FOOD FOR THOUGHT 2020 Health effects of vitamin and mineral BMJ: first published as 10.1136/bmj.m2511 on 29 June 2020. Downloaded from supplements Growing numbers of healthy people are taking dietary supplements but there is little evidence that they protect against non-communicable diseases, say Fang Fang Zhang and colleagues itamin and mineral supple- (fig 1).6 The prevalence of use has increased such as calcium and vitamin D (fig 2).14 ments are the most commonly for some individual nutrients—for example, Despite the high use of supplements, used dietary supplements by there was a fourfold increase in use of vita- inadequate intakes of micronutrients are populations worldwide.1-4 min D supplements among US adults from still common in high income countries, The amount of micronutrients 1999 to 2012, excluding intake obtained where dietary patterns are typically energy Vthey provide ranges from less than rec- from multivitamin and mineral.7 The use rich but nutrient poor. ommended intakes to much more, mak- of omega-3 fatty acid supplements also In low and middle income countries, ing them important contributors to total increased sevenfold.7 where specific micronutrient deficiencies intakes. While supplements can be used to Supplement use is generally less are prevalent (eg, of iodine, iron, zinc, correct micronutrient deficiency or main- prevalent in other countries than in the US and vitamin A), supplementation is tain an adequate intake, over-the-counter and Canada but varies widely (eg, Denmark recommended when food based approa- supplements are most often taken by peo- 51%, South Korea 34%, Australia 43%, UK ches such as dietary modification, fortifi- ple with no clinical signs or symptoms of 36%, Spain 6%, Greece 2%).2-4 Different cation, or food provision are unable to deficiency. However, the effect of vitamin methods for assessing supplement use achieve inadequate intake.15 In the US and mineral supplements on the risk of may contribute to the different prevalence and other countries, food fortification and non-communicable diseases in “gener- in high income countries. National survey enrichment such as the addition of iodine ally healthy” populations is controversial. data for supplement use in the general to salt, vitamin D to milk, and B1 and B3 We examine patterns of supplement use population remain scarce for low and vitamins to refined flour have contributed to and the evidence on their effects from ran- middle income countries. the virtual elimination of their syndromes domised trials. Supplement use varies considerably of deficiency (goitre, rickets, beriberi, and http://www.bmj.com/ among population subgroups within pellagra, respectively).16 17 Who uses supplements? North America and Europe. In the US, The widespread use of vitamin and Vitamin and mineral supplements have a >70% of adults aged ≥65 years use mine ral supplements in high income large worldwide market, but we will focus supplements8 compared with a third of countries seems to contribute to an on their use in North America and Europe, children and adolescents.9 More women increase in population prevalence of where there is most evidence on patterns of than men use supplements.6 Supplement intake above the upper tolerable level 6 use and health outcomes. The use of vita- use correlates positively with educational (box 1). Although the overall proportion on 30 September 2021 by guest. Protected copyright. min, mineral, and fish oil supplements5 is and socioeconomic status.10 It also clusters of US adults with intakes above the upper common among adults in North America with healthy lifestyle factors such as not level is below 5% for most nutrients (fig being a smoker or heavy drinker, not being 2), some population subgroups may have KEY MESSAGES overweight or obese, and being physically high rates of excess intake. For example, active.6 Importantly, people who use in a Canadian national survey, over 80% of • Randomised trial evidence does not supplements tend to have a better overall children aged 1-3 years who took dietary support use of vitamin, mineral, and diet quality than those who don’t use them supplements consumed vitamin A and fish oil supplements to reduce the risk and their nutrient intake from foods mostly niacin at levels above the upper limit.18 of non-communicable diseases meets recommended intake levels.11 12 In the US, excessive intake was noted for • People using supplements tend to be vitamin A (97%) and zinc (68%) among older, female, and have higher educa- Are supplements needed? toddlers who were given supplements.19 tion, income, and healthier lifestyles Use of supplements contributes substan- High quality evidence is lacking on the than people who do not use them tially to total vitamin and mineral intakes at long term adverse effects of excess intake 13 • Use of supplements appreciably the population level. Intake of vitamin B6, for several nutrients so it is unclear reduces the prevalence of inadequate thiamin, and riboflavin among US adults is whether this is a cause for concern. intake for most nutrients but also at least five times higher from supplements increases the prevalence of excess than from foods, and intakes are 15 to 20 Do supplements protect against non- intake for some nutrients times higher for supplements for vitamins communicable diseases? 