MBBS course lecture

4. Dr Mohammad Nurul HuqDr Mohammad Nurul Huq
Bangladesh Medical CollegeBangladesh Medical College

7. V I T A M I N SV I T A M I N S

8. VitaminsVitamins
chemically unrelated substances not made in thechemically unrelated substances not made in the
bodybody (except VD and K);(except VD and K); needed in small amountsneeded in small amounts
for metabolism.for metabolism. 13 vitamins13 vitamins
– Water-soluble (WSV): B, CWater-soluble (WSV): B, C
– fat-soluble (FSV): ADEKfat-soluble (FSV): ADEK
• We getWe get allall V from our balanced foodV from our balanced food
• Vegetarians need B12Vegetarians need B12
vītavīta ( (life) life) + + aminamin from amine from amine

9. DeficienciesDeficiencies
• beriberi (B1), ariboflavinosis (B2), pellagra (B3)beriberi (B1), ariboflavinosis (B2), pellagra (B3)
• megaloblastic anemia (B9, B12)megaloblastic anemia (B9, B12)
• PNP (B1, B6, B12)PNP (B1, B6, B12)
• scurvy (C)scurvy (C)
• rickets (D)rickets (D)
• xerophthalmia (A)xerophthalmia (A)
• hemorrhage (K)hemorrhage (K)
Except B12,Except B12, WSVs have no significant storageWSVs have no significant storage
Some are destroyed by cooking, sunlight, storageSome are destroyed by cooking, sunlight, storage

12. 8 B Vitamins8 B Vitamins
• Needed for energy from food and erythropoiesisNeeded for energy from food and erythropoiesis (B6, B9,(B6, B9,
B12),B12), nerve healthnerve health (B1,B6,B12):(B1,B6,B12):
B1B1 (thiamine),(thiamine), B2B2 (riboflavin),(riboflavin), B3B3 (niacin),(niacin), B5B5 (pantothenic a.),(pantothenic a.),
B6B6 (pyridoxine),(pyridoxine), B7B7 (biotin),(biotin), B9B9 (folic a.)(folic a.) B12B12 (cobalamine)(cobalamine)
SourcesSources:: leafy vege., fruits, fish, poultry, meat, eggs,leafy vege., fruits, fish, poultry, meat, eggs,
dairies, beans, peasdairies, beans, peas
Many cereals and some breads are fortified (not here)Many cereals and some breads are fortified (not here)
Flavins, carotenoids have protective effectsFlavins, carotenoids have protective effects

14. THIAMINETHIAMINE
B1, aneurin, antiberiberi factorB1, aneurin, antiberiberi factor
• CombinedCombined thiazole and pyrimidinethiazole and pyrimidine
• DRA:DRA: 0.5mg/1000 Kcal0.5mg/1000 Kcal
Sources:Sources: yeast, legumes,yeast, legumes, whole grain.whole grain.
Dairies, fruits, vege. are poor sourcesDairies, fruits, vege. are poor sources
Limited storage:Limited storage: daily intake.daily intake. Absorbed in small gutAbsorbed in small gut
Cooking, baking, canning, pasteurization can destroy itCooking, baking, canning, pasteurization can destroy it

17. FunctionsFunctions
– Makes ATP from CHO for growth, function, repairMakes ATP from CHO for growth, function, repair
– nerve signalsnerve signals
– myocardial actionmyocardial action
Measured:Measured: RBC thiamine transketolase (ETKA: mostRBC thiamine transketolase (ETKA: most
reliable), blood level, urinary thiaminereliable), blood level, urinary thiamine

18. Causes of deficiency:Causes of deficiency:
– milled ricemilled rice
– alcoholismalcoholism
– malabsorption, pregnancy,malabsorption, pregnancy, hyperemesis grav.hyperemesis grav.
– poor diet: elderly, children, teenagers, food fadpoor diet: elderly, children, teenagers, food fad
– stressed adults and womenstressed adults and women
– AIDS, wide-spread CaAIDS, wide-spread Ca
– long-term loop diureticslong-term loop diuretics
– long periods of IVF without B1long periods of IVF without B1
– long-term dialysis, thyrotoxicosislong-term dialysis, thyrotoxicosis

19. Deficiencies SyndromesDeficiencies Syndromes
• Beriberi:Beriberi: ac., chr.ac., chr.
– infantileinfantile
– adultadult
• Wernicke-Korsakoff syn.Wernicke-Korsakoff syn.
• Leigh syn.Leigh syn.
History of beriberi goes back to 2697 BCHistory of beriberi goes back to 2697 BC

20. Ac. BeriberiAc. Beriberi
• FatigueFatigue,, irritation, dementia, disorientation, insomnia,irritation, dementia, disorientation, insomnia,
angina, anorexia, confusion, personality changes, abdo.angina, anorexia, confusion, personality changes, abdo.
discomfortdiscomfort
• PNP, difficulty in rising, edema, cardiomegalyPNP, difficulty in rising, edema, cardiomegaly
• Late stages:Late stages: coma and deathcoma and death
• In binge drinkingIn binge drinking (inhibits absorption) it can occur in a few(inhibits absorption) it can occur in a few
days: staggering, eyeball flicking and above …days: staggering, eyeball flicking and above …
• Can causeCan cause Wernicke-Korsakoff Syn. ::
PNP: peripheral neuropathyPNP: peripheral neuropathy

21. Wernicke-Korsakoff syn.Wernicke-Korsakoff syn.
((ExclusivelyExclusively seen in alcoholics)seen in alcoholics)
Wernicke Encephalopathy and Korsakoff Psychosis are ac.
and chr. phases, respectively, of the same d.; often occur
together
• Nystagmus, ophthalmoplegia, ataxiaNystagmus, ophthalmoplegia, ataxia
• Dementia, confabulation with normal cognitionDementia, confabulation with normal cognition
Always delay giving dextrose to alcoholicsAlways delay giving dextrose to alcoholics until B1 is givenuntil B1 is given
(precipitates Wernicke)(precipitates Wernicke)

23. Ac. infantile beriberiAc. infantile beriberi
• Ages: 2-3moAges: 2-3mo
• EBFEBF babies can get it if mother is deficient: CCF,babies can get it if mother is deficient: CCF,
aphonia/dysphonia and areflexiaaphonia/dysphonia and areflexia
• Severe:Severe: cardiomegaly, tachycardia, loud piercing cry,cardiomegaly, tachycardia, loud piercing cry,
cyanosis, dyspnea, NVcyanosis, dyspnea, NV
• MeningismMeningism (CSF is normal) can occur: nystagmus,(CSF is normal) can occur: nystagmus,
purposeless movements, fitpurposeless movements, fit

24. Still common in AsiaStill common in Asia
• Dry:Dry: ANV, constipation, cramps, PNP, tachycardia, fatigue,ANV, constipation, cramps, PNP, tachycardia, fatigue,
depressiondepression
• Wet (edema):Wet (edema): PNP and CCFPNP and CCF
Chr. BeriberiChr. Beriberi

27. DIAGNOSISDIAGNOSIS
Clinical Dx warrants Rx.Clinical Dx warrants Rx.
• Full h/of, diet, recent illnesses, stress levelsFull h/of, diet, recent illnesses, stress levels
• A thorough PEA thorough PE
• Lab:Lab: ECGECG, urine and blood B1, ETKA, urine and blood B1, ETKA

28. Rx.Rx.
• B1: IV/IM: 50-100mg/d x7-14d; then orally 20mg/d untilB1: IV/IM: 50-100mg/d x7-14d; then orally 20mg/d until
recovery; longer if neuro-symptoms are severerecovery; longer if neuro-symptoms are severe
• Ensure daily intakeEnsure daily intake
OUTCOMESOUTCOMES
• Curable. Permanent brain damage if Rx is delayedCurable. Permanent brain damage if Rx is delayed
PREVENTIONPREVENTION
• Balance diet. For poor diet/malabsorption: MV supplementBalance diet. For poor diet/malabsorption: MV supplement
• More B1 in preg. and BF, hyperthyroidism, F, severe liver DMore B1 in preg. and BF, hyperthyroidism, F, severe liver D
• Avoid alcoholAvoid alcohol

29. Peripheral NeuropathyPeripheral Neuropathy
Paraesthesia, glove-sock anesthesia, tender calf; atrophy ofParaesthesia, glove-sock anesthesia, tender calf; atrophy of
calf, thigh and small musclescalf, thigh and small muscles
• -/0 reflexes, foot- and toe-drop-/0 reflexes, foot- and toe-drop
CausesCauses
• deficiencies (B1, B3, B5, B6, B12, E)deficiencies (B1, B3, B5, B6, B12, E)
• leprosy, Lyme Dleprosy, Lyme D
• Drugs: INH, hydralazine, vincristine, disulphirumDrugs: INH, hydralazine, vincristine, disulphirum
• Dm, alcoholism, uremiaDm, alcoholism, uremia
• arsenic, lead, mercury, gold, thallium, COarsenic, lead, mercury, gold, thallium, CO
• idiopathicidiopathic

31. RxRx
Underlying causeUnderlying cause
• NCS may be done to see extent of problem and get aNCS may be done to see extent of problem and get a
proper Dxproper Dx
• Dm PNP is Rx by tight controlDm PNP is Rx by tight control
NCS: nerve conduction studyNCS: nerve conduction study

33. B2 (RIBOFLAVIN)B2 (RIBOFLAVIN)
is a part of flavin-adenine dinucleotide (FAD)is a part of flavin-adenine dinucleotide (FAD)
• FAD + protein: flavoproteinsFAD + protein: flavoproteins
– catalysts in redox reactionscatalysts in redox reactions
– transport electron in respiratory chain (electrontransport electron in respiratory chain (electron
transport chain: ETC)transport chain: ETC)
Sources:Sources: meats, fish, eggs, dairies,meats, fish, eggs, dairies,
greens, yeast, enriched foodsgreens, yeast, enriched foods
• Absorbed in small gutAbsorbed in small gut

35. Deficiency isDeficiency is common!common!
Ariboflavinosis.Ariboflavinosis. Often undetected!Often undetected!
Causes:Causes: no dairies, rare IEM, malabsorption, chr. use ofno dairies, rare IEM, malabsorption, chr. use of
barbiturates (oxidation)barbiturates (oxidation)
CF:CF: hyperemic sore throat with edema, cheilitis, stomatitis,hyperemic sore throat with edema, cheilitis, stomatitis,
glossitis, normocytic-normochromic a., and sebo. derma.,glossitis, normocytic-normochromic a., and sebo. derma.,
corneal vascularisationcorneal vascularisation
Pure deficiency is rare!Pure deficiency is rare!

