, EL (2007). "Niacin". Linus Pauling Institute. http://lpi.oregonstate.edu/infocenter/vitamins/niacin/. Retrieved 2008-03-31. 36. ↑ Zhang Y, Schmidt RJ, Foxworthy P, et al. (2005). "[Expression error: Missing operand for > Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A]". Biochem. Biophys. Res. Commun. 334 (2): 729–32. doi:10.1016/j.bbrc.2005.06.141. PMID 16018973. 37. ↑ Zellner C, Pullinger CR, Aouizerat BE, et al. (2005). "[Expression error: Missing operand for > Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors]". Hum. Mutat. 25 (1): 18– 21. doi:10.1002/humu.20121. PMID 15580557. Vitamins (A11) show Categories: Articles containing potentially dated statements from August 2008 | All articles containing potentially dated statements | Hypolipidemic agents | B vitamins | Pyridines | Carboxylic acids | Inositol History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 92. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN B2 Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Riboflavin view original wikipedia article Riboflavin Riboflavin Riboflavin (E101 [1] ), also known overview outline images locations as vitamin B 2 , is an Search this article high easily absorbed IUPAC name 7,8-dimethyl- 10-((2R,3R,4S)- 2,3,4,5- tetrahydroxypentyl) Riboflavin micronutrient benzo [g] pteridine- 2,4 (3H,10H)- dione with a key Identifiers Discovery role in CAS number 83-88-5 Toxicity maintaining PubChem 1072 Industrial synthesis health in MeSH Riboflavin Riboflavin in food: Occurrence, sources humans and SMILES Cc1cc2c(cc1C)n(c- stability 3nc(=O)[nH]c(=O)c3n2)C[C@@H]([C@@H]([C@@H](CO)O)O)O Nutrition-Recommended Dietary Allowan animals. It is Properties (RDA) the central Molecular formula C17 H20 N4 O 6 Recommended Dietary Allowance (RD component of Molar mass 376.36 g/mol Riboflavin deficiency the cofactors Melting point 290 °C (dec.) Assessment of Riboflavin Status FAD and FMN, and is Supplementary data page Function therefore Structure and n, εr , etc. Mechanism of Action properties Clinical uses required by Thermodynamic Phase behaviour all Industrial Uses data Solid, liquid, gas flavoproteins. Spectral data UV, IR, NMR, MS Good sources As such, (what is this?) (verify) See also vitamin B2 is Except where noted otherwise, data are given for materials in their standard state (at References 25 °C, 100 kPa) required for a External links Infobox references wide variety of cellular processes. Like the other B vitamins, it plays a key role in energy 1 Locations metabolism, and is required for the metabolism of fats, ketone bodies, carbohydrates, South Korea view all and proteins. Milk, cheese, leafy green vegetables, liver, kidneys, legumes such as mature Images Videos soybeans, [2] yeast, mushrooms and almonds [3] are good sources of vitamin B2 , but exposure to light destroys riboflavin. The name "riboflavin" comes from "ribose" and "flavin". view all 24 view all 15 Discovery Vitamin B was originally considered to have two components, a heat-labile vitamin B1 and a heat- stable vitamin B2 (1). In the 1920s, vitamin B2 was thought to be the factor necessary for preventing pellagra. In 1923, Paul Gyorgi in Heidelberg was investigating egg white injury in rats, the curative factor for this condition was called vitamin H. Since both pellagra and vitamin H deficiency were Fluorescent spectra of Riboflavin associated with dermatitis, Gyorgi decided to test the effect of vitamin B2 on vitamin H deficiency in rat. He enlisted the service of Wagner-Jauregg in Kuhan’s laboratory (1). In 1933, Kuhn, Gyorgy, and Wagner found that thiamin-free extracts of yeast, liver, or rice bran prevented the growth failure of rats fed a thiamin supplemented diet. Further, they noted that a yellow-green fluorescence in each extract promoted rat growth, and that the intensity of fluorescence was proportional to the effect on growth. This observation enabled them to develop a rapid chemical and bioassay to isolate the factor from egg white in 1933, they called it Ovoflavin. The same group then isolated the same preparation (a growth-promoting compound with yellow-green fluorescence) from whey using the same procedure (lactoflavin). In 1934 Kuhan’s group identified the structure of so-called flavin and synthesised vitamin B2 (1).
  • 93. Toxicity Riboflavin is not toxic when taken orally, as its low solubility keeps it from being absorbed in dangerous amounts from the gut.[4] Although toxic doses can be administered by injection, [4] any excess at nutritionally relevant doses is excreted in the urine, [5] imparting a bright yellow color when in large quantities. In humans, there is no evidence for riboflavin toxicity produced by excessive intakes. Even when 400 mg/d of riboflavin was given orally to subjects in one study for three months to investigate the efficacy of riboflavin in the prevention of migraine headache, no short-term side effects were reported. [6][7] Industrial synthesis Various biotechnological processes have been developed for industrial scale riboflavin biosynthesis using different microorganisms, including filamentous fungi such as Ashbya gossypii, Candida famata and Candida flaveri as well as the bacteria Corynebacterium ammoniagenes and Bacillus subtilis. [8] The latter organism has been genetically modified to both increase the bacteria's production of riboflavin and to introduce an antibiotic (ampicillin) resistance marker, and is now successfully employed at a commercial scale to produce riboflavin for feed and food fortification purposes. The chemical company BASF has installed a plant in South Korea, which is specialized on riboflavin production using Ashbya gossypii. The concentrations of riboflavin in their modified strain are so high, that the mycelium has a reddish / brownish color and accumulates riboflavin crystals in the vacuoles, which will eventually burst the mycelium. Riboflavin in food: Occurrence, sources and stability Riboflavin is yellow or yellow-orange in color and in addition to being used as a food coloring, it is also used to fortify some foods. It is used in baby foods, breakfast cereals, pastas, sauces, processed cheese, fruit drinks, vitamin-enriched milk products, and some energy drinks. Regarding occurrence and sources of vitamin B2, Yeast extract is considered to be exceptionally rich in vitamin B2, and liver and kidney are also rich sources. Wheat bran, eggs, meat, milk, and Riboflavin powder. cheese are important sources in diets containing these foods. Cereals grains contain relatively low concentrations of flavins, but are important sources in those parts of the world where cereals constitute the staple diet. [9][10] The milling of cereals results in considerable loss (up to 60%) of vitamin B2, so white flour is enriched in some countries such as USA by addition of the vitamin. The enrichment of bread and ready-to-eat breakfast cereals contributes significantly to the dietary supply of vitamin B2. Polished rice is not usually enriched, because the vitamin’s yellow color would make the rice visually unacceptable to the major rice- consumption populations. However, most of the flavins content of the whole brown rice is retained if A riboflavin solution. the rice is steamed prior to milling. This process drives the flavins in the germ and aleurone layers into the endosperm. Free riboflavin is naturally present in foods along with protein-bound FMN and FAD. Bovine milk contains mainly free riboflavin, with a minor contribution from FMN and FAD.[11] In whole milk, 14% of the flavins are bound noncovalently to specific proteins.[12] Egg white and egg yolk contain specialized riboflavin-binding proteins, which are required for storage of free riboflavin in the egg for use by the developing embryo. It is difficult to incorporate riboflavin into many liquid products because it has poor solubility in water. Hence the requirement for riboflavin-5'-phosphate (E101a), a more
  • 94. expensive but more soluble form of riboflavin. Riboflavin is generally stable during the heat processing and normal cooking of foods if light is excluded. The alkaline conditions in which riboflavin is unstable are rarely encountered in foodstuffs. Riboflavin degradation in milk can occur slowly in dark during storage in the refrigerator. [13] (7). Nutrition-Recommended Dietary Allowance (RDA) Recommended Dietary Allowance (RDA) The latest (1998) RDA recommendation for vitamin B2 are similar to the 1989 RDA, which for adults, suggested a minimum intake of 1.2 mg for persons whose caloric intake may be > 2,000 Kcal.[14] The current RDAs for Riboflavin for adult men and women are 1.3 mg/day and 1.1 mg/day, respectively; the estimated average requirement for adult men and women are 1.1 mg and 0.9 mg, respectively. Recommendations for daily riboflavin intake increase with pregnancy and lactation to 1.4 mg and 1.6 mg, respectively (1in advanced). For infants the RDA is 0.3-0.4 mg/day and for children it is 0.6-0.9 mg/day. [15] Riboflavin deficiency Further information: Ariboflavinosis Riboflavin is continuously excreted in the urine of healthy individuals, [2] making deficiency relatively common when dietary intake is insufficient. However, riboflavin deficiency is always accompanied by deficiency of other vitamins. [2] A deficiency of riboflavin can be primary - poor vitamin sources in one's daily diet - or secondary, which may be a result of conditions that affect absorption in the intestine, the body not being able to use the vitamin, or an increase in the excretion of the vitamin from the body. In humans, signs and symptoms of riboflavin deficiency (ariboflavinosis) include cracked and red lips, inflammation of the lining of mouth and tongue, mouth ulcers, cracks at the corners of the mouth (angular cheilitis), and a sore throat. A deficiency may also cause dry and scaling skin, fluid in the mucous membranes, and iron-deficiency anemia. The eyes may also become bloodshot, itchy, watery and sensitive to bright light. Riboflavin deficiency is classically associated with the oral-ocular-genital syndrome. Angular cheilitis, photophobia, and scrotal dermatitis are the classic remembered signs. In animals, riboflavin deficiency results in lack of growth, failure to thrive, and eventual death. Experimental riboflavin deficiency in dogs results in growth failure, weakness, ataxia, and inability to stand. The animals collapse, become comatose, and die. During the deficiency state, dermatitis develops together with hair-loss. Other signs include corneal opacity, lenticular cataracts, hemorrhagic adrenals, fatty degeneration of the kidney and liver, and inflammation of the mucus membrane of the gastrointestinal tract. Post-mortem studies in rhesus monkeys fed a riboflavin-deficient diet revealed that about one-third the normal amount of riboflavin was present in the liver, which is the main storage organ for riboflavin in mammals. These overt clinical signs of riboflavin deficiency are rarely seen among inhabitants of the developed countries. However, about 28 million Americans exhibit a common ‘sub-clinical’ stage. [16] characterized by a change in biochemical indices (e.g. reduced plasma erythrocyte glutathione reductase levels). Although the effects of long-term sub-clinical riboflavin deficiency are unknown, in children this deficiency results in reduced growth. Subclinical riboflavin deficiency has also been observed in women taking oral contraceptives, in the elderly, in people with eating disorders, and in disease states such as HIV, inflammatory bowel disease, diabetes and chronic heart disease. The fact that riboflavin deficiency does not immediately lead to gross clinical manifestations indicates that the systemic levels of this essential vitamin are tightly regulated. Assessment of Riboflavin Status Biochemical tests are essential for confirming clinical cases of riboflavin deficiency and for establishing subclinical deficiencies. Among these tests: Erythrocyte glutathione reductase activity:
