Vitamins Deficiencies & Toxicities

Vitamins Organic molecules needed in small quantities for normal metabolism and other biochemical functions, such as growth or repair of tissue Organic molecules needed in small quantities for normal metabolism and other biochemical functions, such as growth or repair of tissue Attach to enzymes or coenzymes and help them activate anabolic (tissue- building) processes Attach to enzymes or coenzymes and help them activate anabolic (tissue- building) processes

Vitamins Essential part of enzymatic reactions Essential part of enzymatic reactions Natural sources from both plants and animals Natural sources from both plants and animals Insufficient amounts result in various deficiencies Insufficient amounts result in various deficiencies

Vitamins (cont'd) Vitamin K and vitamin B complex vitamins obtained by synthesis in the small intestine Vitamin K and vitamin B complex vitamins obtained by synthesis in the small intestine Vitamin D can be synthesized by the skin when exposed to sunlight Vitamin D can be synthesized by the skin when exposed to sunlight

Water-Soluble Vitamins B-complex group and vitamin C B-complex group and vitamin C Can be dissolved in water Can be dissolved in water Cannot be stored by the body in large amounts Cannot be stored by the body in large amounts Daily intake required to prevent deficiencies Daily intake required to prevent deficiencies

Fat-Soluble Vitamins Vitamins A, D, E, K Vitamins A, D, E, K Present in both plant and animal foods Present in both plant and animal foods Stored in the liver and fatty tissues Stored in the liver and fatty tissues Daily intake not required Daily intake not required

Fat-Soluble Vitamins (cont'd) Deficiency occurs only after prolonged deprivation Deficiency occurs only after prolonged deprivation Can become toxic if excessive amounts are consumed Can become toxic if excessive amounts are consumed

Vitamins: Other Issues Nutrient mega dosing Nutrient mega dosing Toxic hypervitaminosis Toxic hypervitaminosis

Vitamin A Fat soluble Fat soluble Vitamin A (retinol) derived from animal fats (butter and milk), eggs, meat, liver, fish liver oils Vitamin A (retinol) derived from animal fats (butter and milk), eggs, meat, liver, fish liver oils The vitamin A in animal tissues is derived from carotenes, which are found in plants (green and yellow vegetables and yellow fruits) The vitamin A in animal tissues is derived from carotenes, which are found in plants (green and yellow vegetables and yellow fruits)

Vitamin A Required for growth and development of bones and teeth Required for growth and development of bones and teeth Necessary for other processes Necessary for other processes –Reproduction –Integrity of mucosal and epithelial surfaces –Cholesterol and steroid synthesis –Essential for night vision

Vitamin A: Deficiency states Hyperkeratosis of the skin Hyperkeratosis of the skin Night blindness Night blindness Skin conditions Skin conditions –Acne, psoriasis, keratosis follicularis

Vitamin A: Toxicity Ingestion of excessive amounts causes toxicity Ingestion of excessive amounts causes toxicity –Irritability, drowsiness, vertigo, delirium, other symptoms –Increased intracranial pressure in infants –Generalized peeling of the skin and erythema over several weeks

DIAGNOSIS Abnormalities of dark adaptation are strongly suggestive of vitamin deficiency.Serum level below the normal range of 30-65mg/dl are commonly seen in advance deficiency. Abnormalities of dark adaptation are strongly suggestive of vitamin deficiency.Serum level below the normal range of 30-65mg/dl are commonly seen in advance deficiency.

TREATMENT Orally: DOSE 30,000 iu of vit A daily for 1 week. Orally: DOSE 30,000 iu of vit A daily for 1 week. Advance deficiency with corneal damage -20,000 ius/kg orally for 5 days. Advance deficiency with corneal damage -20,000 ius/kg orally for 5 days.

