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Study of healthy adults over 20 years shows that daily intake of multivitamin supplements is not associated with a reduction in mortality

Study of healthy adults over 20 years shows that daily intake of multivitamin supplements is not associated with a reduction in mortality
Study of healthy adults over 20 years shows that daily intake of multivitamin supplements is not associated with a reduction in mortality

A recently published study in the JAMA Network Open determined the relationship between regular multivitamin (MV) supplement use and the risk of death among adults in the United States.

Study: Multivitamin use and risk of death in three prospective US cohorts. Image credit: Sergii Sobolevskyi/Shutterstock.com

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One in three people in the United States takes multivitamins to maintain or improve their health and prevent disease, so understanding the association between multivitamin use and risk of death is critical to public health guidelines.

In 2022, the United States Preventive Services Task Force (USPSTF) examined data on multivitamin use and risk of death from randomized controlled trials and concluded that due to short follow-up periods and external validation, there is insufficient evidence to determine the benefit-risk ratio.

Observational studies provide conflicting results, and differences in multivitamin content or confounding factors may explain the different results. Multivitamin users may be more health conscious, leading to a healthier diet, increased physical activity, and less smoking. However, people over 65 years of age with comorbidities are more likely to use multivitamins because they are at higher risk of death.

About the study

In the present study, researchers investigated whether regular multivitamin intake can reduce the risk of death in the U.S. adult population.

The study included adults who were free of chronic diseases and cancer and who participated in the Prostate, Lung, Colon, and Ovarian Cancer Screening Study (PLCO, 42,732 individuals), 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 multivitamin use at baseline between 1993 and 2001, followed by further assessments between 1998 and 2004 and characterization of confounders. Researchers followed participants until study end (NIH-AARP and AHS: December 2019; PLCO: December 2020) or death. They determined mortality using the National Death Index (NDI) and cause-specific deaths using International Classification of Diseases, 9th Revision (ICD-9) or ICD-10 codes.

Study exposure consisted of self-reported multivitamin supplement use, and the primary study outcome was death. Participants completed baseline questionnaires to provide data on multivitamin supplement use. Time-dependent analyses included data from dietary questionnaires collected five, three, and nine years after the start of the AHS, PLCO, and NIH-AARP studies.

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

The researchers excluded people who responded by proxy: those who died before receiving the study questionnaires; those who had cancer at the start of the study and had it confirmed in the registry or self-reported; those who had a heart attack, diabetes, end-stage renal failure, or stroke at the start of the study (n=105,871); those with extreme caloric intake; or those whose covariate data were missing.

Results

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

In total, the researchers registered 164,762 deaths during the observation period; 41% of them had never smoked and 40% had completed a university education. Of the 164,762 deaths, 49,836 were due to cancer, 35,060 to cardiovascular disease and 9,275 to cerebrovascular disease.

Among regular multivitamin users, 49% and 42% were female and had a college degree, respectively, compared with 39% and 38% among those who did not take multivitamins. In contrast, 11% of regular multivitamin users currently smoke, compared with 13% of non-users.

Multivitamin use was not associated with a lower risk of death from any cause during the initial or subsequent follow-up periods. Hazard ratios were comparable for the major causes of death and the time-dependent assessments.

The team found qualitative effect changes by age, BMI, and smoking status, but not by sex, HEI-2015 scores, race, or ethnicity. In the first follow-up analysis (FP1), the HRs for regular multivitamin use and death from any cause were higher in people younger than 55 years (HR: 1.2).

In FP1, HR estimates for irregular multivitamin use and death from any cause were higher in former and current smokers and in those with normal BMI. The meta-analysis including time-varying estimates from all cohorts showed that regular multivitamin use was associated with a 4.0% higher risk of death from any cause in FP1, but not in FP2, compared with non-use.

Diploma

The study results do not provide evidence of increased life expectancy in regular multivitamin users. However, one cannot rule out the possible effects of regular multivitamin use on other age-related health outcomes. Further research should include non-observational study designs and more diverse populations to increase the generalizability of the study results.

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