A dietary supplement is a manufactured product intended to supplement the diet when taken by mouth as a pill, capsule, tablet, or liquid. A supplement can provide nutrients either extracted from food sources or synthetic, individually or in combination, in order to increase the quantity of their consumption. The class of nutrient compounds includes vitamins, minerals, fiber, fatty acids and amino acids. Dietary supplements can also contain substances that have not been confirmed as being essential to life, but are marketed as having a beneficial biological effect, such as plant pigments or polyphenols. Animals can also be a source of supplement ingredients, as for example collagen from chickens or fish. These are also sold individually and in combination, and may be combined with nutrient ingredients. In the United States and Canada, dietary supplements are considered a subset of foods, and are regulated accordingly. The European Commission has also established harmonized rules to help insure that food supplements are safe and properly labeled. Among other countries, the definition of dietary supplements may vary as drugs or other classes of ingredients used in supplement products.
Creating an industry estimated to have a 2015 value of $37 billion, there are more than 50,000 dietary supplement products marketed just in the United States, where about 50% of the American adult population consumes dietary supplements. Multivitamins are the most commonly used product. For those who fail to consume a balanced diet, the United States National Institutes of Health states that certain supplements "may have value."
In the United States, it is against federal regulations for supplement manufacturers to claim that these products prevent or treat any disease. Companies are allowed to use what is referred to as "Structure/Function" wording if there is substantiation of scientific evidence for a supplement providing a potential health effect. An example would be "_____ helps maintain healthy joints", but the label must bear a disclaimer that the Food and Drug Administration (FDA) "has not evaluated the claim and that the dietary supplement product is not intended to "diagnose, treat, cure or prevent any disease," because only a drug can legally make such a claim. The FDA enforces these regulations, and also prohibits the sale of supplements and supplement ingredients that are dangerous, or supplements not made according to standardized good manufacturing practices (GMPs).
In the United States, the Dietary Supplement Health and Education Act of 1994 provides this description: "The Dietary Supplement Health and Education Act of 1994 (DSHEA) defines the term “dietary supplement” to mean a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract, or combination of any of the aforementioned ingredients. Furthermore, a dietary supplement must be labeled as a dietary supplement and be intended for ingestion and must not be represented for use as conventional food or as a sole item of a meal or of the diet. In addition, a dietary supplement cannot be approved or authorized for investigation as a new drug, antibiotic, or biologic, unless it was marketed as a food or a dietary supplement before such approval or authorization. Under DSHEA, dietary supplements are deemed to be food, except for purposes of the drug definition."
Per DSHEA, dietary supplements are consumed orally, and are mainly defined by what they are not: conventional foods (including meal replacements), medical foods, preservatives or pharmaceutical drugs. Products intended for use as a nasal spray, or topically, as a lotion applied to the skin, do not qualify. FDA-approved drugs cannot be ingredients in dietary supplements. Supplement products are or contain vitamins, nutritionally essential minerals, amino acids, essential fatty acids and non-nutrient substances extracted from plants or animals or fungi or bacteria, or in the instance of probiotics, are live bacteria. Dietary supplement ingredients may also be synthetic copies of naturally occurring substances (example: melatonin). All products with these ingredients are required to be labeled as dietary supplements. Like foods and unlike drugs, no government approval is required to make or sell dietary supplements; the manufacturer confirms the safety of dietary supplements but the government does not; and rather than requiring risk–benefit analysis to prove that the product can be sold like a drug, such assessment is only used by the FDA to decide that a dietary supplement is unsafe and should be removed from market.
A vitamin is an organic compound required by an organism as a vital nutrient in limited amounts. An organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. The term is conditional both on the circumstances and on the particular organism. For example, ascorbic acid (vitamin C) is a vitamin for anthropoid primates, humans, guinea pigs and bats, but not for other mammals. Vitamin D is not an essential nutrient for people who get sufficient exposure to ultraviolet light, either from the sun or an artificial source, as then they synthesize vitamin D in skin. Humans require thirteen vitamins in their diet, most of which are actually groups of related molecules, "vitamers", (e.g. vitamin E includes tocopherols and tocotrienols, vitamin K includes vitamin K1 and K2). The list: vitamins A, C, D, E, K, Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic Acid (B5), Vitamin B6, Biotin (B7), Folate (B9) and Vitamin B12. Vitamin intake below recommended amounts can result in signs and symptoms associated with vitamin deficiency. There is little evidence of benefit when consumed as a dietary supplement by those who are healthy and consuming a nutritionally adequate diet.
