expert opinion

What can be expected from the use of dietary supplements?

February 1, 2014

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Balz Frei, Ph.D., Professor of Biochemistry and Biophysics, Oregon State University, USA.

“Insufficient intakes and deficiencies of selected micronutrients are not only wide- spread in developing countries (1) but also in industrialized nations (2–5). According to data from a big US survey (NHANES), for example, more than 93% of US adults 19 years and older do not meet dietary intake recommendations for vitamins D and E, 61% for magnesium, about 50% for vitamin A and calcium, and 43% for vitamin C(3). In addition to people who generally do not meet intake recommendations, the following individuals may be at increased risk for micronutrient deficiencies: Women of childbearing age (folate, vitamin D and/or iron deficiency), pregnant and lactating women (vitamin B6, folate, vitamin D, iron), people who consume less than 1,200 cal/day (multiple micronutrients), obese individuals (multiple micronutrients), infants, children, and adolescents (vitamin D), people with dark-colored skin (vitamin D), those who cover all exposed skin or use sunscreen whenever outside (vitamin D), older adults (vitamin B12, vitamin D, zinc), people with low socioeconomic status (multiple micronutrients), patients with fat malab- sorption syndromes (fat-soluble vitamins A, D, E, and K), alcoholics (vitamin A, B vitamins), smokers (vitamins C and E), vegans and those with limited intake of animal products (vitamin B12, vitamin D, calcium) and people taking medications that interfere with the absorption and/or metabolism of certain micronutrients (e.g., proton pump inhibitors used to treat heartburn may impair vitamin B12 absorption; frequent aspirin use can lower vitamin C status).

Inadequate intake of certain micronutrients may increase risk for developing chronic diseases, such as cardiovascular diseaseosteoporosis and cancer, and may also be linked to cognitive dysfunction. It has hypothesized that when intakes are lower than the recommended levels, short-term requirements for micro- nutrients in metabolic reactions take precedence over long-term needs, thereby resulting in long-term, cumulative oxidative damage to macromolecules (DNA, RNA, proteins), declines in mitochondrial function, and accelerated cellular aging, increasing the risk of age-related diseases (6). In contrast, micronutrient intakes at the recommended level would allow sufficient amounts for normal metabolism, and intakes higher than these levels may be needed for optimum health promotion and chronic disease prevention. Given the fact that many people are not meeting micronutrient intake recommendations, a daily multivitamin/mineral supplement would offer insurance that most micronutrient needs are met. Studies have shown that people who take a daily multivitamin/mineral supplement with the recommended doses of micronutrients can fill most of these nutritional gaps at very low cost (7, 8) – a year's supply of a high-quality supplement can be purchased for less than a nickel a day.

The known biological functions of vitamins, minerals and trace elements are to maintain normal cell function, metabolism, growth and development, mainly through their roles as essential cofactors or cosubstrates in thousands of enzymes (9). In addition, several observational studies (prospective cohort studies and case-control studies) and randomized controlled trials (RCTs) have examined if taking a daily multivitamin/ mineral supplement can reduce the risk of various chronic diseases. In 2006, a National Institutes of Health (NIH) conference on multivitamin/mineral supplements and chronic disease prevention concluded that there was insufficient evidence to recommend in favor of or against taking a supplement (10). However, the panel limited their ‘evidence-based’ review to only long-term RCTs, ignoring the results of other epidemiologic studies as well as the mechanistic and biochemical research that suggest an adequate supply of micronutri- ents is essential for optimal health (11). While RCTs are considered the ‘gold standard’ to evaluate the effect of pharmaceutical drugs, they have a number of limitations and are not well-suited to study the effects of nutrients (12, 13). For example, trials of micronutrient supplementation compare low intakes (from diet) with higher intakes (from supplements) in subjects who have a lifelong intake of these micronutrients; by cont- rast, drug trials compare the absence of the drug with its presence in subjects who have not been exposed to this drug before. Therefore, the ‘placebo’ group in RCTs of micronutrient supplements is not a true placebo or ‘non-exposed’ group, in contrast to the placebo group in RCTs of drugs. Such a nutrient-free state in RCTs is not possible, and causing micronutrient deficiencies in the control group is unethical. Additionally, primary disease prevention trials using supplemental micronutrients are evaluated in healthy well-nourished people, not diseased individuals, meaning that any effects of supplementation would be likely small and take years, perhaps decades, to be observed.

