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Water-Soluble Vitamins

Water-Soluble Vitamins. Andrew Ukleja, M.D., C.N.S.P. Assistant Professor of Medicine Director of Nutrition Support Team Department of Gastroenterology Cleveland Clinic Weston, FL.

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Water-Soluble Vitamins

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  1. Water-Soluble Vitamins Andrew Ukleja, M.D., C.N.S.P. Assistant Professor of Medicine Director of Nutrition Support Team Department of Gastroenterology Cleveland Clinic Weston, FL

  2. Objectives • To review • Functions of water-soluble vitamins • Symptoms and signs of vitamin deficiencies • Treatment of the vitamin deficiencies

  3. The Location of Vitamin Absorption Thiamin Riboflavin Niacin Biotin Preferentially absorbed in jejunum Fat-soluble vitamins Folate (Jejunum only) Colon Vitamin B12 (Ileum only)

  4. B Vitamins • Coenzymes in the same energy metabolic pathways • Overlap in clinical symptoms of deficiency between B vitamins • Cheilosis • Glossitis • Dermatitis

  5. Vitamin B1 (Thiamine) • Thiamine was named "the antiberiberi factor“ (1926) • Absorption: jejunum/ileum • Biologic half-life: ~10-20 days • Limited tissue storage • Continuous supplementation is required

  6. Thiamine • Functions: Cofactor for enzymes in AA and CHO metabolism • Dietary sources: yeast, legumes, rice, cereals, pork • RDI: 1.2-1.5 mg/d; parenteral dose - 3 mg/d • Thiamine requirement: • based on the total caloric intake • 0.5 mg of vit. B1 daily /1000 Kcal for adults

  7. Individuals at Risk for Thiamine Deficiency • Alcoholics • Calorie-protein poor diet • Severe malnutrition • Malabsorption • Gastric bypass • Chronic renal failure on HD • Prolonged febrile illness

  8. Thiamine Deficiency • Beriberi • Wernicke-Korsakoff syndrome • Leigh's syndrome

  9. Beriberi Adult beriberi: • Dry beriberi: distal symmetrical peripheral neuropathy of the extremities (sensory and motor impairment) • Wet beriberi: neuropathy / cardiac involvement – high output CHF (cardiomegaly, cardiomyopathy, tachycardia, pitting peripheral edema) • Other symptoms: anorexia, weight loss, confusion, muscle wasting, weakness Infantile beriberi (infants, 2-3 months of age)

  10. Wernicke-Korsakoff Syndrome • Almost exclusively described in chronic alcoholics • Wernicke’s encephalopathy: horizontal nystagmus, ophthalmoplegia, gait ataxia, confusion, weakness • Korsakoff's psychosis • Impaired short-term memory and confabulation • ? genetic predisposition - impaired synthesis of erythrocyte transketolase

  11. Thiamine Deficiency Detection: • Erythrocyte thiamine transketolase activity (ETKA) • Serum thiamine concentration • Urinary thiamine/transketolase excretion Treatment: • Vitamin B1: 50-100 mg/d (IV. or IM.) for 7-14 days, then 5-10 mg/d orally until full recovery Sensitivity to thiamine I.V. has been reported: • Tingling, pruritus, nausea, sweating, anaphylactic reaction (IgE-mediated)

  12. Vitamin B2 (Riboflavin) • Stored in the body as flavoproteins • Poorly soluble in water • Functions: • Involved in cellular metabolism, oxidation - reduction reactions; electron transporter • Essential component of coenzymes • flavin mononucleotide (FMN) • flavin-adenine dinucleotide (FAD)

  13. RIBOFLAVIN • Dietary sources • Milk, green vegetables • Yeast, enriched foods • Liver, meats, fish, eggs • Daily values: 0.6 mg/1000 kcal • Adults 1.2-1.7 mg/d • Infants 0.4 mg/d

  14. Deficiency of Vitamin B2 • Pure deficiency of vit. B2 is rare • Often accompanied by other water-soluble vitamin deficiencies • Alcoholics • Malabsorption • Detection of deficiency: • Urinary riboflavin excretion • Erythrocyte glutathione reductase assay

  15. Patients at Risk for Vit. B2 Deficiency • Avoidance of dairy products • lactose intolerance • Anorexia nervosa • Malabsorptive syndromes • Celiac sprue • Malignancies • Short bowel syndrome • Inborn errors of metabolism • defect in riboflavin synthesis

  16. Manifestations of Vit. B2 Deficiency • Angular stomatitis • Cheilosis • Glossitis • Sore throat • Hyperemia, pharyngeal mucous membranes • Seborrheic dermatitis • Pruritus • Photophobia • Normocytic, normochromic anemia • Treatment: Vit. B2 • 5 mg bid for a few weeks • 3 mg/d - prophylaxis in malabsorption syndrome

  17. NIACIN (Vitamin B3) Forms • Nicotinic acid • Nicotinamide Functions: • Component of NAD/NADP - essential for redox reactions and hydrogen transport, metabolism of carbohydrates, fatty acids, and proteins Dietary sources: • Meats (liver), milk, fish, whole-grain, nuts RDI: 17-20 mg/d