The U.S. Institute of Medicine sets Tolerable upper intake levels (ULs) for some of the vitamins. This does not prevent dietary supplement companies from selling products with content per serving higher than the ULs. For example, the UL for vitamin D is 100 µg (4,000 IU), but products are available without prescription at 10,000 IU.
Minerals are the exogenous chemical elements indispensable for life. Four minerals: carbon, hydrogen, oxygen, and nitrogen, are essential for life but are so ubiquitous in food and drink that these are not considered nutrients and there are no recommended intakes for these as minerals. The need for nitrogen is addressed by requirements set for protein, which is composed of nitrogen-containing amino acids. Sulfur is essential, but for humans, not identified as having a recommended intake per se. Instead, recommended intakes are identified for the sulfur-containing amino acids methionine and cysteine. There are dietary supplements which provide sulfur, such as taurine and methylsulfonylmethane.
The essential nutrient minerals for humans, listed in order by weight needed to be at the Recommended Dietary Allowance or Adequate Intake are potassium, chlorine, sodium, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, chromium, molybdenum, selenium and cobalt (the last as a component of vitamin B12). There are other minerals which are essential for some plants and animals, but may or may not be essential for humans, such as boron and silicon. Essential and purportedly essential minerals are marketed as dietary supplements, individually and in combination with vitamins and other minerals.
Although as a general rule, dietary supplement labeling and marketing are not allowed to make disease prevention or treatment claims, the U.S. FDA has for some foods and dietary supplements reviewed the science, concluded that there is significant scientific agreement, and published specifically worded allowed health claims. An initial ruling allowing a health claim for calcium dietary supplements and osteoporosis was later amended to include calcium supplements with or without vitamin D, effective January 1, 2010. Examples of allowed wording are shown below. In order to qualify for the calcium health claim, a dietary supplement much contain at least 20% of the Reference Dietary Intake, which for calcium means at least 260 mg/serving.
- "Adequate calcium throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis."
- "Adequate calcium as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life."
- "Adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis."
- "Adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life."
In the same year, the European Food Safety Authority also approved a dietary supplement health claim for calcium and vitamin D and the reduction of the risk of osteoporotic fractures by reducing bone loss. The U.S. FDA also approved Qualified Health Claims (QHCs) for various health conditions for calcium, selenium and chromium picolinate. QHCs are supported by scientific evidence, but do not meet the more rigorous “significant scientific agreement” standard required for an authorized health claim. If dietary supplement companies choose to make such a claim then the FDA stipulates the exact wording of the QHC to be used on labels and in marketing materials. The wording can be onerous: "One study suggests that selenium intake may reduce the risk of bladder cancer in women. However, one smaller study showed no reduction in risk. Based on these studies, FDA concludes that it is highly uncertain that selenium supplements reduce the risk of bladder cancer in women."
Proteins and amino acids
Protein-containing supplements, either ready-to-drink or as powders to be mixed into water, are marketed as aids to people recovering from illness or injury, those hoping to thwart the sarcopenia of old age, to athletes who believe that strenuous physical activity increases protein requirements, to people hoping to lose weight while minimizing muscle loss, i.e., conducting a protein-sparing modified fast, and to people who want to increase muscle size for performance and appearance. Whey protein is a popular ingredient, but products may also incorporate casein, soy, pea, hemp or rice protein.
According to US & Canadian Dietary Reference Intake guidelines, the protein Recommended Dietary Allowance (RDA) for adults is based on 0.8 grams protein per kilogram body weight. The recommendation is for sedentary and lightly active people. Scientific reviews can conclude that a high protein diet, when combined with exercise, will increase muscle mass and strength, or conclude the opposite. The International Olympic Committee recommends protein intake targets for both strength and endurance athletes at about 1.2-1.8 g/kg body mass per day. One review proposed a maximum daily protein intake of approximately 25% of energy requirements, i.e., approximately 2.0 to 2.5 g/kg.
