Vitamins

1. Vitamins

2. Vitamins • Essential • organic compounds • Micronutrients • Involved in growth, metabolism, healing/health, immunity

4. Vitamins • Water-soluble or fat-soluble • Dietary reference intakes (DRI) • Deficiency associated with malnutrition, malabsorption from chronic disorders or genetically inherited diseases • Toxicity from Vitamin A & D

5. Forms all-trans-retinol: alcohol form Pro-Vitamin Acarotenoids (-,-,- carotenes) Retinyl palmitate: storage form Retinal: aldehyde form Retinoic acid Source Carotenoids from plants, green & yellow vegetables, yellow fruits liver, fish liver oils dairy fat egg yolk Vitamin A

6. Vitamin A Forms and Function • Retinoic Acidmost important vit A metabolite • Acts as a ligand for specific nuclear transcription factors • Retinoic acid gene receptors vital in fundamental biological activities of all cells: division, death, differentiation • Retinal: rhodopsin in rods of the retina

7. Vitamin A deficiency • Night- blindness, photophobia: absence of retinal in rhodopsin of the retina • Xerophthalmia  keratomalacia • Bitot’s spots • conjunctival xerosis

8. At risk for Vitamin A deficiency • Undernourished of mother & child • Measles

9. Tx of Vitamin A deficiency Oral dose to be given on Day 1, 2 & 2 wks later • for age >12 months 200,000 IU • for age 6-12 months 100,000 IU • for age 0-5 months 50,000 IU (unless there is definite evidence that a dose has been given in the last month)

10. Tx of Xerophthalmia • Vitamin A • 5000 IU/kg BW OD PO x 5days followed by 25000 IU IM in oil • until recovery

11. Vitamin A for Mother 200,000 IU OD x 2 doses post-partum Vitamin A for Newborn 25,000 IU x 3 doses at 1-3 months of age Prevention of Vitamin A deficiency in High Risk Areas

12. Hypervitaminosis A • Excess over weeks or months • Adults 50000 IU Child 20000 IU • Sx: headache, vomiting, anorexia, seborrhea, oral fissures, alopecia, bone abnormalities: hyperostosis, hepatosplenomegaly, diplopia, irritability, stupor • Sx resolve on withdrawal of Vit A

13. Hypervitaminosis A • Congenital malformations & abortions: 0.5-1.5mg/kg oral retinoic acid for acne or cancer, >20% incidence • Carotenemia: yellow discoloration of skin due to excessive intake of carotenoids (low enzymes, liver dse, DM or hypothyroidism)

14. Vitamin B Complex • Thiamine • Riboflavin • Niacin • Vitamin B6 • Folate • Vitamin B12 • Biotin • Pantothenic Acid • (Choline) • (Inositol)

15. Thiamine (Vitamin B1) • Source • meat (lean pork) • legumes • cereal • Forms/ functions • Coenzyme thiamine pyrophosphate (glycolysis) • Hexose monophosphate shunt • Synthesis of acetylcholine (nerve conduction)

16. Prevention of Thiamine deficiency • Undernourishment of mother & child • Diseases of the gastrointestinal tract and liver • Increased requirement if CHO in diet is high: TPN, Alcoholics • Thiamine dependence: megaloblastic anemia, maple syrup urine disease, Leigh encephalomyelopathy

17. Clinical Manifestation of Thiamine deficiency • Fatigue, apathy, irritability, depression, poor concentration, anorexia, nausea, abdominal discomfort • Peripheral neuritis (paresthesias of the toes and feet),  DTR’s, loss of vibration sense, leg cramps, psychic disturbances, ptosis, atrophy of optic nerve • Hoarseness, aphonia

18. Clinical Manifestation of Thiamine deficiency • Muscle atrophy, tenderness of nerve trunks, loss of deep sensation •  ICP, meningismus, coma • Wernicke encephalopathy: encephalopathy, opthalmoplegia + ataxia • CHF death

19. Wet Undernourished, pale, edema Dyspnea Vomiting Tachycardia Waxy skin Urine albumin, casts Dry Plump Pale Flabby Listless Dyspnea Tachycardia Hepatomegaly Beriberi

20. Treatment of Thiamine deficiency • Vitamin B1 10mg OD PO (child) • Vitamin B1 50 mg OD PO (adult) • If with CHF, give IV or IM • Tx over several weeks • Clinical response to thiamine is best confirmation of thiamine deficiency

21. Niacin • Source • Meat • Fish poultry • Legumes • Fortified bread and cereal • Tryptophan from milk & eggs (6mg= 1mg niacin) • Forms/ functions • Nicotinamide, nicotinic acid & derivatives • Coenzyme NADP, NAD (electron transfer and glycolysis)

22. At risk for Niacin deficiency • Inadequate intake • Regions where corn is a staple

23. Clinical Manifestations of Niacin deficiency • Anorexia • Lassitude • Weakness • Burning sensation • Numbness • Dizziness • Glossitis, GI symptoms, symmetric dermatitis

24. Pellagra • Triad: dermatitis, diarrhea and dementia • Dermatitis symmetric, sharply demarcated from surrounding healthy skin, sun-exposed areas • Scaling, crusting, vesicles, bullae • Pellagrous glove, boot, Casal necklace • Alternating diarrhea and constipation • Depression, disorientation, insomnia, delirium

