[Recommended dietary allowance of folic acid is insufficient for optimal homocysteine levels]

Abstract

Objective: To determine the effect of short term supplementation of vitamin B6 (pyridoxine) followed by folic acid in apparently healthy volunteers on the fasting plasma homocysteine concentrations (hyperhomocysteinaemia is an independent risk factor for premature atherosclerosis).

Design: Prospective, descriptive.

Setting: Academic Hospital Groningen, the Netherlands.

Methods: Apparently healthy Dutch volunteers, aged 20-75 years, were supplemented with vitamin B6 1 mg/kg/day during 7 days followed by folic acid 5 mg/day during another 7 days. On days 0, 7 and 14 the fasting plasma homocysteine concentrations were measured. A change of an individual's plasma homocysteine level was considered statistically significant if the change in percentage exceeded 2.8 times the sum of the analytical and the intraindividual biological variation.

Results: There were 103 participants, 45 males and 58 females, with average ages of 43 and 44 years, respectively (on day 7, data were available on 101 participants). Baseline folic acid concentrations of all participants were above the lower limit of the reference range. Eight and two of them had vitamin B6 and vitamin B12 concentrations below the reference range, respectively. Plasma homocysteine was inversely related to plasma levels of folic acid and vitamin B12 at that moment. During vitamin B6 supplementation the mean plasma homocysteine level did not change; one participant exhibited a significant plasma homocysteine decrease. During folic acid supplementation the mean plasma homocysteine decreased from 11.7 mumol/l (SD: 5.6) to 9.1 (SD: 3.4); 40 participants (40%) exhibited significant plasma homocysteine decreases. At the end of the study plasma homocysteine was still related to plasma vitamin B12.

Conclusion: The folic acid status of the participants at baseline was not associated with the lowest plasma homocysteine levels. Since atherosclerosis risk may increase continuously with increasing plasma homocysteine, it may be wise to keep plasma homocysteine levels as low as possible. To reach this goal, the recommended dietary allowance of folic acid may have to be increased.