The same protein ingredients marketed as dietary supplements can be incorporated into meal replacement and medical food products, but those are regulated and labeled differently from supplements. In the United States, "meal replacement" products are foods and are labeled as such. These typically contain protein, carbohydrates, fats, vitamins and minerals. There may be content claims such as "good source of protein", "low fat" or "lactose free." Medical foods, also nutritionally complete, are designed to be used while a person is under the care of a physician or other licensed healthcare professional. Liquid medical food products - example Ensure - are available in regular and high protein versions.
Proteins are chains of amino acids. Nine of these proteinogenic amino acids are considered essential for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Recommended intakes, expressed as milligrams per kilogram of body weight per day, have been established. Other amino acids may be conditionally essential for certain ages or medical conditions. Amino acids, individually and in combinations, are sold as dietary supplements. The claim for supplementing with the branched chain amino acids leucine, valine and isoleucine is for stimulating muscle protein synthesis. A review of the literature concluded this claim was unwarranted. In elderly people, supplementation with just leucine resulted in a modest (0.99 kg) increase in lean body mass. The non-essential amino acid arginine, consumed in sufficient amounts, is thought to act as a donor for the synthesis of nitric oxide, a vasodilator. A review confirmed blood pressure lowering. Taurine, a popular dietary supplement ingredient with claims made for sports performance, is technically not an amino acid. It is synthesized in the body from the amino acid cysteine.
Bodybuilding supplements are dietary supplements commonly used by those involved in bodybuilding, weightlifting, mixed martial arts, and athletics for the purpose of facilitating an increase in lean body mass. The intent is to increase muscle, increase body weight, improve athletic performance, and for some sports, to simultaneously decrease percent body fat so as to create better muscle definition. Among the most widely used are high protein drinks, branched-chain amino acids (BCAA), glutamine, arginine, essential fatty acids, creatine, HMB, and weight loss products. Supplements are sold either as single ingredient preparations or in the form of "stacks" – proprietary blends of various supplements marketed as offering synergistic advantages. While many bodybuilding supplements are also consumed by the general public the frequency of use will differ when used specifically by bodybuilders. One meta-analysis concluded that for athletes participating in resistance exercise training and consuming protein supplements for an average of 13 weeks, total protein intake up to 1.6 g/kg of body weight per day would result in an increase in strength and fat-free mass, i.e. muscle, but that higher intakes would not further contribute. The muscle mass increase was statistically significant but modest - averaging 0.3 kg for all trials and 1.0–2.0 kg, for protein intake ≥1.6 g/kg/day.
Essential fatty acids
Fish oil is a commonly used fatty acid supplement because it is a source of omega-3 fatty acids. Fatty acids are strings of carbon atoms, having a range of lengths. If links are all single (C-C), then the fatty acid is called saturated; with one double bond (C=C), it is called monounsaturated; if there are two or more double bonds (C=C=C), it is called polyunsaturated. Only two fatty acids, both polyunsaturated, are considered essential to be obtained from the diet, as the others are synthesized in the body. The "essential" fatty acids are alpha-linolenic acid (ALA), an omega-3 fatty acid, and linoleic acid (LA), an omega-6 fatty acid. ALA can be elongated in the body to create other omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
Plant oils, particularly seed and nut oils, contain ALA. Food sources of EPA and DHA are oceanic fish, whereas dietary supplement sources include fish oil, krill oil and marine algae extracts. The European Food Safety Authority (EFSA) identifies 250 mg/day for a combined total of EPA and DHA as Adequate Intake, with a recommendation that women pregnant or lactating consume an additional 100 to 200 mg/day of DHA. In the United States and Canada are Adequate Intakes for ALA and LA over various stages of life, but there are no intake levels specified for EPA and/or DHA.
Supplementation with EPA and/or DHA does not appear to affect the risk of death, cancer or heart disease. Furthermore, studies of fish oil supplements have failed to support claims of preventing heart attacks or strokes. In 2017, the American Heart Association issued a science advisory stating that it could not recommend use of omega-3 fish oil supplements for primary prevention of cardiovascular disease or stroke, although it reaffirmed supplementation for people who have a history of coronary heart disease.
