Vitamin D basics

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Vitamin D

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  • Although called “a vitamin”, vitamin D is in fact a hormone, which is synthesized in the skin after exposure to UV-B radiation from the sun. It can also be obtained thorough diet, although most foods contain only small amounts or no vitamin D. The main natural dietary source is fish, but the concentration varies between fish species and even between individual fish. Because the intake is often very low, some foods are fortified with small amounts of of vitamin D (e.g. margarine, milk). In many countries vitamin D supplementation is recommended for infants and other special groups which often have restricted intake (e.g. elderly individuals). It has been known for long time that vitamin D is essential for bone health, severe deficiency leading to rickets in children or osteomalasia in adults. During recent years scientific literature has suggested a wide-range of health effects for vitamin D, although only a few associations have been well demonstrated to date. Vitamin D receptors have been discovered from all over the body (e.g. immune-cells, brain, heart, pancreas, intestine) suggesting that vitamin D is likely to have some kind of function in these tissues. It is already known that vitamin D affects the immune system in humans. How would you measure vitamin D intake in an epidemiological study? What aspects would you need to consider? Links: Vitamin D http://cancerweb.ncl.ac.uk/cgi-bin/omd?Vitamin+D Rickets http://cancerweb.ncl.ac.uk/cgi-bin/omd?rickets
  • Global Vitamin D Status Although a consensus regarding the optimal level of serum 25(OH)D has not yet been established, most experts define vitamin D deficiency as a 25(OH)D level of 20 ng/ml (50 nmol/l) and vitamin D insufficiency as 21 to 29 ng/ml (Table 1). 1 Vitamin D insufficiency is prevalent worldwide. Vitamin D deficiency is very common in the Middle East and South Asia. 2
  • Vitamin D basics

    1. 1. Evolving concepts & importance in overall health status
    2. 2. Is there deficiency in sunny India? INDIA Latitude of 22 ° 00 N Longitude of 77 ° 00‘ W Can there be chances of deficiency in India?
    3. 3. 1. ↓ Intake or synthesis of cholecalciferol  ↓ sunlight: ageing, veiling, illness, immobility  ↓ synthesis for a given UV exposure: ageing, dark skin  As above combined with low dietary intake1. Disorders associated with abnormal gut function and malabsorption  Small bowel disorders: coeliac disease, sprue, IBD, infiltrative disorders, small bowel resection  Pancreatic insufficiency: chronic pancreatitis, cystic fibrosis  Biliary obstruction: 1° biliary cirrhosis, external biliary drainage
    4. 4. 3. ↓ synthesis or enhanced degradation of 25OHD  chronic hepatic disorders: hepatitis, cirrhosis  drugs: rifampicin, anticonvulsants4. AHA 2010 Conference revealed that Vitamin-D deficiency is highly prevalent in U.S. black populations.  Melanin in the skin blocks the UVB synthesis of vitamin D.  Silent epidemic, often unrecognized by clinicians
    5. 5.  Cod liver oil – 1 TBS  1,360 IU Salmon 3.5 oz.  360 Fish Mackerel 3.5 oz.  345 Tuna, canned, in oil, 3 oz.  200 Sardines 3.5 oz.  250 Milk (fortified) 8 oz.  98 Ready to eat cereal (fortified) ¾  40 - 1 cup Egg 1 whole  20 Liver, 3.5 oz.  15 Cheese, swiss 1 oz.  12
