Does daily supplementation with multivitamins and multiminerals reduce the risk of cancer and cardiovascular disease? Original paper

Multivitamin-multimineral (MVM) supplements lack a universal definition but typically provide at least 100% of the recommended daily value of most essential vitamins and minerals. They are the most common dietary supplement taken in the U.S.^[1] Many people take MVM supplements for general health and well-being or to reduce the risk of chronic diseases, but there is a lack of evidence to support their use for the latter effect.

This randomized controlled trial examined the effect of a daily MVM supplement use on the incidence of cancer and cardiovascular disease (CVD) in 10,723 U.S. adults (average age of 72) free of CVD and recently diagnosed cancer over a median follow-up period of 3.6 years. To be included in the study, the participants agreed to forgo personal MVM supplement use and limit supplemental vitamin D and calcium to no more than 1,000 IU/day and no more than 1,200 mg/day during the trial. They also had to complete a placebo run-in phase of at least two months.

Nutrition label for the multivitamin used in the study

The primary outcome was total invasive cancer, excluding nonmelanoma skin cancer. The secondary outcomes included site-specific cancers (i.e., melanoma, breast cancer, colorectal cancer, lung cancer, and prostate cancer), all-cause mortality, individual cardiovascular events, and total CVD, defined as a composite outcome that included incident heart attack, stroke, coronary revascularization, cardiovascular mortality, carotid artery surgery, peripheral artery surgery, and unstable angina requiring hospitalization.

During follow-up, there were 1,053 cases of cancer. Total cancer incidence did not differ between the MVM and placebo groups. There was also no effect of MVM on cancer incidence in participants with a history of cancer. In terms of secondary outcomes, there was no difference between MVM and placebo for the incidence of breast cancer, colorectal cancer, prostate cancer, or melanoma. However, MVM decreased the incidence of lung cancer by 38%, compared to placebo.

During follow-up, there were 866 cases of CVD. Total CVD incidence did not differ between the MVM and placebo groups. There was also no difference between groups for individual cardiovascular events, CVD mortality, or all-cause mortality.

This trial was limited by a short intervention. A longer intervention duration might be needed to observe a decrease in cancer and CVD incidence with MVM supplementation. Another limitation is the population that was studied. Among the participants, only 35% reported consuming less than 4 servings of fruit and vegetables per day, and only 4% were current smokers, although 41.3% were former smokers. Therefore, the results may not be generalizable to less health-conscious populations.

The researchers did not adjust for multiple comparisons, despite the inclusion of several outcomes, which increases the risk of false-positive results. Therefore, the secondary outcomes should be considered exploratory.

The rationale behind advocating for the use of MVM supplements to prevent CVD and cancer is primarily related to the role of inflammation and oxidative stress in the development of these diseases and that several nutrients are known to have antioxidant and anti-inflammatory effects.^[2] Additionally, the inadequacy of certain nutrients (e.g., vitamin A, vitamin D) impairs normal immune function, which may increase the risk of cancer, and the inadequacy of other nutrients (e.g., potassium) is associated with elevations in blood pressure and an increased risk of cardiovascular disease.^[3]

Despite the mechanistic plausibility of MVM supplements being able to reduce the risk of CVD and cancer and the popularity of these supplements, there is a dearth of evidence from long-term randomized controlled trials to support their use. Besides the present study, there has been one other large-scale randomized controlled trial that assessed the effects of a broad-spectrum MVM supplement on cancer and CVD incidence. It included 14,641 male physicians (average age of 64) and found that, compared to a placebo, a MVM supplement reduced the incidence of total cancer by 8% over a median follow-up of 11.2 years.^[4] However, there was no effect on total CVD incidence.^[5]

People who volunteer to participate in these types of studies are typically interested in healthy behaviors. Notably, 4% of the male physicians were current smokers, and 76% used aspirin, which supports the assumption that they were more health-conscious than the general population. This limitation was also present in the summarized study.

Virtually all nutrients have a nonlinear, inverted U-shaped association with optimum physiological function.^[6] Very low nutrient levels in the diet or tissues result in poor function, and as nutrient levels increase, so does function. Optimum function can occur over a fairly wide range of nutrient levels due to individual differences, but at some point, higher nutrient levels become toxic and counterproductive.

In these studies, most of the participants were likely consuming a healthy and balanced diet, so there generally weren’t any nutrient inadequacies or deficiencies present for the MVM to fix,^[6] which is the general use for these products.

Another large-scale randomized controlled trial published in 2004 assigned participants to receive either a supplement containing vitamin C, vitamin E, beta-carotene, selenium, and zinc or a placebo over a median follow-up of 7.5 years.^[7] The researchers found a 31% reduced incidence of total cancer in men who received the nutrient supplement compared to men who received the placebo, but there was no effect in women. There was also no effect of the nutrient supplement on CVD incidence.

The data from observational studies are mixed, but the majority of studies have found no association between MVM supplement use and CVD and cancer risk.^[8][3][9]

Altogether, there is weak evidence to support the efficacy of MVM supplements for decreasing CVD and cancer risk in generally healthy people. But that doesn’t necessarily mean that MVM supplements serve no purpose, it’s just that their utility is reserved for certain populations. For example, MVM supplements may provide health benefits for older adults, pregnant women, people consuming a low-calorie diet for weight loss or due to poor appetite from an illness, and people consuming a strict vegan diet or a diet that excludes one or more food groups.^[10]

Many healthy people who consume a balanced diet view MVM supplements as an “insurance policy” to help achieve adequate micronutrient intake. This is a fine approach, as micronutrient gaps can occur from time to time despite a balanced diet, and the long-term safety of MVM supplements doesn’t seem to be a concern.^[11] However, the available evidence does not demonstrate that MVM supplements reliably provide a health benefit for healthy people with adequate micronutrient intake, so the benefit-cost ratio of this approach should be considered on an individual basis. Further long-term randomized controlled trials are needed to confirm whether MVM supplements provide a health benefit to healthy people consuming a balanced diet.