  18. Niacin Deficiency Pellagra • Pellagra - meaning "raw skin" • First described in Spain/Italy in the mid 18th century • Epidemic amongst the corn eating population of southeastern US in the early 1900s • Seen mainly in alcoholics • Reported in carcinoid syndrome, Hartnup disease, Isoniazid therapy

  19. Pellagra Symptoms (three D’s) • Dermatitis • Photosensitive symmetric pigmented in sun-exposed areas • Diarrhea • Dementia Glossitis/red tongue Neurologic symptoms • insomnia, anxiety, disorientation, delusions, encephalopathy, seizures • Detection: serum niacin level

  20. Treatment of Pellagra • Niacin: Oral 100 mg tid. until symptoms resolved • Nicotinamide: • 100mg IM if needed • Only available IV form • Clinical response: • GI and neurologic symptoms resolve rapidly • Dermatitis subsides over a few months after treatment

  21. Vitamin B6 (PYRIDOXINE) • Forms • Pyridoxine (plant foods) active form • Pyridoxal (animal foods) Pyridoxal phosphate • Pyridoxamine (PLP) • Functions • Transamination and decarboxylation of AA • Gluconeogenesis • Formation of niacin/serotonin from tryptophan • Synthesis of lecithin, RNA, sphingolipids, heme • Immune function (IL-2, lymphocyte proliferation) • Steroid hormone modulation

  22. PYRIDOXINE • Dietary sources: • Meats, fish • Whole grains • Vegetables • Nuts • Recommended daily requirements • Children 0.6 mg • Female 1.6 mg • Pregnancy 1.9 mg • Male 2.0 mg

  23. Vitamin B6 Deficiency • Overt deficiencies are rare • Manifestations • Stomatitis, glossitis, cheilosis • Seborrheic dermatitis • Irritability, confusion, depression • Sideroblastic anemia •  serum homocysteine with deficiency • risk factor for atherosclerosis / DVT

  24. Detection of Vitamin B6 Deficiency • Plasma pyridoxal-5-phophate (PLP) • Males 27-75 nmol/L • Females 26-93 nmol/L • Erythrocyte transaminase activity • Urinary excretion of 4-pyridoxic acid > 3.0 mmol/d • indicates adequate short-term vit. B6 status • Urinary excretion of xanthurenic acid (< 65 mmol/d) after a 2 g tryptophan load

  25. PYRIDOXINE • Treatment: • Oral 50-150 mg/d • 50 mg/d prophylactic dose with Isoniazide Rx • Toxicity (long-term megadoses > 250 mg/d) • Peripheral neuropathy/paresthesias • Dermatoses • Photosensitivity • Dizziness • Nausea

  26. Vitamin B12 (Cobalamin) • Functions • A carrier for methyl group and hydrogen • Synthesis of nucleic acids, porphyrins, methionine, and fatty acids • Dietary source • Meat • Dairy products • Daily requirement: 4-5 mcg/d • Total body stores: 2-5 mg (½ stored in the liver)

  27. Factors Affecting Vitamin B12 Absorption • Dietary intake • Acid-pepsin in the stomach • Secretion of IF by gastric parietal cells • Pancreatic proteases • Presence of ileum

  28. Causes of Vitamin B12 Deficiency • Diet • Strict vegetarians • Vegetarian diet in pregnancy • Gastric abnormalities • Pernicious anemia* • Gastritis, Helicobacter pylori infection • Gastrectomy/gastric bypass • Atrophic gastritis (autoimmune)

  29. Causes of Vitamin B12 Deficiency • Small bowel disease • Malabsorption syndromes • Ileal resection/ bypass* • Crohn’s disease, tuberculous ileitis, lymphoma, radiation enteritis • Blind loops/bacterial overgrowth • Fish tapeworm (Diphyllobothrium latum) • Pancreatic exocrine failure • Chronic alcoholism • Drugs • Antibiotic, Biguanides, PPI, Neomycin • HIV infection

  30. Vitamin B12 Deficiency Pernicious Anemia • Common in whites (northern European) • Older patients > 50years • Associated with autoimmune diseases under the age of 30 • Lack of intrinsic factor • The classic description of patient with PA • Lemon colored skin (anemia/icterus) • Shiny tongue (atrophic glossitis) • Mentally sluggish • Shuffling broad gait

  31. Hematologic Manifestations ofVitamin B12 Deficiency • Macrocytic anemia •  serum bilirubin / LDH levels • Low-normal WBC/platelet count • Peripheral blood smear • Megaloblasts • Hypersegmented neutrophils >5% with 5 +more lobes • Bone marrow aspiration • hypercellular marrow: megaloblastic erythroid hyperplasia, giant metamyelocytes

  32. Neurologic Manifestations of Vitamin B12 Deficiency • Subacute combined degeneration of the posterior/lateral spinal columns • Defect in myelin formation • Symmetrical neuropathy (legs >> arms) • Paresthesias (stocking/glove distribution) •  vibratory and position sense • severe weakness, ataxia, spasticity, clonus, paraplegia, fecal and urinary incontinence • Dementia, memory loss, irritability