    6. 6. Most Indians suffer from Vitamin D Deficiency1. Am J Clin Nutr. 2000;72: 472-75 2. Data on file
    7. 7. Is there deficiency in sunny India? INDIA Latitude of 22 ° 00 N Longitude of 77 ° 00‘ W More than 80 % of adult Indians not getting enough Vitamin D
    8. 8. Osteomalacia & Rickets are the most common disorders due to Vitamin D deficiency in IndiaOsteomalacia present in 35.3% adults with Vitamin D deficiency1Rickets present in 30.3 % Indian infants with 25(OH)D <10ng/ml.2  1. Indian J Med Res. 2008;127:219-228.  2. Indian J Med Res. 2011;133:267-273
    9. 9. Softening of bones due to insufficient vitamin D, or problems with metabolism of this vitamin.Osteomalacia in children is known as Rickets.Signs & Symptoms  Bone Weakness  Bone Pain  Muscle Weakness
    10. 10. Osteomalacia OsteoporosisWeakening of BonesIn osteoporosis, bones become weak, fragile and brittle due to loss of minerals like calcium and get fractured more easily than normal bone.1 out of 8 males & 1 out of 3 females in India suffer from Osteoporosis Normal Bone Osteoporosis
    11. 11. Osteomalacia Osteoporosis ↑ risk &Muscle weakness Rate of Fall ↑ Risk of #Over 90% of Fractures occur after fall and fall rate increases due to poor muscle strength and function.1Adequate dose of Vitamin D found to be useful in ↓ of persistent non specific pain & Fractures  Medicographia. 2010;32(4):384-390
    12. 12. Osteomalacia OsteoporosisPhysiology Abnormal bone building Degeneration of built boneOccurrence Adults Elderly Muscle Weakness Frequent fracturesSymptoms Bone Weakness & Pain Loss on height (due to compression of spine Bone softeningComplications Results in bone fragility & fractures Bone bending Can be prevented by Ca &Prognosis Cannot be prevented. Can only be treated Vitamin D supplementsOutcome Osteoporosis Fractures
    13. 13. What is its role?
    14. 14. Musculoskeletal disorders  Low back pain, joint painFatigue and Muscular WeaknessIncreased susceptibility to infectionsIt thus adversely effects Quality of Life [QOL].Is it common in adults or children?
    15. 15. It is a fat soluble vitamin.  Not just a vitamin it is a prehormoneFound in some food and made in the body after exposure to UV rays  Major biological function is to maintain normal blood levels of Ca and Po4  Other tissues like macrophages, prostrate tissue also have Vitamin D Receptor [VDR].
    16. 16. Existed over 500 million years  Industrial revolution: rickets  Cod liver oil: common folklore medicine  Discovery of Vit D as the antirachitic factor in cod liver oil(1920)Discovery of conversion of 7-dehydrocholesterol in the skin to vit D (1937)Antirachitic property in food & fortification of food with vitamin D was patented.
    17. 17. Vitamin D3 and D2 (made in skin or ingested) are transported to liver and metabolised to 25(OH)D  25(OH)D is the major circulating formFurther hydroxylation occurs in kidney to form highly biologically active 1,25(OH)2D that promotes  Absorption of calcium and phosphate from small intestine  Extracellular calcium homeostasis  Mineralisation of skeleton (DeLuca and Zierold 1998)
    18. 18.  Vitamin D3 is not secreted by a classical endocrine gland - the active form of the hormone is released from the kidney - and acts at distant sites or locally. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. Only remains in a free form in the circulation and has a serum t1/2 of about 5 hours, for a small proportion of vitamin D.
