Multivitamin/Mineral supplements and prevention of chronic disease: executive summary.

The Johns Hopkins University Evidence-based Practice Center (EPC) reviewed and synthesized the published literature on four Key Questions: 1. What is the efficacy of multivitamin/mineral supplement use in the prevention of chronic disease for the general adult population? 2. What is the safety of multivitamin/mineral supplementation in the general population of adults and children? 3. What is the efficacy of single nutrients or functionally related nutrient pairs in preventing chronic disease in the general adult population? 4. What is the safety of single nutrients or functionally related nutrient pairs in the general population of adults and children? Multivitamin/mineral supplements are the most commonly used nutritional supplements in the United States. Most multivitamin/mineral supplements contain at least 10 vitamins or minerals with a wide range of doses. Many individuals use multivitamin/mineral supplements for prophylactic or disease-mitigating purposes. Chronic disease is estimated to account for 35 million deaths worldwide. Cardiovascular disease and cancer comprise a major proportion of chronic diseases in both developed and developing countries. Other than cardiovascular disease and cancer, obesityrelated diseases such as type 2 diabetes, end-stage renal disease, and osteoarthritis are also becoming significant public health problems. Many of these chronic diseases share common risk factors and underlying pathologic mechanisms that may be modified by nutrients. Examples include reduction of oxidative damage by antioxidants, DNA methylation regulated by folate and B vitamins, bone metabolism regulated by vitamin D and calcium, and cell differentiation, proliferation, and growth regulated by retinol, calcium, and vitamin D. The biological effects of a nutrient are heavily dependent on its bioavailability. Key factors determining the bioavailability of micronutrients are the chemical form in which the nutrient is presented to the intestinal absorptive surface, the presence of other competing chemicals in the intestinal lumen, the concentration of food constituents (such as phytates and other chelating agents) that bind to the nutrient and make it unavailable for absorption, intestinal transit time, and enzyme activity. A nutrient may affect not only the absorption of other nutrients, but also the transport, tissue uptake, function and metabolism of other nutrients. Hence, concurrent ingestion of several nutrients may result in synergistic, antagonistic, or threshold effects as compared to a single nutrient. The efficacy of a single nutrient or multiple nutrients should be considered separately unless no interactive or threshold effects can be found. The United States Food and Nutrition Board has established the tolerable upper intake levels (ULs) for several nutrients. By definition, a UL is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population. Since the time when ULs were determined, several large-scale randomized controlled trials of vitamin/mineral supplementation have been completed. An update of the data on adverse effects/events will help to evaluate the appropriateness of the ULs.