Nevertheless, the largest and longest RCT of multivitamin/mineral supplements conducted to date, the Physicians’ Health Study II (PHS II), found a significant 8% reduction in epithelial cell cancer incidence in male physicians, and a 12% reduction in total cancer incidence excluding prostate cancer (14). The PHS II also found a significant 9% reduction in the incidence of total and nuclear cataract (15). These findings are consistent with those of several other RCTs (16, 17). A recent review on the potential benefits of multivita- min/mineral supplements in the primary prevention of cancer, cardiovascular disease, or all-cause mortality in healthy, well-nourished adults concluded that there is insufficient evidence to support or refute a health effect (18). The researchers suggested that future studies are needed to clarify whether multivitamin supple- mentation may be more beneficial in persons with less optimal nutritional status or vitamin deficiencies. Systematic reviews or meta-analyses of epidemiological studies evaluating multivitamin/mineral supple- mentation use in chronic disease prevention showed no effects for breast and prostate cancer (19, 20), and positive (21, 22) or no effects for cardiovascular disease and mortality risk (23). Inconsistent findings in epidemiological studies, which can only detect associations, not establish cause-and-effect relationships, may in part be due to wide variations in supplement composition, dose, and duration of use.

Multivitamin/mineral supplements are generally considered as safe in healthy individuals. Excessive intakes of select micronutrients can be unsafe, but amounts of micronutrients typically included in the supplements approximate or equal the Daily Values (DVs); for adults, the DV for most micronutrients is considerably lower than the tolerable upper intake level (UL) – the highest level of daily intake of a specific nutrient likely to pose no risk of adverse health effects in almost all individuals of a specified age. The intake from foods, fortified foods, and supplements should not exceed the UL for each micronutrient. Only a very small, non- significant fraction of US adults, for example, exceeds the UL of micronutrients from diet and supplements (3). People taking pharmaceutical drugs to treat certain medical conditions need to be aware of any potential drug-nutrient interactions.

Nutrition education campaigns have yet to convince people to make better food choices: the reality is that most Americans eat an energy-dense, nutrient-poor diet lacking in fruits and vegetables (24). Consequently, micronutrient inadequacies are widespread in the US and around the world. Given the facts that dietary habits are difficult to change and that some people cannot afford nutrient-rich fruits and vegetables, a daily multivitamin/mineral supplement is a sensible public health recommendation. By definition, they are ‘sup- plements’ and should be used to complement (not replace) a healthy diet. Eating a balanced diet is important to obtain also other nutrients and phytochemicals that benefit health. The specific consequences of chronic insufficient micronutrient intakes are difficult to document, and, for reasons already mentioned, it is not realistic that a long-term RCT would provide definitive proof on whether supplements are effective in chronic disease prevention. Short-term RCTs that assess DNA damage, inflammation, insulin sensitivity, lipid profile, blood pressure, immune function or other intermediary biomarkers or independent risk factors of chronic disease are more practical and may inform this question.”

Based on: Frei B. et al. Keep Taking Your Vitamins. The Linus Pauling Institute. Published online December 2013.

References

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2.    Troesch B. et al. Dietary surveys indicate vitamin intakes below recommendations are common in representative Western countries. Br J Nutr. 2012; 108(4):692-698.

3.    Fulgoni V. L. III. et al. Foods, fortificants, and supplements: Where do Americans get their nutrients? J Nutr. 2011; 141:1847-1854.

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15.    Christen W. G. et al. A multivitamin supplement and cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. Published online November 2013.

16.    Maraini G. et al. A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities. Clinical trial of nutritional supplements and age-related cataract report no. 3. Ophthalmology. 2008; 115:599-607.

17.    Hercberg S. et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004; 164:2335-2342.

18.    Fortmann S. P. et al. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824–834.

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24.    US Centers for Disease Control and Prevention. State indicator report on fruits and vegetables. 2009.