Abstract Background Homocysteine, an intermediate metabolite derived from dietary methionine, plays a pivotal role in deoxyribonucleic acid expression and contribute to its antioxidant capabilities. Elevated homocysteine levels can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorder; however, low levels of homocysteine are generally not considered harmful. This study evaluates the association between all levels of homocysteine-both low and high-and the risk of all-cause and cause-specific mortality in Korean adult men. Methods A study involving 221,356 Korean adult men categorized them into quintiles based on their homocysteine levels. The main outcomes examined were mortality from all causes, cardiovascular disease (CVD), cancer, and dementia. Hazard ratios (HRs) were determined using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further analyzed using a restricted cubic splines model. Results Compared to the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high homocysteine levels after adjusting for multiple variables (Pinteraction=0.002). Furthermore, spline regression revealed a U-shaped relationship between homocysteine levels and both all-cause and CVD mortality, with an inflection point at 9.1 µmol/L. This U-shaped association was not observed in the subgroup that received vitamin supplements. Conclusions Among young and middle-aged Korean adult men, both low and high homocysteine levels were found to increase the risk of all-cause and CVD mortality, demonstrating a U-shaped relationship. However, this association lost statistical significance with vitamin supplementation. These findings underscore the importance of monitoring both low and high homocysteine levels as potential mortality risk factors in men and suggest a possible protective role of vitamins. Key messages • Both low and high levels of homocysteine in young and middle-aged Korean men are associated with increased risks of all-cause and cardiovascular mortality, demonstrating a U-shaped relationship. • Vitamin supplementation appears to nullify this association, suggesting a potential protective effect against mortality.
Read full abstract