The causal association between plasma caffeine and frailty: A two-sample mendelian randomization study

Abstract

Background

Frailty is one of the most common and challenging consequences of aging, which negatively affects older adults, their families, and society. Caffeine has been shown to be associated with a reduced risk of frailty by observational studies, yet its causal relationship with frailty remains to be tested using more robust methods.

Aims

This study aimed to explore the causal association between plasma caffeine and frailty using a two-sample Mendelian Randomization (MR) analysis.

Methods

Single nucleotide polymorphisms related to plasma caffeine concentrations were selected as instrumental variables. Data on the Frailty Index (FI) were sourced from the UK Biobank and TwinGen meta-analysis (n = 175,226), while data on the Fried Frailty Score (FFS) were obtained from the UK Biobank (n = 386,565). The causal association between plasma caffeine levels and frailty was tested using five MR methods, with the inverse-variance weighted method as the primary approach.

Results

Our results consistently showed significantly negative associations between genetically predicted plasma caffeine with FI (β = -0.050, 95 % CI:0.077 to -0.023, P < 0.001) and FFS (β = -0.049, 95 % CI:0.064 to -0.034, P < 0.001). These results remained robust in further sensitivity analyses using a leave-one-out approach.

Conclusion

Our findings confirm a causal relationship between plasma caffeine and frailty and suggest that increasing plasma caffeine levels may help prevent and reduce the risk of frailty.