(Sponsored by Medical Utilization Management, L.L.C.)
TOXICITY AND DRUG INTERACTIONS
There are several ways in which a vitamin or herbal may cause health problems. The direct effect of excessive intake may "gear up" a bodily function beyond what is beneficial for example, or be directly toxic to a tissue. A Tolerable Upper Intake Level (UL) is the highest level of daily intake of a nutrient that is likely to pose no risk of adverse health effects for most people (See Appendix A). Interactions with medications may enhance or weaken the drug's effect. It's important to review with your health care provider all your medications, including vitamins and herbals!
Vitamin A: Vitamin A refers to a group of structurally related fat-soluble substances. "Vitamin A" usually refers to retinol, found in animal-derived sources such as liver and dairy foods. The carotenoids, include alph-,beta-, gamma- and delta- carotene, zeaxanthin, lutein, and lycopene come from fruits and vegetables. One IU is equal to 0.30 micrograms of all-trans retinol or to 0.60 micrograms of all-trans beta carotene. Deficiency of Vitamin A may be caused by inadequate dietary intake, malabsorption syndromes (e.g. Crohn's disease, ulcerative colitis), pancreatic disease and chronic liver disease (e.g. cirrhosis).
Toxicity: Too much Vitamin A can result in dry, itchy skin, headache, fatigue, hair loss and liver damage. In pregnant women excess may induce birth defects (as can deficiency). Beta-carotene's conversion is very much slowed when there is sufficient Vitamin A in the body, and is therefore not felt to be a potential risk for toxicity. A recent clinical trial in Finnish smokers who supplemented their diet with 20 mg of beta-carotene had an increased risk of lung cancer, but there may be a relationship between alcohol because "only those men who consumed more than 11g/day of alcohol (approximately one drink/day) showed an adverse response...in the lung cancer trial".
Tolerable Upper Limits: Because of the potential risk the FDA does not recommend beta-carotene at this time. The TULs for Vitamin A are:
Pregnant and lactating women: 5000 IU
Men and women 11y and older:10,000 IU
Children 1-3 1000 IU; 4-8 1,333 IU; 9-13 2000 IU; >14 3000 IU.
Drug Interactions: Absorption of Vitamin A is decreased by cholestyramine and other drugs resulting in fat malabsorption (e.g. Olestra), colestipol, mineral oil, and neomycin. Oral contraceptives may increase serum retinol. Supplemental vitamin A may add to the toxicity of retinoid drugs (e.g. isotretinoin, acitretin).
Thiamin (B1): Thiamin is essential in carbohydrate and branch chain amino acid metabolism. Classical deficiency is called berberi, which may be manifested by peripheral neuropathy, congestive heart failure, lactic acidosis and central nervous system changes. It may be seen in alcoholics, malabsorption states, patients with HIV, thyrotoxicosis, and patients on loop diuretics (e.g. furosamide).
Toxicity: None reported.
Tolerable Upper Limits: Not established.
Drug interactions: Loop diuretics, sulfites, tea, coffee and decaffinated coffee may all decrease thiamin.
Riboflavin (Vitamin B2): Riboflavin plays a vital role in energy production. Flavoenzymes are key in cellular respiration, acting as hydrogen receptors in mitochondrial electron transport. Riboflavin deficiency is known as pelegra, usually found in those who do not consume a diet rich in organ meats, dairy, leafy greens and whole grains. It is seen in the elderly, alcoholics and those with chronic liver disease and those on total parenteral nutrition. Deficiency may be associated with severe lactic acidosis, especially in HIV patients on triple antibiotics. It also functions as an antioxidant. Riboflavin absorption is decreased in hyperthyroidism.
Toxicity: Rare cases of diarrhea and polyurea in patients on 400 mg/day for migraines have been reported.
Tolerable Upper Limits: Not established.
Drug Interactions: Cholestyramine, Colestapol, oral contraceptives and probenecid may interfere with riboflavin absorption. Chlorpromazine, doxorubicin, and tricyclic antidepressants may interfere with its action.
Niacin (Vitamin B3): Niacin refers to both nicotinic acid and nicotinamide, which have identical vitamin properties but different pharmacologic activities. Niacin is involved in the production of energy, the synthesis of fatty acids, cholesterol, steroids and the regulation of genes. Nicotinic acid is used as a lipid lowering agent in pharmacologic dosages. Niacin deficiency causes pellagra (dermatitis, diarrhea and dementia), most often seen in alcoholism, malabsorption syndromes, cirrhosis and those receiving total parenteral nutrition.
Toxicity: Nicotinic acid can cause flushing from cutaneous diditation of blood vessels. High dosages (3 grams/day) may cause glucose intolerance, blurred vision, macular edema, and elevated uric acid. Those on high dosages should have liver function tests monitored on a regular basis for liver toxicity.
Tolerable Upper Level: Not determined.
Drug interactions: Use of nicotinic acid in conjunction with calcium channel blockers,alpha1-blockers and nitrate patches may potentiate the hypotensive effects of these drugs. Use of nicotinic acid and alpha-glocosidase inhibitors, sulfonureas, biguanides, and meglitinides may decrease their anti-diabetic effects. Use with warfarin may result in significant increase in prothrombin time. Aminoglycosides, tetracyclines, cephaolsporins and penicillins may deplete B3; Cholestyramine and colestipol may reduce absorption of nicotinic acid. Nicotinamide may increase levels of carbamazepine.
