Benefits of Dietary Supplements Journal Article Peer Reviewed

Analysis Food for Thought 2020

Health effects of vitamin and mineral supplements

BMJ 2020; 369 doi: https://doi.org/x.1136/bmj.m2511 (Published 29 June 2020) Cite this as: BMJ 2020;369:m2511

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Fang Fang Zhang , acquaintance professori,
Susan I Barr , professor2,
Helene McNulty , professor3,
Duo Li , professoriv,
Jeffrey B Blumberg , professor1

ⁱFriedman School of Nutrition Science and Policy, Tufts University, Boston, Usa
ⁱⁱUniversity of British Columbia, Vancouver, Canada
³Diet Innovation Centre for Food and Wellness, Ulster University, Coleraine, United kingdom
⁴Institute of Nutrition and Health, Qingdao University, Qingdao, China

Correspondence to: F F Zhang fang_fang.zhang{at}tufts.edu

Growing numbers of good for you people are taking dietary supplements but in that location is piffling evidence that they protect against non-infectious disease, say Fang Fang Zhang and colleagues

Vitamin and mineral supplements are the most commonly used dietary supplements past populations worldwide.1234 The amount of micronutrients they provide ranges from less than recommended intakes to much more, making them important contributors to total intakes. While supplements can be used to right micronutrient deficiency or maintain an adequate intake, over-the-counter supplements are nigh often taken by people with no clinical signs or symptoms of deficiency. All the same, the effect of vitamin and mineral supplements on the risk of not-infectious disease in "by and large salubrious" populations is controversial. We examine patterns of supplement employ and the evidence on their effects from randomised trials.

Who uses supplements?

Vitamin and mineral supplements take a large worldwide market, but we volition focus on their apply in Due north America and Europe, where there is nearly evidence on patterns of use and health outcomes. The use of vitamin, mineral, and fish oil supplements5 is mutual amid adults in Due north America (fig i).half-dozen The prevalence of use has increased for some private nutrients—for example, in that location was a fourfold increment in employ of vitamin D supplements among US adults from 1999 to 2012, excluding intake obtained from multivitamin and mineral.seven The use of omega-3 fatty acid supplements likewise increased sevenfold.7

Supplement use is generally less prevalent in other countries than in the US and Canada but varies widely (eg, Denmark 51%, Due south Korea 34%, Australia 43%, United kingdom 36%, Kingdom of spain vi%, Greece two%).234 Different methods for assessing supplement use may contribute to the different prevalence in high income countries. National survey data for supplement use in the general population remain scarce for low and middle income countries.

Supplement utilise varies considerably among population subgroups within North America and Europe. In the US, >70% of adults aged ≥65 years use supplements8 compared with a third of children and adolescents.9 More women than men use supplements.six Supplement use correlates positively with educational and socioeconomic status.10 Information technology likewise clusters with healthy lifestyle factors such as non existence a smoker or heavy drinker, not existence overweight or obese, and being physically active.6 Chiefly, people who use supplements tend to have a improve overall nutrition quality than those who don't utilize them and their nutrient intake from foods mostly meets recommended intake levels.1112

Are supplements needed?

Apply of supplements contributes substantially to total vitamin and mineral intakes at the population level.13 Intake of vitamin B₆, thiamin, and riboflavin amidst The states adults is at to the lowest degree five times college from supplements than from foods, and intakes are xv to 20 times higher for supplements for vitamins B₁₂ and E.6 Consequently, supplement use considerably reduces the proportion of the full general population with inadequate nutrient intake (box one).

Box 1

Population nutrient intake—definitions

Estimated average requirement is the daily level of nutrient intake estimated to see the requirement of half of healthy people in a population
Inadequate food intake—The population prevalence of inadequate intake is estimated as the percentage of the population with nutrient intake below the estimated boilerplate requirement
Tolerable upper intake is the highest daily nutrient intake that is likely to pose no risk of adverse health effects to well-nigh all good for you people in a population. As intake increases above the upper level, the potential risk of adverse effects increases.
Excess intake—The population prevalence of excess intake is estimated as the percentage of the population with nutrient intake to a higher place the upper level

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This is particularly true for vitamins and minerals identified as "shortfall" nutrients such as calcium and vitamin D (fig 2).fourteen Despite the high use of supplements, inadequate intakes of micronutrients are still common in high income countries, where dietary patterns are typically free energy rich but nutrient poor.