37. Corneal vascularization:
from limbus. Commonly
from contact L, more with
older hydarogel L. This
material has a relatively low
O2 transmissibility so the
cornea is starved of O2

38. DxDx
urinary level and RBC glutathione reductase assayurinary level and RBC glutathione reductase assay
RDA:RDA: 0.4mg for infants. 1.2 mg/d for adults0.4mg for infants. 1.2 mg/d for adults
• Some intramitochondrial beta-oxidation defects maySome intramitochondrial beta-oxidation defects may
respond to B2respond to B2
• Zidovudine/stavudineZidovudine/stavudine in HIV can cause lactic acidosis that isin HIV can cause lactic acidosis that is
fixed by B2fixed by B2

39. Angular stomatitisAngular stomatitis
• Deficiency:Deficiency: B2, B3, B6, Fe, B12, ZnB2, B3, B6, Fe, B12, Zn
• Old ageOld age
• DentureDenture
• Cold exposureCold exposure
• Drugs: isotretinoin, hypervitaminosis ADrugs: isotretinoin, hypervitaminosis A
• Contact dermatitis (lip balm)Contact dermatitis (lip balm)

43. NIACINNIACIN ((Nicotinic a./nicotinamide)Nicotinic a./nicotinamide)
water-soluble, need daily supplywater-soluble, need daily supply
• 50%50% fromfrom tryptophantryptophan (60mg =1 mg B3)(60mg =1 mg B3)
• Acts as coenzyme: NAD in redox reactions and HActs as coenzyme: NAD in redox reactions and H++
transport, synthesis of fatty a., steroidstransport, synthesis of fatty a., steroids
• Widely distributed. GoodWidely distributed. Good sourcessources:: yeast, liver, cereals,yeast, liver, cereals,
legumes, seeds, high protein diet (100 g/d) (tryptophan)legumes, seeds, high protein diet (100 g/d) (tryptophan)
NAD: nicotinamide
adenine
dinucleotide

44. RDA:RDA: 15-20mg/d15-20mg/d
• This dosage is far <than lipid lowering dosesThis dosage is far <than lipid lowering doses
• Deficiency:Deficiency: pellagrapellagra
Therapeutic usesTherapeutic uses
• Lipid lowering:Lipid lowering: 1-3g/d lowers lipid (total, LDL). Niacin +1-3g/d lowers lipid (total, LDL). Niacin +
colestipol significantly lower atherosclerosis (52 vs 15%)colestipol significantly lower atherosclerosis (52 vs 15%)
Lower doses with aspirin can decrease SELower doses with aspirin can decrease SE

45. PellagraPellagra (raw skin).(raw skin). Once epidemic amongst corn (lowOnce epidemic amongst corn (low
niacin, tryptophan) eaters of USniacin, tryptophan) eaters of US
3Ds:3Ds: Photo-Photo-ddermatitisermatitis (classic rash like sunburn),(classic rash like sunburn), ddiarrhea,iarrhea,
ddementiaementia (insomnia, disorientation, delusions).(insomnia, disorientation, delusions). Glossitis, VDGlossitis, VD
Causes of deficiencyCauses of deficiency
Dietary:Dietary: chiefly cereals; corn eater. Common in alcoholicchiefly cereals; corn eater. Common in alcoholic
Non-dietary:Non-dietary: seen inseen in
• CCarcinoid syn.:arcinoid syn.: tryptophan is not converted to B3tryptophan is not converted to B3
• INH:INH: depletes tryptophandepletes tryptophan
• Hartnup D:Hartnup D: defect in transport of tryptophandefect in transport of tryptophan

51. ToxicityToxicity
• Best known:Best known: flushingflushing (nicotinic a. only)(nicotinic a. only)
• High dose:High dose:
– 1-3g/d:1-3g/d: NV, constipation, pruritus, hives, rise in ALT,NV, constipation, pruritus, hives, rise in ALT,
AST, uric a. Rarely myopathyAST, uric a. Rarely myopathy
– 2-6g/d:2-6g/d: Severe. May hamper growthSevere. May hamper growth
Toxic vitamins: B3, B6, VA, VDToxic vitamins: B3, B6, VA, VD

52. B5 (Panhothenic A.):B5 (Panhothenic A.): active form is CoAactive form is CoA
• CoA is essential for synthesis of vit. A, D, heme, cholesterol,CoA is essential for synthesis of vit. A, D, heme, cholesterol,
steroids, fatty a., amino a., proteinssteroids, fatty a., amino a., proteins
– CoA is converted in gut to PA. Inside cell, PA againCoA is converted in gut to PA. Inside cell, PA again
becomes CoAbecomes CoA
Sources:Sources: egg, liver, kidney, broccoli, milkegg, liver, kidney, broccoli, milk
Deficiency:Deficiency: rare. Seen in severe Mn, faminerare. Seen in severe Mn, famine
CF:CF: paresthesias and dysesthesiasparesthesias and dysesthesias (burning feet syn.)(burning feet syn.)

55. PYRIDOXINEPYRIDOXINE (B6)(B6)
Function:Function: amino a. metabolism; gluconeogenesisamino a. metabolism; gluconeogenesis,,
tryptophan to B3; synthesis of NT, steroid H andtryptophan to B3; synthesis of NT, steroid H and
sphingolipid; erythropoiesis, immunitysphingolipid; erythropoiesis, immunity
Sources:Sources: meats, grains, vegetables, nutsmeats, grains, vegetables, nuts
Cooking, processing, storage reduce contentCooking, processing, storage reduce content
Toxicity (>250mg/d):Toxicity (>250mg/d): Long term HD: anesthesia in handsLong term HD: anesthesia in hands
and feet, permanent nerve damage, dermatoses,and feet, permanent nerve damage, dermatoses,
photosensitivity, dizziness, nauseaphotosensitivity, dizziness, nausea

57. DeficiencyDeficiency
• Rarely severe. PNP, stomatitis, glossitis, cheilosis, irritability,Rarely severe. PNP, stomatitis, glossitis, cheilosis, irritability,
confusion, depression. Seizure in infantsconfusion, depression. Seizure in infants
• Mimics homocystinuria, cystathionuria, xanthurenic aciduriaMimics homocystinuria, cystathionuria, xanthurenic aciduria
• B6 has been used in Down S, autism (with Mg), GDM, CarpalB6 has been used in Down S, autism (with Mg), GDM, Carpal
TS, Premenstrual S, depression, Dm neuropathy, INHTS, Premenstrual S, depression, Dm neuropathy, INH
• Many people take B6 to fight stress and increase energyMany people take B6 to fight stress and increase energy

58. BIOTIN (B7)BIOTIN (B7)
• In several enzymes for meta. of CHO, fats and amino a.In several enzymes for meta. of CHO, fats and amino a.
• It is often recommended for strengthening hair and nails,It is often recommended for strengthening hair and nails,
and it's found in many cosmeticsand it's found in many cosmetics
• Needs daily intakeNeeds daily intake
• Bacteria in gut can synthesize itBacteria in gut can synthesize it
• Absorbed in small gutAbsorbed in small gut

59. Deficiency.Deficiency. RareRare
• Huge raw egg white (avidin binds biotin) intake: moodHuge raw egg white (avidin binds biotin) intake: mood
changes, myalgia, dysesthesias, ANVchanges, myalgia, dysesthesias, ANV
• In neonates; 1In neonates; 1stst
week:week: lethargy, hypotonia, NV., acrallethargy, hypotonia, NV., acral
dermatitis. Death from severe metabolic A.dermatitis. Death from severe metabolic A.
• Late onset (infants):Late onset (infants): acral D, hypotonia, myoclonus, seizureacral D, hypotonia, myoclonus, seizure
• Meta. acidosis and aciduria may occurMeta. acidosis and aciduria may occur
• Chr. deficiency: maculosquamous dermatitis, sebo. D,Chr. deficiency: maculosquamous dermatitis, sebo. D,
alopeciaalopecia

63. Folic AcidFolic Acid (B9, folacin, folate, THF, folinic a.,(B9, folacin, folate, THF, folinic a.,
pteroylglutamic a.)pteroylglutamic a.)
• EssentialEssential for making new cellsfor making new cells
• B9 before and during pregnancy can prevent NTDsB9 before and during pregnancy can prevent NTDs
• Sources:Sources: leafy veg., fruits, beans, peas, nuts, dairies,leafy veg., fruits, beans, peas, nuts, dairies,
poultry, meat, eggs, seafood.poultry, meat, eggs, seafood. Spinach, liver, yeast,Spinach, liver, yeast,
asparagus, brussels sprouts (highest concn.).asparagus, brussels sprouts (highest concn.). Bread, cereal,Bread, cereal,
flour, cornmeal, pasta, rice, other grains can be fortifiedflour, cornmeal, pasta, rice, other grains can be fortified
• Damaged by sun, boilingDamaged by sun, boiling
• Stored in the liverStored in the liver

65. • Active form:Active form: THF (folinic acid)THF (folinic acid)
– synthesis of DNA-RNA, metabol. of amino a.synthesis of DNA-RNA, metabol. of amino a.
– conversion of homocysteine to methionineconversion of homocysteine to methionine
• RBC folate is good index. Blood homocysteine is commonlyRBC folate is good index. Blood homocysteine is commonly
used for B9 statusused for B9 status
• RDA:RDA: 400 mcg/d400 mcg/d

66. DeficiencyDeficiency
• Isolated B9 deficiency is uncommonIsolated B9 deficiency is uncommon
• Megaloblastic a.Megaloblastic a.,, glossitis, mucositis;glossitis, mucositis; changes in skin, hair,changes in skin, hair,
fingernail pigmentationfingernail pigmentation
• Large nucleated RBC, is the primary s/of B9/B12Large nucleated RBC, is the primary s/of B9/B12
• NTDs, LBW, prematurity, IUGR, cleft, hypospadiusNTDs, LBW, prematurity, IUGR, cleft, hypospadius