Pyrodoxine (Vitamin B6): Vitamin B6 (pyridoxine, pyridoxal and pyridoxamine) is involved in a wide range of biochemical reactions, including the synthesis of DNA and RNA, formation of blood and nerve tissue, neurotransmittors, and amino acids, including homocysteine. In one study, one-third of elderly patients were found to be boarderline deficient in B6; those with uremia and HIV are also at increased risk.
Toxicity: There is concern for development off sensory neuropathy in dosages exceeding 500 mg/day.
Tolerable Upper Limits:
Children: 0-12 mos unknown; 1-3 yrs 30 mg/day; 4-8 yrs 40 mg/day; 9-13 60 mg/day;14-18 1.2 mg/day
Adults: 100 mg/day
Pregnancy and lactation: 14-18 yrs 80 mg/day;19 yrs and older 100 mg/day
Drug Interactions: Carbamazepam, cycloserine, theophylline, ethionamide, isoniazid (INH), oral contraceptives, valproic acid, HCTZ, hydralazine and alcohol may all increase vitamin B6 requirements. High doses of B6 may lower drug levels of dilantin, negate the effects of patients taking levdopa without carbidopa, and inactivate phenelzine.
Vitamin B12: Vitamin B12 is critical to building DNA and RNA, the maintenance of the nervous system, fatty acid synthesis, homocysteine metabolism and energy production. It is estimated that B12 deficiency occurs in 10-15% of the elderly and 30% of those who have had gastric surgery.
Toxicity: There are occasional reports of hypersensitivity reactions in patients receiving parenteral doses of B12. Oral B12 is tolerated well even in very high doses.
Tolerable upper limits: None reported.
Drug Interactions: Anitbiotics, cholestyramine, colchecine, proton pump inhibitors, H2 blockers and metformin may decrease B12 levels.
Vitamin C: Under construction
Vitamin D: Under construction
Vitamin E: Vitamin E is an antioxidant. It also has antithrombotic activity, and may have anti-atherogenic, anti-viral, neuroprotective and immune-boosting activity. Its precise mechanism(s) of action is unknown. Deficiency results in sensory peripheral neuropathy, myopathy and cerebellar ataxia. It is a fat-soluble vitamin, and diseases that cause fat malabsorption (such as Crohn's, pancreatitis, and cystic fibrosis) may result in Vitamin E deficiency. It should be noted that in synthetic Vitamin E (dl-alpha-tocopheryl) half of the content is not usable by the body, but still has anti-clotting activity! Look for natural Vitamin E. Vitamin E should be stopped before surgery.
Toxicity: There are no reports of drug overdosage with Vitamin E.
Tolerable Upper Limits: Children 1-3,200 mg; 4-8, 300 mg; 9-13, 600 mg; 14-18children and pregnant or lactating children, 800 mg; Adults, including pregnant and lactating women 1,000 mg.
Drug Interactions: Anticonvulsants, cholestyramine, colestipol, INH, mineral oil, neomycin,orlistat and sucralfate may decrease Vitamin E absorption or impair utilization. High doses of Vitamin E may enhance the effects of antiplatelet drugs and the anticoagulant response to warfarin. Some herbs, such as garlic and ginko, possess antithrombotic effect and Vitamin E may enhance that effect as well. Vitamin C may spare Vitamin E after it has been oxidized. Selenium may enhanve Vitamin E's effects.
Vitamin K: Under construction
Folate: Folate is involved in a number of important biological processes, including formation of DNA, RNA, and proteins, and regulation of homocysteine production. Deficiency can result in megaloblastic anemia, neural tube defects in fetuses of pregnant women, depression, fatigue and shortness of breath. Alcohol increases renal folate excretion. Malabsorption syndromes, hemodyalysis and hemolytic diseases such as sickle may lead to deficiency.
Toxicity: There is no reported direct toxicity attributed to folate, but in B12 deficient patients (e.g. some alcoholics) administration of folate without B12 may precipitate or exacerbate neurologic conditions.
Tolerable Upper Limit: Children 1-3 yrs 300 mcg; 4-8 yrs 400 mcg; 9-13 yrs 600 mcg; 14-18 yrs 800 mcg; pregnancy 14-18 800 mcg; >19 yrs and other adults 1000 mcg.
Drug Interactions: Anticonvulsants, Cholestyramine, colestipol, colchicine, nonsteroidal anti-inflammatory agents and sulfasalazine may decrease folate absorption or block its action. Folate used in conjunction with fluoxetine or lithium may enhance antidepressant effects. Long-term effects of administration of metformin, associated with elevated homocysteine, may be ofset by administration of folate. Folate administration with methotrexate in treatment of rheumatoid arthritis may reduce toxic side effects without impact on therapy.. Vitamins B6 and B12 work synergistically with folate to decrease homocysteine levels.
Calcium: Under construction
Glucosamine: Under construction
Saw Palmetto: Under construction
Soy and Soy isoflavones: Under construction
Zinc: Under construction
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