Treatment With Folate to Lower Homocysteine

Erica Brownfield, MD


July 29, 2004


What should be done about an elevated homocysteine level that persists despite administration of high-dose folic acid and high blood levels of folic acid?

Response from Erica Brownfield, MD

High homocysteine levels are associated with an increased risk of cardiovascular and cerebrovascular disease. Hyperhomocysteinemia can be caused by several mechanisms: (1) genetic defects in the enzymes involved in the metabolism of homocysteine, (2) nutritional deficiencies in vitamin cofactors, or (3) some chronic medical conditions and drugs. Smoking may increase homocysteine levels in the blood.

In the absence of known cardiovascular or cerebrovascular disease, it is controversial whether or not to treat patients with elevated homocysteine levels. There is no clear evidence for treating patients who do not have severe hyperhomocysteinemia in the absence of cardiovascular or thrombotic disease.[1] There are conflicting data on the efficacy of supplementation aimed at lowering homocysteine levels to prevent vascular events and death in patients with established vascular disease.[2,3,4] For patients who are treated, the treatment should target the underlying cause, if known.

In general, a diet rich in fruits, vegetables, and low-fat dairy products as well as low in saturated and total fat can help to decrease serum homocysteine. For patients with known cardiovascular disease, it is generally recommended to treat with folic acid (1 mg/day), vitamin B6 (10 mg/day), and vitamin B12 (0.4 mg/day). Folic acid can be increased up to 5 mg/day to reach a goal of lowering homocysteine levels below 15 mmol/L. In patients refractory to 5 mg/day of folic acid, 750 mg twice daily of trimethylglycine have been used, but there are only limited data demonstrating efficacy.[1] It is known that trimethylglycine enhances the methylation metabolism of homocysteine.

Although treating hyperhomocysteinemia can be very important, it should go without question that the more significant cardiovascular risk factors, such as diabetes, hypertension, hypercholesterolemia, and tobacco use, must also be addressed.