67. CF of anaemiaCF of anaemia
A. GeneralA. General
• Weakness, palpitation, anorexia, poor sleep and concn.,Weakness, palpitation, anorexia, poor sleep and concn.,
depression, loss of initiative, excess sweats, poor exercisedepression, loss of initiative, excess sweats, poor exercise
tolerance, irritabilitytolerance, irritability
B. SpecificB. Specific
• Iron:Iron: glossitis, angular stomatitis, dysphagia, irritability,glossitis, angular stomatitis, dysphagia, irritability,
koilonychia, micro-hypochromic a.koilonychia, micro-hypochromic a.
• B12:B12: paraesthesia, loss of balance, poor concn.paraesthesia, loss of balance, poor concn.
• B9:B9: glossitis, megaloblastic a.glossitis, megaloblastic a.
• B6:B6: paraesthesiaparaesthesia

69. 2 NTDs:2 NTDs: open (commoner)open (commoner)::
brain and/or SC are exposed via abrain and/or SC are exposed via a
defect in skull/vertebrae:defect in skull/vertebrae:
anencephaly, encephalocele,anencephaly, encephalocele,
hydaranencephaly, iniencephaly,hydaranencephaly, iniencephaly,
schizencephaly, spina bifida.schizencephaly, spina bifida.
ClosedClosed : defect is covered by: defect is covered by
skin: lipomyelomeningocele,skin: lipomyelomeningocele,
lipomeningocele and tetheredlipomeningocele and tethered
cordcord
NTDs:NTDs: the commonestthe commonest
major cong. defects ofmajor cong. defects of
CNS: NT fails to close at itsCNS: NT fails to close at its
end during 3-4w preg.end during 3-4w preg.
Periconceptional B9 canPericonceptional B9 can
prevent (50-60%). GDM,prevent (50-60%). GDM,
obesity, B12, etc. are alsoobesity, B12, etc. are also
believed to affect NTDsbelieved to affect NTDs

71. Atrophic glossitis:Atrophic glossitis: bald smooth raw tonguebald smooth raw tongue
• Change in taste with pain, tenderness and burningChange in taste with pain, tenderness and burning
• Causes:Causes: lack of B9, B12, niacin, IDA; typhoidlack of B9, B12, niacin, IDA; typhoid

72. Geographic tongue/benign migratory glossitisGeographic tongue/benign migratory glossitis
• 3% popn., common in children. Idiopathic. Ulcer enlarges/3% popn., common in children. Idiopathic. Ulcer enlarges/
decreases and migrate. Self-limiting.decreases and migrate. Self-limiting. Leave it aloneLeave it alone

73. At Risk of B9At Risk of B9 InadequacyInadequacy
• Alcoholism:Alcoholism: poor-quality diets; low absorption,poor-quality diets; low absorption,
metabolism and accelerates breakdownmetabolism and accelerates breakdown
• Pregnancy and lactation:Pregnancy and lactation: additional B9 for fetusadditional B9 for fetus
• Malabsorption:Malabsorption: tropical sprue, celiac, IBD, atrophictropical sprue, celiac, IBD, atrophic
gastritis, gastric surgery, etc.gastritis, gastric surgery, etc.

74. Folate and HealthFolate and Health
• Cancer:Cancer: inverse association with colorectal, lung,inverse association with colorectal, lung,
pancreatic, breast, esophageal, stomach, Cx, ovarian Ca.pancreatic, breast, esophageal, stomach, Cx, ovarian Ca.
• CV disease and stroke:CV disease and stroke: raised homocysteine level hasraised homocysteine level has
anan increased risk of CVDincreased risk of CVD
• Dementia, cognition, Alzheimer:Dementia, cognition, Alzheimer: raised homocysteineraised homocysteine
has more risk of Alzheimer. Low B9 causes poor cognitivehas more risk of Alzheimer. Low B9 causes poor cognitive
function, dementiafunction, dementia

75. Depression:Depression: Low B9 lowers action of antidepressants; mayLow B9 lowers action of antidepressants; may
have a role as a supplement to Rx for depressionhave a role as a supplement to Rx for depression
NTDs:NTDs:
Preterm, cong. HD, other anomalies:
• B9 lengthen gestational age; lower the risk of preterm
birth; minimizes risk of cong. HD (24%)
• B9 with MV have reduced UT anomalies, facial clefts, limb
defects, hydrocephalus

79. Excessive FolateExcessive Folate
can correct megaloblastic a., but not neurological
damage from low B12. It might "mask” B12
deficiency until irreversible or precipitate cognitive
symptoms from low B12
• HD B9 might accelerate preneoplastic lesions
increasing the risk of colorectal or other Ca
• High dietary intake of B9 has no SE

80. Interactions withInteractions with
• Methotrexate:Methotrexate: a B9 antagonist. B9 could interferea B9 antagonist. B9 could interfere
its effects. In its low-dose (RhA/psoriasis), B9 mightits effects. In its low-dose (RhA/psoriasis), B9 might
reduce its GI SEreduce its GI SE
• AEDs:AEDs: phenytoin, carbamazepine, valproate canphenytoin, carbamazepine, valproate can
reduce B9 level and vice versareduce B9 level and vice versa
• SulfasalazineSulfasalazine ( in( in UC) inhibits gut absorption of B9UC) inhibits gut absorption of B9

82. B12B12
• CobalaminsCobalamins (contains(contains cobaltcobalt))
• Several forms: methylcobalamin, 5-deoxy-Several forms: methylcobalamin, 5-deoxy-
adenosylcobalamin areadenosylcobalamin are active formsactive forms
• EssentialEssential forfor erythropoiesiserythropoiesis,, nerve functionnerve function,, DNADNA,,
change ofchange of homocysteinehomocysteine to methionineto methionine

83. • B12:B12: bound to protein in food, released by HCl andbound to protein in food, released by HCl and
gastric protease. But B12 in fortified foods/ supplements isgastric protease. But B12 in fortified foods/ supplements is
in free form. Free B12 joinsin free form. Free B12 joins Intrinsic FactorIntrinsic Factor (glycoprotein)(glycoprotein)
to be absorbed in distal ileumto be absorbed in distal ileum
• Only 2% oral dose is absorbed (capacity ofOnly 2% oral dose is absorbed (capacity of IFIF))
• Cyano-/ hydroxocobalamin can be given IMCyano-/ hydroxocobalamin can be given IM
• RDA:RDA: 6.0 mcg6.0 mcg

84. Maternal–Fetal B12–Bone AxisMaternal–Fetal B12–Bone Axis

86. ““Nutrients should come mainly from foodsNutrients should come mainly from foods
containing also fiber and functional substances forcontaining also fiber and functional substances for
positive health effects”positive health effects”
Sources:Sources:
• OnlyOnly inin food animal:food animal: fish, meat, poultry, eggs,fish, meat, poultry, eggs,
dairies;dairies; notnot in food plant until fortified. Some yeastin food plant until fortified. Some yeast
products contain B12products contain B12
• Strict vegans are at more risk than lacto-ovo vegansStrict vegans are at more risk than lacto-ovo vegans
• Fortified breakfast cereals can be sources for themFortified breakfast cereals can be sources for them

88. PA:PA: Autoim. atrophic gastritisAutoim. atrophic gastritis
(10–30% elderly). Destroys(10–30% elderly). Destroys
parietal cells: achlorhydria, no IF.parietal cells: achlorhydria, no IF.
1% oral B12 can still be absorbed1% oral B12 can still be absorbed

89. CF:CF:
• After age 30y (average 60y)After age 30y (average 60y)
• May beMay be asymptomaticasymptomatic or mildly ..or mildly ..
General:General: CF of anaemia;CF of anaemia; diarrhea/constipation, light-diarrhea/constipation, light-
headedness, anorexia, glossitis, sore mouth orheadedness, anorexia, glossitis, sore mouth or
bleeding gumsbleeding gums
Neurological:Neurological: PNP, ataxia, depression, confusion,PNP, ataxia, depression, confusion,
dementia.dementia. Anaemia may be absentAnaemia may be absent
PNP- peripheral neuropathyPNP- peripheral neuropathy

90. Diseases associated with PA
• Addison D
• Hypopituitarism, Chr. thyroiditis, Grave D
• Hypoparathyroidism, T1DM
• Myasthenia gr
• 2y amenorrhea, testicular dysfunction
• Vitiligo

91. Large, dense RBCs in
megaloblastic A

94. TestsTests
• B12 level (<170pg/mL)B12 level (<170pg/mL)
• CBC: macrocytes, hypersegmented neutrophils, retic.,CBC: macrocytes, hypersegmented neutrophils, retic.,
Schilling test, LDHSchilling test, LDH
• Raised methylmalonic a. (MMA) and homocysteineRaised methylmalonic a. (MMA) and homocysteine
Pernicious APernicious A maymay affect test results of:affect test results of:
• Bilirubin, cholesterol, gastrinBilirubin, cholesterol, gastrin
• Leukocyte al. phos., peripheral smear, TIBCLeukocyte al. phos., peripheral smear, TIBC
• May cause false positive Pap smear as the epithelialMay cause false positive Pap smear as the epithelial
cells look abnormalcells look abnormal

95. RxRx
• B12 IM once/mo. Severe D may need more shotsB12 IM once/mo. Severe D may need more shots
• Well-balanced diet.Well-balanced diet. PrognosisPrognosis:: uusually excellent.sually excellent.
Nerve damage can be permanent if late (6mo)Nerve damage can be permanent if late (6mo)
ComplicationsComplications
• There may be gastric polyps, more likely to have gastric CaThere may be gastric polyps, more likely to have gastric Ca
and gastric carcinoid tumorsand gastric carcinoid tumors
• Permanent neuronal damagePermanent neuronal damage
PreventionPrevention:: None for autoimmune DNone for autoimmune D
• Early Rx can reduce complicationsEarly Rx can reduce complications

96. B12 and HealthB12 and Health
Cardiovascular disease:Cardiovascular disease: raisedraised HCHC promotes clottingpromotes clotting
and atherosclerosisand atherosclerosis
• B6, B9, B12 are involved in HC metabolismB6, B9, B12 are involved in HC metabolism
DementiaDementia
• High HC might decrease NT, increase risk of Alzheimer andHigh HC might decrease NT, increase risk of Alzheimer and
dementia. Cognitive declinedementia. Cognitive decline
IInteractionsnteractions
• Chloramphenicol:Chloramphenicol: can interfere with RBC response to B12can interfere with RBC response to B12
• PPI, H2B, Metformin:PPI, H2B, Metformin: can interfere with B12 absorptioncan interfere with B12 absorption
HC: homocysteineHC: homocysteine

