Are multivitamin/mineral supplements beneficial? How do they relate to personalized nutrition? What even is a multivitamin? These questions were discussed at the “Multivitamin/Mineral Supplements in the Age of Personalized Nutrition” session Sunday during ASN’s Scientific Sessions and Annual Meeting. The chair of the session, Jeffrey Blumberg, PhD, introduced the session by noting that we don’t have a good consensus definition of either multivitamins or personalized nutrition. Multivitamins currently market for health claims such as bone health, vision, achieving nutrient recommendations etc… are these personalization or just marketing segmentation?

Regan Bailey, PhD, MPH, RD, was the first speaker who brought her expertise in epidemiology for an overview of multivitamin research, particularly from the National Health and Nutrition Examination Survey (NHANES) data. She discussed the various ways the definition of a “multi” can be operationalized: multivitamin to multivitamin/multimineral, and that there is no standard or regulatory definition. This has led to different ways of assessing multi use in NHANES research; for instance > 3 vitamins, > 30 vitamins & > 1 mineral, > 10 vitamins, etc. Depending on how you define, it you could change the estimate of how many people use these products in the U.S. by a couple million people. This also makes it difficult to monitor trends over time. Survey data tells us that the #1 reason why people use multis is to improve health, and associations with health behaviors suggests that these are people who are looking to take an active role in their health. In addition, multis are the #1 recommended product by physicians, although the use of multis is usually not disclosed to physicians. Other findings from NHANES tell us that adult users of multi products tend to have higher vitamin and mineral intakes from foods than non-users, that supplements help users meet recommendations for all micronutrients except potassium, but also that supplements increase the potential for intakes above Tolerable Upper Intake Levels for some nutrients. There are concerns with the level of nutrients on labels versus the actual amounts.This can vary by quite a bit in certain products, as well as bioavailability, nutrient and drug interactions, and keeping databases up to date. To solve some of these issues, more funding is needed. Dr. Bailey provided perspective that if annual supplement sales represent a $100 bill, the amount of funding that the entire National Institutes of Health (NIH) receives is only $1.

Cornelia Ulrich, PhD, spoke to the relationship between micronutrients and nutrigenomics/epigenetics, focusing on folate as an example of the bigger picture. An issue, she says, is that adults with cancer or cancer survivors frequently use vitamin and mineral supplements. This may put folic acid intakes well over the requirement, combined with folic acid fortification of foods. Antifolates are used in cancer therapy, and some research suggests an increased risk for certain cancers such as prostate with folate supplementation. In silico modeling of folate metabolism based on known kinetics and biochemical properties also suggests that high folic acid can impact cancer biomarkers, particularly in those with a genetic predisposition (i.e. MTHFR polymorphisms). Biological changes with high folate include a reduction leukocyte global DNA methylation, and a reduction in natural killer cell cytotoxicity, which may explain some of the relationships with cancers. Folate appears to modify associations between DNA methylation and outcomes such as fasting glucose, and its effects may be passed on in uterine development. Dr. Ulrich concluded with a summary that folate may have potential dual roles dependent on dose and context that warrants caution with supplementation or fortification, and that genetic make-up can affect these associations which will no doubt be a consideration going forward toward nutrition personalization.

Lastly, Howard Sesso, SCD, MPH, discussed the evidence from randomized controlled trials of multivitamin interventions. The U.S. Preventive Services Task Force (USPSTF)’s latest recommendations concluded that there is insufficient evidence regarding the long-term chronic disease effects of multivitamins on chronic disease risk. A big issue stemming from the lack of a standardized definition of a multivitamin is that it makes the meta-analyses on the topic more difficult to interpret. In recent years several large randomized trials have explored the effects of multis on primary and secondary disease prevention. With regard to cancer, the SU.VI.MAX study suggested a possible benefit on cancer incidence and mortality in men but not women. A trial in Linxian, China indicated a reduction in total and cancer mortality and stomach cancer, and the Physicians’ Health Study II also found a reduction in total cancer. For cardiovascular outcomes, multis reduced blood pressure and C-reactive protein, TACT showed no effect on cardiovascular events, and the Linxian Dysplasia Nutrition Intervention showed no effect on overall mortality. The Physicians’ Health Study II also indicated a reduction in cataracts. This overview led to their trial currently in progress: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). It will consist of 18,000 participants who undergo a 4 year treatment and follow-up, due to be completed around 2020. Ancillary studies will look at cognition, eye disease, and other chronic diseases like diabetes, cancer, etc. Sesso concluded by reiterating the need for multivitamin trials given their high prevalence of use and recommendation by clinicians, that more short-term mechanistic trials are needed, but that we need to improve the designs of larger, longer prevention trials as well.

Multivitamins are used by a large percentage of the population, yet despite large trials we are still unclear of their efficacy on many health outcomes. It is important to standardize definitions and databases so further trials can be adequately designed to answer such questions. More short-term trials should explore the plausibility by which multivitamins could be acting to reduce disease risk in various populations, including genetic subgroups to explore those who may benefit most from a move toward personalization.