    19. 19. Multifaceted
    20. 20. Association of low intake of milk and vit D during pregnancy with decreased birth weight. C.A. Mannion, Katherine Gray-Donald, kristine G. Koski. CMAJ April 25, 2006  Women between ages 19-45yrs in Calgary  </= 250 ml of milk = low birth weight  milk or vit D independent predictor of BW 1 cup milk = 41 gm increase in BW 1 Mcg increase in dietary vit D = 11 gm increase in BW
    21. 21. Maternal vitamin D status during pregnancy and childhood bone mass at age 9yrs. M.K. Javaid, SR Crozeir at al. Lancet Jan 7 2006198 children born in 1991-92 in South Hampton UK, were followed up at age 9yrs  31% mother had insufficient and 18% had deficient serum vit D during late pregnancy  Decrease vit D in mothers = decrease bone mineral content in children at age 9 yrs  Mother’s exposure to UV rays and use of vit D predicted vit D and childhood bone mass
    22. 22. Vitamin D deficiency in breastfed infants in Iowa. Ekhard E. Ziegler, Bruce w. Hollis, Steven E Nelson and Janice M. Jeter. Pediatrics 2006  84 breastfed infants were followed, their blood samples and dietary records were taken 35 infants were unsupplemented 49 infants were either supplemented with formula or vit D 10% were vit D deficient
    23. 23. Prevalence of vitamin D deficiency among healthy adolescents. Catherine M Gordon, Kerrin C. DePeter, Henry A. Feldman, Estherann Grace, Jean Emans. Arch pediatr Adolesc med June 2004  307 healthy adolescents 11-18 yrs, 24.1% of the participants were vit D deficient Highest prevalence in african american No difference in prevalence between girls and boys + Correlation between soft drink consumption and vit D deficiency Inverse correlation between vit D deficiency and milk and cold cereal consumption.
    24. 24. Traditionally: regulation of calcium homeostasis and bone metabolism More recently Vitamin D is known to modulate immune function in humans and affect a wide-range of diseases, including autoimmune disorders, cancer, metabolic syndrome – suppresses (overaggressive) reactions  Type 1 diabetes prevented by 1,25-(OH)2D in animal models with some evidence for protective effect in humans / only a few studies published to date.
    25. 25.  Vitamin D facilitates the intestinal absorption of calcium by stimulating the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. Calcium absorption is transported across the epithelial cell, greatly enhanced by the carrier protein calbindin, synthesis of which is totally dependent on vitamin D.
    26. 26.  The adjoining figure shows expressed Calbindins and how they facilitate transport of Calcium through the membranes. In the absence of vitamin D, dietary calcium is not absorbed efficiently. Vitamin D also plays an important part in regulating the proliferation and differentiation of both types of bone remodeling cells - those responsible for bone breakdown and those that reform the bone anew…and more.
    27. 27.  Net result is: Calcium absorption and remodeling….outweighs resorption
    28. 28. Vitamin D deficiency  Abnormal motor performance, ↑ body sway and quadriceps weakness reported for 25OHD < 20-30 nmol/L (Glerup 2000, Dhesi 2002)  An independent predictor of falls in older women in residential care (Flicker 2003)  Linked with falls and fractures in elderly men and women (Pfeifer 2000, Bischoff 2003, Flicker 2005).
    29. 29. Aim: to determine if vitD supplementation (D2) reduced falls in older people in residential care, not classically vitD deficientRCT, two years duration  60 hostels, 89 nursing homes across Australia, 625 residents (mean age 83.4yr),  25OHD 25-90nmol/L↓ falls by 27% - 37%Estimated that 8 people need to be treated to prevent 1 fall/yr Flicker 2005
    30. 30. Pivotal trial relating fracture reduction in high risk group: 800 IU D3 for 18 mo  41% ↓ hip fracs elderly women in residential care (Chapuy NEJM 1992)389 people from community:  benefit from daily Ca (500mg) + vitD (700 IU) on bone loss & frac (Dawson-Hughes NEJM 1997)Double-blind RCT oral 100,000 IU every 4mo for 5yr ↓ risk of first hip, wrist, forearm, vert frac in 2686 people from community by 33% (Trivedi, BMJ 2003).
