Vitamin B levels in older adults with pre-frailty and frailty: the impact of MTHFR and TCN2 polymorphisms and their association with global DNA methylation and physical performance.

Background: Frailty syndrome poses significant challenges in older populations. Understanding the genetic and biochemical factors associated with frailty is essential for effective management strategies.

Methods: In this study, Thai older adults (≥ 60 years, n = 170) were assessed for physical parameters, levels of B vitamins, creatinine, and homocysteine. The polymorphisms of methylenetetrahydrofolate reductase (MTHFR) (677 C > T) and Transcobalamin II (TCN2) 776G > C were identified. Global DNA methylation (global DNAm) was assessed using a colorimetric assay.

Results: Participants were categorised into robust (n = 61), pre-frail (n = 62), and frail (n = 47) groups by Fried criteria and Kihon checklist. The physical parameters, including chair stand, functional reach, gait speed, and handgrip strength, showed highly significant differences among the groups (p < 0.01). Significant differences in folate and vitamin B concentrations were observed between MTHFR and TCN2 genotypes, respectively. In addition, global DNAm levels were significantly lower in pre-frail individuals, particularly among those carrying the MTHFR C677T genotype, compared to both robust and frail groups. Notably, lower global DNAm was associated with a higher likelihood of being classified as pre-frail rather than frail, and a lower likelihood of being pre-frail compared to robust individuals. Moreover, correlation analyses revealed significant associations among physical parameters, clinical characteristics, and global DNAm.

Conclusions: This study demonstrated the interplay between genetic variants, micronutrient status, and epigenetic modifications in the context of frailty among older adults. These findings highlight the potential of epigenetic and metabolic markers in identifying early frailty, though longitudinal and mechanistic studies are needed to further clarify causal pathways.

Trial Registration: This study was duly registered with the Thai Clinical Trial under the identifier TCTR20240626002 (date of registration: 21/06/2024).