BACKGROUND/AIMS: In ageing, low folates and vitamin B12 status are frequent and can explain the increase of plasma homocysteine level. Zinc is involved in the folates and vitamin B12 metabolism with opposite actions. The aim of this study was to investigate the effects of zinc supplementation on homocysteine and vitamin B12 plasma levels as well as red blood cell folate level in French ageing subjects participating in the ZENITH study. METHODS: Apparently healthy middle-aged (55-70 years) and free-living older (70-85 years) subjects were enrolled. They were randomly allocated to three groups: 0, 15 or 30 mg Zn per day for 6 months as zinc gluconate in addition to their usual dietary intake. RESULTS: At baseline, plasma homocysteine levels (15.2+/-3.5 micromol/L) in older people were higher than in the middle-aged subjects (12.7+/-2.7 micromol/L) and was negatively correlated with vitamin B12 values (p=0.0036, r=-0.215) and with RBC folate levels (p<0.0001, r=-0.30). These results are in agreement with previous data. However, we found no correlation between the biomarkers of zinc status and homocysteine, vitamin B12 or folate levels at baseline. Moreover, 6-month zinc supplementation did not modify homocysteine, vitamin B12 and RBC folate values in either of the groups. CONCLUSIONS: Zinc supplementation at moderate doses do not lead to deleterious effect on folate or vitamin B12 status in ageing healthy free-living people, but does not have any beneficial effects on homocysteine metabolism either.