  • 95. Glutathione reductase is a nicotinamide adenine dinucleotide phosphate (NADPH), a FAD-dependent enzyme, and the major flavoproteins in erythrocyte. The measurement of the activity coefficient of erythrocyte glutathione reductase (EGR) is the preferred method for assessing riboflavin status. [17] It provides a measure of tissue saturation and long-term riboflavin status. In vitro enzyme activity in terms of activity coefficients (AC) is determined both with and without the addition of FAD to the medium. ACs represent a ratio of the enzyme’s activity with FAD to the enzyme’s activity without FAD. An AC of 1.2 to 1.4, riboflavin status is considered low when FAD is added to stimulate enzyme activity. An AC > 1.4 suggests riboflavin deficiency. On the other hand, if FAD is added and AC is < 1.2, then riboflavin status is considered acceptable. [18] Tillotson and Baker (1972) [19] reported that a decrease in the intakes of riboflavin was associated with increase in EGR AC. in the U.K. study of Norwich elderly (Bailey et al., 1997), initial EGR AC values for both males and females were significantly correlated with those measured 2 years later, suggesting that EGR AC may be a reliable measure of long- term biochemical riboflavin status of individuals. These findings are consistent with earlier studies (Rutishauser et al., 1979).[20] Urinary riboflavin excretion: Experimental balance studies indicate that urinary riboflavin excretion rates increase slowly with increasing intakes, until intake level approach 1.0 mg/d, when tissue saturation occurs. At higher intakes, the rate of excretion increases dramatically.[21] Once intakes of 2.5 mg/d are reached, excretion becomes approximately equal to the rate of absorption (Horwitt et al., 1950)(18). At such high intake a significant proportion of the riboflavin intake is not absorbed.If urinary riboflavin excretion is <19 µg/g creatinine (without recent riboflavin intake) or < 40 µg per day are indicative of deficiency. Function FMN and FAD function as coenzymes for a wide variety of oxidative enzymes and remain bound to the enzymes during the oxidation-reduction reactions. Flavins can act as oxidizing agents because of their ability to accept a pair of hydrogen atoms. Reduction of isoalloxazine ring (FAD, FMN oxidized form) yields the reduced forms of the flavoproteins (FMNH2 and FADH2)(5). Mechanism of Action Flavoproteins exhibit a wide range of redox potential and therefore can play a wide variety of roles in intermediary metabolism (5). Some of these roles are: Flavoproteins play very important roles in the electron transport chain(5) Decarboxylation of pyruvate and α-Ketoglutarate requires FAD() Fatty acyl CoA dehydrogenase requires FAD in fatty acid oxidation (5) FAD is required to the production of pyridoxic acid from pyridoxal (vitamin B6) The primary coenzyme form of vitamin B6 (Pyridoxal phosphate) is FMN dependent(5) FAD is required to convert retinal (Vitamin A) to retinoic acid Synthesis of an active form of folate (5-methyl THF) is FADH2 dependent FAD is required to convert tryptophan to niacin (vitamin B3) Reduction of the oxidized form of glutathione (GSSG) to its reduced form (GSH) is also FAD dependent (5) Clinical uses Riboflavin has been used in several clinical and therapeutic situations. For over 30 years, riboflavin supplements have been used as part of the phototherapy treatment of neonatal jaundice. The light used to irradiate the infants breaks down not only the toxin causing the jaundice, but the naturally occurring riboflavin within the infant's blood as well. More recently there has been growing evidence that supplemental riboflavin may be a useful additive along with beta-blockers in the prevention of migraine headaches. [22] Development is underway to use riboflavin to improve the safety of transfused blood by reducing pathogens found in collected blood. Riboflavin attaches itself to the nucleic acids (DNA and RNA) in cells, and when light is applied, the nucleic acids are broken,
  • 96. effectively killing those cells. The technology has been shown to be effective for inactivating pathogens in all three major blood components: (platelets, red blood cells, and plasma). It has been shown to inactivate a broad spectrum of pathogens, including known and emerging viruses, bacteria, and parasites. Recently riboflavin has been used in a new treatment to slow or stop the progression of the corneal disorder keratoconus. This is called corneal collagen crosslinking (CXL). In corneal crosslinking, riboflavin drops are applied to the patient’s corneal surface. Once the riboflavin has penetrated through the cornea, Ultraviolet A light therapy is applied. This induces collagen crosslinking, which increases the tensile strength of the cornea. The treatment has been shown in several studies to stabilize keratoconus. Industrial Uses Because riboflavin is fluorescent under UV light, dilute solutions (0.015-0.025% w/w) are often used to detect leaks or to demonstrate coverage in an industrial system such a chemical blend tank or bioreactor. (See the ASME BPE section on Testing and Inspection for additional details.) Good sources Riboflavin is found naturally in asparagus, bananas, persimmons, okra, chard, cottage cheese, milk, yogurt, meat, eggs and fish, each of which contain at least 0.1 mg of the vitamin per 3–10.5 oz (85–300 g) serving.(5). Riboflavin is destroyed by exposure to ultraviolet light, so milk sold in transparent (glass/plastic) bottles will likely contain less riboflavin than milk sold in opaque containers. See also Ariboflavinosis (riboflavin deficiency) Flavin Riboflavin synthase Riboflavin kinase References 1. ↑ "Current EU approved additives and their E Numbers". UK Food Standards Agency. July 27, 2007. http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist. Retrieved December 3, 2009. 2. ↑ 2.0 2.1 2.2 Brody, Tom (1999). Nutritional Biochemistry. San Diego: Academic Press. ISBN 0-12-134836-9. OCLC 162571066 212425693 39699995 51091036. 3. ↑ Higdon, Jane; Victoria J. Drake (2007). "Riboflavin". Micronutrient Information Center. Linus Pauling Institute at Oregon State University. http://lpi.oregonstate.edu/infocenter/vitamins/riboflavin/. Retrieved December 3, 2009. 4. ↑ 4.0 4.1 Unna, Klaus and Greslin, Joseph G. (1942). "[Expression error: Missing operand for > Studies on the toxicity and pharmacology of riboflavin]". J Pharmacol Exp Ther 76 (1): 75–80. 5. ↑ Zempleni, J and Galloway, JR and McCormick, DB (1996). "[Expression error: Missing operand for > Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans]". Am J Clin Nutr (The American Society for Nutrition) 63 (1): 54–66. PMID 8604671. 6. ↑ Boehnke C., Reuter U., Flach U., and et al., High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre 2004 Jul;11(7):475-7 7. ↑ Gropper S.S., Smith J.L., and Groff J.L., Riboflavin, Chapter 9, in Advanced Nutrition and Human Metabolism, 5th ed. Wadsworth CENGAG Learning, 2009, P329-333 8. ↑ Stahmann KP, Revuelta JL and Seulberger H. (2000). "[Expression error: Missing operand for > Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production]". Appl Microbiol Biotechnol 53 (5): 509–516. doi:10.1007/s002530051649. 9. ↑ Food Standards Agency, McCance and Widdowson’s The Composition of Foods, 6th summary ed, Royal Society of Chemistry, Cambridge, 2002
  • 97. 10. ↑ Ball F.M. George, Riboflavin in Vitamins in Foods, Analysis, Bioavailability, and Stability. Taylor and Francis Group, New York, 2006. P168-175 11. ↑ Ball F.M. George, Riboflavin in Vitamins in Foods, Analysis, Bioavailability, and Stability. Taylor and Francis Group, New York, 2006. P168-175 12. ↑ Kanno, C., Kanehara, N., Shirafuji, K., and et al. Binding Form of Vitamin B2 in Bovine Milk: its concentration, distribution, and binding linkage, J. Nutr. Sci. Vitaminol., 37, 15, 1991 13. ↑ Faron G, Drouin R, Pedneault L, et al. Recurrent cleft lip and palate in siblings of a patient with malabsorption syndrome, probably caused by hypovitaminosis A associated with folic acid and riboflavin deficiencies. Teratology 2001;63:161–3 14. ↑ National Research Council. RDAs, 10th ed. Washington, DC: National Academy Press, 1989, PP.132-37 15. ↑ Gropper S.S., Smith J.L., and Groff J.L., Riboflavin, Chapter 9, in Advanced Nutrition and Human Metabolism, 5th ed. Wadsworth CENGAG Learning, 2009, P329-333 16. ↑ Powers J. Hilary. Riboflavin (vitamin B-2) and health, Review Article. Am J Clin Nutr 2003;77:1352–60 17. ↑ 10. Gibson S. Rosalind, Riboflavin in Principles of Nutritional Assessment, 2nd ed. OXFORD university press, 2005 18. ↑ Gropper S.S., Smith J.L., and Groff J.L., Riboflavin, Chapter 9, in Advanced Nutrition and Human Metabolism, 5th ed. Wadsworth CENGAG Learning, 2009, P329-333 19. ↑ Tilloston JA, Bashor EM. An enzymatic measurement of the riboflavin status in man. American J. Of Clin. Nutr., 1972; 72:251-261 20. ↑ Rutishauser IHE, Bates CJ, Paul AA, and et al. Long term vitamin status and dietary intake of health elderly subjects. I. Riboflavin. British J. of Nutr. , 1979; 42:33-42 21. ↑ Gibson S. Rosalind, Riboflavin in Principles of Nutritional Assessment, 2nd ed. OXFORD university press, 2005. 22. ↑ Sándor PS, Afra J, Ambrosini A, Schoenen J. Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials. Headache. 2000 Jan;40(1):30-5. External links Jane Higdon, "Riboflavin", Micronutrient Information Center, Linus Pauling Institute Mirasol PRT includes a brief description of riboflavin as an agent to inactivate pathogens. Vitamins (A11) show Categories: Flavins | Vitamins | Coenzymes History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 98. