Date Posted: 4/22/2015 3:28:36 PM
Is Supplement Use Linked to Increased Cancer Risk?
By Lise Alschuler, ND, FABNO
TAPintegrative.org

Many integrative healthcare practitioners prescribe multivitamin/mineral supplements to their patients. After all, this can provide a strong foundation of nutrients that may be absent from the standard American diet. A recent (April 2015) presentation by Tim Byers, MD, MPH at the American Association for Cancer Research (AACR) Annual Meeting has challenged the safety of dietary supplementation – linking supplementation to increased cancer risk. While the rationale and data for this conclusion by Dr. Byers are scant in the media reports of the presentation, it would appear that the conclusion is over-generalized and not inclusive of the body of data on this subject. Multivitamins can, in fact, support the overall health of people concerned about, and diagnosed with, cancer.[1] What’s more, we know that multivitamin use is common among people diagnosed with cancer. In one large cohort study, 82% of females diagnosed with cancer used a multivitamin supplement.[2] With supplementation use so prevalent in people diagnosed with, and at risk for, cancer, it is important to assess the safety of this strategy.

It is important to recognize that some nutrients typically found in multivitamin/mineral supplements may, in fact, be contraindicated in the context of cancer prevention. Preliminary data indicates that four nutrients commonly found in multivitamin/mineral supplements may be contraindicated in the context of cancer prevention: beta-carotene, dl-alpha-tocopherol, copper, and boron.

Several studies have shown that supplemented beta-carotene is inversely associated with overall survival in current and former smokers and in some women.[3]^,[4] Beta-carotene, in fact, is often the nutrient responsible for the risk of harm seen in multivitamin trials. This stems from the 1996 CARET trial, which was stopped early due to the fact that beta-carotene supplementation was found to increase risk of lung cancer in smokers.[5] Despite the association of risk from supplemented beta-carotene, it is important to note that many studies have documented a lower risk of multiple cancer types in association with serum carotenoid concentration, presumably a biomarker of food intake of carotenoids.

Alpha-tocopherol is another potentially problematic supplement. Among smokers between the ages of 50 and 62, supplemental alpha-tocopheral has been demonstrated to increase mortality by 19%.[6]^,[7] While dl-alpha-tocopherol has been shown in the ATBC trial to increase risk of prostate cancer[8], other isomers in the vitamin E family have not been associated with this risk. Tocotrienols, for instance, as the most bioactive members of the vitamin E family, and in fact more bioactive than tocopherol,[9] have been shown to safely support immunity.[10]

The inclusion of B vitamins in a multivitamin/mineral is somewhat controversial given the reported association between folic acid and increased colon cancer. However, a recent meta-analysis on the effects of folic acid supplementation on overall and site-specific cancer incidence based on data from 50,000 individuals with study duration ranging from1.8 to 7.4 years (average 5.2 years) found that at daily doses ranging from 0.5mg to 5mg daily, there were no increased risks for the 4 most common cancers – colorectal, lung, breast, or prostate cancers.[11]

Two supplemented minerals – copper and boron – may be of questionable benefit in the context of cancer prevention. Based upon studies of active copper depletion to reduce angiogenesis, the role of copper in carcinogenesis has been established.  Research demonstrates that simple avoidance of supplemental copper is a safer strategy for people at increased risk or with a personal history of cancer.[12] While boron is a desirable supplement for supporting bone health, clinical data indicates that supplemental boron can increase serum estradiol and testosterone. This may be problematic for people at risk for, or with a personal history of, hormone-dependent cancer.[13]
With these nuances, dietary supplementation inclusive of vitamins and minerals, remains a viable and important strategy for people at risk for cancer. In a 2010 study by Wallace et al.[14], large portions of the population had total usual intakes of several critical vitamins and minerals below the estimated average requirement. Specifically, deficiencies were found with regards to vitamins A (35%), C (31%), D (74%), and E (67%) as well as calcium (39%) and magnesium (46%). Only 0%, 8%, and 33% of the population had total usual intakes of potassium, choline, and vitamin K above adequate intake when food and multivitamin/mineral use was considered. The percentage of the population with total intakes greater than the tolerable upper intake level (UL) was very low for all nutrients; excess intakes of zinc were the highest (3.5%) across the population of all of the nutrients assessed in NHANES database. Nutrient deficiencies compromise health and are known to increase the risk of chronic disease, cancer included. Furthermore, there is clinical data to support the benefit of multivitamins to reduce recurrence risk in cancer survivors.  In stratified analyses from the Life After Cancer Epidemiology study, women who consistently used multivitamins before and after diagnosis and ate more fruits/vegetables (P for trend = 0.008) and were more physically active (P for trend = 0.034) had better overall survival.[15]  In the After Breast Cancer Pooling Project, post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine.[16]

Thus, generalized statements that associate multivitamin use with increased cancer risk and/or decreased survival are not evidenced based. Understanding which individual supplemented vitamins pose a potential threat and which nutrients are associated with improved survival is critical. Furthermore, well-designed meta-analyses, such as that published in 2013 in the Annals of Internal Medicine have failed to find evidence of harm from multivitamin supplementation in terms of cancer risk.[17] This meta-analysis, in fact, found two large trials (n = 27,658) which reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324,653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) showed no clear evidence of benefit or harm. Of note, and not unexpected, the same meta-analysis did conclude that beta-carotene supplementation was associated with increased risk of lung cancer. Given this emerging body of data, at this time, there is no clear evidence of harm from multivitamin use although supplemental beta-carotene and dl-alpha-tocopherol are not recommended. Additionally, supplemental copper and boron may also be of questionable value to individuals at high risk for certain cancers.