Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial

Abstract

Background: Although older adults commonly take multivitamin-multimineral (MVM) supplements to promote health, evidence on the use of daily MVMs on invasive cancer is limited.

Objectives: The study objective was to determine if a daily MVM decreases total invasive cancer among older adults.

Methods: We performed a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of a daily MVM and cocoa extract for prevention of cancer and cardiovascular disease (CVD) among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y) free of major CVD and recently diagnosed cancer. The intervention phase was from June 2015 through December 2020. This article reports on the MVM intervention. Participants were randomly assigned to daily MVM or placebo. The primary outcome was total invasive cancer, excluding nonmelanoma skin cancer. Secondary outcomes included major site-specific cancers, total CVD, all-cause mortality, and total cancer risk among those with a baseline history of cancer.

Results: During a median follow-up of 3.6 y, invasive cancer occurred in 518 participants in the MVM group and 535 participants in the placebo group (HR: 0.97; 95% CI: 0.86, 1.09; P = 0.57). We observed no significant effect of a daily MVM on breast cancer (HR: 1.06; 95% CI: 0.79, 1.42) or colorectal cancer (HR: 1.30; 95% CI: 0.80, 2.12). We observed a protective effect of a daily MVM on lung cancer (HR: 0.62; 95% CI: 0.42, 0.92). The composite CVD outcome occurred in 429 participants in the MVM group and 437 participants in the placebo group (HR: 0.98; 95% CI: 0.86, 1.12). MVM use did not significantly affect all-cause mortality (HR: 0.93; 95% CI: 0.81, 1.08). There were no safety concerns.

Conclusions: A daily MVM supplement, compared with placebo, did not significantly reduce the incidence of total cancer among older men and women. Future studies are needed to determine the effects of MVMs on other aging-related outcomes among older adults. This trial is registered at www.clinicaltrials.gov as NCT02422745.

Keywords: cancer; cardiovascular disease; cocoa extract; flavanols; multivitamin; randomized clinical trial.

FIGURE 1

Screening, randomization, and follow-up of the participants. ¹Eligibility was determined by medical history, age, and willingness to forego personal use of cocoa extract and multivitamin pills. ²Eligibility was determined by medical history, age, willingness to forego personal use of cocoa extract and multivitamin pills, caffeine sensitivity, and willingness to limit calcium and vitamin D supplement use. ³Included subjects who never completed the screening phase (n = 2914), eligibility could not be determined (n = 5), and enrollment goal already met (n = 55). ⁴Included subjects who never completed screening phase (n = 168) and enrollment goal already met (n = 54).

FIGURE 2

HRs and 95% CIs¹ for the primary and secondary cancer outcomes, according to randomized assignment, in intention-to-treat analyses. ¹Summary statistics were from Cox regression models that stratified baseline hazard functions by cocoa extract trial randomization group, age, sex, and recruitment cohort. Analyses were not adjusted for multiple comparisons. ²This outcome was a composite of invasive cancers of any site other than nonmelanoma skin cancer.

FIGURE 3

Cumulative incidence rates of invasive cancer events,¹ according to year of follow-up, in multivitamin group and placebo group. ¹Primary outcome: a composite of invasive cancers of any site other than nonmelanoma skin cancer. Summary statistics were from Cox regression models that stratified baseline hazard functions by cocoa extract trial randomization group, age, sex, and recruitment cohort (intention-to-treat analyses). P value was for the effect of randomization group, based on a stratified score (log-rank) test.

FIGURE 4

HRs and 95% CIs¹ for secondary cardiovascular disease outcomes, according to randomized assignment, in intention-to-treat analyses. ¹Summary statistics were from Cox regression models that stratified baseline hazard functions by cocoa extract trial randomization group, age, sex, and recruitment cohort. Analyses were not adjusted for multiple comparisons. ²This outcome was a composite of myocardial infarction, stroke, cardiovascular death, CABG/PCI, unstable angina including hospitalization, carotid artery surgery, and peripheral artery surgery or angioplasty. ³This outcome was a composite of myocardial infarction, stroke, and cardiovascular death. CABG/PCI, coronary artery bypass graft and percutaneous coronary intervention; CVD, cardiovascular disease.