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN B1 Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Thiamine view original wikipedia article Thiamine Thiamine or thiamin,[1] sometimes Thiamine called aneurin, is a water-soluble vitamin of the B complex (vitamin B1 ), overview outline images locations whose phosphate derivatives are involved in many cellular processes. Search this article high The best characterized form is thiamine diphosphate (ThDP), a coenzyme in the catabolism of sugars and amino Thiamine acids. In yeast, ThDP is also required History: The discovery of vitamins and th biochemical lesion in the first step of alcoholic Chemical properties fermentation. Biosynthesis Thiamine is synthesized in bacteria, Nutrition fungi and plants. Animals must cover References all their needs from their food and Reference Daily Intake and high doses insufficient intake results in a disease Antagonists called beriberi affecting the peripheral IUPAC name 2-[3-[(4-amino- 2-methyl- pyrimidin- 5-yl) methyl]- 4-methyl- thiazol- 5-yl] Absorption and transport nervous system (polyneuritis) and/or ethanol Absorption the cardiovascular system, with fatal Other names Aneurine hydrochloride, thiamin Bound to serum proteins outcome if not cured by thiamine Identifiers Cellular uptake administration. [2] In less severe CAS number 59-43-8 (Cl - ) ,67-03-8 (Cl - .HCl hydrochloride) Tissue distribution deficiency, nonspecific signs include PubChem 1130 Excretion malaise, weight loss, irritability and MeSH Thiamine Thiamine phosphate derivatives and func confusion. [3] Today, there is still a lot of SMILES [Cl-].Cc1c(CCO)sc[n+]1Cc2cncnc2N Thiamine monophosphate work devoted to elucidating the exact ChemSpider ID 5819 Thiamine diphosphate mechanisms by which thiamine Properties Thiamine triphosphate deficiency leads to the specific Molecular C12 H17 N4 OS+Cl - .HCl formula Adenosine thiamine triphosphate symptoms observed (see below). Molar mass 337.27 Adenosine thiamine diphosphate Finally, new thiamine phosphate Melting point 248-260 °C (hydrochloride salt) Deficiency derivatives have recently been Hazards Beriberi discovered, [4] emphasizing the MSDS External MSDS Alcoholic brain disease complexity of thiamine metabolism and Main hazards Allergies Thiamine deficiency in poultry the need for more research in the field. Supplementary data page Thiamine deficiency in ruminants Structure and n, εr , etc. Idiopathic paralytic disease in wild bir properties Thermodynamic Phase behaviour Analysis and diagnostic testing History: The data Solid, liquid, gas Genetic diseases discovery of vitamins Spectral data UV, IR, NMR, MS Research (what is this?) (verify) Understanding the mechanism by whi and the biochemical Except where noted otherwise, data are given for thiamine deficiency leads to selective materials in their standard state (at 25 °C, 100 kPa) neuronal death lesion Infobox references Catalytic mechanisms in thiamine diphosphate-dependent enzymes Thiamine was the first of the water-soluble vitamins to be described,[2] leading to the Non-cofactor roles of thiamine derivat discovery of more such trace compounds essential for survival and to the notion of Persistent carbenes vitamin. Chinese medical texts referred to beriberi (a thiamine deficiency disease) as See also early as 2700 BC.[5] It was not until AD 1884 that Kanehiro Takaki (1849-1920), a References surgeon general in the Japanese navy, rejected the previous germ theory and attributed External links the disease to insufficient nitrogen intake (protein deficiency). In 1897 Christiaan Eijkman (1858-1930), a military doctor in the Dutch Indies, Images Videos discovered that fowl fed on a diet of cooked, polished rice developed paralysis, which could be reversed by discontinuing rice polishing.[6] He attributed that to a nerve poison in the endosperm of rice, from which the outer layers of the grain gave protection to the body. Eijkman was awarded the Nobel Prize in Physiology and Medicine in 1929, because his observations led to the discovery of vitamins. An associate, Gerrit Grijns view all 24 view all 15 (1865-1944), correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901: he concluded that rice contained an essential nutrient in the outer layers of the grain that was removed by polishing.[7] In 1911 Casimir Funk isolated an antineuritic substance from rice bran that he called a
  • 99. “vitamine” (on account of its containing an amino group). Dutch chemists, Barend Coenraad Petrus Jansen (1884-1962) and his closest collaborator Willem Frederik Donath (1889-1957), went on to isolate and crystallize the active agent in 1926, [8] whose structure was determined by Robert Runnels Williams (1886-1965), a US chemist, in 1934. Thiamine (“sulfur-containing vitamin”) was synthesized in 1936 by the same group [9] . It was first named “aneurin” (for anti-neuritic vitamin). [10] Sir Rudolph Peters, in Oxford, introduced thiamine-deprived pigeons as a model for understanding how thiamine deficiency can lead to the pathological-physiological symptoms of beriberi. Indeed, feeding the pigeons upon polished rice leads to an easily recognizable behavior of head retraction, a condition called opisthotonos. If not treated, the animal will die after a few days. Administration of thiamine at the stage of opithotonos will lead to a complete cure of the animal within 30 min. As no morphological modifications were observed in the brain of the pigeons before and after treatment with thiamine, Peeters introduced the concept of biochemical lesion[11] When Lohman and Schuster (1937) showed that the diphosphorylated thiamine derivative (thiamine diphosphate, ThDP) was a cofactor required for the oxydative decarboxylation of pyruvate, [12] (a reaction now known to be catalyzed by pyruvate dehydrogenase), the mechanism of action of thiamine in the cellular metabolism seemed to be elucidated. Presently, this view seems to be oversimplified: pyruvate dehydrogenase is only one of several enzymes requiring thiamine diphosphate as a cofactor, moreover other thiamine phosphate derivatives have been discovered since then, and they may also contribute to the symptoms observed during thiamine deficiency. Finally, the mechanism by which the thiamine moiety of ThDP exerts its coenzyme function by proton substitution on position 2 of the thiazolium ring was elucidated by Ronald Breslow in 1958. [13] Chemical properties Thiamine is a colorless compound with a chemical formula C 12 H 17 N 4 OS. Its structure contains a pyrimidine ring and a thiazole ring linked by a methylene bridge. Thiamine is soluble in water, methanol, and glycerol and practically insoluble in acetone, ether, chloroform, and benzene. It is stable at acidic pH, but is unstable in alkaline solutions.[2][14] Thiamine is unstable to heat, but stable during frozen storage. It is unstable when exposed to ultraviolet light[14] and gamma irradiation.[15][16] Thiamine reacts strongly in Maillard-type reactions.[2] Biosynthesis Complex thiamine biosynthetic pathways occur in bacteria, some protozoans, plants and fungi.[17][18] The thiazole and pyrimidine moieties are synthesized separately and then assembled to form ThMP by thiamine-phosphate synthase (EC 2.5.1.3). The exact biosynthetic pathways may differ among organisms. In E. coli and other enterobacteriaceae ThMP may be phosphorylated to the cofactor ThDP by a thiamine-phosphate kinase (ThMP + ATP → ThDP + ADP, EC 2.7.4.16). In most bacteria and in eukaryotes, ThMP is hydrolyzed to thiamine, that may then be pyrophosphorylated to ThDP by thiamine diphosphokinase (thiamine + ATP → ThDP + AMP, EC 2.7.6.2). The biosynthetic pathways are regulated by riboswitches in all organisms that synthesise thiamine. If there is sufficient thiamine present in A 3D representation of the TPP the cell then the thiamine binds to the mRNA riboswitch with thiamine bound encoding genes required in the pathway preventing the translation of the enzymes. If there is no thiamine present then there is no inhibition and the enzymes required for the biosynthesis are produced. The specific riboswitch, the TPP riboswitch, is the only riboswitch that has been identified in both eukaryotic and
  • 100. prokaryotic organisms. [19] Nutrition References Thiamine is found in a wide variety of foods at low concentrations. Yeast and pork are the most highly concentrated sources of thiamine. Cereal grains, however, are generally the most important dietary sources of thiamine, by virtue of their ubiquity. Of these, whole grains contain more thiamine than refined grains, as thiamine is found mostly in the outer layers of the grain and in the germ (which are removed during the refining process). For example, 100 g of whole wheat flour contains 0.55 mg of thiamine, while 100 g of white flour only contains 0.06 mg of thiamine. In the US, processed flour must be enriched with thiamine mononitrate (along with niacin, ferrous iron, riboflavin and folic acid) to replace that lost in processing. Some other foods rich in thiamine are oatmeal, flax and Sunflower seeds, brown rice, whole grain rye, asparagus, kale, cauliflower, potatoes, oranges, liver (beef, pork and chicken) and eggs. [3] Thiamine hydrochloride is a food additive used to add a brothy/meaty flavor to gravies or soups. Reference Daily Intake and high doses The RDA in most countries is set at about 1.4 mg. However, tests on volunteers at daily doses of about 50 mg have claimed an increase in mental acuity.[20] There are no reports available of adverse effects from consumption of excess thiamine by ingestion of food and supplements. Because the data are inadequate for a quantitative risk assessment, no Tolerable Upper Intake Level (UL) can be derived for thiamine. Antagonists Thiamine in foods can be degraded in a variety of ways. Sulfites, which are added to foods usually as a preservative, [21] will attack thiamine at the methylene bridge in the structure, cleaving the pyrimidine ring from the thiazole ring. [3] The rate of this reaction is increased under acidic conditions. Thiamine is degraded by thermolabile thiaminases (present in raw fish and shellfish[2] ). Some thiaminases are produced by bacteria. Bacterial thiaminases are cell surface enzymes that must dissociate from the membrane before being activated; the dissociation can occur in ruminants under acidotic conditions. Rumen bacteria also reduce sulfate to sulfite, therefore high dietary intakes of sulfate can have thiamine-antagonistic activities. Plant thiamine antagonists are heat stable and occur as both the ortho and para hydroxyphenols. Some examples of these antagonists are caffeic acid, chlorogenic acid and tannic acid. These compounds interact with the thiamine to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamine antagonists. [3] Absorption and transport Absorption Thiamine is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations the process is carrier mediated and at higher concentrations, absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum (it is inhibited by alcohol consumption and by folic deficiency. [2] Decline in thiamine absorption occurs at intakes above 5 mg.[22] The cells of the intestinal mucosa have thiamine pyrophosphokinase activity, but it is unclear whether the enzyme is linked to active absorption. The majority of thiamine present in the intestine is in the pyrophosphorylated form ThDP, but when thiamine arrives on the serosal side of the intestine it is often in the free form. The uptake of thiamine by the mucosal cell is likely coupled in some way to its phosphorylation/dephosphorylation. On the serosal side of the intestine, evidence has shown that discharge of the vitamin by