Dietary supplements can be manufactured using intact sources or extracts from plants, animals, algae, fungi or lichens, including such examples as ginkgo biloba, curcumin, cranberry, St. John’s wort, ginseng, resveratrol, glucosamine and collagen. Products bearing promotional claims of health benefits are sold without requiring a prescription in pharmacies, supermarkets, specialist shops, military commissaries, buyers clubs, direct selling organizations, and the internet. While most of these products have a long history of use in herbalism and various forms of traditional medicine, concerns exist about their actual efficacy, safety and consistency of quality. Canada has published a manufacturer and consumer guide describing quality, licensing, standards, identities, and common contaminants of natural products. In 2016, sales of herbal supplements just in the United States were $7.5 billion, with the market growing at about 8% per year. Italy, Germany and Eastern European countries were leading consumers of botanical supplements in 2016, with European Union market growth forecast to be $8.7 billion by 2020.
In humans, the large intestine is host to more than 1,000 species of microorganisms, mostly bacteria, numbering in the tens of trillions. "Probiotic" in the context of dietary supplements is the theory that by orally consuming specific live bacteria (or yeast) species, it is possible to influence the large intestine microbiota, with consequent health benefits. Although there are numerous claimed benefits of using probiotic supplements, such as maintaining gastrointestinal health, in part by lowering risk of and severity of constipation or diarrhea, and improving immune health, including lower risk of and severity of acute upper respiratory tract infections, i.e., the common cold, such claims are not all supported by sufficient clinical evidence. A review based on interviews with dozens of experts in microbiome research expressed concern about "...how biomedical research is co-opted by commercial entities that place profit over health." The concern is timely, as through 2021, probiotic supplements are expected to be the fastest growing segment of the dietary supplement market worldwide, while at the same time, the global health benefits market for probiotic-containing yogurt (a food, not a dietary supplement) is declining.
As with all dietary supplements, in the United States inappropriate label health claims such as preventing or treating disease are opposed by the FDA and deceptive advertisements by the Federal Trade Commission. Probiotic foods and dietary supplements are allowed to make claims using Structure:Function vocabulary as long as human trial evidence is adequate. In 2005, the FDA issued a Warning Letter to UAS Laboratories for disease treatment claims (colds, flu, ulcers, elevated blood cholesterol, colon cancer...). The company revised label and website content and continued to sell the product. In 2011 the company was found to have resumed the label and website claims, and the FDA seized product and stopped production. In 2010 a FTC action was brought against a probiotic food company for exaggerated health claims, resulting in a multimillion-dollar fine and revisions to future advertising. In the European Union a more restrictive approach has been taken by the EFSA. All proposed health claims were rejected on the grounds that the science was not sufficient, and no health claims are permitted. Foods with live microorganisms (yogurt, kefir) can be sold, but without claims.
Probiotic supplements are generally regarded as safe. The greatest concern, evidenced by reviews reporting on case studies, is that for people with compromised gut wall integrity there may be a risk of systemic infection. For this reason, probiotic research is expected to exclude bacteria species that are antibiotic resistant.
In 2015, the American market for dietary supplements was valued at $37 billion, with the economic impact in the United States for 2016 estimated at $122 billion, including employment wages and taxes. One 2016 analysis estimated the total market for dietary supplements could reach $278 billion worldwide by 2024.
Over the period 2008 to 2011, the Government Accountability Office (GAO) of the United States received 6,307 reports of health problems (identified as adverse events) from use of dietary supplements containing a combination of ingredients in manufactured vitamins, minerals or other supplement products, with 92% of tested herbal supplements containing lead and 80% containing other chemical contaminants. Using undercover staff, the GAO also found that supplement retailers intentionally engaged in "unequivocal deception" to sell products advertised with baseless health claims, particularly to elderly consumers. Consumer Reports also reported unsafe levels of arsenic, cadmium, lead and mercury in several protein powder products. The Canadian Broadcasting Corporation (CBC) reported that protein spiking, i.e., the addition of amino acids to manipulate protein content analysis, was common. Many of the companies involved challenged CBC's claim.
A 2013 study on herbal supplements found that many products were of low quality, one third did not contain the active ingredient(s) claimed, and one third contained unlisted substances. In a genetic analysis of herbal supplements, 78% of samples contained animal DNA that was not identified as an ingredient on the product labels. In some botanical products, undeclared ingredients were used to increase the bulk of the product and reduce its cost of manufacturing, while potentially violating certain religious and/or cultural limitations on consuming animal ingredients, such as cow, buffalo or deer. In 2015, the New York Attorney General identified four major retailers with dietary supplement products that contained fraudulent and potentially dangerous ingredients, requiring the companies to remove the products from retail stores.
