Elevated homocysteine is associated with poorer self-perceived physical health in older men: the Health in Men Study.

Objectives: To determine the relationship between high total homocysteine (tHcy) and self-perceived physical health, by investigating the associations between tHcy, the methylenetetrahydrofolate reductase (MTHFR) 677T polymorphism and physical health-related quality of life (HRQOL).

Study Design: We conducted a cross-sectional study using a cohort of 4248 community-dwelling men aged 70-88 years.

Main Outcome Measures: In addition to clinical determinants of physical health, tHcy was measured by immunoassay, the MTHFR 677T polymorphism was detected by a polymerase chain reaction (PCR)-based method, and physical HRQOL were assessed with the SF-36 Health Survey.

Results: In multiple regression analyses, the odds of being in the lowest quartile of the physical component summary (PCS) scores (i.e. <35) was 1.47 (95% CI 1.21-1.78) for men with high tHcy (≥15 μmol/l), after adjusting for age, smoking, history of hazardous alcohol use, polypharmacy, prevalent falls and weighted Charlson co-morbidity index. When history of hypertension, heart disease, stroke, arthritis and osteoporosis were included in place of the Charlson's index, the result was unchanged (OR 1.45, 95% CI 1.20-1.75). Men with the MTHFR TT homozygosity had significantly higher tHcy concentration than those with the CC genotype (mean difference of 1.38 μmol/l, 95% CI 0.77-1.99). However, there was no apparent association between the MTHFR polymorphism and PCS.

Conclusion: Elevated tHcy is associated with poorer self-perceived physical health in community-dwelling older men. The results of this study support further longitudinal investigations to assess this relationship prospectively.