Objective: Elevated levels of plasma total homocysteine (tHcy) are identified as independent risk factors for coronary heart disease and for fetal neural tube defects. tHcy levels are negatively associated with folic acid, pyridoxine and cobalamine, and positively associated with coffee consumption and smoking. A total of 600 ml of filtered coffee results in a tHcy increase that 200 mug of folic acid or 40 mg of pyridoxine supplementation might eliminate.

Design: Randomised, blinded study with two consecutive trial periods.

Setting: Free living population. Volunteers.

Subjects: A total of 121 healthy, nonsmoking men and women (78%) aged 29-65 y.

Interventions: (1) A coffee-free period of 3 weeks, (2) 600 ml coffee/day and a supplement of 200 mug folic acid/day or placebo for 4 weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks.

Main outcome measures: The difference between the change in tHcy in the supplement group and the change in tHcy in the placebo group during the 4-week trial period.

Results: Coffee abstention resulted in a tHcy decrease of 1.04 mumol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mumol/l was observed in the folic acid group whereas an increase of 1.26 mumol/l was observed in the placebo group, the difference was 1.43 mumol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels.

Conclusions: Supplementation of 200 mug folic acid/day eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not have the same effect.