In depression and middle income countries, where specific micronutrient deficiencies are prevalent (eg, of iodine, fe, zinc, and vitamin A), supplementation is recommended when nutrient based approaches such every bit dietary modification, fortification, or nutrient provision are unable to achieve inadequate intake.15 In the United states and other countries, food fortification and enrichment such as the addition of iodine to common salt, vitamin D to milk, and B₁ and B₃ vitamins to refined flour accept contributed to the virtual elimination of their syndromes of deficiency (goitre, rickets, beriberi, and pellagra, respectively).1617

The widespread utilise of vitamin and mineral supplements in high income countries seems to contribute to an increase in population prevalence of intake higher up the upper tolerable level (box 1).vi Although the overall proportion of Usa adults with intakes higher up the upper level is below 5% for most nutrients (fig two), some population subgroups may have high rates of excess intake. For instance, in a Canadian national survey, over 80% of children aged 1-three years who took dietary supplements consumed vitamin A and niacin at levels to a higher place the upper limit.eighteen In the US, excessive intake was noted for vitamin A (97%) and zinc (68%) among toddlers who were given supplements.19 Loftier quality bear witness is lacking on the long term adverse furnishings of backlog intake for several nutrients so it is unclear whether this is a cause for concern.

Do supplements protect against non-infectious disease?

Information technology remains controversial whether supplements are effective in reducing the risk of non-infectious disease. In contrast to results of observational studies, the accumulated evidence from randomised controlled trials does non support benefits of supplements in reducing risks of cardiovascular disease, cancer, or blazon ii diabetes in healthy people with no clinical nutritional deficiencies.

Cardiovascular affliction

An updated systematic review of fifteen randomised trials published later on the 2013 US Preventive Service Chore Forcefulness (USPSTF) review20 confirmed the lack of benefits of supplements on cardiovascular events, mostly amid patients with risk factors.21 Although randomised trials of folic acid, alone or in combination with vitamins B₁₂ or B₆, constitute meaning reductions in plasma homocysteine levels, total cardiovascular events were non reduced. Some other systematic review reported a reduced risk of stroke in association with supplementation of homocysteine lowering B vitamins,22 merely the upshot was largely driven by 1 large trial in China.23 Overall, there is no consistent testify to back up the use of antioxidant supplements for reducing cardiovascular risk.2224

The Vitamin D and Omega-3 Trial (VITAL), one of the few randomised trials of supplements for principal prevention of cardiovascular disease, found no effect of vitamin D supplementation (2000 IU/twenty-four hours) on its master endpoint (myocardial infarction, stroke, or cardiovascular expiry) in healthy people.25 Previous large calibration trials such as the Women's Health Initiative Calcium and Vitamin D Supplementation Study26 and the Vitamin D Assessment Study27 also showed vitamin D supplements, alone or in combination with calcium, had no effect on cardiovascular adventure.

Supplementation with omega-three fatty acids (1 g/day) did not reduce the chance of major cardiovascular events among healthy people in the VITAL trial.28 However, benefits were establish for some secondary endpoints such as total myocardial infarctions. This result is largely consistent with findings from meta-analyses that fish oil supplementation did not have substantial effects on the primary or secondary prevention of cardiovascular illness.2930 However, a meta-assay including the most recent trials reported a meaning reduction in gamble of myocardial infarction.31 Farther studies are needed to determine whether fish oil supplementation has a greater effect on risk of heart affliction than of stroke.32

