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 diet ary folic acid on the concentration of plasma homocysteine, an indepen dent risk factor for occlusive vascular disease, in a general populati on. Design: A randomized double-blind placebo-controlled intervention study. Subjects: One hundred and nineteen healthy volunteers, whose in take of fortified or supplemental folic acid was low, were recruited b y 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 presupplemen t and at 4, 8 and 24 weeks on treatment and analysed for plasma homocy steine, 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 fo rtification of cereals led to significant increases (P < 0.001) in ser um folate (66%), and red cell folate (24%), and a decrease in plasma h omocysteine (10%; P < 0.001). There were no changes in vitamin B12 or cysteine. The homocysteine decrease persisted until the end of the stu dy and was primarily seen in those who initially had the highest plasm a homocysteine or the lowest serum folate. Conclusions: If homocystein e is found to be a causative risk factor in occlusive vascular disease , food fortification with physiological levels of folic acid should ha ve a significant impact on the prevalence of the disease in the genera l population.