Micronutrient Supplementation in Frailty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background/Objectives: Low levels of vitamins and minerals are linked to increased frailty, but the effectiveness of micronutrient supplementation remains debated. Methods: A systematic search of PubMed and Embase (end of search 10 June 2025) identified 21 randomized controlled trials from 33 articles assessing supplementation in frail individuals. Results: Regarding vitamin D supplementation, seven studies (2600 participants) reported all-cause mortality (pooled RR: 1.04, 95% CI: 0.83 to 1.31, I² = 35%) with moderate certainty of evidence, whereas only one study reported on the change in frailty levels. For multicomponent supplementation, four studies (180 participants) were identified on all-cause mortality, and two studies on change in frailty levels (pooled MD = -0.28, 95% CI: -0.71 to 0.16, I² = 0%) with very low certainty of evidence for both outcomes. Only one study investigated nicotinamide supplementation. Conclusions: Further research is needed to justify the prescription of micronutrient supplementation in this population. Future research in frailty should focus on longitudinal change in frailty levels, cognitive function, and functional measures.