    31. 31. One meta-analysis concluded vitD (Papadimitopoulos Endocr Rev 2002)  ↓ vertebral frac risk 37% (RR 0.63; 95%CI 0.45-0.88)  but no sig ↓ in non-vert fracs (RR 0.77; 0.57-1.04)More recent meta-analysis showed vitD (Bischoff-Ferrari JAMA 2005)  ↓ hip frac (RR=0.74, 0.61-0.88) and  ↓ non-vert frac (RR=0.77, 0.68-0.87)
    32. 32. Greatest benefits:  High-risk vitamin D-deficient patients, with ↓BMDUnlikely that supplementation effective in vitamin D replete individuals but optimal 25OHD levels unknown: thresholds 50-110 nmol/L reported (Parfitt 1990, Mithal 2000)  Vitamin D examined in fracture prevention trials but differences in baseline PTH and 25OHD make comparisons difficult  Adequate calcium AND vitamin D likely to be required to reduce fracture risk
    33. 33. Low 25OHD↓ Muscle strength ↓ Mineralisation ↑ PTH ↑ Falls ↑ Bone fragility ↑ Fractures
    34. 34. A single dose of Vit D enhances immunity to Mycobacteria  ( Martineau et al. Am J Respir Crit Care Med 176;208-213, 2007)Double-blind RCT in 192 healthy adult TB contacts in London  Single oral dose of 2.5mg Vit D vs placebo  Measured response to BCG-lux (measures the ability of whole blood to restrict the growth of recombinant reporter mycobacteria in vitro) Single dose of Vit D significantly enhances TB pts’ antimycobacterial immunity in vitro
    35. 35. Indonesian study in 2006  Double-blind RCT, Vit D vs placebo (in addition to RIPE) in 67 pts with active pulmonary TB  Rate of sputum conversion as follows Vit D 100% Placebo 76% (p=0.002)  More subjects with radiologic improvement in Vit D group
    36. 36. In 1986-1987, Rook and Crowle infected human monocytes and macrophages with M. Tb. and added 1,25D3, which triggered significant antimicrobial activity  Subsequently, Toll-like receptors were discovered.  TLRs are pattern-recognition receptors whose activation induces expression of antimicrobial peptides  11 subtypes of TLRs are expressed on various types of immune and non-immune cells  TLRs trigger direct antimicrobial activity against intracellular bacteria as well as apoptosis, cytokine secretion, and so on
    37. 37.  Upregulation of macrophage 1α,25(OH)2D synthesis following administration of pharmacologic doses of vitamin D in active Mycobacterium tuberculosis infection. In the granuloma both IFNγ and ligation of macrophage TLR2/1 by M. tuberculosis induces macrophage expression of 25(OH)D-1α- hydroxylase. Administration of pharmacologic doses of vitamin D results in increased circulating concentrations of free 25(OH)D, which is metabolised by upregulated 1α-hydroxylase to 1α,25(OH)2D. DEFENSINs are antimicrobial peptides produced by activation of TLR.
    38. 38.  TLR2–TLR1 stimulation results in the upregulation of the expression of Cyp27B1 and of VDR. Cyp27B1 converts inactive vitamin D (25D3) into its active form (1,25D3). The intracellular pool of 25D3 is shuttled into the cell via the vitamin D binding protein (DBP). Once activated, 1,25D3 can then bind to and activate the VDR, and induce transcription of antimicrobial factors, including the antimicrobial peptide cathelicidin (Cath.). The cathelicidin peptide can then traffic into intracellular compartments harboring mycobacteria. The cathelicidin peptide has been demonstrated to kill Mycobacterium tuberculosis directly. Therefore, cathelicidin probably has an important role in the TLR2–TLR1-mediated antimicrobial activity, but is probably not the only effector. The induction of host-defense mechanisms by TLR2–TLR1 depends on the amount of 25D3 present in the serum.
    39. 39.  TLR2–TLR1 stimulation results in the upregulation of the expression of Cyp27B1 and of VDR. Cyp27B1 converts inactive vitamin D (25D3) into its active form (1,25D3). The intracellular pool of 25D3 is shuttled into the cell via the vitamin D binding protein (DBP). Once activated, 1,25D3 can then bind to and activate the VDR, and induce transcription of antimicrobial factors, including the antimicrobial peptide cathelicidin (Cath.). The cathelicidin peptide can then traffic into intracellular compartments harboring mycobacteria. The cathelicidin peptide has been demonstrated to kill Mycobacterium tuberculosis directly. Therefore, cathelicidin probably has an important role in the TLR2–TLR1-mediated antimicrobial activity, but is probably not the only effector. The induction of host-defense mechanisms by TLR2–TLR1 depends on the amount of 25D3 present in the serum.
