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* Wageningen Centre for Food Sciences, Nutrition and Health Programme, Wageningen, the Netherlands;
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, the Netherlands; and
** Department of Nutritional Physiology, TNO Nutrition and Food Research, Zeist, the Netherlands
4To whom correspondence should be addressed. E-mail: petra.verhoef{at}wur.nl.
Elevated levels of plasma total homocysteine are associated with a higher risk of cardiovascular disease. Betaine and 5-methyltetrahydrofolate can remethylate homocysteine into methionine via independent reactions. We determined the effect of daily betaine supplementation, compared with both folic acid and placebo, on plasma concentrations of total homocysteine after an overnight fast and after methionine loading in men and women with mildly elevated homocysteine. Groups of twelve subjects ingested 6 g betaine, 800 µg folic acid with 6 g placebo or 6 g placebo each day for 6 wk. A methionine-loading test (i.e., ingestion of 100 mg L-methionine/kg body mass) was performed before and after 6 wk of supplementation. Fasting plasma homocysteine decreased by 1.8 µmol/L (95% confidence interval [CI]: -3.6, 0.0, P < 0.05) in the betaine group and by 2.7 µmol/L (95% CI: -4.5, –0.9, P < 0.05) in the folic acid group. These changes are relative to the change in the placebo group, in which fasting plasma homocysteine rose by 0.5 µmol/L. Furthermore, betaine suppressed the total area under the plasma homocysteine-time curve after methionine loading by 221 µmol · 24 h/L (95% CI: -425, –16, P < 0.05) compared with placebo, whereas folic acid had no effect. In conclusion, betaine appears to be highly effective in preventing a rise in plasma homocysteine concentration after methionine intake in subjects with mildly elevated homocysteine. It is not known whether this potential of betaine to "stabilize" circulating homocysteine concentrations lowers the risk of cardiovascular disease.
KEY WORDS: • homocysteine metabolism • betaine • folic acid • methionine-loading test • intervention study
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