Five hundred and six individuals (aged 40-89 years) with a plasma homocysteine level greater than 8.5 umol/L but without diabetes or cardiovascular disease were randomly assigned to receive, in double-blind fashion, daily B vitamins (5 mg of folic acid, 50 mg of vitamin B6, and 0.4 mg of vitamin B12) or placebo for 3.1 years. Among subjects with a baseline homocysteine level of 9.1 umol/L or greater, the rate of progression of carotid artery intima media thickness (a measure of the severity of atherosclerosis) was significantly less in the active-treatment group than in the placebo group (p=0.02). Treatment with B vitamins had no significant effect among subjects with a baseline homocysteine level less than 9.1 umol/L.
Comment by Alan Gaby, MD
An elevated plasma homocysteine level is a risk factor for cardiovascular disease, thromboembolism, stroke, osteoporosis, recurrent miscarriages, other pregnancy complications, and cognitive decline (including dementia and Alzheimer's disease). Numerous studies have examined whether homocysteine actually causes disease, or whether it is simply a risk indicator. Several lines of evidence support the concept that homocysteine, a byproduct of methionine metabolism, is a toxic molecule. However, clinical trials in which homocysteine-lowering therapies were administered have produced conflicting results. One possible explanation for the failure of some studies to show a benefit is that treatment with just a few nutrients may cause imbalances of other nutrients. For example, supplementation with vitamin B6 may increase magnesium requirements, and administration of large doses of folic acid may deplete zinc. Thus, a comprehensive nutritional program might produce better results than simply giving a few B vitamins.
In addition, folic acid, vitamin B6, and vitamin B12 work primarily by lowering fasting homocysteine levels, whereas they have less of an effect on postprandial homocysteine levels. In contrast, betaine and choline, which have not been used in any of the homocystieine-lowering clinical trials, are more effective for decreasing postprandial homocysteine. Most of us spend most of our waking hours and some of our sleeping hours in the postprandial state, and there is evidence that the adverse effects of homocysteine are related more to peak (i.e.: postprandial) than to the fasting concentrations. Therefore, it might be necessary to include betaine and choline in homocysteine-lowering regimens in order to achieve the maximum clinical benefit.
Hodis HN, Mack WJ, Dustin L, et. al. High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial. Stroke. 2009;40:730-736.
Reprinted with exclusive permission of Townsend Letter for Doctors and Patients, Jan 2010