Multivitamin supplements and cancer risk: what do studies say?

IN BRIEF

• A large randomized trial (Physicians' Health Study II) observed a modest and statistically marginal reduction in the total incidence of cancer among men taking a daily multivitamin compared to placebo.
• Systematic reviews and meta-analyses on individual nutrients and multivitamins show heterogeneous results: some studies report small benefits on specific cancers, others no effect or neutral effects on overall mortality.
• Evidence does not establish a certain causal relationship; effects may depend on population, duration, formulation, and baseline nutritional status.
• For the general population without known deficiencies, official recommendations suggest caution: focus first on diet and lifestyle; the use of supplements can be evaluated on a case-by-case basis with a doctor.

Abstract: what does science say?

The topic concerns the regular intake of multivitamin and multimineral supplements and their possible effect on the onset of cancer. Available evidence includes large-scale randomized clinical trials, systematic reviews, and observational studies. A large randomized trial that evaluated the daily use of a multivitamin in adult men reported a modest reduction in the total incidence of cancer; however, the effect was marginally significant and not uniform across all cancer sites. Reviews and meta-analyses have yielded conflicting results: some indicate a slight reduction in risk for specific cancers (e.g., colorectal), while others show no clear benefits or highlight an absence of effect on mortality. Interpretation requires caution: differences between studies (duration, population, multivitamin formulation, baseline nutritional status) limit generalizability. Overall, the evidence suggests a plausible small benefit in selected contexts, but does not allow for a generalizable causal effect for the entire population.

Clinical evidence and observational studies: what has been measured

The largest randomized trial on the subject, conducted on over 14,000 male physicians, evaluated the effect of daily intake of a standardized multivitamin supplement compared to placebo for an average follow-up of over ten years. The study reported a relative reduction of about 8% in the total incidence of cancer in the treated group, a marginally statistically significant difference, with heterogeneity for specific tumor sites. [1]

In parallel, systematic reviews and meta-analyses have combined the results of multiple randomized trials and cohort studies: some syntheses show a slight decrease in the incidence of any cancer in subjects taking multivitamins in some experimental contexts, while other works show no effects on total mortality or cancer mortality. This picture reflects the presence of conflicting results and the need to contextualize each outcome based on the study design. [2][3]

The PHS II trial: main results

The large-scale randomized trial used a consistent commercial formulation and followed participants for over 11 years. The results show a modestly significant reduction in the overall incidence of cancer in the treatment group compared to placebo, but no statistically significant reduction in cancer mortality. The enrolled population (adult physicians with relatively healthy lifestyles) makes the results particularly relevant for estimating effects in low-risk contexts, but leaves room for uncertainty about applicability to populations with different profiles. [1]

Observational studies and other signals

Large-scale cohort studies have provided mixed evidence. Some observational analyses have suggested modest inverse associations between prolonged multivitamin use and the risk of specific cancers (e.g., colorectal), while other studies have observed no effect or even small increases in risk for different outcomes. It should be noted that observational designs are subject to confounding by lifestyle and initial nutritional status. [4][5]

Plausible mechanisms and biological interpretation

The biological hypothesis supporting a possible protective effect of multivitamins is based on multiple mechanisms: support for DNA repair processes, modulation of oxidative stress, maintenance of critical enzymatic functions, and the role of individual micronutrients in regulating cell growth. However, the actual impact depends on the nature, dose, and synergy between nutrients present in the formulation. Some micronutrients (e.g., vitamin D, folates, antioxidant vitamins) have been studied individually with not always convergent results: vitamin D supplementation has been associated with a reduction in cancer mortality in some meta-analyses, but not with a clear decrease in incidence, while studies on folates show variable results. [6][7][8]

It is important to distinguish biological plausibility from causal evidence: the presence of a consistent mechanism does not guarantee that supplementation will clinically significantly modify cancer risk in the general population, especially when the initial nutritional status is already adequate.

What it means in practice

For the average person without diagnosed deficiencies, the main practical messages are clear and cautious: a varied diet, rich in fruits, vegetables, dietary fiber, and low in processed foods remains the primary prevention tool; regular physical activity, weight control, and reduced tobacco and alcohol consumption have a consolidated impact on reducing oncological risk. The use of a multivitamin supplement can be considered to fill specific nutritional deficiencies or in the presence of conditions that reduce absorption or dietary intake, but it should not be presented as a substitute for healthy lifestyle choices.