Vitamin D Fat soluble Fat soluble “Sunshine vitamin” “Sunshine vitamin” Responsible for proper utilization of calcium and phosphorus Responsible for proper utilization of calcium and phosphorus Actually a group of analog steroid chemicals Actually a group of analog steroid chemicals

Vitamin D (Fat Soluble) Different chemicals, produce same effect Different chemicals, produce same effect Vitamin D 2 (ergocalciferol) Vitamin D 2 (ergocalciferol) –Plant vitamin D –Obtained through dietary sources Vitamin D 3 (cholecalciferol) Vitamin D 3 (cholecalciferol) –Produced in the skin by ultraviolet irradiation (sunshine)

Vitamin D (cont'd) Vitamin D 2 -containing foods Vitamin D 2 -containing foods –Fish oils, salmon, sardines, herring –Fortified milk, breads, cereals –Animal livers, tuna fish, eggs, butter Endogenous synthesis in the skin Endogenous synthesis in the skin

Vitamin D: Function Regulates absorption of and use of calcium and phosphorus Regulates absorption of and use of calcium and phosphorus Necessary for normal calcification of bone and teeth Necessary for normal calcification of bone and teeth

Vitamin D: Indications Dietary supplement Dietary supplement Treatment of vitamin D deficiency Treatment of vitamin D deficiency Treatment and correction of conditions related to long-term deficiency: rickets, tetany, osteomalacia Treatment and correction of conditions related to long-term deficiency: rickets, tetany, osteomalacia Prevention of osteoporosis Prevention of osteoporosis

Vitamin D: Deficiency States Vitamin D deficiency generally results from an inadequate dietary intake of vitamin D, or too little exposure to sunlight. Vitamin D deficiency generally results from an inadequate dietary intake of vitamin D, or too little exposure to sunlight. Vitamin D Vitamin D The vitamin D deficiency has also been found to occur in overcrowded urban areas. The vitamin D deficiency has also been found to occur in overcrowded urban areas. The absence of sunlight or smog limitations inhibit the absorption of the D vitamin. The absence of sunlight or smog limitations inhibit the absorption of the D vitamin.

Vitamin D: Toxicity Long-term ingestion of excessive amounts causes toxicity Long-term ingestion of excessive amounts causes toxicity –Hypertension, weakness, fatigue, headache, many others –GI tract effects –CNS effects

Forms of Vitamin D calcifediol calcifediol calcitriol calcitriol dihydrotachysterol dihydrotachysterol ergocalciferol ergocalciferol

DIAGNOSIS Serum 25(OH)D and PTH level. Serum 25(OH)D and PTH level. Alkaline phosphatase level elevated. Alkaline phosphatase level elevated. Serum calcium and phosphate low. Serum calcium and phosphate low. Treatment Treatment microgram daily for 3-4 month, than decrease the dose microgram or stop the therapy microgram daily for 3-4 month, than decrease the dose microgram or stop the therapy.

Vitamin E Fat soluble Fat soluble Tocopherols Tocopherols Dietary plant sources Dietary plant sources –Fruits, grains, cereals, vegetables, oils, wheat germ Animal sources Animal sources –Eggs, chicken, meats, fish

Vitamin E: Function Exact biologic function of vitamin E is unknown Exact biologic function of vitamin E is unknown Believed to act as an antioxidant Believed to act as an antioxidant

Vitamin E: Deficiencies The Vitamin E deficiency is commonly found in infants and usually results from them having consumed formulas high in polyunsaturated fatty acids that are fortified with iron but not vitamin E. The Vitamin E deficiency is commonly found in infants and usually results from them having consumed formulas high in polyunsaturated fatty acids that are fortified with iron but not vitamin E. Also, because vitamin E is a fat-soluble vitamin, a deficiency also develops in conditions associated with fat malabsorption, such as cystic fibrosis. Also, because vitamin E is a fat-soluble vitamin, a deficiency also develops in conditions associated with fat malabsorption, such as cystic fibrosis.

Vitamin E: Indications Dietary supplement Dietary supplement Antioxidant Antioxidant Treatment of deficiency Treatment of deficiency –Highest risk of deficiency in premature infants

Diagnosis Plasma vitamin E levels can be measured; normal levels are 0.5–0.7 mg/dL or higher. Since vitamin E is normally transported in lipoproteins, the serum level should be interpreted in relation to circulating lipids. Plasma vitamin E levels can be measured; normal levels are 0.5–0.7 mg/dL or higher. Since vitamin E is normally transported in lipoproteins, the serum level should be interpreted in relation to circulating lipids.