Litigation against false health claims
The United States Food and Drug Administration, Office of Inspections, Compliance, Enforcement, and Criminal Investigations, monitors supplement products for accuracy in advertising and labeling, and when finding violations, warns manufacturers of impending enforcement action, including search and seizure, injunction, and/or financial penalties, such as for a Maine supplement company in 2017. The United States Federal Trade Commission, which litigates against deceptive advertising, established a consumer center to assist reports of false health claims in product advertising for dietary supplements, and, in 2017, successfully sued nine manufacturers for deceptive advertising of dietary supplements.
In the United States, manufacturers of dietary supplements are required to demonstrate safety of their products before approval is granted for commerce. Despite this caution, numerous adverse effects have been reported, including muscle cramps, hair loss, joint pain, liver disease, and allergic reactions, with 29% of the adverse effects resulting in hospitalization, and 20% in serious injuries or illnesses. By more than five-fold, the highest incidence of health problems derived from "combination products", whereas supplements for vitamins and minerals, lipid products, and herbal products were less likely to cause adverse effects.
Among general reasons for the possible harmful effects of dietary supplements are: a) absorption in a short time, b) manufacturing quality and contamination, and c) enhancing both positive and negative effects at the same time. The incidence of liver injury from herbal and dietary supplements is about 16–20% of all supplement products causing injury, with the occurrence growing globally over the early 21st century. The most common liver injuries from weight loss and bodybuilding supplements involve hepatocellular damage with resulting jaundice, and the most common supplement ingredients attributed to these injuries are green tea catechins, anabolic steroids, and the herbal extract, aegeline. Weight loss supplements have also had adverse psychiatric effects.
Society and culture
Work done by scientists in the early 20th century on identifying individual nutrients in food and developing ways to manufacture them raised hopes that optimal health could be achieved and diseases prevented by adding them to food and providing people with dietary supplements; while there were successes in preventing vitamin deficiencies, and preventing conditions like neural tube defects by supplementation and food fortification with folic acid, no targeted supplementation or fortification strategies to prevent major diseases like cancer or cardiovascular diseases have proved successful.
For example, while increased consumption of fruits and vegetables are related to decreases in mortality, cardiovascular diseases and cancers, supplementation with key factors found in fruits and vegetable, like antioxidants, vitamins, or minerals, do not help and some have been found to be harmful in some cases. In general as of 2016, robust clinical data is lacking, that shows that any kind of dietary supplementation does more good than harm for people who are healthy and eating a reasonable diet but there is clear data showing that dietary pattern and lifestyle choices are associated with health outcomes.
As a result of the lack of good data for supplementation and the strong data for dietary pattern, public health recommendations for healthy eating urge people to eat a plant-based diet of whole foods, minimizing processed food, salt and sugar and to get exercise daily, and to abandon Western pattern diets and a sedentary lifestyle.:10
The regulation of food and dietary supplements by the U.S. Food and Drug Administration is governed by various statutes enacted by the United States Congress and interpreted by the U.S. Food and Drug Administration ("FDA"). Pursuant to the Federal Food, Drug, and Cosmetic Act ("the Act") and accompanying legislation, the FDA has authority to oversee the quality of substances sold as food in the United States, and to monitor claims made in the labeling about both the composition and the health benefits of foods.
Substances which the FDA regulates as food are subdivided into various categories, including foods, food additives, added substances (man-made substances which are not intentionally introduced into food, but nevertheless end up in it), and dietary supplements. The specific standards which the FDA exercises differ from one category to the next. Furthermore, the FDA has been granted a variety of means by which it can address violations of the standards for a given category of substances.
Dietary supplement manufacture is required to comply with the good manufacturing practices established in 2007. The FDA can visit manufacturing facilities, send Warning Letters if not in compliance with GMPs, stop production, and if there is a health risk, require that the company conduct a recall.
The European Union's (EU) Food Supplements Directive of 2002 requires that supplements be demonstrated to be safe, both in dosages and in purity. Only those supplements that have been proven to be safe may be sold in the EU without prescription. As a category of food, food supplements cannot be labeled with drug claims but can bear health claims and nutrition claims.