Institutions evaluating the evidence recommend caution: for the prevention of cancer and cardiovascular diseases, the documentation does not support a generalized indication for the use of multivitamins for preventive purposes in the adult population without known deficiencies. The personal choice must therefore be made with one's doctor, evaluating age, nutritional status, any clinical conditions, and concomitant medications. [2]

Limitations of the evidence

The available evidence is affected by important limitations that require cautious interpretation. First, it is necessary to distinguish observational studies from causal evidence provided by randomized trials: the former can be influenced by confounding factors related to lifestyle and access to care; the latter, although more rigorous, may have generalizability limitations if the studied population is selected. [3][4]

Observational vs. causal

Cohort studies that associate supplement use with reduced risks of some cancers do not prove causality: it is possible that supplement users inherently have healthier habits (diet, exercise, regular screenings) that explain part of the result. Randomized trials reduce this bias, but often focus on specific categories (e.g., healthcare professionals) and a fixed formulation, limiting the applicability of the results. [2][5]

Variability of formulation, dose, and population

There is no single "multivitamin": formulations, dosages, and quality differ between products. Potential effects may depend on initial nutritional status (those who are deficient may benefit more than those who are adequate), age, sex, interaction with medications, and duration of intake. Furthermore, some nutrients administered in excess can have adverse effects in specific groups. These variables make it difficult to generalize results obtained with a given product in a given context. [6][7]

Key takeaways

• A large randomized trial observed a modest reduction in the total incidence of cancer in men taking a multivitamin; the effect is marginal and did not significantly reduce cancer mortality. [1]
• Systematic reviews and cohort evidence provide heterogeneous results: small benefits for some outcomes, neutral effects for others. [2][5]
• The evidence does not allow for a universal recommendation: the decision on supplementation should be personalized and discussed with a doctor. [2]
• A balanced diet and healthy lifestyles remain the primary strategies for cancer prevention.

Editorial conclusion

Research on the role of multivitamin supplements in cancer prevention has yielded interesting but not conclusive results. A large-scale randomized trial reported a modest reduction in cancer incidence, but overall reviews show heterogeneity and methodological limitations. For this reason, a cautious and informed approach is the most appropriate choice: prioritize diet and proven lifestyles, evaluate the use of supplements based on individual needs and documented deficiencies, and always discuss with your doctor before starting prolonged supplementation. The scientific community continues to monitor the topic and investigate which subgroups may eventually benefit.

Editorial note

This article was previously published and updated for synthesis and evidence according to scientific and divulgative criteria. The text is for informational purposes and does not replace the advice of the treating physician; for decisions related to diagnosis, therapy, or personal supplementation, consult a healthcare professional.

SCIENTIFIC RESEARCH

1. Gaziano JM et al. Multivitamins in the Prevention of Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial. JAMA. DOI: https://doi.org/10.1001/jama.2012.14641. [1]
2. US Preventive Services Task Force. Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Recommendation Statement. JAMA. DOI: https://doi.org/10.1001/jama.2022.8970. [2]
3. Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Am J Clin Nutr. DOI: https://doi.org/10.3945/ajcn.112.055111. [3]
4. Mursu J et al. Dietary supplements and mortality rate in older women: The Iowa Women's Health Study. Arch Intern Med. DOI: https://doi.org/10.1001/archinternmed.2011.445. [4]
5. Meta-analysis: Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies. Int J Cancer. DOI: https://doi.org/10.1002/ijc.29277. [5]
6. Massa J et al. Long-term use of multivitamins and risk of colorectal adenoma in women. Br J Cancer. DOI: https://doi.org/10.1038/bjc.2013.664. [6]
7. Meta-analysis: Vitamin D supplements and cancer incidence and mortality. Br J Cancer. DOI: https://doi.org/10.1038/bjc.2014.294. [7]
8. Qin T et al. Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials. Sci Rep. DOI: https://doi.org/10.1038/srep12044. [8]