QJM, Vol 90, Issue 8 519-524, Copyright © 1997 by Oxford University Press
M Ward, H McNulty, J McPartlin, JJ Strain, DG Weir and JM Scott
Elevated plasma homocysteine, an independent risk factor for cardiovascular
disease (CVD) can be lowered by administration of pharmacological doses of
folic acid. The effect of lower doses in apparently normal subjects is
currently unknown but is highly relevant to the question of food
fortification. Healthy male volunteers (n = 30) participated in a chronic
intervention study (26 weeks). Folic acid supplements were administered
daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms
(6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected
before, during and 10 weeks post intervention were analysed for plasma
homocysteine, serum and red- cell folate levels. Results, expressed as
tertiles of baseline plasma homocysteine concentration, showed significant
(p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83
mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low
tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84
mumol/l, no significant response was observed. Of the three folic acid
doses, 200 micrograms appeared to be as effective as 400 micrograms, while
100 micrograms was clearly not optimal. There is thus a minimal level of
plasma homocysteine below which folic acid has no further lowering effect,
probably because an optimal folate status has been reached. A dose as low
as 200 micrograms/day of folic acid is effective in lowering plasma
homocysteine concentrations in apparently normal subjects. Any public
health programme for lowering homocysteine levels, with the goal of
diminishing CVD risk, should not be based on unnecessarily high doses of
folic acid.
ORIGINAL PAPERS
Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid
Human Nutrition Research Group, University of Ulster, Coleraine, UK.
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