The dietary supplements industry in the United Kingdom (UK), one of the 28 countries in the bloc, strongly opposed the Directive. In addition, a large number of consumers throughout Europe, including over one million in the UK, and various doctors and scientists, had signed petitions by 2005 against what are viewed by the petitioners as unjustified restrictions of consumer choice. In 2004, along with two British trade associations, the Alliance for Natural Health (ANH) had a legal challenge to the Food Supplements Directive referred to the European Court of Justice by the High Court in London.
Although the European Court of Justice's Advocate General subsequently said that the bloc's plan to tighten rules on the sale of vitamins and food supplements should be scrapped, he was eventually overruled by the European Court, which decided that the measures in question were necessary and appropriate for the purpose of protecting public health. ANH, however, interpreted the ban as applying only to synthetically produced supplements, and not to vitamins and minerals normally found in or consumed as part of the diet. Nevertheless, the European judges acknowledged the Advocate General's concerns, stating that there must be clear procedures to allow substances to be added to the permitted list based on scientific evidence. They also said that any refusal to add the product to the list must be open to challenge in the courts.
Examples of ongoing government research organizations to better understand the potential health properties and safety of dietary supplements are the European Food Safety Authority, the Office of Dietary Supplements of the United States National Institutes of Health, the Natural and Non-prescription Health Products Directorate of Canada, and the Therapeutic Goods Administration of Australia. Together with public and private research groups, these agencies construct databases on supplement properties, perform research on quality, safety, and population trends of supplement use, and evaluate the potential clinical efficacy of supplements for maintaining health or lowering disease risk.
As continual research on the properties of supplements accumulates, databases or fact sheets for various supplements are updated regularly, including the Dietary Supplement Label Database, Dietary Supplement Ingredient Database, and Dietary Supplement Facts Sheets of the United States. In Canada where a license is issued when a supplement product has been proven by the manufacturer and government to be safe, effective and of sufficient quality for its recommended use, an eight-digit Natural Product Number is assigned and recorded in a Licensed Natural Health Products Database. The European Food Safety Authority maintains a compendium of botanical ingredients used in manufacturing of dietary supplements.
In 2015, the Australian Government's Department of Health published the results of a review of herbal supplements to determine if any were suitable for coverage by health insurance. Establishing guidelines to assess safety and efficacy of botanical supplement products, the European Medicines Agency provided criteria for evaluating and grading the quality of clinical research in preparing monographs about herbal supplements. In the United States, the National Center for Complementary and Integrative Health of the National Institutes of Health provides fact sheets evaluating the safety, potential effectiveness and side effects of many botanical products.
Quality and safety
To assure supplements have sufficient quality, standardization, and safety for public consumption, research efforts have focused on development of reference materials for supplement manufacturing and monitoring. High-dose products have received research attention, especially for emergency situations such as vitamin A deficiency in malnutrition of children, and for women taking folate supplements to reduce the risk of breast cancer.
In the United States, the National Health and Nutrition Examination Survey (NHANES) has investigated habits of using dietary supplements in context of total nutrient intakes from the diet in adults and children. Over the period of 1999 to 2012, use of multivitamins decreased, and there was wide variability in the use of individual supplements among subgroups by age, sex, race/ethnicity, and educational status. Particular attention has been given to use of folate supplements by young women to reduce the risk of fetal neural tube defects.
Research initiatives to improve knowledge of the possible health benefits of supplementing with essential nutrients to lower disease risk have been extensive. As examples, just in 2017 were reviews on
- vitamin D, providing evidence for protection against acute respiratory tract infections
- iron, to deter maternal iron deficiency anemia and adverse effects on the fetus
- folate, to lower the risk of stroke and cardiovascular disease
- multiple supplements for which there was no evidence of benefit to lower risk of death, cardiovascular disease or cancer
Absence of benefit
The potential benefit of using essential nutrient dietary supplements to lower the risk of diseases has been refuted by findings of no effect or weak evidence in numerous clinical reviews, such as for cardiovascular diseases, cancer, HIV, or tuberculosis.
A review of clinical trials registered at clinicaltrials.gov, which would include both drugs and supplements, reported that nearly half of completed trials were sponsored wholly or partially by industry. This does not automatically imply bias, but there is evidence that because of selective non-reporting, results in support of a potential drug or supplement ingredient are more likely to be published than results that do not demonstrate a statistically significant benefit. One review reported that fewer than half of the registered clinical trials resulted in publication in peer-reviewed journals.