  • 101. those cells is dependent on Na+ -dependent ATPase.[3] Bound to serum proteins The majority of thiamine in serum is bound to proteins, mainly albumin. Approximately 90% of total thiamine in blood is in erythrocytes. A specific binding protein called thiamine-binding protein (TBP) has been identified in rat serum and is believed to be a hormonally regulated carrier protein that is important for tissue distribution of thiamine.[3] Cellular uptake Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion. [2] About 80% of intracellular thiamine is phosphorylated and most is bound to proteins. In some tissues, thiamine uptake and secretion appears to be mediated by a soluble thiamine transporter that is dependent on Na+ and a transcellular proton gradient. [3] Tissue distribution Human storage of thiamine is about 25 to 30 mg with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys. ThMP and free (unphosphorylated) thiamine is present in plasma, milk, cerebrospinal fluid, and likely all extracellular fluids. Unlike the highly phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing cell membranes. Thiamine contents in human tissues are less than those of other species.[3][23] Excretion Thiamine and its acid metabolites (2-methyl-4-amino-5-pyrimidine carboxylic acid, 4- methyl-thiazole-5-acetic acid and thiamine acetic acid) are excreted principally in the urine. [14] Thiamine phosphate derivatives and function Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. There are four known natural thiamine phosphate derivatives: thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and the recently discovered adenosine thiamine triphosphate (AThTP) and adenosine thiamine diphosphate (AThDP). Thiamine monophosphate There is no known physiological role of ThMP. Thiamine diphosphate The synthesis of thiamine diphosphate (ThDP), also known as thiamine pyrophosphate (TPP) or cocarboxylase, is catalyzed by an enzyme called thiamine diphosphokinase according to the reaction thiamine + ATP → ThDP + AMP (EC 2.7.6.2). ThDP is a coenzyme for several enzymes that catalyze the transfer of two-carbon units and in particular the dehydrogenation (decarboxylation and subsequent conjugation with coenzyme A) of 2-oxoacids (alpha-keto acids). Examples include: Present in most species pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase (also called α- ketoglutarate dehydrogenase) branched-chain α-keto acid dehydrogenase 2-hydroxyphytanoyl-CoA lyase transketolase Present in some species: pyruvate decarboxylase (in yeast) several additional bacterial enzymes
  • 102. The enzymes transketolase, pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase (OGDH) are all important in carbohydrate metabolism. The cytosolic enzyme transketolase is a key player in the pentose phosphate pathway, a major route for the biosynthesis of the pentose sugars deoxyribose and ribose. The mitochondrial PDH and OGDH are part of biochemical pathways that result in the generation of adenosine triphosphate (ATP), which is a major form of energy for the cell. PDH links glycolysis to the citric acid cycle, while the reaction catalyzed by OGDH is a rate-limting step in the citric acid cycle. In the nervous system, PDH is also involved in the production of acetylcholine, a neurotransmitter, and for myelin synthesis.[24] Thiamine triphosphate Thiamine triphosphate (ThTP) was long considered a specific neuroactive form of thiamine. However, recently it was shown that ThTP exists in bacteria, fungi, plants and animals suggesting a much more general cellular role. [25] In particular in E. coli, it seems to play a role in response to amino acid starvation.[26] Adenosine thiamine triphosphate Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recently been discovered in Escherichia coli where it accumulates as a result of carbon starvation.[4] In E. coli, AThTP may account for up to 20 % of total thiamine. It also exists in lesser amounts in yeast, roots of higher plants and animal tissue. [27] Adenosine thiamine diphosphate Adenosine thiamine diphosphate (AThDP) or thiaminylated adenosine diphosphate exists in small amounts in vertebrate liver, but its role remains unknown.[27] Deficiency Thiamine derivatives and thiamine-dependent enzymes are present in all cells of the body, thus, a thiamine deficiency would seem to adversely affect all of the organ systems. However, the nervous system and the heart are particularly sensitive to thiamine deficiency, because of their high oxidative metabolism. Thiamine deficiency can lead to severe fatigue of eyes and myriad problems including neurodegeneration, wasting and death. A lack of thiamine can be caused by malnutrition, a diet high in thiaminase-rich foods (raw freshwater fish, raw shellfish, ferns) and/or foods high in anti-thiamine factors (tea, coffee, betel nuts) [28] and by grossly impaired nutritional status associated with chronic diseases, such as alcoholism, gastrointestinal diseases, HIV-AIDS, and persistent vomiting. [29] It is thought that many people with diabetes have a deficiency of thiamine and that this may be linked to some of the complications that can occur. [30][31] Well-known syndromes caused by thiamine deficiency include beriberi and Wernicke- Korsakoff syndrome, diseases also common with chronic alcoholism. Beriberi Beriberi is a neurological and cardiovascular disease. The three major forms of the disorder are dry beriberi, wet beriberi, and infantile beriberi.[14] Dry beriberi is characterized principally by peripheral neuropathy consisting of symmetric impairment of sensory, motor, and reflex functions affecting distal more than proximal limb segments and causing calf muscle tenderness.[29] Wet beriberi is associated with mental confusion, muscular wasting, edema, tachycardia, cardiomegaly, and congestive heart failure in addition to peripheral neuropathy.[2] Infantile beriberi occurs in infants breast-fed by thiamin-deficient mothers (who may show no sign of thiamine deficiency). Infants may manifest cardiac, aphonic, or pseudomeningitic forms of the disorder. Infants with cardiac beriberi frequently exhibit a loud piercing cry, vomiting, and tachycardia. [14] Convulsions are not uncommon, and death may ensue if thiamine is not administered promptly. [29]
  • 103. Following thiamine treatment, rapid improvement occurs generally within 24 hours. [14] Improvements of peripheral neuropathy may require several months of thiamine treatment. [32] Alcoholic brain disease Nerve cells and other supporting cells (such as glial cells) of the nervous system require thiamine. Examples of neurologic disorders that are linked to alcohol abuse include Wernicke’s encephalopathy (WE, Wernicke-Korsakoff syndrome) and Korsakoff’s psychosis (alcohol amnestic disorder) as well as varying degrees of cognitive impairment.[33] Wernicke’s encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society, [34] though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease, [34] those with HIV-AIDS, and with the injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation. [35] This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function. [36] Alcoholics may have thiamine deficiency because of the following: inadequate nutritional intake: alcoholics tend to intake less than the recommended amount of thiamine. decreased uptake of thiamine from the GI tract: active transport of thiamine into enterocytes is disturbed during acute alcohol exposure. liver thiamine stores are reduced due to hepatic steatosis or fibrosis.[37] impaired thiamine utilization: magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency. Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP). [38] Korsakoff Psychosis is generally considered to occur with deterioration of brain function in patients initially diagnosed with WE. [39] . This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.< [29] Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed; particularly poor brain functionality, although in more severe cases, Wernicke-Korsakoff syndrome leaves permanent damage. (See delirium tremens.) Thiamine deficiency in poultry As most feedstuffs used in poultry diets contain enough quantities of vitamins to meet the requirements in this species, deficiencies in this vitamin does not occur with commercial diets. This was, at least, the opinion in the 1960s. [40] Mature chickens show signs 3 weeks after being fed a deficient diet. In young chicks, it can appear before 2 weeks of age. Onset is sudden in young chicks. There is anorexia and an unsteady gait. Later on, there are locomotor signs, beginning with an apparent paralysis of the flexor of the toes. The characteristic position is called "stargazing", meaning a chick "sitting on its hocks and the head in opisthotonos. Response to administration of the vitamin is rather quick, occurring a few hours later.[41][42] Differential diagnosis include riboflavin deficiency and avian encephalomyelitis. In riboflavin deficiency, the "curled toes" is a characteristic symptom. Muscle tremor is typical of avian encephalomyelitis. A therapeutic diagnosis can be tried by supplementing Vitamin B1 only in the affected bird. If the animals do not respond in a few hours, Vitamin B1 deficiency can be excluded. Thiamine deficiency in ruminants
  • 104. Polioencephalomalacia(PEM), is the most common thiamine deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient diarrhea, listlessness, circling movements, star gazing or opisthotonus (head drawn back over neck), and muscle tremors.[43] The most common cause is high- carbohydrate feeds, leading to the overgrowth of thiaminase-producing bacteria, but dietary ingestion of thiaminase (e.g. in bracken fern), or inhibition of thiamine absorption by high sulfur intake are also possible. [44] Idiopathic paralytic disease in wild birds Recently thiamine deficiency has been identified as the cause of a paralytic disease affecting wild birds in the Baltic Sea area dating back to 1982. [45] In this condition, there is difficulty in keeping the wings folded along the side of the body when resting, loss of the ability to fly and voice with eventual paralysis of the wings and legs and death. It affects primarily 0.5–1 kg sized birds such as the herring gull (Larus argentatus), Common Starling (Sturnus vulgaris) and Common Eider (Somateria mollissima). Researches noted "Because the investigated species occupy a wide range of ecological niches and positions in the food web, we are open to the possibility that other animal classes may suffer from thiamine deficiency as well."[45]p. 12006 Analysis and diagnostic testing A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte Transketolase Activation Assay). Thiamine, as well as its phosphate derivatives, can also be detected directly in whole blood, tissues, foods, animal feed Oxidation of thiamine derivatives to fluorescent thiochromes by and pharmaceutical preparations following the potassium ferricyanide under conversion of thiamine to fluorescent thiochrome alkaline conditions derivatives (Thiochrome Assay) and separation by high performance liquid chromatography (HPLC).[46][47][48] In recent reports, a number of Capillary Electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as potential alternative techniques for the determination and monitoring of thiamine in samples. [49] Genetic diseases Genetic diseases of thiamine transport are rare but serious. Thiamine Responsive Megaloblastic Anemia with diabetes mellitus and sensorineural deafness (TRMA) [50] is an autosomal recessive disorder caused by mutations in the gene SLC19A2,[51] a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high affinity thiamine transporter, SLC19A3. [52][53] Leigh Disease (Subacute Necrotising Encephalomyelopathy) is an inherited disorder which affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase complex [54] Other disorders in which a putative role for thiamine has been implicated include Subacute Necrotizing Encephalomyelopathy, Opsoclonic Cerebellopathy (a paraneoplastic syndrome), and Nigerian Seasonal Ataxia. In addition, several inherited disorders of ThDP-dependent enzymes have been reported, [55] which may respond to thiamine treatment. [29] Research Research in the field mainly concerns the mechanisms by which thiamine deficiency leads to neuronal death in relation to Wernicke Korsakoff Psychosis. Another important field concerns the understanding of the molecular mechanisms involved in ThDP catalysis. More recently, research has been devoted to the understanding of the possible non-cofactor roles of other derivatives such as ThTP and AThTP.