6 • Further research is needed to assess B12 and E. Consequently, supplement use It remains controversial whether supple- the long term effects of supplements considerably reduces the proportion of the ments are effective in reducing the risk of on the health of the general popula- general population with inadequate nutri- non-communicable diseases. In contrast to tion and in individuals with specific ent intake (box 1). results of observational studies, the accu- nutritional needs, including those This is especially true for vitamins and mulated evidence from randomised con- from low and middle income countries minerals identified as “shortfall” nutrients trolled trials does not support benefits of the bmj | BMJ 2020;369:m2511 | doi: 10.1136/bmj.m2511 1 FOOD FOR THOUGHT 2020 40 Cancer BMJ: first published as 10.1136/bmj.m2511 on 29 June 2020. Downloaded from Current evidence does not support a role 30 of vitamin and mineral supplements in reducing cancer risk, with some evidence Prevalence (%) suggesting potential harm. β-Carotene 20 supplementation increased the risk of lung cancer among high risk individuals in 10 two randomised trials. The α-Tocopherol, β-Carotene Cancer Prevention Study 0 reported an 18% increase in relative risk among smokers randomised to β-carotene Zinc Calcium Copper (20 mg/day) compared with those who did Vitamin C Vitamin E Selenium Vitamin D Vitamin B6 33 Vitamin B12 Magnesium not. The β-Carotene and Retinol Efficacy Trial found that β-carotene (30 mg/day) EicosapentaenoicDocosahexaenoic acid acid plus vitamin A as retinol (25 000 IU/day) increased risk by 28% among smokers Fig 1 | Proportion of US adults taking commonly vitamin, mineral, and fish oil supplements, and workers with occupational exposure 6 National Health and Nutrition Examination Survey 1999-2014 to asbestos.34 The Selenium and Vitamin E Cancer Prevention Trial found that vita- supplements in reducing risks of cardiovas- of vitamin D supplementation (2000 IU/ min E (400 IU/day) supplementation was cular disease, cancer, or type 2 diabetes in day) on its primary endpoint (myocardial associated with a 17% increase in prostate 35 healthy people with no clinical nutritional infarction, stroke, or cardiovascular death) cancer risk among men. deficiencies. in healthy people.25 Previous large scale Although maternal folic acid supplemen- trials such as the Women’s Health Initiative tation has been proved to reduce the risk Cardiovascular disease Calcium and Vitamin D Supplementation of neural tube defects, concerns have been An updated systematic review of 15 ran- Study26 and the Vitamin D Assessment raised that high folic acid exposure may domised trials published after the 2013 Study27 also showed vitamin D supplements, promote cancer progression, especially in 36 US Preventive Service Task Force (USPSTF) alone or in combination with calcium, had countries with mandatory fortification. review20 confirmed the lack of benefits of no effect on cardiovascular risk. Most notably, folic acid supplementation supplements on cardiovascular events, Supplementation with omega-3 fatty at ≥1 mg/day may promote the growth http://www.bmj.com/ 37 mostly among patients with risk factors.21 acids (1 g/day) did not reduce the risk of undiagnosed colorectal adenomas. Although randomised trials of folic acid, of major cardiovascular events among However, a meta-analysis of 11 rando- alone or in combination with vitamins healthy people in the VITAL trial.28 mised trials concluded that folic acid supplementation neither increased nor B12 or B6, found significant reductions in However, benefits were found for some plasma homocysteine levels, total cardio- secondary endpoints such as total decreased site specific cancer risk within 38 vascular events were not reduced. Another myocardial infarctions. This result is the first five years of supplementation. systematic review reported a reduced risk largely consistent with findings from meta- Randomised trials have failed to detect on 30 September 2021 by guest. Protected copyright. of stroke in association with supplementa- analyses that fish oil supplementation a benefit of vitamin D supplementation, tion of homocysteine lowering B vitamins,22 did not have substantial effects on the alone or combined with calcium, on cancer 25 39 but the result was largely driven by one primary or secondary prevention of risk at either high or low doses despite large trial in China.23 Overall, there is no cardiovascular disease.29 30 However, a some evidence suggesting reduced total 25 40 consistent evidence to support the use of meta-analysis including the most recent cancer mortality. The limited evidence antioxidant supplements for reducing car- trials reported a significant reduction in on fish oil supplementation suggests it does 28 41 diovascular risk.22 24 risk of myocardial infarction.31 Further not reduce cancer risk.