Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS

Am J Clin Nutr. 2024 Jan 18:S0002-9165(23)66342-7. doi: 10.1016/j.ajcnut.2023.12.011. Online ahead of print.


Background: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline.

Objectives: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition.

Methods: COSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472).

Results: In COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (-0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (-0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y.

Conclusions: 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. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults. This trial was registered at COSMOS-clinicaltrials.gov as NCT02422745, at COSMOS-Mind-clinicaltrials.gov as NCT03035201, and at COSMOS-Web-clinicaltrials.gov as NCT04582617.

Keywords: cognition; geriatric; meta-analysis; multivitamin-multimineral supplementation; randomized clinical trial.

Associated data

  • ClinicalTrials.gov/NCT03035201
  • ClinicalTrials.gov/NCT04582617
  • ClinicalTrials.gov/NCT02422745