Multivitamins in the prevention of cancer and cardiovascular disease

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

The objective of this study was therefore to determine if a daily MVM decreases total invasive cancer among older adults. For this purpose,  a team of researchers 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.

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). No significant effect was observed 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). The researchers 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.

The authors concluded that 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 is an excellent and important study with clear findings. Nevertheless, the authors insist that several limitations should be considered. First, the COSMOS intervention was relatively short to detect a potential small-to-moderate effect on cancer outcomes given the long duration of time typically required for nutritional interventions to potentially reduce cancer risk. Second, the secondary and exploratory analyses should be interpreted with caution, especially given an overall lack of effect of an MVM on the primary outcome of total invasive cancer. Third, the authors successfully leveraged existing cohorts with mass mailings to expedite recruitment and randomization of 21,442 participants into COSMOS. However, generalizability may be limited, with modest diversity of 10% non-Whites and 2.6% Hispanics plus healthy volunteer bias for participants willing and eligible to enroll in a mail-based clinical trial.