  • 105. Understanding the mechanism by which thiamine deficiency leads to selective neuronal death Experimentally induced beriberi polyneuropathy in chickens may be a good model for studying these forms of neuropathy in view of diagnosis and treatment. [56] From studies using rat models, a link between thiamine deficiency and colon carcinogenesis was suggested. [57] Rat model is used also in research of Wernicke's encephalopathy. [58] Thiamine deprived mice are a classic model of systemic oxidative stress, used in research of Alzheimer’s disease. [59] Catalytic mechanisms in thiamine diphosphate-dependent enzymes A lot of work is devoted to the understanding of the interplay between ThDP and ThDP- dependent enzymes in catalysis. [60][61] Non-cofactor roles of thiamine derivatives Thiamine compounds other than ThDP exist in most cells from many organisms, including bacteria, fungi, plants and animals. Among those compounds are thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP) are thought to have non-cofactor roles, though at present it is not known to what extent they participate in the symptoms [4][27][62][63] Persistent carbenes The production of furoin from furfural is catalyzed by thiamine through a relatively stable carbene (organic radical). This reaction, studied in 1957 by R. Breslow, was the frst evidence for the existence of persistent carbenes. See also Thiamine oxidase, an enzyme for producing thiamine acetic acid. References 1. ↑ Thiamine is pronounced "Thigh-a-min". 2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Mahan LK, Escott-Stump S, editors. Krause's food, nutrition, & diet therapy. 10th ed. Philadelphia: W.B. Saunders Company; 2000 3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Combs, G. F. Jr. The vitamins: Fundamental Aspects in Nutrition and Health. 3rd Edition. Ithaca, NY: Elsevier Academic Press; 2008 4. ↑ 4.0 4.1 4.2 Bettendorff L, Wirtzfeld B, Makarchikov AF, Mazzucchelli G, Frédérich M, Gigliobianco T, Gangolf M, De Pauw E, Angenot L and Wins P (2007). "[Expression error: Missing operand for > Discovery of a natural thiamine adenine nucleotide]". Nature Chem. Biol. 3: 211–212. doi:10.1038/nchembio867. 5. ↑ McCollum EV. A History of Nutrition. Cambridge, MA: Riverside Press, Houghton Mifflin; 1957. 6. ↑ Eijkman, C. (1897). Eine Beriberiähnliche Krankheit der Hühner. Virchows Arch. Pathol. Anat. 148: 523. 7. ↑ Grijns, G. (1901) Over polyneuritis gallinarum. I. Geneesk. Tijdscht. Ned. Ind. 43, 3-110 8. ↑ Jansen, B.C.P. and Donath, W.F. (1926) On the isolation of antiberiberi vitamin. Proc. Kon. Ned. Akad. Wet. 29: 1390-1400. 9. ↑ Williams, R.R. and Cline, J.K. (1936). Synthesis of vitamin B1. J. Am. Chem. Soc. 58: 1504-1505. 10. ↑ Carpenter KJ. Beriberi, white rice, and vitamin B: a disease, a cause, and a cure. Berkeley, CA: University of California Press; 2000 11. ↑ Peters, R.A. (1936). The biochemical lesion in vitamin B1 deficiency. Application of modern biochemical analysis in its diagnosis. Lancet 1: 1161-1164. 12. ↑ Lohmann, K. and Schuster, P. (1937). Untersuchungen über die Cocarboxylase. Biochem. Z. 294, 188- 214. 13. ↑ Breslow R (1958). "[Expression error: Missing operand for > On the mechanism of thiamine action. IV.1 Evidence from studies on model systems]". J Am Chem Soc 80: 3719–3726. doi:10.1021/ja01547a064. 14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 Tanphaichitr V. Thiamin. In: Shils ME, Olsen JA, Shike M et al., editors. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999 15. ↑ Luczak M, Zeszyty Probi PostepoLc Vauh Roln 1968;80,497; Chem Abstr 1969;71,2267g 16. ↑ Syunyakova ZM, Karpova IN, Vop Pitan 1966;25(2),52; Chem Abstr 1966;65,1297b 17. ↑ Webb ME, Marquet A, Mendel RR, Rebeille F & Smith AG (2007) Elucidating biosynthetic pathways for vitamins and cofactors. Nat Prod Rep 24, 988-1008. 18. ↑ Begley TP, Chatterjee A, Hanes JW, Hazra A & Ealick SE (2008) Cofactor biosynthesis—still yielding fascinating new biological chemistry. Curr Opin Chem Biol 12, 118-125. 19. ↑ Switching the light on plant riboswitches. Samuel Bocobza and Asaph Aharoni Trends in Plant Science Volume 13, Issue 10, October 2008, Pages 526-533 doi:10.1016/j.tplants.2008.07.004 20. ↑ Thiamine's Mood-Mending Qualities, Richard N. Podel, Nutrition Science News, January 1999.
  • 106. 21. ↑ McGuire, M. and K.A. Beerman. Nutritional Sciences: From Fundamentals to Foods. 2007. California: Thomas Wadsworth. 22. ↑ Hayes KC, Hegsted DM. Toxicity of the Vitamins. In: National Research Council (U.S.). Food Protection Committee. Toxicants Occurring Naturally in Foods. 2nd ed. Washington DCL: National Academy Press; 1973. 23. ↑ Bettendorff L., Mastrogiacomo F., Kish S. J., and Grisar T. (1996). "[Expression error: Missing operand for > Thiamine, thiamine phosphates and their metabolizing enzymes in human brain]". J. Neurochem. 66: 250–258. 24. ↑ Butterworth RF. Thiamin. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006 25. ↑ Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P, Grisar T and Bettendorff L (2003). "[Expression error: Missing operand for > Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals]". Cell. Mol. Life Sci 60: 1477–1488. doi:10.1007/s00018-003-3098-4. 26. ↑ Lakaye B, Wirtzfeld B, Wins P, Grisar T and Bettendorff L (2004). "[Expression error: Missing operand for > Thiamine triphosphate, a new signal required for optimal growth of Escherichia coli during amino acid starvation]". J. Biol. Chem. 279: 17142–17147. doi:10.1074/jbc.M313569200. PMID 14769791. 27. ↑ 27.0 27.1 27.2 Frédérich M., Delvaux D., Gigliobianco T., Gangolf M., Dive G., Mazzucchelli G., Elias B., De Pauw E., Angenot L., Wins P. and Bettendorff L. (2009). [Expression error: Missing operand for > Thiaminylated adenine nucleotides — chemical synthesis, structural characterization and natural occurrence FEBS J.]. 276. pp. 3256-3268. doi:10.1111/j.1742-4658.2009.07040.x. 28. ↑ "Thiamin", Jane Higdon, Micronutrient Information Center, Linus Pauling Institute 29. ↑ 29.0 29.1 29.2 29.3 29.4 Butterworth RF. Thiamin. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006. 30. ↑ Thornalley PJ (2005). "[Expression error: Missing operand for > The potential role of thiamine (vitamin B(1)) in diabetic complications]". Curr Diabetes Rev 1 (3): 287–98. doi:10.2174/157339905774574383. PMID 18220605. 31. ↑ Diabetes problems 'vitamin link', BBC News, Tuesday, 7 August 2007 32. ↑ Maurice V, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. 2nd ed. Philadelphia: FA Davis, 1989. 33. ↑ Martin, PR, Singleton, CK, Hiller-Sturmhofel, S (2003). "[Expression error: Missing operand for > The role of thiamine deficiency in alcoholic brain disease]". Alcohol Research and Health 27: 134–142. 34. ↑ 34.0 34.1 Kril JJ (1996). "[Expression error: Missing operand for > Neuropathology of thiamine deficiency disorders]". Metab Brain Dis 11 (1): 9–17. doi:10.1007/BF02080928. 35. ↑ Butterworth RF, Gaudreau C, Vincelette J et al. (1991). "[Expression error: Missing operand for > Thiamine deficiency and wernicke's encephalopathy in AIDS]". Metab Brain Dis 6: 207–12. doi:10.1007/BF00996920. 36. ↑ Harper C. (1979). "[Expression error: Missing operand for > Wernicke’s encephalopathy, a more common disease than realised (a neuropathological study of 51 cases)]". J Neurol Neurosurg Psychol 42: 226–231. doi:10.1136/jnnp.42.3.226. PMID 438830. 37. ↑ Butterworth RF (1993). "[Expression error: Missing operand for > Pathophysiologic mechanisms responsible for the reversible (thiamine-responsive) and irreversible (thiamine non-responsive) neurological symptoms of Wernicke's encephalopathy]". Drug Alcohol Rev 12: 315–22. doi:10.1080/09595239300185371. 38. ↑ Rindi G, Imarisio L, Patrini C (1986). "[Expression error: Missing operand for > Effects of acute and chronic ethanol administration on regional thiamin pyrophosphokinase activity of the rat brain]". Biochem Pharmacol 35: 3903–8. doi:10.1016/0006-2952(86)90002-X. 39. ↑ McCollum EV A History of Nutrition. Cambridge, MA: Riverside Press, Houghton Mifflin; 1957. 40. ↑ Merck Veterinary Manual, ed 1967, pp 1440-1441. 41. ↑ R.E. Austic and M.L. Scott, Nutritional deficiency diseases, in Diseases of poultry, ed. by M.S. Hofstad, Iowa State University Press, Ames, Iowa, USA ISBN 0-8138-0430-2, p. 50. 42. ↑ The disease is described more carefully here: merckvetmanual.com 43. ↑ National Research Council. 1996. Nutrient Requirements of Beef Cattle, Seventh Revised Ed. Washington, D.C.: National Academy Press. 44. ↑ Polioencephalomalacia: Introduction, Merck Veterinary Manual 45. ↑ 45.0 45.1 Balk L, Hägerroth PA, Akerman G, Hanson M, Tjärnlund U, Hansson T, Hallgrimsson GT, Zebühr Y, Broman D, Mörner T, Sundberg H. (2009). Wild birds of declining European species are dying from a thiamine deficiency syndrome. Proc Natl Acad Sci U S A. 106:12001–12006. PMID 19597145 doi:10.1073/pnas.0902903106 46. ↑ Bettendorff L, Peeters M., Jouan C., Wins P., and Schoffeniels E. (1991) Determination of thiamin and its phosphate esters in cultured neurons and astrocytes using an ion-pair reversed-phase high-performance liquid chromatographic method. Anal. Biochem. 198: 52-59. 47. ↑ Losa R, Sierra MI, Fernández A, Blanco D, Buesa JM. (2005) Determination of thiamine and its phosphorylated forms in human plasma, erythrocytes and urine by HPLC and fluorescence detection: a preliminary study on cancer patients.J Pharm Biomed Anal. 37:1025-1029. 48. ↑ Lu J, Frank EL. (2008) Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem. 2008 May;54(5):901-906. 49. ↑ Shabangi M, Sutton JA. Separation of thiamin and its phosphate esters by capillary zone electrophoresis and its application to the analysis of water-soluble vitamins. Journal of Pharmaceutical and Biomedical Analysis 2005; 38:1:66-71. 50. ↑ [Expression error: Missing operand for > Thiamine Responsive Megaloblastic Anemia with severe diabetes mellitus and sensorineural deafness (TRMA)]. PMID 249270. 51. ↑ Kopriva, V; Bilkovic, R; Licko, T (Dec 1977). "[Expression error: Missing operand for > Tumours of the small intestine (author's transl)]". Ceskoslovenska gastroenterologie a vyziva 31 (8): 549–53. ISSN 0009- 0565. PMID 603941. 52. ↑ Beissel, J (Dec 1977). "[Expression error: Missing operand for > The role of right catheterization in valvular prosthesis surveillance (author's transl)]". Annales de cardiologie et d'angeiologie 26 (6): 587–9. ISSN 0003-3928. PMID 606152. 53. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 249270 54. ↑ Butterworth RF. Pyruvate dehydrogenase deficiency disorders. In: McCandless DW, ed. Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Publishing Corp.; 1985. 55. ↑ Blass JP. Inborn errors of pyruvate metabolism. In: Stanbury JB, Wyngaarden JB, Frederckson DS et al., eds. Metabolic Basis of Inherited Disease. 5th ed. New York: McGraw-Hill, 1983. 56. ↑ Djoenaidi W, Notermans SL, Gabreëls-Festen AA, Lilisantoso AH, Sudanawidjaja A (1995). "[Expression
