Do multivitamin supplements increase cancer risk?

Multivitamin Supplementation and Cancer Risk

For the general healthy adult population, multivitamins do not meaningfully increase overall cancer risk, but they also provide no proven cancer prevention benefit. The U.S. Preventive Services Task Force concludes there is insufficient evidence to determine the balance of benefits and harms of multivitamin supplementation for cancer prevention 1, 2, 3.

Overall Cancer Risk Assessment

The evidence shows multivitamins are largely neutral for cancer risk in most populations:

• Multiple randomized controlled trials found no significant effect of multivitamin supplementation on overall cancer incidence or cancer mortality in the general population 1, 4
• The USPSTF systematically reviewed the evidence and found inadequate data to determine whether multivitamins prevent or increase cancer risk, issuing an "I statement" (insufficient evidence) 1, 2, 3
• Two large trials showed a modest decrease in cancer incidence in men only after more than 10 years of use, but this benefit was not seen in women, limiting the generalizability of any protective effect 2, 4

Important Exceptions: Specific Nutrients That Increase Cancer Risk

Certain individual vitamin supplements DO increase cancer risk and should be avoided:

β-Carotene (Grade D Recommendation - Recommend Against)

• β-carotene supplementation significantly increases lung cancer risk in smokers and individuals with asbestos exposure 1, 3
• Six clinical trials consistently demonstrated this harm, with a meta-analysis showing increased lung cancer risk (pooled odds ratio 1.24,95% CI 1.10-1.39) in current smokers 1
• The ATBC and CARET trials showed increased lung cancer incidence, lung cancer mortality, and all-cause mortality in high-risk populations 1
• This harm is specific to smokers and asbestos-exposed individuals; no increased cancer risk was observed in nonsmokers 1

Vitamin E

• Vitamin E supplementation shows no benefit for cancer prevention and has mixed evidence regarding prostate cancer 1, 3
• The SELECT trial reported an increased risk for prostate cancer after extended follow-up, though the ATBC study initially showed decreased prostate cancer incidence that did not persist 1
• The USPSTF recommends against vitamin E supplementation for disease prevention (Grade D recommendation) 3

Folic Acid

• One trial found increased cancer incidence with folic acid supplementation, attributed to excess prostate cancer deaths in the intervention group 1

Recent Observational Data Showing Slight Risk Increases

A 2022 large cohort study found small increases in certain cancers with daily multivitamin use:

• In the NIH-AARP Diet and Health Study (489,640 participants), men taking one or more multivitamins daily had a slightly higher overall cancer risk (HR 1.02-1.03) compared to non-users 5
• This reflected higher risks specifically for prostate cancer (HR 1.04), lung cancer (HR 1.07), and leukemia (HR 1.26) in men 5
• Women taking more than one multivitamin daily had increased oropharyngeal cancer risk (HR 1.53) 5
• However, daily multivitamin use was inversely associated with colon cancer risk in both sexes (HR 0.82) 5

These findings must be interpreted cautiously: This was an observational study subject to confounding, and the absolute risk increases were small. The study does not establish causation 5.

Clinical Pitfalls and Caveats

Fat-soluble vitamins accumulate and can cause toxicity:

• Vitamins A, D, E, and K accumulate over time with repeated high-dose supplementation 2, 6
• High-dose vitamin A reduces bone mineral density at moderate doses and is hepatotoxic and teratogenic at high doses 2, 6
• Exceeding tolerable upper intake levels of vitamins A and D has known harms 2

Supplements do not replace dietary sources:

• Diets rich in fruits, vegetables, and whole grains consistently demonstrate health benefits that surpass isolated vitamin supplements 6
• Whole foods provide vitamins, minerals, and bioactive compounds that act synergistically, a complexity not replicated by supplements 6

Evidence-Based Recommendations for Clinical Practice

For healthy adults requesting multivitamins:

• Assess dietary intake and emphasize that supplements do not replace a healthy diet 2
• If patients choose to take multivitamins despite lack of evidence, there is little reason to discourage use, except for β-carotene in smokers 2
• Recommend adherence to Dietary Reference Intakes and avoid doses greatly exceeding the Recommended Dietary Allowance 2

Specific populations that may benefit:

• Older adults (age >65) with reduced energy intake may benefit from vitamin D (600 IU daily), calcium (≥1,200 mg daily), and vitamin B12 (4-6 μg/day) supplementation 2
• Screen for specific deficiency risk factors including restrictive diets, malabsorption, and medications like proton pump inhibitors 2

Clear contraindications:

• Never recommend β-carotene supplementation to current or former smokers or individuals with asbestos exposure 2, 3
• Avoid vitamin E supplementation for disease prevention 3