Written by Marcia Egles, MD.
Homocysteine is an amino acid product formed during the folate-mediated metabolism of methionine, an essential amino acid. Several prospective studies have shown homocysteine to be associated with cardiovascular events. (1) Research is currently ongoing to help determine if homocysteine causes cardiovascular disease or is merely a marker associated with it. (1, 2) Folic acid supplements have been shown to lower homocysteine levels in multiple studies. (3, 4)
A recent study demonstrated that low-dose (400 mg per day) folic acid supplementation was effective in lowering elevated homocysteine levels, particularly in cardiac patients with a genetic variant of homocysteine metabolism. This variant of methylene tetrahydrofolate reductase (MTHFR), an enzyme that metabolizes homocysteine, is found in about 15 % of the white population (1) and is associated with mild to moderate elevations of homocysteine levels, especially in the setting of low folate intake.
Forty–two male and four female coronary artery disease patients completed the eight-week, Taiwanese study. Subjects with diabetes or other major illnesses were excluded, as were those currently taking B vitamin supplements. Participants were randomly assigned to either a placebo group or the low-dose folic acid group. Genetic testing determined that three persons in the control group and five in the treatment group had the MTHFR-variant genes. Patients completed dietary assessments and had blood folate measurements at the start, at 4 weeks and at 8 weeks. Compliance was aided by telephone reminders.
The study found that at baseline, the two groups had similar homocysteine levels and similar normal folate levels. The folate levels were noted to significantly increase in the folic acid group by 8 weeks. Those patients with high homocysteine, but with the normal genetic type, had reductions in homocysteine of 12.6%. Those with the MTHFR genetic type had a 14.4% reduction in homocysteine. Those in the study with normal homocysteine levels stayed at normal levels without reductions. Those in the control group had no changes in homocysteine levels.
The researchers concluded that 400mg folic acid was an appropriate daily dose to lower homocysteine levels in hyperhomocysteinemic patients with coronary artery disease, especially for those with the MTHFR genetic type. Their review of other studies using higher dosages of folic acid suggested a “plateau effect” with no additional reductions in homocysteine levels achieved.
Source: Lin, Ping-Ting, Bor-Jen Lee, Han-Hsin Chang, Chien-Hsiang Cheng, An-Jung Tsai, and Yi-Chia Huang. “Low-dose folic acid supplementation reduces homocysteine concentration in hyperhomocysteinemic coronary artery disease patients.” Nutrition research 26, no. 9 (2006): 460-466.
© 2006 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
Posted July 22, 2008.
References:
- Iftikar J. Kullo, MD, C. Ballatyne, MD, Conditional risk factors for atherosclerosis, Mayo Clinic Proceedings. 2005:80:219-230.
- B- Vitamin Treatment Trialist Collaboration; Homocysteine-lowering trials for the prevention of cardiovascular events: a review of the design and power of large randomized trials. American Heart Journal. 2006 Feb: 151 (2): 282-7.
- J.B. Ubbink et al., Vitamin requirements for the treatment of hyperhomocysteinemia in humans, J. Nutr, 124(1994), 1927-1933
- I.A. Brouwer, et al., Low-dose folic acid supplementation decreases homocysteine concentrations: a randomized trial, American Journal of Clinical Nutrition, 69 (1999), 99-104.