Treatment The potential antioxidant benefits of vitamin E can be achieved with supplements of 100– 400 IU/d. The potential antioxidant benefits of vitamin E can be achieved with supplements of 100– 400 IU/d.

Vitamin K Fat soluble Fat soluble Three types: K 1, K 2, K 3 Three types: K 1, K 2, K 3 Dietary sources of K 1 Dietary sources of K 1 –Green leafy vegetables (cabbage, spinach), meats, milk Vitamin K 2 synthesized by intestinal flora Vitamin K 2 synthesized by intestinal flora

Vitamin K: Functions Essential for synthesis of blood coagulation factors in the liver Essential for synthesis of blood coagulation factors in the liver Vitamin K–dependent clotting factors Vitamin K–dependent clotting factors –II –VII –IX –X

Vitamin K: Indications Dietary supplementation Dietary supplementation Treatment of deficiency states (rare) Treatment of deficiency states (rare) –Antibiotic therapy –Newborn infants –Malabsorption Reverse the effects of certain anticoagulants (warfarin) Reverse the effects of certain anticoagulants (warfarin)

Vitamin K: Deficiencies The Vitamin K deficiency is commonly found among newborns within the first few days postpartum. Poor placental transfer of vitamin K to the infant and also inadequate production of vitamin K-producing intestinal flora is the main culprit. The Vitamin K deficiency is commonly found among newborns within the first few days postpartum. Poor placental transfer of vitamin K to the infant and also inadequate production of vitamin K-producing intestinal flora is the main culprit. The deficiency can also be caused by a prolonged use of drugs, such as antibiotics that destroy normal intestinal bacteria. The deficiency can also be caused by a prolonged use of drugs, such as antibiotics that destroy normal intestinal bacteria. Additionally, other causes are a decreased bile flow to the small intestine from bile duct obstruction, a malabsorption of vitamin K due to bowel resection, ulcerative colitis, or chronic hepatic disease. Additionally, other causes are a decreased bile flow to the small intestine from bile duct obstruction, a malabsorption of vitamin K due to bowel resection, ulcerative colitis, or chronic hepatic disease. The vitamin K deficiency seldom results from an insufficient dietary intake of it. The vitamin K deficiency seldom results from an insufficient dietary intake of it.

Laboratory Findings The prothrombin time (PT) is prolonged to a greater extent than the PTT, and with mild vitamin K deficiency only the PT is defective. Fibrinogen level, thrombin time, and platelet count are not affected. The prothrombin time (PT) is prolonged to a greater extent than the PTT, and with mild vitamin K deficiency only the PT is defective. Fibrinogen level, thrombin time, and platelet count are not affected.

Treatment Vitamin K deficiency responds rapidly to subcutaneous vitamin K, and a single dose of 15 mg will completely correct laboratory abnormalities in 12– 24 hours. Vitamin K deficiency responds rapidly to subcutaneous vitamin K, and a single dose of 15 mg will completely correct laboratory abnormalities in 12– 24 hours.

Water-Soluble Vitamins Vitamin B complex Vitamin B complex –thiamine (B 1 )– pyridoxine (B 6 ) –riboflavin (B 2 )– folic acid (B 9 ) –niacin (B 3 )– cyanocobalamin (B 12 ) –pantothenic acid (B 5 ) Vitamin C Vitamin C –ascorbic acid

Water-Soluble Vitamins (cont'd) Can dissolve in water Can dissolve in water Excessive amounts excreted in the urine, not stored in the body Excessive amounts excreted in the urine, not stored in the body Toxic reactions are very rare Toxic reactions are very rare

Vitamin B 1 (Thiamine) Water soluble Water soluble Food sources Food sources –Whole grains, liver, beans Deficiencies Deficiencies –Beriberi –Wernicke’s encephalopathy

Vitamin B 1 (Thiamine) Deficiencies Beriberi Beriberi –Brain lesions, polyneuropathy of peripheral nerves, serous effusions, cardiac anatomic changes Wernicke’s encephalopathy Wernicke’s encephalopathy –Cerebral beriberi