    40. 40.  1,25-D3 and the VDR then together induce the expression of the gene encoding the human antimicrobial peptide LL-37. Vitamin D3 enters the systemic circulation and is converted to 25-D3 by the liver. Circulating monocytes are activated by TLR2/1 agonists present on specific microbes. The genes encoding VDR and CYP 27B1 are induced. CYP27B1 converts 25-D3 from the circulation to 1,25-D3, joins with the VDR and activates the gene encoding LL- 37, leading to an increase in cellular LL-37 and enhanced microbicidal activity of the phagocyte.  Nature Medicine - 12, 388 - 390 (2006)
    41. 41. May influence both incidence and mortality  Linked with GI cancer, prostate and breast cancers, lymphomas, endometrial and lung cancersVitamin D receptors[VDR] found in malignant melanoma cells and myeloid leukemia cells  1,25(OH)2D inhibited melanoma cell proliferation and induced myeloid cell differentiation
    42. 42. Altered vitamin D &calcium homeostasis may play a role in development of type 2 diabetesLow serum levels of 25(OH)D = impaired pancreatic β cell function & insulin resistanceHigh calcium intake is inversely associated with body weightDaily intake of >1,200 mg calcium & >800IU vitamin D - associated with a 33% lower risk of type 2 diabetes compared with an intake of <600 mg calcium & <400 IU vitamin D Pittas, et al., 2006
    43. 43. • Third National Health & Nutrition Examination Survey (NHANES III) • 14,000 subjects • Dose-response correlation between percent predicted FEV1 and FVC values and circulating 25(OH)D • Plausibility: vitamin D shown to prevent experimental inflammatory diseases in mice including allergic asthma • Black, et al., Chest, 2005
    44. 44. • 50 COPD >70 year patients with a history of exacerbations were assigned to receive a monthly dose of vitamin D [100,000 IUs (international units) of vitamin D] or placebo. • All patients participated in a pulmonary rehabilitation program for 3 months. • At the beginning and again at the completion of the rehabilitation program, peripheral and respiratory muscle strength, exercise capacity and vitamin D levels were measured. • Patients were also asked to complete a quality of life survey both before and after rehabilitation.
    45. 45. • At the end of the study, researchers found that patients treated with vitamin D had a significant• improvement in exercise capacity and respiratory muscle strength compared to those in the placebo group.• The genetic association of VDR with COPD may be mediated by effects on macrophage activation, since VDR relates to FEV1, and affects macrophage activation. • Thorax 2011;66:205-210 , Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages by A M Wood et al.
    46. 46. • Respiratory epithelial cells constitutively activate vitamin D and are capable of creating a microenvironment that has high levels of active form of the vitamin. • Activation has effects that include up-regulation of the cathelicidin antimicrobial peptide gene and the toll-like receptor, co-receptor. • Viral infection leads to increased activation of vitamin D and further increases in cathelicidin mRNA. • Local vitamin D activation might be an important component of host defense. • J Immunol. 2008 November 15; 181(10): 7090–7099.
    47. 47. Recent association studies demonstrating a significant inversecorrelation between the serum 25D level and an increase in components of the human metabolic syndromeMortality causes First author Year Ref. All causes Melamed 2008 Arch Intern Med 168:1629 Dobnig 2008 Arch Intern Med 168:1340 Cardiovascular Kim 2008 Am J Cardiol disease 102:1540 (34) Wang 2008 Circulation 117:503 Kendrick 2009 Atherosclerosis 205:255 Hypertension Judd 2008 Am J Clin Nutr 87:136 BMI Looker 2008 Am J Clin Nutr 88:1519 (14)Insulin resistance Liu 2009 J Nutr 139:329 Wu 2009 J Nutr 139:547
    48. 48. Supplementation dosage and safety
    49. 49. Vitamin D insufficiency, 25(OH)D levels <30ng/ml is prevalent, worldwide, especially in Middle East and South Asia. 2J Am Coll Cardiol. 2008;52:1949–1956.Osteoporos Int. 2010 Jul;21(7):1151-4.
