A recent study published in JAMA Network Open determined the relationship between regular multivitamin (MV) supplementation and mortality risk among United States adults.

Background

One in three individuals residing in the United States consumes multivitamins to preserve or enhance health status and prevent disease; hence, knowing the association between MV supplementation and mortality risk is vital for public health guidelines.

The 2022 United States Preventive Services Task Force (USPSTF) examined data on multivitamin use and death risk from randomized controlled trials and concluded that owing to short follow-up duration and external validation, there is inadequate evidence to determine risk-benefit ratios.

Observational studies provide contradictory results, and differences in multivitamin content or confounding factors may explain their varied outcomes. Multivitamin users may be more health-conscious, leading to healthier diets, increased physical activity, and reduced smoking. However, individuals aged >65 years with comorbidities are more likely to use multivitamins, as they have a higher death risk.

About the study

In the present study, researchers investigated whether regular multivitamin usage can lower death risk in the adult US population.

The study included adults with no previous histories of chronic medical conditions and cancer who enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO, 42,732 individuals) trial; the Agricultural Health Study (AHS, 19,660 individuals) or the National Institutes of Health-AARP Diet and Health Study (NIH-AARP, 327,732 individuals).

Each cohort study assessed baseline multivitamin usage between 1993 and 2001, followed by subsequent assessments between 1998 and 2004, and confounder characterization. The researchers followed participants until study termination (NIH-AARP and AHS: December 2019; PLCO: December 2020) or death. They ascertained mortality using the National Death Index (NDI) and cause-specific deaths using the International Classification of Diseases, Ninth Revision (ICD-9) or ICD-10 codes.

The study exposure was self-documented multivitamin usage, and the primary study outcome was death. Participants completed baseline questionnaires to provide multivitamin usage data. The time-varying analyses incorporated follow-up dietary questionnaire data five years, three years, and nine years after initiating the AHS, PLCO, and NIH-AARP studies, respectively.

The researchers performed Cox proportional hazards regression modeling to calculate hazard ratios (HR), adjusting for variables such as age, biological sex, body mass index (BMI), race, ethnicity, educational attainment, physical activity, marital status, alcohol intake, smoking habits, coffee intake, Healthy Eating Index 2015 (HEI-2015) scores, and cancer among family members. They analyzed data between June 2022 and April 2024.

The researchers excluded individuals responding via proxy: those who died before receiving study questionnaires; those who had registry-confirmed or self-reported cancer at study initiation; those who suffered from myocardial infarction, diabetes, end-stage renal disease, or stroke at baseline (n=105,871); those with extreme calorie intake; or those with missing covariate data.

Results

The study included 390,124 individuals: 327,732 from NIH-AARP, 42,732 from PLCO, and 19,660 from AHS. There were 7,861,485 individual years of follow-up. The median participant age was 62 years, and 55% were male.

In total, the researchers noted 164,762 demises in the follow-up period; 41% never smoked, and 40% had attained college-level education. Of the 164,762 deaths, 49,836 resulted from cancer, 35,060 from cardiovascular diseases, and 9,275 from cerebrovascular diseases.

Among regular multivitamin users, 49% and 42% were female with a college-level education, compared to 39% and 38% among those not using multivitamins, respectively. Contrastingly, 11% of regular multivitamin users, compared to 13% of non-users, smoke in current times.

Multivitamin usage was unrelated to a lower risk of any-cause death in the initial or subsequent) follow-up durations. Hazard ratios were comparable for the primary causes of mortality and time-varied assessments.

The team observed qualitative effect modifications by age, BMI, and smoking status but not by biological sex, HEI-2015 scores, race, or ethnicity. In the initial follow-up analysis (FP1), HR values for regular multivitamin usage and any-cause death were higher for individuals aged below 55 years (HR, 1.2).

In FP1, HR estimates for non-regular multivitamin usage and any-cause death were higher for previous and current smokers and individuals with normal BMI. The meta-analysis, incorporating time-varying estimates from all cohorts, showed that regular multivitamin usage, compared to non-usage, was related to a 4.0% higher risk of any-cause death in FP1 but not in FP2.

Conclusion

The study findings do not provide evidence of increased longevity among regular multivitamin users. However, one cannot rule out the possible effects of regular multivitamin usage on other aging-related health outcomes. Further research should include non-observational study designs and more diverse populations to increase the generalizability of the study findings.