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Nutrient-Drug Interactions

By Adrienne Youdim, MD, FACP

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Nutrition can affect the body’s response to drugs; conversely, drugs can affect the body’s nutrition.

Foods can enhance, delay, or decrease drug absorption. Foods impair absorption of many antibiotics. They can alter metabolism of drugs; eg, high-protein diets can accelerate metabolism of certain drugs by stimulating cytochrome P-450. Eating grapefruit can inhibit cytochrome P-450 34A, slowing metabolism of some drugs (eg, amiodarone, carbamazepine, cyclosporine, certain Ca channel blockers). Diets that alter the bacterial flora may markedly affect the overall metabolism of certain drugs. Some foods affect the body’s response to drugs. For example, tyramine, a component of cheese and a potent vasoconstrictor, can cause hypertensive crisis in some patients who take monoamine oxidase inhibitors and eat cheese.

Nutritional deficiencies can affect drug absorption and metabolism. Severe energy and protein deficiencies reduce enzyme tissue concentrations and may impair the response to drugs by reducing absorption or protein binding and causing liver dysfunction. Changes in the GI tract can impair absorption and affect the response to a drug. Deficiency of Ca, Mg, or zinc may impair drug metabolism. Vitamin C deficiency decreases activity of drug-metabolizing enzymes, especially in the elderly.

Many drugs affect appetite, food absorption, and tissue metabolism (see Table: Effects of Some Drugs on Nutrition). Some drugs (eg, metoclopramide) increase GI motility, decreasing food absorption. Other drugs (eg, opioids, anticholinergics) decrease GI motility. Some drugs are better tolerated if taken with food.

Certain drugs affect mineral metabolism. For example, diuretics, especially thiazides, and corticosteroids can deplete body K, increasing susceptibility to digoxin-induced cardiac arrhythmias. Repeated use of laxatives may deplete K. Cortisol, desoxycorticosterone, and aldosterone cause marked Na and water retention, at least temporarily; retention is much less with prednisone, prednisolone, and some other corticosteroid analogs. Sulfonylureas and lithium can impair the uptake or release of iodine by the thyroid. Oral contraceptives can lower blood zinc levels and increase copper levels. Certain antibiotics (eg, tetracyclines) reduce iron absorption, as can certain foods (eg, vegetables, tea, bran).

Certain drugs affect vitamin absorption or metabolism. Ethanol impairs thiamin utilization, and isoniazid interferes with niacin and pyridoxine metabolism. Ethanol and oral contraceptives inhibit folate absorption. Most patients receiving phenytoin, phenobarbital, primidone, or phenothiazines develop folate (folic acid) deficiency, probably because hepatic microsomal drug-metabolizing enzymes are affected. Folate supplements may make phenytoin less effective. Anticonvulsants can cause vitamin D deficiency. Malabsorption of vitamin B12 can occur with use of aminosalicylic acid, slow-release K iodide, colchicine, trifluoperazine, ethanol, and oral contraceptives. Oral contraceptives with a high progestin dose can cause depression, probably because of metabolically induced tryptophan deficiency.

Effects of Some Drugs on Nutrition



Increases appetite

Alcohol, antihistamines, corticosteroids, dronabinol, insulin, megestrol acetate, mirtazapine, many psychoactive drugs, sulfonylureas, thyroid hormone

Decreases appetite

Antibiotics, bulk agents (methylcellulose, guar gum), cyclophosphamide, digoxin, glucagon, indomethacin, morphine, fluoxetine

Decreases absorption of fats


Increases blood glucose levels

Octreotide, opioids, phenothiazines, phenytoin, probenecid, thiazide diuretics, corticosteroids, warfarin

Decreases blood glucose levels

ACE inhibitors, aspirin, barbiturates, β-blockers, insulin, monoamine oxidase inhibitors (MAOIs), oral antihyperglycemic drugs, phenacetin, phenylbutazone, sulfonamides

Decreases blood lipid levels

Aspirin and p -aminosalicylic acid, l-asparaginase, chlortetracycline, colchicine, dextrans, glucagon, niacin, phenindione, statins, sulfinpyrazone, trifluperidol

Increases blood lipid levels

Adrenal corticosteroids, chlorpromazine, ethanol, growth hormone, oral contraceptives (estrogen-progestin type), thiouracil, vitamin D

Decreases protein metabolism

Chloramphenicol, tetracycline

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