    50. 50. Prevent disease of deficiency – rickets, osteomalaciaPrevent complications of insufficiency – impaired calcium absorption and increased bone resorptionMinimize risks of future disease – cancer, cardiopulmonary diseases, diabetes, other immune- related diseases
    51. 51. Age Children Men Women Pregnancy lactationBirth-13 5mcgsyrs =200IU14-18yrs 5mcgs 5mcgs 5mcgs 5mcgs =200IU =200IU =200IU =200IU19-50 5mcgs 5mcgs 5mcgs 5mcgsYrs =200IU =200IU =200IU =200IU51-70 10 mcg 10 mcgYrs =400 IU =400 IU71+ 15 mcg 15 mcg =600 IU =600 IU
    52. 52. 100 I.U./day of Vitamin D(3) increases circulating 25(OH)D by 1 ng/ml when taken for 2 months  If the typical serum 25 (OH)D level in Indians is 10 ng/ml…  And if the target serum 25 (OH)D level is 30 ng/ml… Patients would require about 2000 IU/Day or 60000 IU per month 50-60% fractures can be reduced at ~30 ng/ml serum Vitamin D.1  1. Alt Med Rev. 2008;13(1):21-33.
    53. 53. To raise Serum 25- (OH)D by 1 ng./ml. [2.5 nmol / L] one needs 100 additional i.u. / day of vitamin D3  Hence, to raise a patient’s Vitamin D level from 15 to 30 ng. / ml.; there will be an additional requirement of 1500 i.u./ day.  Great inter-patient variability in Cmax levels, too.
    54. 54. With oral vitamin D supplements, serum levels can be expected to plateau after 3-4 months.Among patients with osteoporosis, check 25-OH-D levels at baseline and 3 months after initiation of vitamin D supplementation.Vitamin D3 is the preferred supplement for adults. Calcitriol (1,25-dihydroxyvitamin D) has a narrow safety index and should not be used for routine supplementation.
    55. 55. Vitamin D deficient ( < 10 ng /ml) population:  Prevention of Osteoporosis: 60,000 IU (1gm Sachet /Month)In Osteomalacia, treatment of osteoporosis  60,000 IU (1 gm sachet )/week* 8 weeks Followed by 60,000 IU (1 gm Sachet ) /monthDose safe to be used, upto:  Pediatrics 0 – 12 months – 1000 IU / Day  All others – 2000 IU / Day
    56. 56. To prevent deficiency disease – > 25 nmol / LTo prevent complications of insufficiency – > 50 nmol/LFor maximum bone health and prevention of chronic disease – 75 – 100 nmol/L
    57. 57. Routine screening / Annual testing of 25(OH)DRectify deficiency / insufficiencyMaintain levels through a patient-specific combination of diet, supplementation, and sun exposure25(OH)D closely reflects total amount of vit D produced in the skin and from diet
    58. 58. In the elderly, to maintain recommended levels, if not getting enough sun exposure to maintain vitamin D levels :  1000 - 2000 IU / day or  60,000 IU monthly OR MORE
    59. 59. ‘…the present recommended allowance for vitamin D – 400 IU – for individuals aged 50 – 70 years is inadequate even to maintain skeletal health and is probably too low for meaningful anticancer effects.’ Schwartz & Blot, J National Cancer Institute, 2006
    60. 60. “to minimize the health risks associated with UVB radiation exposure while maximizing the potential benefits of optimum vitamin D status, {dietary} supplementation and small amounts of sun exposure are the preferred methods of obtaining vitamin D.” Consensus statement, 2006
    61. 61. Depends on:  Age  Amount of vitamin D obtained from diet  Skin darkness  Sunshine intensity
    62. 62. Flashback MCQs
    63. 63.  Q. 1 What is Vitamin D? (a) Fat Soluble vitamin (b) Hormone necessary for the body (c) Water Soluble vitamin (d) Both (a) & (b)
    64. 64.  Q. 2 Conversion of Vitamin D3 to 25(OH) vitamin D3 takes place in the (a) Liver (b) Heart (c) Kidney (d) All of the above
