Effect of drugs on homocysteine concentrations

Many studies conducted over the last two decades have shown that drug treatment for common medical conditions may have an adverse effect on plasma total homocysteine (tHcy) concentrations. The mechanism for the effects of individual drugs on tHcy concentrations is frequently unknown, as the mechanism of action of the drug may not be established, or the drug is typically administered in combination with other drugs. Some drugs are believed to alter tHcy concentrations by interfering in the metabolism of folate or vitamins B (12) or B (6) or by altering renal function, but the underlying mechanisms for the effects on tHcy concentrations of many drugs remains to be discovered. Several widely used drugs, such as lipid-lowering drugs (like fibrates and niacin) or oral hypoglycemic drugs (like metformin), insulin, drugs used in rheumatoid arthritis, and anticonvulsants cause elevated tHcy concentrations. Sex hormones have variable effects on tHcy levels, and N-acetylcysteine lowers tHcy. The mechanisms of action of drugs on tHcy concentrations and strategies to avoid tHcy elevation have been studied. Assuming that the association of tHcy with cardiovascular disease is causal, this article focuses on the adverse effect on tHcy levels of fibrates, statins and niacin, antihypertensive drugs, metformin, methotrexate and sulfasalazine, anticonvulsant drugs, and levodopa and reviews strategies to avoid such effects. The clinical significance, if any, of these adverse effects on plasma tHcy concentrations remains to be determined.