Cancer

Current evidence does not support a role of vitamin and mineral supplements in reducing cancer risk, with some evidence suggesting potential harm. β-Carotene supplementation increased the risk of lung cancer among high risk individuals in two randomised trials. The α-Tocopherol, β-Carotene Cancer Prevention Study reported an 18% increment in relative take a chance amongst smokers randomised to β-carotene (20 mg/mean solar day) compared with those who did not.33 The β-Carotene and Retinol Efficacy Trial constitute that β-carotene (30 mg/day) plus vitamin A every bit retinol (25 000 IU/day) increased risk past 28% among smokers and workers with occupational exposure to asbestos.34 The Selenium and Vitamin E Cancer Prevention Trial establish that vitamin Due east (400 IU/twenty-four hours) supplementation was associated with a 17% increase in prostate cancer risk among men.35

Although maternal folic acid supplementation has been proved to reduce the hazard of neural tube defects, concerns accept been raised that loftier folic acid exposure may promote cancer progression, specially in countries with mandatory fortification.36 Most notably, folic acid supplementation at ≥ane mg/twenty-four hour period may promote the growth of undiagnosed colorectal adenomas.37 However, a meta-analysis of 11 randomised trials concluded that folic acid supplementation neither increased nor decreased site specific cancer adventure inside the first five years of supplementation.38

Randomised trials have failed to detect a benefit of vitamin D supplementation, alone or combined with calcium, on cancer risk at either loftier or low doses2539 despite some evidence suggesting reduced total cancer mortality.2540 The limited evidence on fish oil supplementation suggests information technology does not reduce cancer risk.2841

Type 2 diabetes

Current evidence does non support the use of supplements with vitamins C or E, β-carotene, or fish oil to reduce the chance of type 2 diabetes, although the overall evidence from randomised trials is express.4243 A recent placebo controlled trial of vitamin D supplementation (4000 IU/24-hour interval) failed to reduce the risk of type 2 diabetes despite significantly increasing serum 25-hydroxyvitamin D concentrations.44

Osteoporosis

Recent evidence regarding the furnishings of vitamin D and calcium supplementation is inconsistent. A meta-analysis of trials in community living older adults plant that vitamin D or calcium supplementation did not reduce the run a risk of hip fracture or total fracture,45 whereas some other meta-analysis reported that while vitamin D alone did non reduce fracture chance, combined calcium and vitamin D supplementation decreased the relative risk of hip fracture (16%) and all fractures (6%) amidst older adults.46 Ongoing inquiry is assessing the effect of high dose vitamin D supplements on several health outcomes, including fractures,46 but a recent iii twelvemonth trial of 400, 4000, or 10 000 IU/day reported that the higher doses reduced volumetric bone density, suggesting potential for harm.47 In the absenteeism of clear evidence on supplementation, information technology is prudent to ensure that dietary recommendations on calcium and vitamin D intakes are met through food and supplementation.

What adjacent?

To date, randomised trials have largely shown no benefit of vitamin, mineral, and fish oil supplements on the risk of major not-infectious disease in people without clinical nutritional deficiency. These results contrast with findings from observational studies, where supplemental nutrient intakes are often associated with a reduced risk of these diseases. The credible associations from observational studies may result from unknown or unmeasured confounding factors such equally socioeconomic condition and lifestyle factors, including a better overall diet.

Although randomisation reduces confounding, relying exclusively on the results of randomised trials also has limitations. Trials are oft conducted among high risk populations with pre-existing conditions, so the findings may not exist applicable to healthy individuals. Supplements may also have health benefits for population subgroups, such as people with inadequate nutrient intake from foods, but randomised trials are not normally designed to evaluate subgroup differences. Furthermore, financial and practical constraints mean that most trials are able to investigate only a unmarried dose, which may effect in selection of a dose that is either too low (no efficacy) or likewise high (untoward outcomes).

Nutrients obtained from foods and supplements may confer dissimilar health effects. The Cancer Prevention Study (CPS)-2 Nutrition Cohort found that supplemental calcium intake at ≥1000 mg/day was associated with an increased risk of all-crusade mortality in men whereas loftier levels of calcium intake from foods had no impairment.48 Amid US adults in the National Health and Nutrition Examination Survey, adequate intake of nutrients from foods, just non supplements, was associated with a lower gamble of all-crusade mortality.half dozen The benefits of food intake from foods may reflect synergistic interactions among multiple nutrients and other bioactive substances in foods.