97. Peculiarities of B vitaminsPeculiarities of B vitamins
• All are water solubleAll are water soluble
• Poor storage except B12Poor storage except B12
• All are present in fruits, cereals and vege. except B12All are present in fruits, cereals and vege. except B12
• Mostly destroyed by cooking, sun, storageMostly destroyed by cooking, sun, storage
• All are essential for metabolismAll are essential for metabolism
• Some are essential for nerve health: B1,B3, B6, B12; CVSome are essential for nerve health: B1,B3, B6, B12; CV
function (B1, B9)function (B1, B9)

101. Scurvy took a terrible
toll in the ages of
sailing, killing more
sailors than all sea
battles combined

104. Vitamin C:Vitamin C: Ascorbic acid, ascorbateAscorbic acid, ascorbate
• ImportantImportant for con. tissue, skin, bones, immunityfor con. tissue, skin, bones, immunity
• AnAn antioxidant.antioxidant. Helps healing, Fe absorptionHelps healing, Fe absorption
• Deficiency causesDeficiency causes SCURVYSCURVY
Sources:Sources: citrus, vege., pepperscitrus, vege., peppers
Absent in grains and starchy foods; fizzy drinksAbsent in grains and starchy foods; fizzy drinks
Fortified to some BF cereals, fruit juicesFortified to some BF cereals, fruit juices
5 varied servings5 varied servings of fruits-vege./d provide enough VCof fruits-vege./d provide enough VC
DestroyedDestroyed by heat, air, light, alkali, storage, cookingby heat, air, light, alkali, storage, cooking
BF: breakfastBF: breakfast

106. Common scurvy grass

107. Extra VC need:Extra VC need: pregnancy/BF, smokers, healing, burn,pregnancy/BF, smokers, healing, burn,
urine acidification,urine acidification, F, diarrhea, IDA, coldF, diarrhea, IDA, cold
RDA:RDA: 60mg/d; pregnancy: 80 mg, l60mg/d; pregnancy: 80 mg, lactation: 100 mgactation: 100 mg
• 90% absorbed. >1 g/d: <50%; extra excreted in90% absorbed. >1 g/d: <50%; extra excreted in urineurine
• Body:Body: 2g; highest in wbc, eyes, adrenals, pituitary, brain2g; highest in wbc, eyes, adrenals, pituitary, brain
• VC is assessed by plasma levelsVC is assessed by plasma levels

108. Groups at RiskGroups at Risk
• Smokers/passive “smokers”Smokers/passive “smokers”
• Fed on evaporated/boiled milkFed on evaporated/boiled milk (cow's milk: v. little VC)(cow's milk: v. little VC)
• Limited food variety:Limited food variety: lonelone elderly; alcoholic, drug user; foodelderly; alcoholic, drug user; food
faddists; mental illness; children;faddists; mental illness; children; malabsorptionmalabsorption
• ESRD, chr. hemodialysis, some Ca might increase riskESRD, chr. hemodialysis, some Ca might increase risk

109. VitaminVitamin CC
• CCitrus fruitsitrus fruits
• CConnective tissueonnective tissue
• CCollagen fibreollagen fibre
(Proline(Proline hydroxyproline)hydroxyproline)
Functions:Functions: C C C CC C C C

110. PathologyPathology
A. Defective collagenA. Defective collagen
• Poor healing, weak capillaryPoor healing, weak capillary ⇒⇒ bleedbleed
• Weak dentinWeak dentin ⇒⇒ loose teethloose teeth
• ,, osteoid,, osteoid ⇒⇒ ⇓⇓ ossificationossification
• loose periosteumloose periosteum ⇒⇒ subperiosteal bleedsubperiosteal bleed
B.B. Defective iron absorption:Defective iron absorption: IDAIDA
C.C. Impaired B9:Impaired B9: aanemianemia

111. Anemia in ScurvyAnemia in Scurvy
• Poor Fe absorptionPoor Fe absorption
• Poor intake (severe anorexia in scurvy)Poor intake (severe anorexia in scurvy)
• Impaired B9 metabolismImpaired B9 metabolism
• HemorrhageHemorrhage
• BM depressionBM depression

112. CF:CF: fatigue/weakness,fatigue/weakness, ssevere anorexiaevere anorexia, wt loss, wt loss, gingivitis,, gingivitis,
bleed, loose teeth, LGF, depression, irritability, apathy,bleed, loose teeth, LGF, depression, irritability, apathy,
tender muscles: crying on handling,tender muscles: crying on handling, pseudoparesispseudoparesis,,
subperiosteal bleedsubperiosteal bleed
Mother may bring her baby laid on pillows!Mother may bring her baby laid on pillows!
• Severe scurvySevere scurvy ⇒⇒ degen. of sk. muscles, cardiomegaly,degen. of sk. muscles, cardiomegaly,
BM depression, adrenal atrophy:BM depression, adrenal atrophy: ultimate deathultimate death
Causes of pseudoparalysisCauses of pseudoparalysis
• Scurvy, fracture, rickets, osteochondritis, myositisScurvy, fracture, rickets, osteochondritis, myositis

113. Signs (many!)Signs (many!)
• Weak con. tissues:Weak con. tissues: miserable; purpura, bruises, joint p.,miserable; purpura, bruises, joint p.,
poor healing, corkscrew hairs, hyperkeratosis, pallor,poor healing, corkscrew hairs, hyperkeratosis, pallor,
tender all over, typical frog position,tender all over, typical frog position, pseudoparalysispseudoparalysis
• Spongy gumsSpongy gums⇒⇒ bleed (bleed (No teeth: no gum bleed!)No teeth: no gum bleed!)
• Edema:Edema: capillary leakage and hge.capillary leakage and hge.
• Jerks are normalJerks are normal
• Scorbutic rosaryScorbutic rosary:: tendertender beads,beads, sharp angulationsharp angulation

114. Rickets
Scurvy

117. Cork screw hairCork screw hair
Purpura

118. Vitamin C and HealthVitamin C and Health
Cancer preventionCancer prevention
plenty of fruits, vege. lower risk of most Ca. VC can limitplenty of fruits, vege. lower risk of most Ca. VC can limit
carcinogens like nitrosamines, modulate immunity;carcinogens like nitrosamines, modulate immunity;
attenuate oxidative damageattenuate oxidative damage
Cancer RxCancer Rx
Very highVery high VC (plasma concn. 26,000 micromol/L) isVC (plasma concn. 26,000 micromol/L) is
cytotoxic to tumor cellscytotoxic to tumor cells
Cardiovascular d.Cardiovascular d.
• Plenty of fruits and vege. can reduce CVDPlenty of fruits and vege. can reduce CVD
• Antioxidants attenuate oxidative damage and lower LDLAntioxidants attenuate oxidative damage and lower LDL
• VC can prevent atherosclerosisVC can prevent atherosclerosis

119. AMD and cataractsAMD and cataracts
are leading c/of blindness in elderly. Oxidative stress mightare leading c/of blindness in elderly. Oxidative stress might
be a cause; VC might slow AMD progression and lower riskbe a cause; VC might slow AMD progression and lower risk
of cataract (70–75%)of cataract (70–75%)
Common coldCommon cold
• VC 250mg-1g/d reduced cold incidence by 50%; by anti-VC 250mg-1g/d reduced cold incidence by 50%; by anti-
histamine effect of high-dose VChistamine effect of high-dose VC
• VC after onset of cold is not beneficialVC after onset of cold is not beneficial
UTI:UTI: VC can acidify urine and can clear UTIVC can acidify urine and can clear UTI

120. DxDx
• Typical CF andTypical CF and dietary historydietary history
• X-ray findings are diagnosticX-ray findings are diagnostic
• Leukocyte conc. of VC confirmsLeukocyte conc. of VC confirms
• Oral VC is very effective. Dramatic response
• Excellent prognosis
RxRx

121. X-ray (knee)X-ray (knee)
• Ground glass opacityGround glass opacity
• ‘‘Pencil point’ thin cortexPencil point’ thin cortex
• ‘‘Ringing’ of epiphysisRinging’ of epiphysis
• Frankel’s ‘white line’Frankel’s ‘white line’
(well calcified)(well calcified)
• Raised periosteumRaised periosteum
• Zone of rarefaction (aZone of rarefaction (a
linear break) proximal andlinear break) proximal and
parallel to the white lineparallel to the white line

122. Excessive VCExcessive VC
• Low toxicity; no serious SE. Common: D, nausea, APLow toxicity; no serious SE. Common: D, nausea, AP
• Increases urinary oxalate and uric a.:Increases urinary oxalate and uric a.: renal stonesrenal stones
• In hemochromatosis it can exacerbate FeIn hemochromatosis it can exacerbate Fe overloadoverload
InteractionsInteractions
• Chemotherapy and radiation:Chemotherapy and radiation: antioxidants might protectantioxidants might protect
tumor from radio-therapy or chemotherapytumor from radio-therapy or chemotherapy
• Statins:Statins: may attenuate the increase in HDL effectmay attenuate the increase in HDL effect

123. MCQMCQ
ScurvyScurvy
• is caused by deficiency of ascorbic acidis caused by deficiency of ascorbic acid
• can killcan kill
• can cause hemorrhagecan cause hemorrhage
• can cause bone swellingcan cause bone swelling
• causes gum bleeding in neonatescauses gum bleeding in neonates
• can cause pseudoparalysiscan cause pseudoparalysis

124. • VC can ward off cold
• HD of VC can cause renal stone
• B6 is potentially neurotoxic
• B9 prevents birth defects
• B12 is available from plant sources
MCQMCQ

134. Vitamin AVitamin A
Retinoids: retinol, retinal, retinoic acid, retinylRetinoids: retinol, retinal, retinoic acid, retinyl
Active forms:Active forms: retinal and retinoic a.retinal and retinoic a.
PProvitamin forms are carotenoidsrovitamin forms are carotenoids
RetinolRetinol is found in food animal.is found in food animal. ββ-carotene-carotene changes to retinolchanges to retinol
RDA:RDA: 400-1300mcg/d.400-1300mcg/d. Plasma retinal is measuredPlasma retinal is measured
Sources:Sources: colorful fruits and vege., fish, liver, milk; fortifiedcolorful fruits and vege., fish, liver, milk; fortified
cereals. 90% is stored in liver (several months)cereals. 90% is stored in liver (several months)

