ORIGINAL COMMUNICATION Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study E Strandhagen 1 *, S Landaas 2 and DS Thelle 1 1 Department of Medicine, Cardiovascular Institute, Sahlgrenska University Hospital/O ¨ stra, Go¨teborg, Sweden; and 2 Department of Clinical Chemistry, Ulleva˚l University Hospital, Oslo, Norway 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 mg 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 mg 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 mmol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mmol/l was observed in the folic acid group whereas an increase of 1.26 mmol/l was observed in the placebo group, the difference was 1.43 mmol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels. Conclusions: Supplementation of 200 mg 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. Sponsorship: None. European Journal of Clinical Nutrition (2003) 57, 1411–1417. doi:10.1038/sj.ejcn.1601703 Keywords: controlled study; filtered coffee; homocysteine; folic acid; pyridoxine Introduction Elevated concentrations of the endogenous sulphur amino compound, homocysteine (total homocysteine, tHcy), have been identified as an independent risk factor for coronary heart disease (Clarke et al, 1991; Boushey et al, 1995; Ueland et al, 2000), recurrent early spontaneous abortions (Wouters et al, 1993; Goddijn-Wessel et al, 1996; Nelen et al, 2000), neural tube defects (Vollset et al, 2000a, b; Refsum, 2001) as well as other reproductive and fetal hazards (Leeda et al, 1998; Sorensen et al, 1999). The levels of plasma and serum tHcy are increased not only in folate deficiency, but also at folate levels in the lower reference range (Jacobsen et al, 1994). tHcy levels are also depending upon the availability of the other B-vitamins, pyridoxine (vitamin B 6 ) and cobala- mine (vitamin B 12 ). These associations are reflected in population studies such as the Hordaland Homocysteine Study where the major determinants for tHcy variation were age, sex, smoking, dietary folic acid intake, vitamin supple- ments and coffee consumption (Nygard et al, 1995). The relation between coffee and tHcy has been observed in a number of cross-sectional studies around the world and the effect of coffee on tHcy varies between 0.8 and 1.3 mmol/l for a change in coffee consumption of three to four cups (Stolzenberg-Solomon et al, 1999; Jacques et al, 2001; Saw Received 8 June 2002; revised 26 November 2002; accepted 28 November 2002 *Correspondence: E Strandhagen, Department of Medicine, Cardiovascular Institute, Sahlgrenska University Hospital/O ¨ stra SE-416 85 Go ¨teborg, Sweden. E-mail: elisabeth.strandhagen@hjl.gu.se European Journal of Clinical Nutrition (2003) 57, 1411–1417 & 2003 Nature Publishing Group All rights reserved 0954-3007/03 $25.00 www.nature.com/ejcn