Vitamin B 1 (Thiamine): Causes of Deficiencies Poor diet Poor diet Extended fever Extended fever Hyperthyroidism Hyperthyroidism Liver disease Liver disease Alcoholism Alcoholism Malabsorption Malabsorption Pregnancy and breast-feeding Pregnancy and breast-feeding

Vitamin B 1 (Thiamine) Functions Essential for: Essential for: –Carbohydrate metabolism –Many metabolic pathways, including Krebs’ cycle Maintains integrity of: Maintains integrity of: –Peripheral nervous system –Cardiovascular system –GI tract

Diagnosis Erythrocyte transketolase activity. Coefficient greater than 15-20% suggest thiamine deficiency. Erythrocyte transketolase activity. Coefficient greater than 15-20% suggest thiamine deficiency. Urinary thiamine excretion. Urinary thiamine excretion.

Vitamin B 1 (Thiamine): Indications Treatment of thiamine deficiency Treatment of thiamine deficiency –Beriberi –Wernicke’s encephalopathy –Peripheral neuritis associated with pellagra Metabolic disorders Metabolic disorders

Vitamin B 1 (Thiamine): Indications (cont'd) Dietary supplement Dietary supplement –Malabsorption induced by alcoholism, cirrhosis, GI disease Thiamine deficiency is treated with large parental doses of thiamine mg/d.All patients should simultaneously receive therapeutic doses of other water soluble vitamins Other uses Thiamine deficiency is treated with large parental doses of thiamine mg/d.All patients should simultaneously receive therapeutic doses of other water soluble vitamins Other uses

Vitamin B 2 (Riboflavin) Water soluble Water soluble Food sources Food sources –Leafy green vegetables –Eggs –Nuts –Meats –Yeast

Vitamin B 2 (Riboflavin) Causes of Deficiency Alcoholism is a major cause Alcoholism is a major cause Deficiency also caused by: Deficiency also caused by: –Intestinal malabsorption –Long-term infections –Liver disease –Malignancy –Probenecid therapy

Vitamin B 2 (Riboflavin) Functions Converted into enzymes essential for tissue respiration Converted into enzymes essential for tissue respiration Required to activate vitamin B 6 (pyridoxine) Required to activate vitamin B 6 (pyridoxine) Converts tryptophan into niacin Converts tryptophan into niacin Maintains erythrocyte integrity Maintains erythrocyte integrity

Vitamin B 2 (Riboflavin) Deficiency Deficiency results in: Deficiency results in: –Cutaneous, oral, and corneal changes –Cheilosis –Seborrheic dermatitis –Keratitis

Vitamin B 2 (Riboflavin): Indications Dietary supplement Dietary supplement Treatment of deficiency Treatment of deficiency Microcytic anemia Microcytic anemia Acne Acne Migraine headaches Migraine headaches Many other uses Many other uses

Vitamin B 2 (Riboflavin): Side Effects No side effects or toxic effects No side effects or toxic effects Large doses will discolor urine to a yellow-orange Large doses will discolor urine to a yellow-orange

Vitamin B 3 (Niacin) Water soluble Water soluble Food sources Food sources –Meats, beans, liver, yeast, wheat Also synthesized from tryptophan (an essential amino acid obtained from protein digestion) Also synthesized from tryptophan (an essential amino acid obtained from protein digestion)

Vitamin B 3 (Niacin): Functions Once ingested, converted to nicotinamide Once ingested, converted to nicotinamide Nicotinamide is converted to two coenzymes Nicotinamide is converted to two coenzymes These enzymes are required for: These enzymes are required for: –Glycogenolysis, tissue respiration –Lipid, protein, and purine metabolism

Vitamin B 3 (Niacin): Indications Antihyperlipidemic agent Antihyperlipidemic agent –Lowers serum cholesterol and triglyceride levels by reducing VLDL synthesis –Doses required for this effect are higher than those required for its nutritional and metabolic effects