135. Its liver is the highest source of VA. 1 oz can killIts liver is the highest source of VA. 1 oz can kill

136. FunctionsFunctions
• Essential part of rhodopsinEssential part of rhodopsin
• Integrity of conjunctiva + corneaIntegrity of conjunctiva + cornea
• AntioxidantAntioxidant
• Epithelial integrity, immunityEpithelial integrity, immunity
• Reproduction, fertility, embryogenesisReproduction, fertility, embryogenesis
• Cell growth and communicationCell growth and communication
• Skeletal growthSkeletal growth

137. VA DeficiencyVA Deficiency
V. common in L&MICsV. common in L&MICs (expensive food animal and poor(expensive food animal and poor ββ--
carotene intake). Bangladesh: 28% population affectedcarotene intake). Bangladesh: 28% population affected
CausesCauses
a. poor intakea. poor intake
b. more loss (chr. D, RRTI, measles, malabsorption)b. more loss (chr. D, RRTI, measles, malabsorption)
cc.. ⇑⇑ demand:demand: vegans, children, alcoholics; liver D,vegans, children, alcoholics; liver D, Crohn, CF,Crohn, CF,
pregnancy, lactationpregnancy, lactation

138. VADX: WHO: 190 million U-5; 9.1 million pregnant women
• 250,000-500,000 VAD children become blind every year.
Half of them die within 12mo of blindness
• >1 million U-5MR is associated with VAD
Why children are vulnerable?
• Diarrhea, RRTI, poor vegetable intake
• Bottle feeding, faulty feeding
• Increasing growth

139. Impact of VADImpact of VAD
– blindnessblindness
– more child mortalitymore child mortality
– more infx.: D and ARImore infx.: D and ARI
XerophthalmiaXerophthalmia:: ocular features of VADocular features of VAD
NyctalopiaNyctalopia:: poor dim light visionpoor dim light vision
KeratomalaciaKeratomalacia:: corneal softening and meltingcorneal softening and melting

140. XerophthalmiaXerophthalmia
• body VA is nil!body VA is nil!
• Night blindness, conjunctival xerosis, Bitot spots, cornealNight blindness, conjunctival xerosis, Bitot spots, corneal
xerosis and keratomalacia, photophobia, fundal xerosisxerosis and keratomalacia, photophobia, fundal xerosis
Extra-ocular featuresExtra-ocular features
• Dry scaly skin, follicular keratosisDry scaly skin, follicular keratosis
• More RTI, GITI. Death is more in VADMore RTI, GITI. Death is more in VAD
Dx
• Ocular features are diagnosticOcular features are diagnostic
• Conjunctival cytology suggestiveConjunctival cytology suggestive
• Serum retinol level confirmatorySerum retinol level confirmatory

141. Classification of XerophthalmiaClassification of Xerophthalmia
• XN : Night blindness
X1 : Conjunc. xerosis. XIB : Bitot's spots
X2 : Corneal xerosis
X3A : Corneal ulceration/KM <1/3 cornea
X3B : ‘do’ >1/3 cornea
XS : Corneal scar. XF : fundal xerosis

143. Bitot: from heaping up of desquamated,
keratinized epithelial cells; foamy, may
be solid and cheesy

146. PreventionPrevention
Short term strategyShort term strategy
• HPVAC (200,000 iu retinol, 40 iu of VE) to U-6 childrenHPVAC (200,000 iu retinol, 40 iu of VE) to U-6 children
• VA rich foods (leafy veg., yellow fruits)VA rich foods (leafy veg., yellow fruits)
• HPVAC to mother after delivery (within 14d). EBFHPVAC to mother after delivery (within 14d). EBF
Long term strategyLong term strategy
• Immunization, Health educationImmunization, Health education
• Female literacy, Family planningFemale literacy, Family planning
• Production of vegetables and fruitsProduction of vegetables and fruits
• Commercial fortification of foodsCommercial fortification of foods

147. VA and Health
Cancer: high intakes of carotenoids have lower risk of
lung Ca in smokers
AMD: not conclusive
Measles: VAD is a great risk for severe measles. VA
supplement reduces MM and blindness

148. Hypervitaminosis AHypervitaminosis A
AcuteAcute ((>400,000i.u. stat)>400,000i.u. stat)
• ANV, HA,ANV, HA, AP, blurred vision, myalgia-weakness, fit, dryingdrying
and cracking of skin, painful swelling of long bones (~Cafeyand cracking of skin, painful swelling of long bones (~Cafey
disease), bone fragility, HSM, idisease), bone fragility, HSM, irritability, drowsiness
• Pseudotumor cerebriPseudotumor cerebri
• RetinoidsRetinoids:: used for psoriasis, skin effects of T-cellused for psoriasis, skin effects of T-cell
lymphoma. They can raise the risk if taken with VAlymphoma. They can raise the risk if taken with VA
Large amounts of carotenoids have no major SELarge amounts of carotenoids have no major SE

149. Chr. Hypervitaminosis AChr. Hypervitaminosis A (>20,000 iu/d over several w)
• ANV, irritability, wt. loss/FTT, itch, alopecia, apathy, HSM,
dizziness, HA, pseudotumor C, coma, even death, dry
mucosae/fissured lips, F, insomnia, fatigue,
hyperlipidemia, hypercalcemia, anemia, D, menstrual
abnormalities, epistaxis
• Bone and joint pains, increased fracture
• Liver damage. Desquamation in palms, soles, hyperostosis
on XR of several long bones

150. DxDx
• H/of, SS, XR findings and serum retinol levelH/of, SS, XR findings and serum retinol level
RxRx
Stop intakeStop intake
Message!Message!
• HDVA, topical retinoids are teratogenicHDVA, topical retinoids are teratogenic
• Malformations of eye, skull, lungs, heartMalformations of eye, skull, lungs, heart
• For adequate VA in BM give VA within 2w of birthFor adequate VA in BM give VA within 2w of birth

151. Pseudotumor cerebriPseudotumor cerebri
• Mimics IC tumor but is not; often reversibleMimics IC tumor but is not; often reversible
CausesCauses
• Women more, especially obese women near menopause.Women more, especially obese women near menopause.
Can occur in children. Cause is unknown.Can occur in children. Cause is unknown. Drugs:Drugs:
– VA,VA, OCP, cyclosporine, isotretinoin, minocycline,OCP, cyclosporine, isotretinoin, minocycline,
– nalidixic A,nalidixic A, nitrofurantoin, phenytoin, sulfasnitrofurantoin, phenytoin, sulfas
– SteroidsSteroids
– Tamoxifen, tetracyclineTamoxifen, tetracycline

152. Other factors related to PC:Other factors related to PC:
• Addison's disease, CKD, CushingAddison's disease, CKD, Cushing
• Hypoparathyroidism, IDA, obesityHypoparathyroidism, IDA, obesity
• Menarche, pregnancyMenarche, pregnancy
CF:CF: Blurred vision, tinnitus, dizziness, diplopia, nauseaBlurred vision, tinnitus, dizziness, diplopia, nausea
• May get worse in physical activityMay get worse in physical activity
alertalert, bulged fontanelle,, bulged fontanelle, ⇑⇑ OFC, papilledemaOFC, papilledema

153. DxDx
• Dx by exclusion (hydrocephalus, tumor venous sinusDx by exclusion (hydrocephalus, tumor venous sinus
thrombosis)thrombosis)
• CT, MRI with MR venographyCT, MRI with MR venography
• Eye exam, CSFEye exam, CSF
RxRx
• Aim: what is the cause. CSF to relieve pressure, fluid saltAim: what is the cause. CSF to relieve pressure, fluid salt
restriction, steroids, acetazolamide, furosemiderestriction, steroids, acetazolamide, furosemide
• Shunt, surgery to relieve pressure on optic nerve, weightShunt, surgery to relieve pressure on optic nerve, weight
loss, vision closely monitoredloss, vision closely monitored

154. MCQMCQ
Vitamin AVitamin A
• is essential for bright light visionis essential for bright light vision
• is found in active form in plenty in vege. and fruitsis found in active form in plenty in vege. and fruits
• is potentially teratogenicis potentially teratogenic
• can cause hyperostosis in toxic dosagecan cause hyperostosis in toxic dosage
• deficiency is more in under-5 childrendeficiency is more in under-5 children
• is the greatest c/of nutritional blindnessis the greatest c/of nutritional blindness

158. saber

161. Vitamin DVitamin D
• Group of sterols. Deficiency:Group of sterols. Deficiency: RICKETSRICKETS
• 2 forms:2 forms: VD-2VD-2 (ergocalciferol: main dietary, therapeutic(ergocalciferol: main dietary, therapeutic
source ): made from UV irradiation ofsource ): made from UV irradiation of ergosterolergosterol in yeastin yeast..
VD-3VD-3 (cholecalciferol): in skin from(cholecalciferol): in skin from 7-dehydrocholesterol7-dehydrocholesterol
• Stable to heat, acid, alkali, oxidationStable to heat, acid, alkali, oxidation

162. AActivationctivation
• VD is inert and must have 2 OH: first inVD is inert and must have 2 OH: first in liverliver (25-OH-D or(25-OH-D or
calcidiol); 2calcidiol); 2ndnd
inin kidneykidney (active 1,25(OH)(active 1,25(OH)22D, or calcitriol)D, or calcitriol)
Functions:Functions: at 3 sitesat 3 sites
• GITGIT (helps absorb Ca, P),(helps absorb Ca, P), KidneysKidneys (prevents Ca, P loss),(prevents Ca, P loss),
BoneBones (bones grow and remodel)s (bones grow and remodel)
Intestine is a locked door to Ca; VD is the key to open itIntestine is a locked door to Ca; VD is the key to open it
Absorption increased by 80%Absorption increased by 80%
Other rolesOther roles
• cell growth, neuromuscular and immune function,cell growth, neuromuscular and immune function,
reduction of inflam., apoptosisreduction of inflam., apoptosis

164. SSources:ources: skin, food, supplementsskin, food, supplements
– V. few foodsV. few foods in nature contain VD. VD rich foods: eggin nature contain VD. VD rich foods: egg
yolks, sea fish, liver. Milk and cereals, are often fortifiedyolks, sea fish, liver. Milk and cereals, are often fortified
(greatest source in the West)(greatest source in the West)
Too much sun exposure can cause skin aging and skin Ca.Too much sun exposure can cause skin aging and skin Ca.
So many people try to get VD from other sourcesSo many people try to get VD from other sources
DeficiencyDeficiency:: rickets, -malacia, osteoporosis, tetanyrickets, -malacia, osteoporosis, tetany
Causes:Causes:
– No sun exposure, malabsorption
– Abnormal metabolism of VD, genetic factors
– Abnormal metabolism of inorganic phosphate
– Prolonged EBF may cause, in dark-skinned infants