  • 107. error: Missing operand for > Experimentally induced beriberi polyneuropathy in chickens]". Electromyogr Clin Neurophysiol 35 (1): 53–60. 57. ↑ Bruce WR, Furrer R, Shangari N, O’Brien PJ, Medline A, Wang Y (2003). "[Expression error: Missing operand for > Marginal dietary thiamin deficiency induces the formation of colonic aberrant crypt foci (ACF) in rats]". Cancer Lett 202: 125–129. doi:10.1016/j.canlet.2003.08.005. 58. ↑ Langlais PJ (1995). "[Expression error: Missing operand for > Pathogenesis of diencephalic lesions in an experimental model of Wernicke's encephalopathy]". Metab Brain Dis 10 (1): 31–44. doi:10.1007/BF01991781. 59. ↑ Frederikse PH, Zigler SJ Jr, Farnsworth PN, Carper DA (2000). "[Expression error: Missing operand for > Prion protein expression in mammalian lenses]". Curr Eye Res 20 (2): 137–43. doi:10.1076/0271- 3683(200002)20:2;1-D;FT137. 60. ↑ Kale S, Ulas G, Song J, Brudvig GW, Furey W & Jordan F (2008) Efficient coupling of catalysis and dynamics in the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex.Proc Natl Acad Sci U S A. 105, 1158-1163 61. ↑ Kluger R & Tittmann K (2008) Thiamin diphosphate catalysis: enzymic and nonenzymic covalent intermediates. Chem Rev 108, 1797-1833 62. ↑ Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P, Grisar T & Bettendorff L (2003) Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals. Cell Mol Life Sci 60, 1477-1488. 63. ↑ Bettendorff L. and Wins P. (2009). "[Expression error: Missing operand for > Thiamin diphosphate in biological chemistry : new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors]". FEBS J. 276: 2917-2925. doi:10.1111/j.1742-4658.2009.07017.x. External links "Branched-Chain Amino Acid Metabolism" at ncbi.nlm.nih.gov Thiamin deficiency in poultry Type of vitamin B1 could treat common cause of blindness Vitamins (A11) show Categories: Poultry diseases | Amines | Pyrimidines | Thiazoles | Vitamins | Coenzymes History View article history All Wikipedia content is licensed under the GNU Free Document License or the Creative Commons CC-BY-SA license or is otherwise used here in compliance with the Copyright Act Go to Bing in English © 2009 Microsoft | Προστασία προσωπικών δεδομένων | Νομικές ανακοινώσεις | Βοήθεια
  • 108. Web Εικόνες Περισσότερα MSN Hotmail Είσοδος | Ελλάδα | Προτιμήσεις Ορίστε το Bing ως τη μηχανή αποφάσεών σας Bing VITAMIN A Beta ΌΛΑ ΤΑ REFERENCE » WIKIPEDIA ARTICLES ΑΠΟΤΕΛΈΣΜΑΤΑ Αναφορά Vitamin A view original wikipedia article Vitamin A Vitamin A is a vitamin which is needed by the overview outline images locations retina of the eye in the form of a Search this article high specific metabolite, the light-absorbing molecule retinal. Vitamin A This molecule is The structure of retinol, the most common dietary form of vitamin A History absolutely Equivalencies of retinoids and carotenoid necessary for both scotopic and color vision. Vitamin A also functions in a very different (IU) role, as an irreversibly oxidized form retinoic acid, which is an important hormone-like Recommended daily intake growth factor for epithelial and other cells. Sources In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl Metabolic functions palmitate, which is converted to an alcohol (retinol) in the small intestine. The retinol Vision form functions as a storage form of the vitamin, and can be converted to and from its Gene transcription visually active aldehyde form, retinal. The associated acid (retinoic acid), a metabolite Dermatology which can be irreversibly synthesized from vitamin A, has only partial vitamin A activity, Retinal/retinol versus retinoic acid and does not function in the retina or some essential parts of the reproductive system. Deficiency Toxicity All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached, Vitamin A and derivatives in medical use called a retinyl group. This structure is essential for vitamin activity. [1] The orange See also pigment of carrots - beta-carotene - can be represented as two connected retinyl References groups, which are used in the body to contribute to vitamin A levels. Alpha-carotene Further reading and gamma-carotene also have a single retinyl group which give them some vitamin External links activity. None of the other carotenes have vitamin activity. The carotenoid beta-cryptoxanthin possesses an ionone group and has vitamin activity in humans. 4 Locations Vitamin A can be found in two principal forms in foods: United States National Academy of Sciences, Yale retinol, the form of vitamin A absorbed when eating animal food sources, is a University, Burkina yellow, fat-soluble substance. Since the pure alcohol form is unstable, the vitamin F view all i U it f is found in tissues in a form of retinyl ester. It is also commercially produced and administred as esters such as retinyl acetate or palmitate. Images Videos The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of which contain beta-ionone rings), but no other carotenoids, function as vitamin A in herbivores and omnivore animals, which possess the enzyme required to convert these compounds to retinal. Carnivores in general are poor converters of ionine-containg carotenoids, and view all 24 view all 15 pure carnivores such as cats and ferets lack beta-carotene 15,15'- monooxygenase and cannot convert any carotenoids to retinal (resulting in none of the carotenoids being forms of vitamin A for these species). History The discovery of vitamin A may have stemmed from research dating back to 1906, indicating that factors other than carbohydrates, proteins, and fats were necessary to keep cattle healthy. [2] By 1917 one of these substances was independently discovered by Elmer McCollum at the University of Wisconsin–Madison , and Lafayette Mendel and Thomas Burr Osborne at Yale University. Since "water-soluble factor B" (Vitamin B) had recently been discovered, the researchers chose the name "fat-soluble factor A" (vitamin A).[2] Vitamin A was first synthesized in 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens. Equivalencies of retinoids and carotenoids (IU) As some carotenoids can be converted into vitamin A, attempts have been made to
  • 109. determine how much of them in the diet is equivalent to a particular amount of retinol, so that comparisons can be made of the benefit of different foods. Unfortunately the situation is confusing because the accepted equivalences have changed. For many years, a system of equivalencies was used in which an international unit (IU) was equal to 0.3 μg of retinol, 0.6 μg of β-carotene, or 1.2 μg of other provitamin-A carotenoids.[3] Later, a unit called retinol equivalent (RE) was introduced. 1 RE corresponded to 1 μg retinol, 2 μg β-carotene dissolved in oil (it is only partly dissolved in most supplement pills, due to very poor solubility in any medium), 6 μg β-carotene in normal food (because it is not absorbed as well as when in oils), and 12 μg of either α-carotene, γ- carotene, or β-cryptoxanthin in food (these molecules only provide 50% of the retinol as β-carotene, due to only half the molecule being convertible to usable vitamin). Newer research has shown that the absorption of provitamin-A carotenoids is only half as much as previously thought, so in 2001 the US Institute of Medicine recommended a new unit, the retinol activity equivalent (RAE). 1 μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta-carotene, or 24 μg of the three other dietary provitamin-A carotenoids.[4] Substance and its chemical Micrograms of retinol equivalent per microgram environment of the substance retinol 1 beta-carotene, dissolved in oil 1/2 beta-carotene, common dietary 1/12 alpha-carotene, common dietary 1/24 gamma-carotene, common 1/24 dietary beta-cryptoxanthin, common 1/24 dietary Because the production of retinol from provitamins by the human body is regulated by the amount of retinol available to the body, the conversions apply strictly only for vitamin A deficient humans. The absorption of provitamins also depends greatly on the amount of lipids ingested with the provitamin; lipids increase the uptake of the provitamin. [5] The conclusion that can be drawn from the newer research is that fruits and vegetables are not as useful for obtaining vitamin A as was thought; in other words, the IU's that these foods were reported to contain were worth much less than the same number of IU's of fat-dissolved oils and (to some extent) supplements. This is important for vegetarians. (Night blindness is prevalent in countries where little meat or vitamin A- fortified foods are available.) A sample vegan diet for one day that provides sufficient vitamin A has been published by the Food and Nutrition Board (page 120[4] ). On the other hand, reference values for retinol or its equivalents, provided by the National Academy of Sciences, have decreased. The RDA (for men) of 1968 was 5000 IU (1500 μg retinol). In 1974, the RDA was set to 1000 RE (1000 μg retinol), whereas now the Dietary Reference Intake is 900 RAE (900 μg or 3000 IU retinol). This is equivalent to 1800 μg of β-carotene supplement (3000 IU) or 10800 μg of β-carotene in food (18000 IU). Recommended daily intake Vitamin A Dietary Reference Intake [6] : RDA/AI* UL Life Stage Group μg/day μg/day Infants 0–6 months 400* 600 7–12 months 500* 600 Children 1–3 years 300 600 4–8 years 400 900 Males 9–13 years 600 1700 14–18 years 900 2800 900 3000 19 - >70 years Females