Improving public information about use of dietary supplements involves investments in professional training programs, further studies of population and nutrient needs, expanding the database information, enhancing collaborations between governments and universities, and translating dietary supplement research into useful information for consumers, health professionals, scientists, and policymakers. Future demonstration of efficacy from use of dietary supplements requires high-quality clinical research using rigorously-qualified products and compliance with established guidelines for reporting of clinical trial results (e.g., CONSORT guidelines).
- "Cod liver oil". Encyclopædia Britannica, Inc. 2018. Retrieved 18 February 2018.
- "Dietary Supplements: Background Information". Office of Dietary Supplements, US National Institutes of Health. 24 June 2011. Retrieved 2 February 2018.
- "Food Supplements". European Food Safety Authority, European Commission. 2009.
- Brodwin, Erin (8 November 2017). "The $37 billion supplement industry is barely regulated — and it's allowing dangerous products to slip through the cracks". Business Insider Inc. Retrieved 31 January 2018.
- "Dietary Supplement Label Database". Office of Dietary Supplements, US National Institutes of Health. 2017.
- Park, Madison. "Half of Americans use supplements". CNN. Retrieved 3 October 2013.
- "FAQs on Dietary Supplements". Office of Dietary Supplements, US National Institutes of Health.
- "Structure/Function Claims". Office of Dietary Supplement Programs, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration. 14 December 2017.
- Dietary Supplement Labels: Key Elements Office of Inspector General, Depart of Health and Human Services (2003).
- Guidance for Industry: Frequently Asked Questions About Medical Foods; Second Edition U.S. Food and Drug Administration (May 2016).
- Committee on the Framework for Evaluating the Safety of Dietary Supplements, Food and Nutrition Board, Board on Life Sciences, Institute of Medicine and National Research Council of the National Academies (2004). Dietary supplements a framework for evaluating safety. Washington, D.C.: National Academies Press. p. ES-1-ES-3. ISBN 0-309-09206-X.
- Lieberman, S and Bruning, N (1990). The Real Vitamin & Mineral Book. NY: Avery Group, 3, ISBN 0-89529-769-8
- Drouin G, Godin JR, Pagé B (2011). "The genetics of vitamin C loss in vertebrates". Curr. Genomics. 12 (5): 371–378. doi:10.2174/138920211796429736. PMC 3145266
. PMID 22294879.
- Fortmann, SP; Burda, BU; Senger, CA; Lin, JS; Whitlock, EP (Nov 12, 2013). "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.". Annals of Internal Medicine. 159 (12): 824–834. doi:10.7326/0003-4819-159-12-201312170-00729. PMID 24217421.
- Dietary Reference Intakes (DRIs): Recommended Intakes for Individuals, Food and Nutrition Board, Institute of Medicine, National Academies, 2004, retrieved 2009-06-09
- Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis U.S. Food and Drug Administration.
- EFSA Journal 2010; 8(5):1609 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA).
- Qualified Health Claims: Letters of Enforcement Discretion U.S. Food and Drug Administration.
- Selenium and a Reduced Risk of Site-specific Cancers, FDA-2008-Q-0323 U.S. Food and Drug Administration.
- Liao CD, Tsauo JY, Wu YT, Cheng CP, Chen HC, Huang YC, Chen HC, Liou TH (2017). "Effects of protein supplementation combined with resistance exercise on body composition and physical function in older adults: a systematic review and meta-analysis". Am. J. Clin. Nutr. 106 (4): 1078–1091. doi:10.3945/ajcn.116.143594. PMID 28814401.
- Colonetti T, Grande AJ, Milton K, Foster C, Alexandre MC, Uggioni ML, Rosa MI (2017). "Effects of whey protein supplement in the elderly submitted to resistance training: systematic review and meta-analysis". Int J Food Sci Nutr. 68 (3): 257–264. doi:10.1080/09637486.2016.1232702. PMID 27653283.
- Nutrition for Athletes, International Olympic Committee Nutrition Working Group of the Medical and Scientific Commission of the International Olympic Committee, Revised and Updated in June 2016.