166. Sun exposureSun exposure
• UV B converts 7-dehydrocholesterol in skin to VDUV B converts 7-dehydrocholesterol in skin to VD33
• 5–30min exposure, 2/w to face, arms, legs, or back5–30min exposure, 2/w to face, arms, legs, or back
• Season, time, length, cloud, smog, skin melanin, sunscreenSeason, time, length, cloud, smog, skin melanin, sunscreen
can affect UVR. Cloud reduces UV 50%; pollution 60%. UVBcan affect UVR. Cloud reduces UV 50%; pollution 60%. UVB
does not penetrate glassdoes not penetrate glass
UVR is carcinogenUVR is carcinogen
• RDA: 0-50 y: 5 µg (200 IU)
51-70 y: 10 µg (400 IU)
71+ y: 15 µg (600 IU)
Extra VD: seniors, EBF, dark skin, liver and CKD,
malabsorption, obesity, gastric bypass

168. • RicketsRickets is failure to mineralizeis failure to mineralize growing bonegrowing bone or osteoidor osteoid
tissuetissue
• Similar failure inSimilar failure in mature bone:mature bone: osteomalaciaosteomalacia
C/by lack of VD; but disruptions in Ca and P homeostasis mayC/by lack of VD; but disruptions in Ca and P homeostasis may
also be responsiblealso be responsible
DefinitionDefinition

169. Groups at RiskGroups at Risk
• EBF:EBF: VD is insufficient in BM (78 IU/L)VD is insufficient in BM (78 IU/L)
• Elderly:Elderly: less efficient skinless efficient skin, more indoors, less intake, more indoors, less intake
• Poor sun exposure, people with dark skinPoor sun exposure, people with dark skin
• Fat malabsorption:Fat malabsorption: liver and pancreatic D, Crohn,liver and pancreatic D, Crohn,
CF, UCCF, UC
• Obese:Obese: Fat steals VD and resists releaseFat steals VD and resists release
• Gastric bypass:Gastric bypass: VDD over time if insufficient intakeVDD over time if insufficient intake

170. PathologyPathology
• EpiphysisEpiphysis stops growing, becomes frayedstops growing, becomes frayed
• MetaphysisMetaphysis widens and bulgeswidens and bulges
• DiaphysisDiaphysis rarifies; softens; deforms or breakrarifies; softens; deforms or break

172. Clinical FeaturesClinical Features
• Age:Age: usually <2yusually <2y
• Nonspecific:Nonspecific: pallor, excess sweats, poor feeding,pallor, excess sweats, poor feeding,
irritability, pot belly, RRTI, etc.irritability, pot belly, RRTI, etc.
• Early signsEarly signs:: thickened wrist-ankle, craniotabesthickened wrist-ankle, craniotabes
• DelayedDelayed (a few months): bowing of legs, rickety rosary,(a few months): bowing of legs, rickety rosary,
pigeon chest, head deformitiespigeon chest, head deformities

174. Head:Head: craniotabes in infants, asymmetry, large and latelycraniotabes in infants, asymmetry, large and lately
closing fontanel, frontal bossing, large headclosing fontanel, frontal bossing, large head
Teeth:Teeth: delayed eruption, enamel defect (extensive caries,delayed eruption, enamel defect (extensive caries,
defective permanent teeth)defective permanent teeth)
Region Based SignsRegion Based Signs

176. ThoraxThorax
– Rachitic rosaryRachitic rosary
– Pigeon chestPigeon chest
– Harrison grooveHarrison groove
Rickets
Scurvy

177. SpineSpine
– KyphosisKyphosis
– ScoliosisScoliosis
– LordosisLordosis
(may occur in combination)(may occur in combination)

178. Pelvis
• Narrow entrance (forwarding of sacral
promontory)
• Narrow outlet (forward displacement of the
sacrococcyx)
These cause obstructed labor
Rickets is very dangerous for females

179. ExtremitiesExtremities
– Broadening of wrists and ankles
– Bowlegs and knock-knees
– Saber tibia
All bone deformities produce rachitic dwarfism

183. LigamentsLigaments
– Relaxation cause
overextension
MusclesMuscles
– Hypotonia and poor
development (late in
standing and walking)
– Pot belly (hypotonic weak
abdo. wall)

184. DxDx
• Dietary history, sun exposureDietary history, sun exposure
• Living conditionLiving condition
• Clinical findingsClinical findings
• Lab:Lab: serum 25(OH)D is the best indicator of VD status.serum 25(OH)D is the best indicator of VD status.
Normal or low calcium, low PO4 (<4mg/dl), raised al. phos.Normal or low calcium, low PO4 (<4mg/dl), raised al. phos.

185. Wrist is the best
Broadening, cupping, fraying
Distance between radius-ulna and
metacarpals is increased
Osteopenia
Initial healing is shown by appearance
of the line of preparatory calcification

187. DDDD
• Familial bow legsFamilial bow legs
• Osteogenesis imperfectaOsteogenesis imperfecta
• Non-rachitic craniotabesNon-rachitic craniotabes
ComplicationsComplications
• Permanent deformities, dwarfism, respiratory infx.,Permanent deformities, dwarfism, respiratory infx.,
obstructed laborobstructed labor

188. RxRx
• Oral VD3: 50-150mcg/d or DHCC 0.5-2mcg/d orOral VD3: 50-150mcg/d or DHCC 0.5-2mcg/d or
• single dose of 200,000 i.u. VD3 (easy; rapid healing)single dose of 200,000 i.u. VD3 (easy; rapid healing)
• Sun exposure, intake of CaSun exposure, intake of Ca
Prognosis:Prognosis: Good.Good. Healing over 2-4w. RHealing over 2-4w. Remodeling (severalemodeling (several
months)months)
Prophylaxis
• Exposure to sun (15 min/d; 10% body surface)Exposure to sun (15 min/d; 10% body surface)
• Fortification of foodsFortification of foods
• Prophylaxis for preterm, EBF, malnourishedProphylaxis for preterm, EBF, malnourished
• Supplement pregnancy and lactationSupplement pregnancy and lactation

189. Non-Vit D Deficiency Rickets
• VD dependent R (lack of 1 alpha hydroxylase or end organVD dependent R (lack of 1 alpha hydroxylase or end organ
response failure)response failure)
• HypophosphatasiaHypophosphatasia
• Familial hypophosphatemic RFamilial hypophosphatemic R
• Renal tubular defect, CRFRenal tubular defect, CRF
• AED: phenytoin, phenobarbitone, primidone x2-3yAED: phenytoin, phenobarbitone, primidone x2-3y

190. Hypophosphatasia

191. Vitamin D and HealthVitamin D and Health
• Osteoporosis isOsteoporosis is low BMD with fragility. It is mostlylow BMD with fragility. It is mostly
associated with low Ca intakes. Adequate VD and Ca mightassociated with low Ca intakes. Adequate VD and Ca might
prevent it in older adults, sedentary people, menopausalprevent it in older adults, sedentary people, menopausal
women, chr. steroid therapywomen, chr. steroid therapy
InteractionInteraction
• Prolonged steroidsProlonged steroids can reduce Ca and impair VD meta.can reduce Ca and impair VD meta.
• Orlistat, cholestyramine reduce absorption of FSVOrlistat, cholestyramine reduce absorption of FSV
• AED increase hepatic metabolism of DAED increase hepatic metabolism of D

193. VITAMINVITAMIN EE
"anti-sterility factor”, tocopherol (8 forms)"anti-sterility factor”, tocopherol (8 forms)
• An antioxidant; role in immunity, metabolismAn antioxidant; role in immunity, metabolism
• Food is abundant in VE: vege. oils, margarine, nuts, seeds.Food is abundant in VE: vege. oils, margarine, nuts, seeds.
It is also added to cerealsIt is also added to cereals
• RDA: 10mg/dRDA: 10mg/d
• Deficiency:Deficiency: uncommon. Raises LDL: atherogenesis. Mayuncommon. Raises LDL: atherogenesis. May
be subclinical, or cause subtle neurologic SSbe subclinical, or cause subtle neurologic SS
Liver diseases, CF, Crohn need extra VELiver diseases, CF, Crohn need extra VE

195. At risk:At risk: malabsorption, CLD, CF, blind loop (bacterialmalabsorption, CLD, CF, blind loop (bacterial
overgrowth), celiac, pancreatic D, IBDovergrowth), celiac, pancreatic D, IBD
• VE deficiency can cause neuromuscular disordersVE deficiency can cause neuromuscular disorders
(spinocerebellar ataxia), hemolysis (common in(spinocerebellar ataxia), hemolysis (common in
premterms), myopathy, pigmented retinopathypremterms), myopathy, pigmented retinopathy
• Thalassemia, SCD, G-6-PD, spherocytosis may have low VEThalassemia, SCD, G-6-PD, spherocytosis may have low VE

196. Vitamin KVitamin K
"antihemorhagic factor”, phyloquinones (K1)"antihemorhagic factor”, phyloquinones (K1)
menaquinone (K2)menaquinone (K2)
• Makes: osteocalcin and tissuesMakes: osteocalcin and tissues, F.: II, VII, IX, X,, F.: II, VII, IX, X, andand
anticoagulant C, Santicoagulant C, S
• User of blood thinners should be careful about how muchUser of blood thinners should be careful about how much
VK s/he gets. VE can interfere with VKVK s/he gets. VE can interfere with VK
• Natural anticoagulant proteins S and C require VK for their
activity. S is a cofactor for C which inhibits thrombin

198. Sources: green vege., dark berries. Gut flora make K2:
AB kill them
RDA: 80 mcg/d
• Extremely HD of VE and A antagonize VK
Deficiency: easy bruising, mucosal bleeding, splinter hge,
melena, hematuria, etc. TPN and long-term ABT can cause
VK deficiency Prolonged fasting decreases its levels

200. Hemorrhagic D of the NewbornHemorrhagic D of the Newborn
• VK deficiency is common in NB (VK clotting factors are 20%VK deficiency is common in NB (VK clotting factors are 20%
of adults; are normalized in a month)of adults; are normalized in a month)
– immature liver, low VK in BM, sterile gutimmature liver, low VK in BM, sterile gut
– poor placental transfer of VKpoor placental transfer of VK
• HDN causes skin, GI, IC hge; typically occurs within 7d of lifeHDN causes skin, GI, IC hge; typically occurs within 7d of life
• Give VK at birth, on 4Give VK at birth, on 4thth
and 28and 28thth
day (4h4d4w)day (4h4d4w)
• Dose:Dose: 1-25mg oral/IM/SC/IV1-25mg oral/IM/SC/IV
• In blood thinning, doses of K should be minimizedIn blood thinning, doses of K should be minimized

