Changes in lifestyle and total homocysteine in relation to MTHFR(C677T) genotype: the Inter99 study

Background: Reduction in total homocysteine (tHcy) may be clinically relevant in the prevention of cardiovascular disease (CVD) in the general population. Objective: To examine the effects of changes in various lifestyle habits and lifestyle related biological CVD risk markers on changes in tHcy in relation to MTHFR(C677T) genotype. Design: A 1 year follow-up study. Setting: Copenhagen County, Denmark. Subjects: Statistical analyses were based on a population-based sample of 915 men and women aged 30-60 years assessed to be at increased CVD risk at baseline and therefore offered lifestyle intervention and re-examination after one year. Results: None of the studied lifestyle changes-smoking, physical activity, dietary habits, and coffee, tea, and alcohol consumption-was significantly associated with changes in tHcy, either overall, or in any of the MTHFR genotype subgroups. In addition, changes in tHcy did not differ between participants randomized to low- and high-intensity lifestyle intervention. However, the MTHFR TT genotype was associated with a significant decrease in tHcy compared with the CC/CT genotype in which an increase was observed. In addition, changes in tHcy were associated with changes in several of the biological CVD risk markers: weight, total cholesterol, HDL cholesterol, LDL cholesterol and systolic blood pressure. Conclusions: Our results indicate that tHcy may not be reduced by lifestyle changes; additionally, they suggest that tHcy may be related to biological CVD risk markers through a lifestyle independent pathway. Sponsorships: Danish Heart Foundation, Danish Medical Research Council, Danish Centre for Evaluation and Health Technology Assessment.