  • 110. 9–13 years 600 1700 14–18 years 700 2800 700 3000 19 - >70 years Pregnancy <19 years 750 2800 19 - >50 years 770 3000 Lactation <19 years 1200 2800 19 - >50 years 1300 3000 RDA = Recommended Dietary Allowances AI* = Adequate Intakes UL = Upper Limit (Note that the limit refers to synthetic and natural retinoid forms of vitamin A. Carotene forms from dietary sources are not toxic.[7][8] ) According to the Institute of Medicine of the National Academies, "RDAs are set to meet the needs of almost all (97 to 98 percent) individuals in a group. For healthy breastfed infants, the AI is the mean intake. The AI for other life stage and gender groups is believed to cover the needs of all individuals in the group, but lack of data prevent being able to specify with confidence the percentage of individuals covered by this intake."[9] Sources Vitamin A is found naturally in many foods: liver (beef, pork, chicken, turkey, fish) (6500 μg 722%) carrot (835 μg 93%) broccoli leaf (800 μg 89%) - According to USDA database broccoli florets have much less.[10] sweet potato (709 μg 79%) kale (681 μg 76%) butter (684 μg 76%) spinach (469 μg 52%) pumpkin (400 μg 41%) collard greens (333 μg 37%) cantaloupe melon (169 μg 19%) egg (140 μg 16%) Egg. apricot (96 μg 11%) papaya (55 μg 6%) mango (38 μg 4%) pea (38 μg 4%) broccoli (31 μg 3%) Note: data taken from USDA database bracketed values are retinol equivalences and percentage of the adult male RDA per 100g. Conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies. [11][12] Metabolic functions Vitamin A plays a role in a variety of functions throughout the body, such as: Vision Gene transcription Immune function Embryonic development and reproduction Bone metabolism Haematopoiesis Skin health Antioxidant Activity
  • 111. Vision The role of vitamin A in the vision cycle is specifically related to the retinal form. Within the eye, 11-cis-retinal is bound to rhodopsin (rods) and iodopsin (cones) at conserved lysine residues. As light enters the eye the 11-cis-retinal is isomerized to the all-"trans" form. The all-"trans" retinal dissociates from the opsin in a series of steps called bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. Upon completion of this cycle, the all-"trans"-retinal can be recycled and converted back to the 11-"cis"-retinal form via a series of enzymatic reactions. Additionally, some of the all-"trans" retinal may be converted to all-"trans" retinol form and then transported with an interphotoreceptor retinol-binding protein (IRBP) to the pigment epithelial cells. Further esterification into all-"trans" retinyl esters allow this final form to be stored within the pigment epithelial cells to be reused when needed.[13] The final conversion of 11-cis-retinal will rebind to opsin to reform rhodopsin in the retina. Rhodopsin is needed to see black and white as well as see at night. It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin and lead to night blindness. [14] Gene transcription Vitamin A, in the retinoic acid form, plays an important role in gene transcription. Once retinol has been taken up by a cell, it can be oxidized to retinal (by retinol dehydrogenases) and then retinal can be oxidized to retinoic acid (by retinal oxidase). The conversion of retinal to retinoic acid is an irreversible step, meaning that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors.[13] Retinoic acid can bind to two different nuclear receptors to initiate (or inhibit) gene transcription: the retinoic acid receptors (RARs) or the retinoid "X" receptors (RXRs). RAR and RXR must dimerize before they can bind to the DNA. RAR will form a heterodimer with RXR (RAR-RXR), but it does not readily form a homodimer (RAR-RAR). RXR, on the other hand, readily forms a homodimer (RXR-RXR) and will form heterodimers with many other nuclear receptors as well, including the thyroid hormone receptor (RXR-TR), the Vitamin D 3 receptor (RXR-VDR), the peroxisome proliferator-activated receptor (RXR-PPAR) and the liver "X" receptor (RXR-LXR). [15] The RAR-RXR heterodimer recognizes retinoid acid response elements (RAREs) on the DNA whereas the RXR-RXR homodimer recognizes retinoid "X" response elements (RXREs) on the DNA. The other RXR heterodimers will bind to various other response elements on the DNA. [13] Once the retinoic acid binds to the receptors and dimerization has occurred, the receptors undergo a conformational change that causes co- repressors to dissociate from the receptors. Coactivators can then bind to the receptor complex, which may help to loosen the chromatin structure from the histones or may interact with the transcriptional machinery. [15] The receptors can then bind to the response elements on the DNA and upregulate (or downregulate) the expression of target genes, such as cellular retinol-binding protein (CRBP) as well as the genes that encode for the receptors themselves. [13] Dermatology Vitamin A appears to function in maintaining normal skin health. The mechanisms behind retinoid's therapeutic agents in the treatment of dermatological diseases are being researched. For the treatment of acne, the most effective drug is 13-cis retinoic acid (isotretinoin). Although its mechanism of action remains unknown, it dramatically reduces the size and secretion of the sebaceous glands. Isotretinoin reduces bacterial numbers in both the ducts and skin surface. This is thought to be a result of the reduction in sebum, a nutrient source for the bacteria. Isotretinoin reduces inflammation via inhibition of chemotatic responses of monocytes and neutrophils. [13] Isotretinoin also has been shown to initiate remodeling of the sebaceous glands; triggering changes in gene expression that selectively induces apoptosis. [16] Isotretinoin is a teratogen and its use is confined to medical supervision. Retinal/retinol versus retinoic acid Vitamin A deprived rats can be kept in good general health with supplementation of retinoic acid. This reverses the growth-stunting effects of vitamin A deficiency, as well as xerophthalmia. However, such rats show infertility (in both male and females) and continued degeneration of the retina, showing that these functions require retinal or
  • 112. retinol, which are intraconvertable but which cannot be recovered from the oxidized retinoic acid. [17] Deficiency Main article: Vitamin A deficiency Vitamin A deficiency is estimated to affect millions of children around the world. Approximately 250,000-500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa.[18] According to the World Health Organization (WHO), vitamin A deficiency is under control in the United States, but in developing countries vitamin A deficiency is a significant concern. With the high prevalence of vitamin A deficiency, the WHO has implemented several initiatives for supplementation of vitamin A in developing countries. Some of these strategies include intake of vitamin A through a combination of breast feeding, dietary intake, food fortification, and supplementation. Through the efforts of WHO and its partners, an estimated 1.25 million deaths since 1998 in 40 countries due to vitamin A deficiency have been averted.[19] Vitamin A deficiency can occur as either a primary or secondary deficiency. A primary vitamin A deficiency occurs among children and adults who do not consume an adequate intake of yellow and green vegetables, fruits and liver. Early weaning can also increase the risk of vitamin A deficiency. Secondary vitamin A deficiency is associated with chronic malabsorption of lipids, impaired bile production and release, low fat diets, and chronic exposure to oxidants, such as cigarette smoke. Vitamin A is a fat soluble vitamin and depends on micellar solubilization for dispersion into the small intestine, which results in poor utilization of vitamin A from low-fat diets. Zinc deficiency can also impair absorption, transport, and metabolism of vitamin A because it is essential for the synthesis of the vitamin A transport proteins and the oxidation of retinol to retinal. In malnourished populations, common low intakes of vitamin A and zinc increase the risk of vitamin A deficiency and lead to several physiological events.[13] A study in Burkina Faso showed major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children. [20] Since the unique function of retinyl group is the light absorption in retinylidene protein, one of the earliest and specific manifestations of vitamin A deficiency is impaired vision, particularly in reduced light - night blindness. Persistent deficiency gives rise to a series of changes, the most devastating of which occur in the eyes. Some other ocular changes are referred to as xerophthalmia. First there is dryness of the conjunctiva (xerosis) as the normal lacrimal and mucus secreting epithelium is replaced by a keratinized epithelium. This is followed by the build-up of keratin debris in small opaque plaques (Bitot's spots) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea (keratomalacia) and total blindness. [21] Other changes include impaired immunity, hypokeratosis (white lumps at hair follicles), keratosis pilaris and squamous metaplasia of the epithelium lining the upper respiratory passages and urinary bladder to a keratinized epithelium. With relations to dentistry, a deficiency in Vitamin A leads to enamel hypoplasia. Adequate supply of Vitamin A is especially important for pregnant and breastfeeding women, since deficiencies cannot be compensated by postnatal supplementation. [22][23] . Toxicity Main article: Hypervitaminosis A Since vitamin A is fat-soluble, disposing of any excesses taken in through diet is much harder than with water-soluble vitamins B and C, thus vitamin A toxicity may result. This can lead to nausea, jaundice, irritability, anorexia (not to be confused with anorexia nervosa, the eating disorder), vomiting, blurry vision, headaches, hairloss, muscle and abdominal pain and weakness, drowsiness and altered mental status. Acute toxicity generally occurs at doses of 25,000 IU/kg of body weight, with chronic toxicity occurring at 4,000 IU/kg of body weight daily for 6–15 months. [24] However, liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day. In people with renal failure 4000 IU can cause substantial damage. Additionally, excessive alcohol intake can increase toxicity. Children can reach toxic levels at 1500IU/kg of body weight. [25] In chronic cases, hair loss, dry skin, drying of the mucous membranes, fever, insomnia,