The event of supplements in specific populations warrants further investigation. Older adults are at an increased gamble of malnutrition because of reduced nutrient intake and age related decreases in the bioavailability of some micronutrients. Vitamin D supplementation is recommended for breastfed infants before the introduction of whole milk and solid foods. Supplements may be more effective in reducing the risk of non-communicable disease in specific ethnic groups or people with low micronutrient intake from foods.28 With a contempo increment in the proportion of people reporting that they follow restricted dietary patterns such as ketogenic, Palaeolithic, vegan, and vegetarian diets, the value of supplements to run across the needs of these specific populations requires evaluation. In addition, potential nutrient-cistron interactions accept rarely been examined in studies of dietary supplements. Future studies on the part of nutrigenetics should help refine and personalise targeted recommendations for supplement use (box two).

Box 2

Areas for research in vitamin and mineral supplementation

Differing health effects of nutrients obtained from foods versus supplements
Synergistic interactions among multiple nutrients and with other bioactive substances
Subpopulation studies (eg, elderly people, ethnic groups, vegans)
Nutrigenetics and "omics" sciences
Personalised supplementation
Specific needs in low and middle income countries

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Information technology is likewise important to recognise that the need for nutrient supplements is different in countries where nutrition deficiency is common. Ensuring adequate nutrition through food fortification and nutrient supplementation can be crucial to prevent serious adverse outcomes of nutrient deficiencies in low and middle income countries, especially among children <5 years, for whom malnutrition contributes to more than one-half their deaths.xv

In summary, current testify does not support recommending vitamin or fish oil supplements to reduce the risk of non-catching diseases among populations without clinical nutritional deficiency. Continuing efforts are warranted to further understand the potentially different roles of nutrients from foods versus supplements in health promotion among a generally healthy population as well as individuals or groups with specific nutritional needs, including those living in low and eye income countries. These efforts, coupled with the integration of new research approaches, will better inform clinical practise and public health policies.

Key letters

Randomised trial evidence does non support use of vitamin, mineral, and fish oil supplements to reduce the risk of non-infectious disease
People using supplements tend to be older, female, and have higher instruction, income, and healthier lifestyles than people who do not utilise them
Use of supplements appreciably reduces the prevalence of inadequate intake for nearly nutrients merely also increases the prevalence of excess intake for some nutrients
Further research is needed to appraise the long term furnishings of supplements on the wellness of the general population and in individuals with specific nutritional needs, including those from depression and centre income countries

Footnotes

Contributors and sources: All authors contributed to drafting the manuscript, with FFZ taking a pb office and serving equally the guarantor. Sources of information for this manuscript included published articles based on national surveys, systematic reviews, and primary inquiry of randomised controlled trials and prospective cohort studies. All authors contributed to critical revision of the manuscript for of import intellectual content and canonical the concluding manuscript.
Competing interests: All authors have read and understood BMJ policy on declaration of interests and alleged the post-obit: FFZ declares funding from the National Institutes of Health, NIMHD (R01 MD 011501) and the Bristol Mayer Squibb Foundation (Bridging Cancer Care Programme). DL declares funding from the National Natural Scientific discipline Foundation of China (NSFC 81773433) and Central Scientific Research Projects in Shandong Providence People's republic of china (2017YYSP007). JBB declares funding from Danone. HM declares funding from DSM Nutritional Products, Switzerland. The funders had no function in the design or comport of the report, collection, management, assay, or the interpretation of the data. JBB reports service on scientific informational boards of AdvoCare International, California Prune Board, California Walnut Committee, Church and Dwight, Cranberry Marketing Committee, Guiding Stars, Quaker Oats, Segterra, and SmartyPants, non related to this work.
Provenance and peer review: Deputed; externally peer reviewed.
This article is role of series commissioned by The BMJ. Open access fees are paid past Swiss Re, which had no input into the commissioning or peer review of the articles. The BMJ thanks the series advisers, Nita Forouhi, Dariush Mozaffarian, and Anna Lartey for valuable communication and guiding pick of topics in the serial.

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Source: https://www.bmj.com/content/369/bmj.m2511