Association between micronutrient supplementation and age-related diseases: a meta-analysis of randomized controlled trial studies

Micronutrients in multiple foods have been considered beneficial for human health. However, the role of micronutrient supplementation in postponing aging remains controversial.

To quantify a comprehensive evidence-based impact of micronutrient supplementation on age-related diseases.

Systematic literature searches were conducted in PubMed, Embase, and Web of Science from inception to 23^rd January 2024 for randomized controlled trial studies indicating the association of micronutrient supplementation comprising vitamins A, E, D, flavanol, and multivitamin-mineral (MVM) with age-related diseases (including neuronal aging and ophthalmic aging). Fifteen randomized controlled trial studies with 129072 participants (adults aged ≥ 18) were finally included in this meta-analysis.

Flavanol showed evidence for postponing neuronal aging. Specifically, participants with flavanol supplementation had a better performance in Trail Making Test A (weighted mean difference (WMD): –4.18; 95% confidence interval (CI): –8.02 to –0.33; Z-score = –2.130; P = 0.033) and Trail Making Test B (WMD: –7.91; 95% CI: –10.83 to –4.98; Z-score = –5.297; P < 0.001). In the Verbal Fluency test, the flavanol supplementation group also indicated an improvement (WMD: 2.54; 95% CI: 0.47 to 4.60; Z-score = 2.41; P = 0.016). MVM supplementation group showed no significant improvement in the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) performance and vitamin D showed no effect on cognitive impairment (relative risk: 0.96; 95% CI: 0.86 to 1.08; P = 0.526). In addition, there was no significant association between vitamin A/vitamin E intake and age-related cataracts.

Flavanol supplementation suggested a potential association with postponing neuronal aging while vitamin D showed no corresponding effect. The unconfirmed neuroprotective effect of MVM supplementation indicated that combined nutrient formulations may not outperform single-nutrient targeting in mitigating neuronal aging processes. No significant associations were observed for vitamin A or E with ophthalmic aging.