  • 113. fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity. [26] It has been estimated that 75% of people may be ingesting more than the RDA for vitamin A on a regular basis in developed nations. Intake of twice the RDA of preformed vitamin A chronically may be associated with osteoporosis and hip fractures. This may be due to the fact that an excess of vitamin A can block the expression of certain proteins that are dependent on vitamin K. This could hypothetically reduce the efficacy of vitamin D, which has a proven role in the prevention of osteoporosis and also depends on vitamin K for proper utilization [27] . High vitamin A intake has been associated with spontaneous bone fractures in animals. Cell culture studies have linked increased bone resorption and decreased bone formation with high vitamin A intakes. This interaction may occur because vitamins A and D may compete for the same receptor and then interact with parathyroid hormone which regulates calcium.[25] Indeed, a study by Forsmo et al. shows a correlation between low bone mineral density and too high intake of vitamin A. [28] Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis.[13] These toxicities only occur with preformed (retinoid) vitamin A (such as from liver). The carotenoid forms (such as beta-carotene as found in carrots), give no such symptoms, but excessive dietary intake of beta-carotene can lead to carotenodermia, which causes orange-yellow discoloration of the skin.[29][30][31] Researchers have succeeded in creating water-soluble forms of vitamin A, which they believed could reduce the potential for toxicity. [32] However, a 2003 study found that water-soluble vitamin A was approximately 10 times as toxic as fat-soluble vitamin.[33] A 2006 study found that children given water-soluble vitamin A and D, which are typically fat-soluble, suffer from asthma twice as much as a control group supplemented with the fat-soluble vitamins. [34] Chronically high doses of Vitamin A can produce the syndrome of "pseudotumor cerebri".[35] This syndrome includes headache, blurring of vision and confusion. It is associated with increased intracerebral pressure. [36] Vitamin A and derivatives in medical use Retinyl palmitate has been used in skin cremes, where it is broken down to retinoic acid, which has potent biological activity, as described above. The retinoids, a class of chemical compounds that are related chemically to retinoic acid, are used in medicine to modulate gene functions in place of this counpound. In general, like retinoic acid itself, these compounds do not have full vitamin A activity. [37] See also Beta carotene Retinoids Hypervitaminosis A References 1. ↑ Carolyn Berdanier. 1997. Advanced Nutrition Micronutrients. pp 22-39 2. ↑ 2.0 2.1 Wolf, George (2001-04-19). "Discovery of Vitamin A". Encyclopedia of Life Sciences. doi:10.1038/npg.els.0003419. http://www.mrw.interscience.wiley.com/emrw/9780470015902/els/article/a0003419/current/html. Retrieved 2007-07-21. 3. ↑ Composition of Foods Raw, Processed, Prepared USDA National Nutrient Database for Standard Reference, Release 20 USDA, Feb. 2008 4. ↑ 4.0 4.1 Chapter 4, Vitamin A of Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, hickel, Silicon, Vanadium, and Zinc, Food and Nutrition Board of the Institute of Medicine, 2001 5. ↑ NW Solomons, M Orozco. Alleviation of Vitamin A deficiency with palm fruit and its products. Asia Pac J Clin Nutr, 2003 6. ↑ Dietary Reference Intakes: Vitamins
  • 114. 7. ↑ "Sources of vitamin A". http://www.vitamins-supplements.org/vitamin-A-sources.php. Retrieved 2007-08- 27. 8. ↑ "Linus Pauling Institute at Oregon State University: Vitamin A Safety". http://lpi.oregonstate.edu/infocenter/vitamins/vitaminA#safety. Retrieved 2007-09-02. 9. ↑ Food and Nutrition Board. Institute of Medicine. National Academies. (2001) "Dietary Reference Intakes" 10. ↑ The RAE value in the USDA data for broccoli leaves is similar to the IU value for broccoli florets, which implies that the leaves have about 20 times as much beta-carotene. 11. ↑ Borel P, Drai J, Faure H, et al. (2005). "[Expression error: Missing operand for > [Recent knowledge about intestinal absorption and cleavage of carotenoids]]" (in French). Ann. Biol. Clin. (Paris) 63 (2): 165– 77. PMID 15771974. 12. ↑ Tang G, Qin J, Dolnikowski GG, Russell RM, Grusak MA (2005). "[Expression error: Missing operand for > Spinach or carrots can supply significant amounts of vitamin A as assessed by feeding with intrinsically deuterated vegetables]". Am. J. Clin. Nutr. 82 (4): 821–8. PMID 16210712. 13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 Combs, Gerald F. (2008). The Vitamins: Fundamental Aspects in Nutrition and Health (3rd ed.). Burlington: Elsevier Academic Press. ISBN 9780121834937. 14. ↑ McGuire, Michelle; Beerman, Kathy A. (2007). Nutritional sciences: from fundamentals to food. Belmont, CA: Thomson/Wadsworth. ISBN 0534537170. 15. ↑ 15.0 15.1 Stipanuk, Martha H. (2006). Biochemical, Physiological and Molecular Aspects of Human Nutrition (2nd ed.). Philadelphia: Saunders. ISBN 978116002093. 16. ↑ Nelson, A. M.; et al. (2008). "[Expression error: Missing operand for > Neutrophil gelatinase- associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells]". Journal of Clinical Investigation 118 (4): 1468–1478. doi:10.1172/JCI33869. 17. ↑ http://la.rsmjournals.com/cgi/content/abstract/5/2/239 Lab Anim 1971;5:239-250. The production of experimental vitamin A deficiency in rats and mice. T. Moore and P. D. Holmes. doi:10.1258/002367771781006492. 18. ↑ "Office of Dietary Supplements. Vitamin A". National Institute of Health. http://www.dietary- supplements.info.nih.gov/factsheets/vitamina.asp. Retrieved 2008-04-08. 19. ↑ "Micronutrient Deficiencies-Vitamin A". World Health Organization. http://www.who.int/nutrition/topics/vad/en/index.html. Retrieved 2008-04-09. 20. ↑ Zeba AN, Sorgho H, Rouamba N, et al. (2008). "Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial". Nutr J 7: 7. doi:10.1186/1475-2891-7-7. PMID 18237394. http://www.nutritionj.com/content/7/1/7. 21. ↑ Roncone DP (2006). "[Expression error: Missing operand for > Xerophthalmia secondary to alcohol- induced malnutrition]". Optometry (St. Louis, Mo.) 77 (3): 124–33. doi:10.1016/j.optm.2006.01.005. PMID 16513513. 22. ↑ Strobel M, Tinz J, Biesalski HK (2007). "[Expression error: Missing operand for > The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women]". Eur J Nutr 46 Suppl 1: I1–20. doi:10.1007/s00394-007-1001-z. PMID 17665093. 23. ↑ Schulz C, Engel U, Kreienberg R, Biesalski HK (2007). "[Expression error: Missing operand for > Vitamin A and beta-carotene supply of women with gemini or short birth intervals: a pilot study]". Eur J Nutr 46 (1): 12–20. doi:10.1007/s00394-006-0624-9. PMID 17103079. 24. ↑ Rosenbloom, Mark. "Toxicity, Vitamin". eMedicine. http://www.emedicine.com/emerg/topic638.htm. 25. ↑ 25.0 25.1 Penniston, Kristina L.; Tanumihardjo, Sherry A. (February 1, 2006). "The acute and chronic toxic effects of vitamin A". Am. J. Clin. Nutr. 83 (2): 191–201. PMID 16469975. http://www.ajcn.org/cgi/content/abstract/83/2/191. 26. ↑ Eledrisi, Mohsen S.. "Vitamin A Toxicity". eMedicine. http://www.emedicine.com/med/topic2382.htm. 27. ↑ Masterjohn, C (December 4, 2006). "Vitamin D toxicity redefined: vitamin K and the molecular mechanism.". http://www.ncbi.nlm.nih.gov/pubmed/17145139. 28. ↑ Forsmo, Siri; Fjeldbo,Sigurd Kjørstad; Langhammer, Arnulf (2008). "[Expression error: Missing operand for > Childhood Cod Liver Oil Consumption and Bone Mineral Density in a Population-based Cohort of Peri- and Postmenopausal Women: The Nord-Trøndelag Health Study]". Am. J. Epidemiol. 167 (4): 406– 411. doi:10.1093/aje/kwm320. PMID 18033763. 29. ↑ Sale TA, Stratman E (2004). "[Expression error: Missing operand for > Carotenemia associated with green bean ingestion]". Pediatr Dermatol 21 (6): 657–9. doi:10.1111/j.0736-8046.2004.21609.x. PMID 15575851. 30. ↑ Nishimura Y, Ishii N, Sugita Y, Nakajima H (1998). "[Expression error: Missing operand for > A case of carotenodermia caused by a diet of the dried seaweed called Nori]". J. Dermatol. 25 (10): 685–7. PMID 9830271. 31. ↑ Takita Y, Ichimiya M, Hamamoto Y, Muto M (2006). "[Expression error: Missing operand for > A case of carotenemia associated with ingestion of nutrient supplements]". J. Dermatol. 33 (2): 132–4. doi:10.1111/j.1346-8138.2006.00028.x. PMID 16556283. 32. ↑ Science News. Water-soluble vitamin A shows promise. 33. ↑ Myhre AM, Carlsen MH, Bøhn SK, Wold HL, Laake P, Blomhoff R (December 2003). "Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil -based preparations". Am. J. Clin. Nutr. 78 (6): 1152–9. PMID 14668278. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=14668278. 34. ↑ Kull I, Bergström A, Melén E, et al. (December 2006). "Early-life supplementation of vitamins A and D, in water-soluble form or in peanut oil, and allergic diseases during childhood". J. Allergy Clin. Immunol. 118 (6): 1299–304. doi:10.1016/j.jaci.2006.08.022. PMID 17157660. http://www.jacionline.org/article/S0091- 6749(06)01775-1/abstract. 35. ↑ Brazis PW (March 2004). "[Expression error: Missing operand for > Pseudotumor cerebri]". Current neurology and neuroscience reports 4 (2): 111–6. doi:10.1007/s11910-004-0024-6. PMID 14984682. 36. ↑ AJ Giannini, RL Gilliland. The Neurologic, Neurogenic and Neuropsychiatric Disorders Handbook. New Hyde Park, NY. Medical Examination Publishing Co., 1982,pp. 182-183. 37. ↑ American Cancer Society: Retinoid Therapy Further reading Litwack, Gerald (2007). Vitamin A. Vitamins and Hormones. 75. San Diego, CA: Elsevier Academic Press. ISBN 9780127098753.
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