    65. 65.  Q. 3 The active form of Vitamin D is (a) Cholecalciferol (b) 25(OH) vitamin D3 (c) Ergocalciferol (d) Calcitriol
    66. 66.  Q. 4 What is the optimum level of Vitamin D in the body? (a) 10 ng/ml (b) 20 ng/ml (c) > 30 ng/ml (d) None of the above
    67. 67.  Q. 5 What is vitamin D Deficiency (a) High level of Vitamin D in the Body (b) Low level of Vitamin D in the Body (c) Optimum level of Vitamin D in the Body (d) None of the above
    68. 68.  Q. 6 How many Indians have Vitamin Deficiency? (a) 20% (b) 30% (c)50% (d) More than 80%
    69. 69.  Q. 7 Vitamin D has the following actions on the body? a) Increases bone mineralization b) Inhibits PTH secretion c) Increase calcium absorption from intestine d) All of the above
    70. 70.  Q. 8 What are Osteoblasts? a) Cells which help bone formation b) Cells which help bone resorption c) Both (a) &(b) d) None of the above
    71. 71.  Q. 9 Vitamin D Deficiency is associated with ? a) Osteomalacia b) Musculoskeletal Disorders c) Osteoporosis & Fractures d) All of the above
    72. 72.  Q. 10 What is Osteomalacia? a) Softening of bones due to Vitamin D Deficiency b) Breaking of bones c) Indigestion d) None of the above
    73. 73.  Q. 11 Rickets occur commonly in? a) Pregnant Women b) Children c) Adults d) All of the above
    74. 74.  Q. 12 What is Osteoporosis? a) Disease caused due to iron deficiency b) Disease caused by bacterial infection c) Disease in which bones become fragile resulting in fractures d) None of the above
    75. 75.  Q. 13 What is the correct statement? a) Vitamin D Deficiency also affects Musculoskeletal health b) Ca & Vitamin D Deficiency can cause fractures c) Vitamin D supplements can cause fractures d) Both (a) & (b)
    76. 76.  Q. 14 What are the advantages of Vitamin D oral supplement Vs. injection? a) Higher absorption of Vitamin D with oral supplement b) Better safety profile with oral supplement c) Both (a) & (b) d) None of the above
    77. 77. As you offer
    78. 78. OsteomalaciaMuscloskeletal disordersOsteoporosisFracture Dosage: 1 sachet/week for 8-12 weeks, followed by 1 sachet every month
    79. 79. Low back painJoint painOsteomalaciaPerimenopausal osteoporosis Dosage: 1 sachet/week for 8-12 weeks, followed by 1 sachet every month
    80. 80. Low back painJoint painOsteomalaciaPerimenopausal osteoporosis Dosage: 1 sachet/week for 8-12 weeks, followed by 1 sachet every month
    81. 81. Rickets Dosage: 1 sachet/week for 8-12 weeks, followed by 1 sachet every month
    82. 82. Most currently available supplements contain Calcium (500 mg)+ Vitamin D (500-800IU)But in Indians ....... High prevalence of Vitamin Deficiency (25 (OH)D ~10 ng/ml)  To achieve Sufficiency (target 25 (OH)D level = 30 ng/ml)… patients would require 2000 IU/Day (60,000 IU/month)  Existing products would increase vitamin D by only 5-8 ng/ml
    83. 83. If you want to convey more info
    84. 84. Environmental: sunlight & diet  Calcitriol (hormonal form of vitamin D) controls the differentiation of many cells that possess vitamin D receptors (VDR)  Induce cell differentiation and apoptosis of cancer cells while inhibiting cell proliferation, angiogenesis, and metastasisGenetic: VDR polymorphisms
    85. 85. Women who regularly took vitamin D3 and calcium had a 60% reduction in all-cancer incidence compared with a group taking placebo and a 77% reduction when the analysis was confined to cancers diagnosed after the first 12 months.
