Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COSMOS trial and meta-analysis of 3 cognitive studies

COSMOS-Clinic randomized 573 older adults to a daily multivitamin or placebo and followed them in person for two years. Episodic memory improved by 0.12 SD (95% CI 0.002-0.23) versus placebo; global cognition narrowly crossed the null and executive function/attention was null. The paper then pooled non-overlapping participants from all three COSMOS cognitive substudies (Clinic 573, Mind 2,158, Web 2,472; total 5,203). The pooled meta-analysis found a global cognition benefit of 0.07 SD (95% CI 0.03-0.11) and an episodic memory benefit of 0.06 SD (95% CI 0.03-0.10). This is replication within one trial program rather than fully independent replication - the same product (Centrum Silver) and overlapping investigator groups. The consistent episodic-memory signal across three substudies is the strongest feature. Effects remain small; a 0.07 SD difference is not noticeable to an individual. The earlier Physicians' Health Study II null trial is not part of this pooled analysis.

In COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory.