In this large multiethnic cohort, we found no associations between multivitamin use and mortality from all causes, cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. In addition, there was no evidence indicating that multivitamin use increased or decreased risk for cancer, overall or at major sites, such as lung, colorectum, prostate, and breast.
The findings from cohort studies that have examined multivitamin use in relation to risk of cancer incidence or mortality are mixed: Most of them were null, while some showed direct associations, and others found inverse associations. In the First National Health and Nutrition Examination Survey (1971–1975) followed through 1987, vitamin and mineral supplement use was not related to mortality (15
). The Physicians’ Health Study reported no association between multivitamin use and cardiovascular disease mortality among low-risk healthy males (16
). The Women's Health Initiative cohorts also provided no evidence that multivitamin use was related to either the risk of incidence of cancer and cardiovascular diseases or total mortality among postmenopausal women (9
The Cancer Prevention Study II investigators have reported on the effects of vitamin supplements on mortality from cardiovascular diseases and from cancer overall or of specific sites. Multivitamin use alone was not associated with cardiovascular diseases and cancer mortality, but the combined use with vitamin A, C, or E decreased cardiovascular disease mortality by 15% compared with nonusers (17
). They found no associations with mortality from non-Hodgkin’s lymphoma (18
) and stomach cancer (19
), while they found a small increase in risk of mortality from prostate cancer (20
) and a moderate decrease of colon cancer mortality among long-term (≥15 years) users (21
). They also found an inverse association for colorectal cancer incidence among past users (10 years before baseline) (22
). An inverse association with colon/colorectal cancer that was observed only after a substantial latency period was also reported by the Health Professionals Follow-up Study (23
) and the Nurses’ Health Study (24
) investigators, where the authors speculated that folic acid contained in multivitamins might contribute to the risk reduction. For breast cancer incidence, the Nurses’ Health Study found no association regardless of the duration of multivitamin use (25
). The Women's Health Study, conducted with female health professionals, reported no effect of multivitamin use on the risk of colorectal (26
) and breast cancer (27
The National Institutes of Health (NIH)-AARP Diet and Health Study found that multivitamin use was not associated with risk of early or localized prostate cancer but was related to an increased risk of advanced and fatal prostate cancer (28
). Two Swedish cohorts examined multivitamin use related to risk of cancer incidence and overall mortality. No association was observed with mortality among men (29
), while an increased risk for breast cancer incidence was found among women (30
). In the Vitamin and Lifestyle Study, multivitamin use was not related to total and cancer mortality but was associated with a decreased risk of cardiovascular disease mortality (31
). No association was found for lung cancer incidence (32
We observed an increased risk of mortality from all causes other than cardiovascular diseases and cancer among men who were frequent users (twice or more per day) or short-term users (<5 years). Causes of death other than cardiovascular diseases and cancer included respiratory, endocrine, nutritional, and metabolic diseases. To investigate the possibility that men who had early symptoms of these diseases might begin using multivitamins frequently, we repeated the analyses after excluding deaths from these causes during the first 3 years of follow-up. However, the results were similar. Because there was no increase in risk among women, the finding among men might simply be due to chance.
Two large clinical trials found that the use of high-dose β-carotene (20–30 mg/day) increased lung cancer risk among smokers (33
). The Cancer Prevention Study II also reported an increased risk of mortality from cancer among male multivitamin users who currently smoked at cohort entry (17
). However, the authors speculated that β-carotene did not explain the findings because this nutrient was not a common component of multivitamins during the time of the study. In the current study, we found no increase in risk of cancer mortality among current smokers who took multivitamins, perhaps reflecting low levels of carotenoids in multivitamin formulations. In a survey of national brand multivitamins in the United States (24 brands and 47 products) in 2008, the majority (70%) contained β-carotene, but the median dosage was only 0.3 mg daily, which was substantially lower than those used in the clinical trials (35
Although our study has numerous strengths, including a prospective design, a large number of subjects, and a capability to control for several confounding factors for mortality, there are also several limitations to consider. Multivitamin users are generally more health conscious than are nonusers (1
), which could confound the relation of multivitamin use with morbidity or mortality. Although we adjusted for well-known potential confounders including health-related behaviors such as smoking status, alcohol consumption, and physical activity (37
), there may still be uncontrolled bias. In particular, we were unable to adjust for changes in potential confounders over time. The longest duration category for multivitamin use in our baseline questionnaire was 5 years and longer, although the effects of multivitamins on longevity and disease might take a longer period. When we examined longer-term use by combining data from both the baseline and the follow-up surveys, administered about 5 years apart, we did not find that long-term use (approximately ≥10 years) of multivitamins was related to mortality. However, the average follow-up period after the second questionnaire was relatively short (5.8 years). Furthermore, there are many multivitamin products available in the marketplace, and their composition can vary widely (38
). Because we did not have information on specific types or brands of supplements for this analysis, misclassification of supplements is possible. However, our questionnaire appears to fairly accurately capture data on multivitamin use in comparison with three 24-hour recalls (13
). We are currently collecting information on the types of multivitamins (e.g., one-a-day, stress-tab, or antioxidant types) from cohort participants and thus will be able to examine the multivitamin-disease/mortality relation in terms of specific types of supplements, as well as a longer duration of use, in the future.
In conclusion, in the current study, there was no clear decrease or increase in mortality from all causes, cardiovascular diseases, or cancer among multivitamin supplement users. Moreover, the risk of morbidity from overall or major cancers did not differ between multivitamin users and nonusers.