Vitamin B 3 (Niacin): Deficiency Pellagra: niacin deficiency Pellagra: niacin deficiency –Mental: various psychotic symptoms –Neurologic: neurasthenic syndrome –Cutaneous: crusting, erythema –Mucous membrane: oral, vaginal, and urethral lesions –GI: diarrhea or bloody diarrhea

Vitamin B 3 (Niacin): Side Effects Side effects seen when higher doses are used in the treatment of hyperlipidemia Side effects seen when higher doses are used in the treatment of hyperlipidemia –Flushing –Pruritus –GI distress

Vitamin B 6 (Pyridoxine) Water soluble Water soluble Sources Sources –Whole grains, wheat germ, nuts, yeast –Fish and organ meats

Vitamin B 6 (Pyridoxine) (cont'd) Composed of three compounds Composed of three compounds –Pyridoxine –Pyridoxal –Pyridoxamine

Vitamin B 6 (Pyridoxine): Function Necessary for many metabolic functions Necessary for many metabolic functions –Protein, lipid, and carbohydrate utilization –Conversion of tryptophan to niacin Necessary for integrity of peripheral nerves, skin, mucous membranes, hematopoietic system Necessary for integrity of peripheral nerves, skin, mucous membranes, hematopoietic system

Vitamin B 6 (Pyridoxine) (cont'd) Signs and symptoms of deficiency Signs and symptoms of deficiency –Sideroblastic anemia –Neurologic disturbances –Seborrheic dermatitis –Cheilosis (chapped, fissured lips) –Xanthurenic aciduria (“stones” in the urine) –Glossitis and stomatitis –Epileptiform convulsions

Vitamin B 6 (Pyridoxine): Causes of Deficiency Inadequate intake Inadequate intake Poor absorption Poor absorption Uremia, alcoholism, cirrhosis, hyperthyroidism, malabsorption, heart failure Uremia, alcoholism, cirrhosis, hyperthyroidism, malabsorption, heart failure Drug induced (isoniazid, hydralazine, others) Drug induced (isoniazid, hydralazine, others)

DIAGNOSIS Blood pyridoxal phosphate.Normal level >50ng/ml. Blood pyridoxal phosphate.Normal level >50ng/ml. TREATMENT TREATMENT VITAMIN B6 Dose mg/day. VITAMIN B6 Dose mg/day. TOXICITY TOXICITY Sensory neuropathy. Sensory neuropathy.

Vitamin B 6 (Pyridoxine) Toxicity Toxic effects occur with large doses, especially neurotoxicity

Vitamin B 12 (Cyanocobalamin) Water soluble Water soluble Synthesized by microorganisms present in the body Synthesized by microorganisms present in the body Food sources Food sources –Liver, kidney, fish, shellfish, meat, dairy foods Contained in minimal amounts in plants Contained in minimal amounts in plants

General Considerations Vitamin B12 belongs to the family of cobalamins and serves as a cofactor for two important reactions in humans. As methylcobalamin, it is a cofactor for methionine synthetase in the conversion of homocysteine to methionine, and as adenosylcobalamin for the conversion of methylmalonyl-coenzyme A (CoA) to succinyl- CoA. All vitamin B12 comes from the diet and is present in all foods of animal origin. The daily absorption of vitamin B12 is 5 mcg. Vitamin B12 belongs to the family of cobalamins and serves as a cofactor for two important reactions in humans. As methylcobalamin, it is a cofactor for methionine synthetase in the conversion of homocysteine to methionine, and as adenosylcobalamin for the conversion of methylmalonyl-coenzyme A (CoA) to succinyl- CoA. All vitamin B12 comes from the diet and is present in all foods of animal origin. The daily absorption of vitamin B12 is 5 mcg.