  33. Manifestationsof Vitamin B12 Deficiency • Glossitis • Beefy red tongue • Loss of taste • Diarrhea, dyspepsia, anorexia • Impotence • Vaginal atrophy

  34. Detection of Vitamin B12 Deficiency • Serum level of Vitamin B12 • Normal >400 pg/ml • Low <210 pg/ml •  serum methylmalonic acid • Schilling test

  35. Schilling Test

  36. Treatment of Vitamin B12 Deficiency • Rx: 100-1000 mcg IM x 5-10 days, then 1000 mcg/monthly • Vegetarians: 3-6 mcg/d orally • Supplements 1) Sublingual tablet: 350 mcg/day 2) Intramuscular injection: 1000mcg/month 3) Nasal spray (Nascobal): 500mcg weekly one nostril 4) MVI (1-15mcg)

  37. Folic Acid • Functions • A carrier of one-carbon groups • Synthesis of nucleic acids and protein • Dietary source • Animal products (liver) • Leafy green vegetables • Small body stores (5-10 mg) • Daily requirements: 0.2-0.4 mg/d • Pregnancy/lactation 0.5-0.8 mg/d

  38. Causes of Folate Deficiency Nutritional deficiency Poor dietary intake Alcoholism (37% of ETOH users) Elderly (10% in pts >75 years) Malabsorption Sprue IBD Gastric bypass Short bowel

  39. Causes of Folic Acid Deficiency • Increased requirements • Pregnancy • Hemolytic anemia (chronic hemolysis) • Exfoliative skin disease * Pregnancy – prophylaxis with FA at 0.8-1.0 mg/d to prevent neural tube defects • Drugs (sulfasalazine) • Interference with folate metabolism

  40. Symptoms of Folate Deficiency • Macrocytic or megaloblastic anemia • Glossitis, fatigue, diarrhea • Progressive neurologic deterioration • Neuropathy, ataxia, seizures, mental retardation • Failure to thrive • Detection • Serum or RBC folate •  Homocysteine level • Rx: • Folate 1mg/d orally x 2-3 weeks • Maintenance 0.4 mg (in MVI) with malabsorption

  41. VITAMIN C • Functions: Antioxidant (biologic reductant) • Provides electrons to reduce molecular oxygen • Involved in iron/copper reactions • RDA: • Adult 75-90 mg/d • Elderly 125 mg/d • Smokers -  requirement by ~ 40%

  42. Vitamin C ASCORBIC ACID • Dietary source: • Citrus fruit • Fresh fruit • Vegetables • Absorption: distal small intestine • Intake up to 100 mg/d - 100% absorbed • Intake >1000 mg/d - <50% absorbed • Excess of vit. C removed by kidneys

  43. Functions of Vitamin C • Collagen synthesis • Formation of hydroxyproline/ hydroxylysine •  synthesis: impaired wound healing, defective tooth formation, osteoblast and fibroblast dysfunction • Neurotransmitters • Cofactor in synthesis of norepinephrine, thyroxin • Prostaglandin metabolism • Immune functions: chemotaxis and phagocytosis modulation

  44. Vitamin C Deficiency Scurvy • Described in Egyptian, Greek, and Roman literature • A major cause of morbidity and death in the US during Civil War and the California gold rush • Ascorbate is an essential nutrient derived from the diet • Scurvy develops 2-3 months with diet deficient in ascorbic acid

  45. Vitamin C Deficiency Groups at Risk Poor dietary intake • Severely malnourished individuals • Drug and alcohol abusers • Poverty • Elderly, institutionalized pts.

  46. Symptoms of Vitamin C Deficiency • Swollen and bleeding gums • Loosened teeth • Arthralgias and joint effusions • Lower extremities weakness • Petechiae and periungual hemorrhage • Ecchymoses • Corkscrew hair • Slow wound healing • Anemia  • Death

  47. Vitamin C Rx: Ascorbic acid 250 mg qid. x 1 week, then 100-200 mg/ day + rich Vit. C diet Toxicity • Seen with large doses of vit. C (grams) • diarrhea/abdominal bloating • calcium oxalate nephrolithiasis • cardiac arrhythmias if iron overload (oxidative injury)

  48. PANTOTHENIC ACID Vitamin B5 • Functions: precursor of coenzyme A (CoA) • Essential cofactor in acetylation reactions • Synthesis of vitamins A, D, cholesterol, fatty acids, proteins, steroids, porphyrins • Dietary sources: • Egg yolk, liver, kidney, milk, broccoli • Adequate daily intake 4-7mg/d

  49. Deficiency of Pantothenic Acid • It is rare • Manifestations • Paresthesias and dysesthesias (burning feet syndrome) • Gastrointestinal: nausea, vomiting, cramping • Growth failure, hemorrhage and necrosis of adrenal cortex, dermatitis, and achromotrichia (gray hair) in rats

  50. BIOTIN • Growth factor found in yeast, called "bios“ • Called vitamin H, coenzyme R, protective factor X • Functions: • Cofactor for the carboxylases involved in CHO and lipid metabolism • Essential in protein and DNA synthesis and cell replication (CO2 carrier)

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