201. Vitamin toxicityVitamin toxicity
VA:VA: ac. toxicity can cause NV, HA, bone pain, ICac. toxicity can cause NV, HA, bone pain, IC
hypertension, alopeciahypertension, alopecia
• Highly teratogenic: >10,000 IU/d (first 8w preg.)Highly teratogenic: >10,000 IU/d (first 8w preg.)
Give VA to mother within 2w post-partumGive VA to mother within 2w post-partum
• Isotretinoin:Isotretinoin: (acne); related to VA (teratogenic, IC(acne); related to VA (teratogenic, IC
hypertension, depression, suicide)hypertension, depression, suicide)
• Carotenemia:Carotenemia: only cosmetic effectonly cosmetic effect

202. B-1, B-2, B-12:B-1, B-2, B-12: non-toxicnon-toxic
B-3:B-3: flushing with 50mg/dflushing with 50mg/d
• 1.5-6g/d can cause liver toxicity, more in preexisting LD1.5-6g/d can cause liver toxicity, more in preexisting LD
B-6B-6
• 300mg/d may be neurotoxic; more in renal damage300mg/d may be neurotoxic; more in renal damage

203. Vitamin C Toxicity
• Upper limit is 2g
• Ac. toxic dose is not estd. Chr. TD: >2g/d
– NVD, AP, HA, Heartburn, Insomnia
– bloating, Kidney stones
Vitamin D Toxicity: Excessive sun exposure: noExcessive sun exposure: no
toxicity.toxicity. Ac. toxic dose not estd.
• Chr. TD: >50,000 IU/d. In <6mo age: 1,000 IU/d is unsafe
• Anorexia, wt. loss, arrhythmias, polyuria. HyperCa causesAnorexia, wt. loss, arrhythmias, polyuria. HyperCa causes
vascular and tissue calcification, damage to heart, BV,vascular and tissue calcification, damage to heart, BV,
kidneys (stone)kidneys (stone)

204. Vitamin E Toxicity
• HD (>1600 IU/d) can prolong prothrombin time; reduces
platelet thromboxane
– with anticoagulants can raise risk of bleed
– may impair hematologic response to iron
– can depress WBC bactericidal activity and lymphocyte
transformation
– increases risk of sepsis and NEC in preemies LBW

205. Vitamin K toxicity
• V. rare; toxic dose not established. VK-3 (menadione) HD
supplements are banned
• Hemolytic a., jaundice, kernicterus in neonates in HD
Folic a. toxicity
• Toxic dose not established, generally nontoxic
• >5000 mcg/d mask pernicious anemia

206. Points to PonderPoints to Ponder
• Sea food once/mo prevents B12 deficiencySea food once/mo prevents B12 deficiency
• Prolonged ABT causes VK deficiencyProlonged ABT causes VK deficiency
• VKD is more common in EBBVKD is more common in EBB
• Vegetarians are prone to B12DVegetarians are prone to B12D
• VC is lost on exposure to air and sunVC is lost on exposure to air and sun
• VC requires daily intakeVC requires daily intake

207. • Measles can totally deplete VA statusMeasles can totally deplete VA status
• Most VD is formed from sun exposureMost VD is formed from sun exposure
• Rickets, scurvy, beriberi, pellagra: eliminated in the WestRickets, scurvy, beriberi, pellagra: eliminated in the West
• Highest body storage of vitamin is that of B12Highest body storage of vitamin is that of B12
• Toxic vitamins: B3, B6, A, DToxic vitamins: B3, B6, A, D
Points to Ponder …Points to Ponder …

208. Free RadicalsFree Radicals
• ““Free"Free" as they float to bind, andas they float to bind, and "radical""radical" as they take anas they take an
electron from many molecules making that moleculeelectron from many molecules making that molecule
another FRanother FR
• Created by pollution, cigarette, radiation, cleanersCreated by pollution, cigarette, radiation, cleaners
herbicidesherbicides
• Responsible for aging, tissue damage, Ca, stroke, CVDResponsible for aging, tissue damage, Ca, stroke, CVD
• FR have key role inFR have key role in phagocytosis; redoxphagocytosis; redox

210. Fly Geyser
Nevada
USA

211. Sunrise @ Nilachol, Bandorban, Bd

218. • Sources of Vitamin B6Sources of Vitamin B6
• FoodFood
Vitamin B6 is found in a wide variety of foods [Vitamin B6 is found in a wide variety of foods [11,,33,,44
]. The richest sources of vitamin B6 include fish, beef]. The richest sources of vitamin B6 include fish, beef
liver and other organ meats, potatoes and otherliver and other organ meats, potatoes and other
starchy vegetables, and fruit (other than citrus). Instarchy vegetables, and fruit (other than citrus). In
the United States, adults obtain most of their dietarythe United States, adults obtain most of their dietary
vitamin B6 from fortified cereals, beef, poultry,vitamin B6 from fortified cereals, beef, poultry,
starchy vegetables, and some non-citrus fruits [starchy vegetables, and some non-citrus fruits [11,,33,,55
]. About 75% of vitamin B6 from a mixed diet is]. About 75% of vitamin B6 from a mixed diet is
bioavailable [bioavailable [11].].
• The table of selected food sources of vitamin B6The table of selected food sources of vitamin B6
suggests many dietary sources of vitamin B6.suggests many dietary sources of vitamin B6.

219. • IntroductionIntroduction
• B6 is water-soluble naturally present in many foods, added to others, or as dietary supplement. It is the generic name for 6 compounds: pyridoxine, an alcohol;B6 is water-soluble naturally present in many foods, added to others, or as dietary supplement. It is the generic name for 6 compounds: pyridoxine, an alcohol;
pyridoxal, an aldehyde; and pyridoxamine, which contains an amino group; and their respective 5'-phosphate esterspyridoxal, an aldehyde; and pyridoxamine, which contains an amino group; and their respective 5'-phosphate esters
• B6 as coenzyme performs a wide variety of functions, in >100 enzyme reactions, mostly protein metabolismB6 as coenzyme performs a wide variety of functions, in >100 enzyme reactions, mostly protein metabolism
• B6 also plays a role in biosynthesis of NT and in maintaining normal homocysteineB6 also plays a role in biosynthesis of NT and in maintaining normal homocysteine
• B6 is involved in gluconeogenesis and glycogenolysis, immune function and Hb formationB6 is involved in gluconeogenesis and glycogenolysis, immune function and Hb formation
• Absorbed in the jejunum. Phosphorylated forms of the vitamin are dephosphorylated, and the pool of free vitamin B6 is absorbed by passive diffusion [Absorbed in the jejunum. Phosphorylated forms of the vitamin are dephosphorylated, and the pool of free vitamin B6 is absorbed by passive diffusion [22].].
• Vitamin B6 concentrations can be measured directly by assessing concentrations of PLP; other vitamers; or total vitamin B6 in plasma, erythrocytes, or urine [Vitamin B6 concentrations can be measured directly by assessing concentrations of PLP; other vitamers; or total vitamin B6 in plasma, erythrocytes, or urine [11].].
Vitamin B6 concentrations can also be measured indirectly by assessing either erythrocyte aminotransferase saturation by PLP or tryptophan metabolites. PlasmaVitamin B6 concentrations can also be measured indirectly by assessing either erythrocyte aminotransferase saturation by PLP or tryptophan metabolites. Plasma
PLP is the most common measure of vitamin B6 status.PLP is the most common measure of vitamin B6 status.
• PLP concentrations of more than 30 nmol/L have been traditional indicators of adequate vitamin B6 status in adults [PLP concentrations of more than 30 nmol/L have been traditional indicators of adequate vitamin B6 status in adults [33]. However, the Food and Nutrition Board]. However, the Food and Nutrition Board
(FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) used a plasma PLP level of 20 nmol/L as the major indicator of(FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) used a plasma PLP level of 20 nmol/L as the major indicator of
adequacy to calculate the Recommended Dietary Allowances (RDAs) for adults [adequacy to calculate the Recommended Dietary Allowances (RDAs) for adults [11,,33].].
• Recommended IntakesRecommended Intakes
• Intake recommendations for vitamin B6 and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the FNB [Intake recommendations for vitamin B6 and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the FNB [11]. DRI is the general term]. DRI is the general term
for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender, include:for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender, include:
• Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals.Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals.
• Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
• Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.
• Table 1 lists the current RDAs for vitamin B6 [Table 1 lists the current RDAs for vitamin B6 [11]. For infants from birth to 12 months, the FNB established an AI for vitamin B6 that is equivalent to the mean intake]. For infants from birth to 12 months, the FNB established an AI for vitamin B6 that is equivalent to the mean intake
of vitamin B6 in healthy, breastfed infants.of vitamin B6 in healthy, breastfed infants.
• Table 1: Recommended Dietary Allowances (RDAs) for Vitamin B6 [Table 1: Recommended Dietary Allowances (RDAs) for Vitamin B6 [11] Age Male Female Pregnancy Lactation Birth to 6 months0.1 mg*0.1 mg* 7–12 months0.3] Age Male Female Pregnancy Lactation Birth to 6 months0.1 mg*0.1 mg* 7–12 months0.3
mg*0.3 mg* 1–3 years0.5 mg0.5 mg 4–8 years0.6 mg0.6 mg 9–13 years1.0 mg1.0 mg 14–18 years1.3 mg1.2 mg1.9 mg2.0 mg 19–50 years1.3 mg1.3 mg1.9mg*0.3 mg* 1–3 years0.5 mg0.5 mg 4–8 years0.6 mg0.6 mg 9–13 years1.0 mg1.0 mg 14–18 years1.3 mg1.2 mg1.9 mg2.0 mg 19–50 years1.3 mg1.3 mg1.9
mg2.0 mg 51+ years1.7 mg1.5 mg * Adequate Intake (AI)mg2.0 mg 51+ years1.7 mg1.5 mg * Adequate Intake (AI)
• Dietary supplementsDietary supplements
Vitamin B6 is available in multivitamins, in supplements containing other B complex vitamins, and as a stand-alone supplement [Vitamin B6 is available in multivitamins, in supplements containing other B complex vitamins, and as a stand-alone supplement [66]. The most common vitamin B6]. The most common vitamin B6
vitamer in supplements is pyridoxine (in the form of pyridoxine hydrochloride [HCl]), although some supplements contain PLP. Vitamin B6 supplements are availablevitamer in supplements is pyridoxine (in the form of pyridoxine hydrochloride [HCl]), although some supplements contain PLP. Vitamin B6 supplements are available
in oral capsules or tablets (including sublingual and chewable tablets) and liquids. Absorption of vitamin B6 from supplements is similar to that from food sourcesin oral capsules or tablets (including sublingual and chewable tablets) and liquids. Absorption of vitamin B6 from supplements is similar to that from food sources
and does not differ substantially among the various forms of supplements [and does not differ substantially among the various forms of supplements [11]. Although the body absorbs large pharmacological doses of vitamin B6 well, it quickly]. Although the body absorbs large pharmacological doses of vitamin B6 well, it quickly
eliminates most of the vitamin in the urine [eliminates most of the vitamin in the urine [77].].
• About 28%–36% of the general population uses supplements containing vitamin B6 [About 28%–36% of the general population uses supplements containing vitamin B6 [88,,99]. Adults aged 51 years or older and children younger than 9 are more likely]. Adults aged 51 years or older and children younger than 9 are more likely
than members of other age groups to take supplements containing vitamin B6.than members of other age groups to take supplements containing vitamin B6.
• Vitamin B6 Intakes and StatusVitamin B6 Intakes and Status
• Most children, adolescents, and adults in the United States consume the recommended amounts of vitamin B6, according to an analysis of data from the 2003–2004Most children, adolescents, and adults in the United States consume the recommended amounts of vitamin B6, according to an analysis of data from the 2003–2004
National Health and Nutrition Examination Survey (NHANES) [National Health and Nutrition Examination Survey (NHANES) [99]. The average vitamin B6 intake is about 1.5 mg/day in women and 2 mg/day in men []. The average vitamin B6 intake is about 1.5 mg/day in women and 2 mg/day in men [11].].
• However, 11% of vitamin B6 supplement users and 24% of people in the United States who do not take supplements containing vitamin B6 have low plasma PLPHowever, 11% of vitamin B6 supplement users and 24% of people in the United States who do not take supplements containing vitamin B6 have low plasma PLP
concentrations (less than 20 nmol/L) [concentrations (less than 20 nmol/L) [99]. In the 2003–2004 NHANES analysis, plasma PLP concentrations were low even in some groups that took 2.0–2.9 mg/day,]. In the 2003–2004 NHANES analysis, plasma PLP concentrations were low even in some groups that took 2.0–2.9 mg/day,
which is higher than the current RDA. Among supplement users and nonusers, plasma PLP levels were much lower in women than men, non-Hispanic blacks thanwhich is higher than the current RDA. Among supplement users and nonusers, plasma PLP levels were much lower in women than men, non-Hispanic blacks than

