Prospective Associations of Serum Vitamin B12, Homocysteine, and Ferritin Levels with Probable Sarcopenia

Background/Objectives: Previous cross-sectional studies investigated the associations of low handgrip strength (HS), a primary indicator of probable sarcopenia (PS), with biomarkers related to anemia. However, existing evidence is inconsistent, and data establishing causality remain limited. The present prospective study aimed to evaluate whether serum vitamin B12, folate, homocysteine (Hcy), and ferritin levels are associated with PS risk. Methods: This study analyzed data from 1930 adults aged 45-76 years who had normal muscle quantity at baseline. Serum biomarkers were assessed at baseline and PS defined by low HS was determined at 6-year follow-up. The modified Poisson regression method was employed to calculate multivariable risk ratios (RRs) and 95% confidence intervals (CIs). Results: Among all participants, PS risk was inversely related to serum vitamin B12 levels (p = 0.06), while it was lowest in the high-normal ranges of serum Hcy (12.1-15 μmol/L) and ferritin (101-200 ng/mL) levels. The RRs (95% CIs) for PS risk were 0.73 (0.60, 0.89) and 0.75 (0.64, 0.87) for high-normal Hcy and ferritin categories, respectively, compared with the lowest category. On examining the associations of elevated Hcy and ferritin levels with PS risk, age was identified as a significant modifier for elevated Hcy levels (>15 μmol/L) (p for interaction < 0.05); a reduced risk was observed in younger participants, whereas an increased risk was noted in older participants. Conclusions: These findings suggest that high-normal ferritin levels may be optimal for alleviating PS risk, irrespective of age, and that elevated Hcy levels could be detrimental for older adults in preventing PS risk.