Protein Nutritional Status and Frailty: A Mendelian Randomization Study

Background: Observational studies have suggested that better protein nutritional status may contribute to prevention of frailty. Objective: We sought to examine this hypothesis using a Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR study using GWAS summary statistics data of the UK Biobank. We applied genetically predicted serum albumin as a primary exposure measure and serum total protein as a secondary exposure measure. The outcome measure was the Rockwood frailty index (FI) based on 49 deficits from 356,432 individuals (53.3% of them were women, with a mean +/- SD age of 56.7 +/- 8.0 y. The association between serum protein measures and FI was mainly analyzed by use of the inverse variance weighted method. Results: A genetically predicted serum albumin concentration was not statistically significantly associated with FI in the full sample. However, in women, we observed a preventive association between genetically predicted serum albumin and FI (beta = -0.172 per g/L; 95% CI: -0.336, -0.007; P= 0.041). In the full sample, genetically predicted serum total protein was inversely associated with FI (beta: -0.153 per g/L; 95% CI: -0.251, -0.056; P= 0.002). In both women and men, higher serum total protein was significantly inversely associated with FI; regression coefficients were -0.148 per g/L (95% CI: -0.287, -0.009; P= 0.037) for women, -0.154 per g/L (95% CI: -0.290, -0.018; P= 0.027) for men. Conclusions: The present MR study implies that better protein nutritional status modestly contributes to reducing the risk of frailty.