    86. 86. 1,25(OH)2D:inhibits proliferation and induces differentiation of lung cancer cell lines (Higashimoto, et al., 1996, Guzey, et al., 1998)inhibits metastatic growth and locoregional recurrence of lung cancer cells in mice (Wiers, et al., 2000)
    87. 87. 456 patients with early stage NSCLC  Median age – 69  96% CaucasianData collection:  Season of surgery  Food frequency questionnaire  Recurrence free survival (RFS)  Overall survival (OS) Zhou, et al., 2005
    88. 88. Patients who had surgery during summer with the highest vitamin D intake had better RFS that patients who had surgery during winter with the lowest vitamin D intake.Similar associations were seen for overall survival. Zhou, et al., 2005
    89. 89. 1,25(OH)2D:inhibits cell proliferation, induces differentiation & apoptosis, and inhibits angiogenesis in normal and breast cancer cells (Colston, et al, 1989, Saez, et al, 1993, Mantell, et al., 2000)suppresses high-fat diet-induced mammary tumorigenesis in rats (Jacobson, et al., 1989, Xue, 1999)
    90. 90. Inverse association between vitamin D & calcium intake and breast densityInconclusive results in studies looking at VDR genetic polymorphisms and breast cancerInverse association between high sunlight exposure and breast cancer riskAssociation may be stronger for premenopausal than postmenopausal women due to interactions between vitamin D, the VDR, estrogen and insulin-like growth factor-I (IGF-I) Cui & Rohan, 2006
    91. 91. Case-control study – 972 women with newly- diagnosed breast cancer & 1,135 healthy controlsInterviews regarding vitamin D-related exposures, e.g. outdoor activities, use of sunscreen, dietary contributions Knight, 2007
    92. 92. More frequent sun exposure during adolescence was associated with a 35% reduction in breast cancer risk later in lifeLower risk also linked to cod liver oil and milk intake > 10 glasses / weekMilder protection seen for people age 20 – 29No protection for people over age 45
    93. 93. Epidemiologic study of different regions of Norway, each with a different annual UV exposurePrognosis 15 – 25% better for women diagnosed / treated in the summer vs. winter <get this article: Breast Cancer Research and Treatment, May>Knight , 2007
    94. 94. Is ultraviolet B irradiance inversely associated withincidence rates of endometrial cancer: an ecological study of 107 countries. Mohr, et al, 2007
    95. 95. Objective: perform an ecological analysis of the relationship between low levels of ultraviolet B irradiance and age-standardized incidence rates of endometrial cancer by country, controlling for known confounders
    96. 96. 107 countries:  UVB irradiance  cloud cover  intake of energy from animal sources  proportion overweight  skin pigmentation  cigarette consumption  health expenditure  total fertility ratesvs. age-standardized incidence of endometrial cancer
    97. 97. Association found between endometrial cancer incidence rates and:  Low UVB irradiance  High intake of energy from animal sources ( IGF-I?)  Per capital health expenditure  Proportion of population overweight
    98. 98. Prospectively collected diet and lifestyle data  Nurses’ Health Study – 75,427 women  Health Professionals Follow-up Study – 46,771 menPancreatic cancer risk 41% lower among those who consumed > 600 IU of vitamin D / day vs. those who consumed < 150 IU / day Skinner, et al., 2006
    99. 99. Summer / Fall (vs. Winter / Spring) diagnosis associated with improved survival in:  Colorectal cancer  Hodgkin’s lymphoma  NSCLC  Breast cancer
    100. 100. Intermittent sun exposure associated with increased survival following a diagnosis of melanoma Berwick, et al., 2005

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