The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study

Objectives: To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine, an independent risk factor for occlusive vascular disease, in a general population. Design: A randomized double-blind placebo-controlled intervention study. Subjects: One hundred and nineteen healthy volunteers, whose intake of fortified or supplemental folic acid was low, were recruited by letter from the patient register of a large inner-city group general practice. Methods: Volunteers were randomized to receive unfortified cereals, or cereals fortified with 200 mu g of folic acid per portion, with or without other vitamins. Blood samples were taken presupplement and at 4, 8 and 24 weeks on treatment and analysed for plasma homocysteine, cysteine and vitamin B12 and serum and red cell folate. Ninety-four subjects completed the study providing blood samples on all four occasions. Results: There were no significant changes in any measured parameter in those eating unfortified cereals. Overall. folic acid fortification of cereals led to significant increases (P < 0.001) in serum folate (66%), and red cell folate (24%), and a decrease in plasma homocysteine (10%; P < 0.001). There were no changes in vitamin B12 or cysteine. The homocysteine decrease persisted until the end of the study and was primarily seen in those who initially had the highest plasma homocysteine or the lowest serum folate. Conclusions: If homocysteine is found to be a causative risk factor in occlusive vascular disease, food fortification with physiological levels of folic acid should have a significant impact on the prevalence of the disease in the general population.