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

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

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

Methods: 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 vitamin A, vitamin E, vitamin D, flavanol and multivitamin-mineral(MVM) with age-related diseases (including neuronal aging and ophthalmic aging). Fifteen randomized controlled trial studies with 129,072 participants (adults aged ≥ 18) were finally included in this meta-analysis.

Results: 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%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: 3.49; 95%CI: 2.66 to 4.31; z-score = 8.303; P < 0.001). Multivitamin-mineral (MVM) supplementation group had no highlight on the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and vitamin D showed no effect on cognitive impairment (Relative Risk [RR]: 0.96; 95%CI: 0.86 to 1.08; p = 0.526). In addition, there’s no significant association between vitamin A/vitamin E intake and age-related cataracts.

Conclusions: Flavanol supplementation suggested a pronounced association with postponing neuronal aging while vitamin D showed no corresponding effect. The absence of ​neuroprotective effect from multivitamin-mineral supplementation indicated that single-nutrient targeting (particularly flavanol) may outperform combined nutrient formulations (e.g., MVM) in mitigating neuronal aging processes. No significant associations were observed for vitamin A or E with ophthalmic aging.