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

## TL;DR

This review finds that evidence for vitamin D and other micronutrient supplements in treating frailty is weak, and more research is needed to determine their effectiveness.

## Contribution

The study provides a systematic review and meta-analysis of randomized trials on micronutrient supplementation for frailty, highlighting the low quality of evidence.

## Key findings

- Vitamin D supplementation showed no significant effect on all-cause mortality with moderate evidence.
- Multicomponent supplementation had very low certainty evidence for changes in frailty levels.
- Frailty measurements in trials are inconsistent, limiting the reliability of results.

## Abstract

What are the main findings?
The quality of published evidence for vitamin D and multicomponent supplementation is low or very low for most outcomes, and clinicians should be aware of this fact before prescribing them.Frailty is inconsistently measured in published clinical trials.
What are the implication of the main findings?
Future research should focus on patient-oriented outcomes, such as changes in frailty levels, functional status, and cognitive function.Providers should be aware of the low certainty of evidence when prescribing micronutrient supplements.

The quality of published evidence for vitamin D and multicomponent supplementation is low or very low for most outcomes, and clinicians should be aware of this fact before prescribing them.

Frailty is inconsistently measured in published clinical trials.

Future research should focus on patient-oriented outcomes, such as changes in frailty levels, functional status, and cognitive function.

Providers should be aware of the low certainty of evidence when prescribing micronutrient supplements.

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.