Vitamin B 12 (Cyanocobalamin): Function Required for many metabolic pathways Required for many metabolic pathways –Fat and carbohydrate metabolism –Protein synthesis –Growth, cell replication –Hematopoiesis –Nucleoprotein and myelin synthesis

Vitamin B 12 (Cyanocobalamin): Deficiency Deficiency leads to: Deficiency leads to: –Neurologic damage –Pernicious anemia Deficiency states caused by: Deficiency states caused by: –Malabsorption –Poor dietary intake (vegetarians)

Vitamin B 12 (Cyanocobalamin): Oral Absorption Oral absorption of vitamin B 12 (extrinsic factor) required presence of the intrinsic factor Oral absorption of vitamin B 12 (extrinsic factor) required presence of the intrinsic factor The intrinsic factor is a glycoprotein secreted from the gastric parietal cells The intrinsic factor is a glycoprotein secreted from the gastric parietal cells

Vitamin B 12 (Cyanocobalamin): Oral Absorption (cont'd) The extrinsic and intrinsic factors form a complex that is then absorbed by the intestines

Treatment Intramuscular injections of 100 mcg of vitamin B12 are adequate for each dose. Replacement is usually given daily for the first week, weekly for the first month, and then monthly for life. It is a lifelong disorder, and if patients discontinue their monthly therapy the vitamin deficiency will recur. Oral cobalamin The dose is 1000 mcg/d and must be continued indefinitely. Intramuscular injections of 100 mcg of vitamin B12 are adequate for each dose. Replacement is usually given daily for the first week, weekly for the first month, and then monthly for life. It is a lifelong disorder, and if patients discontinue their monthly therapy the vitamin deficiency will recur. Oral cobalamin The dose is 1000 mcg/d and must be continued indefinitely. Patients respond to therapy with an immediate improvement in their sense of well-being. A brisk reticulocytosis occurs in 5–7 days, and the hematologic picture normalizes in 2 months. Central nervous system symptoms and signs are reversible if they are of relatively short duration (less than 6 months) but become permanent if treatment is not initiated promptly. Patients respond to therapy with an immediate improvement in their sense of well-being. A brisk reticulocytosis occurs in 5–7 days, and the hematologic picture normalizes in 2 months. Central nervous system symptoms and signs are reversible if they are of relatively short duration (less than 6 months) but become permanent if treatment is not initiated promptly.

Vitamin C (Ascorbic Acid) Water soluble Water soluble Natural sources Natural sources –Citrus fruits and juices –Tomatoes –Cabbage –Cherries –Liver Can also be synthesized Can also be synthesized

Vitamin C (Ascorbic Acid): Functions Acts in oxidation-reduction reactions Acts in oxidation-reduction reactions Required for several metabolic activities Required for several metabolic activities –Collagen synthesis –Maintenance of connective tissue –Tissue repair –Maintenance of bone, teeth, and capillaries –Folic acid metabolism –Erythropoiesis

Vitamin C (Ascorbic Acid): Functions (cont'd) Enhances absorption of iron Enhances absorption of iron Required for the synthesis of: Required for the synthesis of: –Lipids –Proteins –Steroids Aids in cellular respiration Aids in cellular respiration Aids in resistance to infections Aids in resistance to infections

Vitamin C (Ascorbic Acid): Deficiency Prolonged deficiency results in scurvy Prolonged deficiency results in scurvy –Gingivitis and bleeding gums –Loss of teeth –Anemia –Subcutaneous hemorrhage –Bone lesions –Delayed healing of soft tissues and bones

DIAGNOSIS Diagnose on clinical ground. Diagnose on clinical ground. Ascorbic acid level below 0.1mg/dl. Ascorbic acid level below 0.1mg/dl.

TREATMENT mg/d of ascorbic acid. Response occurs within days mg/d of ascorbic acid. Response occurs within days. High intake decrease the risk of cancer, also protect from against coronary heart disease. High intake decrease the risk of cancer, also protect from against coronary heart disease. TOXICITY TOXICITY High doses cause gastric irritation,flatulence,or diarrhea.it may also causes false negative test for faecal occult blood and false positive and false negative test for urine glucose. High doses cause gastric irritation,flatulence,or diarrhea.it may also causes false negative test for faecal occult blood and false positive and false negative test for urine glucose.

Vitamin C (Ascorbic Acid): Megadoses Megadoses may cause: Megadoses may cause: –Nausea, vomiting, headache, abdominal cramps –Acidified urine, with possible stone formation Discontinuing megadoses may result in scurvy-like symptoms Discontinuing megadoses may result in scurvy-like symptoms