Drugs Affecting Homocysteine Metabolism

Abstract

Elevated total plasma homocysteine has been established as an independent risk factor for thrombosis and cardiovascular disease. A strong relationship between plasma homocysteine levels and mortality has been reported in patients with angiographically confirmed coronary artery disease. Homocysteine is a thiol containing amino acid. It can be metabolised by different pathways, requiring various enzymes such as cystathionine beta-synthase and methylenetetrahydrofolate reductase. These reactions also require several co-factors such as vitamin B6 and folate. Medications may interfere with these pathways leading to an alteration of plasma homocysteine levels. Several drugs have been shown to effect homocysteine levels. Some drugs frequently used in patients at risk of cardiovascular disease, such as the fibric acid derivatives used in certain dyslipidaemias and metformin in type 2 (non-insulin-dependent) diabetes mellitus, also raise plasma homocysteine levels. This elevation poses a theoretical risk of negating some of the benefits of these drugs. The mechanisms by which drugs alter plasma homocysteine levels vary. Drugs such as cholestyramine and metformin interfere with vitamin absorption from the gut. Interference with folate and homocysteine metabolism by methotrexate, nicotinic acid (niacin) and fibric acid derivatives, may lead to increased plasma homocysteine levels. Treatment with folate or vitamins B6 and B12 lowers plasma homocysteine levels effectively and is relatively inexpensive. Although it still remains to be demonstrated that lowering plasma homocysteine levels reduces cardiovascular morbidity, surrogate markers for cardiovascular disease have been shown to improve with treatment of hyperhomocystenaemia. Would drugs like metformin, fibric acid derivatives and nicotinic acid be more effective in lowering cardiovascular morbidity and mortality, if the accompanying hyperhomocysteinaemia is treated? The purpose of this review is to highlight the importance of homocysteine as a risk factor, and examine the role and implications of drug induced modulation of homocysteine metabolism.

Proinflammatory Cytokines, Markers of Cardiovascular Risks, Oxidative Stress, and Lipid Peroxidation in Patients With Hyperglycemic Crises

“…Homocysteine is regulated by many factors, and its levels are affected by various drugs (50), but its lack of response may be similar to the observations of Fonseca et al (51), in that homocysteine levels in diabetic patients, unlike nondiabetic subjects, do not respond to insulin because these patients are insulin resistant. Our study confirms this phenomenon and extends these findings to patients in hyperglycemic crises.…”

Plasma Homocysteine Levels in Polycystic Ovary Syndrome and Congenital Adrenal Hyperplasia

“…Metformin decreases these vitamin levels by inhibiting their absorption from the intestinal system. Moreover, folate and vitamin B 12 deficiencies are known to cause a significant elevation in plasma homocysteine levels [22].…”

Effect of ACE inhibitors and β-blockers on homocysteine levels in essential hypertension

“…5,[15][16][17] Recent studies have shown that the drug therapy for common medical conditions may have severe effects on plasma Hcy levels. [18][19][20][21][22] Thiazide-type diuretics are recognized as the cornerstone of antihypertensive therapy (AHT) in elderly because of their extensive track record in preventing stroke and cardiovascular events and their low cost. 23 Outcome benefits of diuretics as first-line agents have been demonstrated only at moderate doses (equivalent to X25 mg hydrochlorothiazide).…”