28. Treatment of Niacin deficiency • Niacin 50-300mg/ day • Niacin 100mg IV, if sever or poor intestinal absorption

29. Vitamin B6 (Pyridoxine) • Source • Meat • Fish • Poultry • liver • Fortified Cereal • Forms/ functions • Pyrodixine • pyridoxal • Pyridoxamine • Coenzymes Pyridoxal 5-phosphate, pyridoxamine phosphate: AA metab, aminotransferases, decarboxylases, racemaces, dehydratases • Neurotransmitter synthesis: serotonin, GABA, dopamine • Synthesis of histamine, heme, porphyrins

30. Functions of Pyridoxine • Metabolism of glycogen • Conversion of tryptophan to Niacin • Synthesis of cysteine from methionine • AA active transport across cell membranes • Chelation of metals • linoleic acid  arachidonic acid • linolenic acid  docosahexaenoic acid

31. At risk for Pyridoxine deficiency • Inadequate intake • Milling of rice, cereal removes Pyridoxine • Vegetarian • Larger requirement if high protein in diet • Inhibited by drugs: Isoniazid,penicillamine, steroids, anti-convulsants, • Women on oral contraceptives • Maintenance dialysis

32. Clinical Manifestation of Pyridoxine deficiency • Irritability & Convulsions in infants • Peripheral neuritis • Dermatitis • anemia • Aggravated startle response • Cheilosis • Glossitis • Seborrheic dermatitis • infections

33. Vitamin B6 dependence Syndromes • Vit B6- dependent convulsions • Vit B6- responsive anemia • Xanthurenic aciduria • Cystathioninuria • homocystinuria

34. Treatment of Pyridoxine deficiency • Vitamin B6 100mg IM for Infantile seizures • Daily Vitamin B6 2-10mg IM or 10-100mg PO if pyridoxine-dependent

35. Folate • Source • Green vegetables • Oranges • Legumes, nuts • Fortified Cereal • liver • yeast • Forms/ functions • Folic acid= pteroylglutamic acid • Folate coenzymes: DNA and purine synthesis, AA intercorversion, homocysteine  methionine

36. Prevention of Folate Deficiency • Inadequate intake • Deficiency during periods of rapid growth or increased cellular metabolism • (sickle cell anemia), psoriasis • NSAIDs, anticonvulsants i.e. diphenylhydantoin, phenobarbital, Methotrexate • Pregnancy,Protective for neural tube defects (spina bifida, anencephaly)

37. Prevention of Folate Deficiency • Malabsorption (hereditary folate malabsorption, celiac, inflammatory bowel disease, alcoholism) • Inborn errors of folate metabolism • Autoantibodies against cerebral folate receptor in the choroid plexus

38. Hereditary Folate Malabsorption • Recurrent diarrhea, failure to thrive, oral ulcers, neurologic deterioration, megaloblastic anemia • At 1-3 months of age • Poor neurologic outcome • poor immunity • DX: low serum folate • Rx: Folinic acid IM or hi dose oral folinic acid

39. Cerebral Folate Deficiency • Irritability, microcephaly, developmental delay, cerebellar ataxia, pyramidal tract signschoreoathetosis, ballismus, seizures • Blindness from optic nerve atrophy • Dx: normal serum folate, low CSF folate • Rx: oral folinic acid

40. Treatment of Folate Deficiency • Women of child-bearing age: Folate 400mcg daily

41. Vitamin B12 (Cobalamin) • Source • Muscle meats • Eggs • Dairy • Tempeh, nori • Fortified cereal

42. Functions of Vitamin B12 (Cobalamin) Forms/ functions • Cofactor for lipid and carbohydrate metabolism • Isomerization of methylmalonyl coenzyme A to succinyl coenzyme A • Maintainance of cellular folate levels; Folate metabolism; homocysteine  methionine • Protein biosynthesis • Synthesis of purines and pyramides • Methylation reactions

43. Prevention of Vitamin B12 deficiency • Inadequate intake i.e. strict vegetarian diet in a nursing Mom • Abnormal absorption (gastric resection, autoimmune pernicious anemia with IF deficiency) • Poor ileal absorption (Crohn’s, tropical sprue, SBS) • Competition for B12 in the gut • IEM of Vit B12

44. Transcobalamin II deficiency • Inherited defect • Defective intestinal transport of Vitamin B12 • Severe megaloblastic anemia, Diarrhea, vomiting

45. Juvenile pernicious anemia • Defective IF production in the stomach • Vit B12 malabsorption • Megaloblastic anemia, growth failure

46. Imerslund Syndrome • Defective ileal absorption of Vit B12 • Normal ileal structure and function • Megaloblastic anemia

47. Treatment of Cobalamin deficiency • Vit B12 100mcg once a month IM • Vit B12 1000 mcg twice a week IM for transcobalamin II deficiency • Once in hematologic remission, intranasal Vit B12 500mcg once weekly • If at risk for Leber Optic atrophy, treat with Vit B12 other than cyanocobalamin

48. Vitamin C • Source • Vegetables • Fruits esp citrus • Forms • Dehydroascorbate: Simple diffusion or Active transport • Ascorbate: plasma transport form

49. Vitamin C functions • Collagen formation: hydroxylation of lysine and proline • Maintains iron and copper in a reduced state for metalloenzymes to convert • Dopamine  norepinephrine • Tryptophan  serotonin • Cholesterol  steroids • Antioxidant • Enhances non-heme iron absorption, transfer of iron from transferrin to ferritin & formation of tetrahydrofolic acid

50. Clinical Manifestation of Vitamin C deficiency • Onset of Sx 6-24 months of age • Fever • Irritability • Tachypnea • Digestive disturbances • Loss of appetite • Generalized tenderness (pseudoparalysis) • Leg edema • Femoral subperiosteal hemorrhage