220. • INTRODUCTION — Vitamins are a number of chemically unrelated families of organic substances that cannot be synthesized by humans but need to be ingested in the diet in small
quantities to prevent disorders of metabolism. They are divided into water-soluble and fat-soluble vitamins (show table 1).
• Many of the vitamin deficiency diseases, such as rickets (vitamin D), scurvy (vitamin C), beriberi (thiamine), and pellagra (niacin), have been almost completely eliminated in
developed countries. Great interest and controversy continues into whether vitamin supplementation can prevent cancer, heart disease, upper respiratory infections, and other
common diseases. (See "Vitamin supplementation in disease prevention").
• The best dietary sources for most of the water-soluble vitamins are fruits and vegetables; these also contain many related substances such as flavins and carotenoids which are
generally not recognized as vitamins but may have protective effects against various diseases. This topic review will focus on the water-soluble vitamins excluding folic acid and
vitamin B12, which are discussed separately. (See "Etiology and clinical manifestations of vitamin B12 and folic acid deficiency"). Minerals and fat-soluble vitamins are also reviewed
elsewhere. (See "Overview of fat-soluble vitamins").
• VITAMIN B3 (NIACIN) — Pellagra (meaning "raw skin") was first described in Spain and Italy in the mid 18th century. It is characterized by a photosensitive pigmented dermatitis
(typically located in sun-exposed areas), diarrhea, and dementia. During the early 1900s, pellagra was epidemic amongst the corn eating population of southeastern United States. It
is now essentially unheard of in the western world. However, pellagra can still be seen in India, in parts of China, and Africa. For centuries since its first description in 1735 by
Spanish physician Casal, it was thought to be an infectious disease [1]. However, in 1937, Elvehjen and his colleagues discovered that nicotinic acid was effective in the Rx of
pellagra in dogs. In the 1950s, tryptophan, a precursor of niacin, replaced it in the Rx of pellagra and research connected the low source of niacin and tryptophan in corn-containing
foods to the development of pellagra [2]. Niacin had been isolated since 1867, but it was not until 1937 that it became known as the anti-pellagra factor [1].
• Structure — Nicotinic acid and nicotinamide are the two common forms of the vitamin most often referred to as niacin. Through a series of biochemical reactions in the mitochondria,
niacin, nicotinamide, and tryptophan form nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP). NAD and NADP are the active forms of niacin.
• Absorption — As the chief dietary forms of niacin, NAD and NADP are first hydrolyzed in the intestinal lumen by enzymes leading to nicotinamide. Nicotinamide is converted by
intestinal flora to nicotinic acid. The two forms of niacin are then absorbed and released into plasma via passive and facilitated diffusion [3]. Through a passive process, niacin is
rapidly taken up by the liver, kidneys, and erythrocytes. Intracellular nicotinamide and nicotinic acid are quickly converted to coenzyme forms NAD and NADP, which are stored in
tissues with high metabolic activities (ie, muscle and liver).
• Activity — Many enzymatic reactions depend upon NAD and NADP. The role of the niacin moiety is to accept electrons or to donate hydrogen ions. The majority of these NAD-
dependent enzymes are involved in reactions such as oxidation of fatty acids and other reactions that yield chemical structures containing high energy bonds [4]. NADP is a cofactor
in the reductive synthesis of the fatty acids and steroids. As essential components of redox reactions and hydrogen transport, NAD and NADP are crucial in the synthesis and
metabolism of carbohydrates, fatty acids, and proteins [4].
• Deficiency — As mentioned above, pellagra is a rare entity in the United States, but is still a common manifestation of niacin deficiency in poorer countries where the local diet
consists of cereal, corn, or sorghum. In industrialized countries, pellagra tends to occur in alcoholics.
• The most characteristic finding is the presence of a symmetric hyperpigmented rash, similar in color to a sunburn, which is present in the exposed areas of skin [4]. Other clinical
findings are a red tongue and many non-specific symptoms, such as diarrhea and vomiting. Neurologic symptoms include insomnia, anxiety, disorientation, delusions, dementia, and
encephalopathy.
• Niacin deficiency can also be seen in three other settings:
• Carcinoid syndrome, in which metabolism of tryptophan is to 5-OH tryptophan and serotonin rather than to nicotinic acid. This leads to the deficiency of active forms of niacin and the
development of pellagra. (See "The carcinoid syndrome").
• Prolonged use of isoniazid since isoniazid depletes stores of pyridoxal phosphate, which enhances the production of tryptophan, a precursor of niacin.
• Hartnup disease, an autosomal recessive congenital disorder [5]. Hartnup disease is associated with a defect of a membrane transport in the intestinal and renal cells normally
responsible for the absorption of tryptophan (one of the precursors of nicotinamide-adenine dinucleotide). Through this pathway, around 50 percent of the daily niacin needs are
synthesized. Due to the resulting niacin deficiency, all the symptoms of pellagra can be expected. The diagnosis is made by detecting a number of neutral amino acids in the urine,
something that is not seen with dietary pellagra. The Rx is aimed towards depleting stores and supplementing the diet with niacin as well as proteins and amino acids [6]. (
See "Overview of the hereditary ataxias").
• Toxicity — The most documented and best known side effect of niacin is the flushing reaction associated with the crystalline nicotinic acid and not nicotinamide [7]. Symptoms are
dose-dependent yet variable from person to person. The flushing can be experienced in a mild form while taking doses as small as 10 mg per day [8]. Despite the inconvenience and
the undesirability of the reactions, there are no serious sequelae from flushing [7].
• In pharmacological doses (eg, 1000 to 3000 mg/day), other common side effects of niacin are flushing, nausea, vomiting, pruritus, hives, elevation in serum aminotransferases [9],
and constipation. A niacin-induced myopathy has also been described [10]. Caution should be used in patients with a history of gout, since niacin is also known to elevate serum uric
acid concentration.
• Severe toxicity reactions are reported in doses of 2 to 6 grams per day [8]. At such high doses, the hepatic metabolism becomes saturated, and side effects of this drug can be more
frequently encountered. When less than 1 g of nicotinic acid was ingested per day, only a handful of anecdotal cases of toxicity have been reported in the literature [11]. One clinical
trial assigned two groups of subjects to either a long or a short-acting formula of niacin, each starting at 500 mg per day [12]. Subjects were followed for several months during which
the dose of niacin was raised every six weeks by about 500 mg. There was no gastrointestinal or liver toxicity below 1000 mg of niacin per day. The extent of the toxicity was minimal
and mostly gastrointestinal in the immediate release group, while mild liver enzyme elevation was noticed only in the slow release group [12]. There is some speculation that the
metabolites of nicotinic acid in these high concentrations may lead to growth retardation in infants and children [13].
• Therapeutic roles — In moderate to high doses (1 to 3 grams a day) niacin is a well-established antihyperlipidemic agent, decreasing total and LDL cholesterol [14]. The Cholesterol-

221. Leigh Syn.Leigh Syn.
• Autosomal R; mitochondrial;Autosomal R; mitochondrial;
X-linkedX-linked
• Infantile subac. necrotisingInfantile subac. necrotising
encephalomyelopathy: ataxia,encephalomyelopathy: ataxia,
dysarthria, areflexia, muscle atrophy, hypotonia; feedingdysarthria, areflexia, muscle atrophy, hypotonia; feeding
difficulties; FTT; motor regression; brain stem signsdifficulties; FTT; motor regression; brain stem signs
• Symmetrical foci of spongy necrosis and demyelination inSymmetrical foci of spongy necrosis and demyelination in
thalami, brainstem, pons, peripheral nervesthalami, brainstem, pons, peripheral nerves