- Stonehouse W, Wycherley T, Luscombe-Marsh N, Taylor P, Brinkworth G, Riley M (2016). "Dairy Intake Enhances Body Weight and Composition Changes during Energy Restriction in 18-50-Year-Old Adults-A Meta-Analysis of Randomized Controlled Trials". Nutrients. 8 (7): 394. doi:10.3390/nu8070394. PMC 4963870
. PMID 27376321.
- Naclerio F, Larumbe-Zabala E (2016). "Effects of Whey Protein Alone or as Part of a Multi-ingredient Formulation on Strength, Fat-Free Mass, or Lean Body Mass in Resistance-Trained Individuals: A Meta-analysis". Sports Med. 46 (1): 125–137. doi:10.1007/s40279-015-0403-y. PMID 26403469.
- Miller PE, Alexander DD, Perez V (2014). "Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials". J Am Coll Nutr. 33 (2): 163–175. doi:10.1080/07315724.2013.875365. PMID 24724774.
- Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids, Institute of Medicine. National Academy Press, 2005
- Bilsborough, Shane; Neil Mann (2006). "A Review of Issues of Dietary Protein Intake in Humans". International Journal of Sport Nutrition and Exercise Metabolism. 16 (2): 129–152. doi:10.1123/ijsnem.16.2.129. Retrieved 6 December 2012.
- Tarnopolsky MA, Atkinson SA, MacDougall JD, Chesley A, Phillips S, Schwarcz HP (1992). "Evaluation of protein requirements for trained strength athletes". Journal of Applied Physiology. 73 (5): 1986–1995. PMID 1474076.
- Lemon, PW (1995). "Do athletes need more dietary protein and amino acids?". Int J Sport Nutr. 5 Suppl: S39–561. PMID 7550257.
- Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM (2017). "A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults". Br J Sports Med. 52 (6): bjsports–2017–097608. doi:10.1136/bjsports-2017-097608. PMC 5867436
. PMID 28698222.
- Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ (2012). "Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis". Am. J. Clin. Nutr. 96 (6): 1454–1464. doi:10.3945/ajcn.112.037556. PMID 23134885.
- Finger D, Goltz FR, Umpierre D, Meyer E, Rosa LH, Schneider CD (2015). "Effects of protein supplementation in older adults undergoing resistance training: a systematic review and meta-analysis". Sports Med. 45 (2): 245–255. doi:10.1007/s40279-014-0269-4. PMID 25355074.
- "Regulatory Issues: Meal Replacements – Convenience or Compromise?". Food Processing.
- Medical Foods Guidance Documents & Regulatory Information U.S. Food and Drug Administration.
- Medical Foods - Guidance for Industry: Frequently Asked Questions About Medical Foods; Second Edition U.s. Food and Drug Administration (May 2016)
- Charles EJ, Johnston LE, Herbert MA, Mehaffey JH, Yount KW, Likosky DS, Theurer PF, Fonner CE, Rich JB, Speir AM, Ailawadi G, Prager RL, Kron IL (2017). "Impact of Medicaid Expansion on Cardiac Surgery Volume and Outcomes". Ann. Thorac. Surg. 104 (4): 1251–1258. doi:10.1016/j.athoracsur.2017.03.079. PMID 28552372.
- Komar B, Schwingshackl L, Hoffmann G (2015). "Effects of leucine-rich protein supplements on anthropometric parameter and muscle strength in the elderly: a systematic review and meta-analysis". J Nutr Health Aging. 19 (4): 437–446. doi:10.1007/s12603-014-0559-4. PMID 25809808.
- Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W (2011). "Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials". Am. Heart J. 162 (6): 959–965. doi:10.1016/j.ahj.2011.09.012. PMID 22137067.
- "the definition of amino acid". Dictionary.com. Retrieved 2017-02-22.
- Cruz-Jentoft AJ (May 2017). "Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia". Current Protein & Peptide Science. 18 (7): 668–672. doi:10.2174/1389203718666170529105026. PMID 28554316.
HMB is widely used as an ergogenic supplement by young athletes.
- McGinn, Dave (7 November 2010). "Are protein shakes the weight-loss magic bullet?". Globe and Mail. Retrieved 1 December 2010.
- "Omega−3 Fatty Acids and Health: Fact Sheet for Health Professionals". US National Institutes of Health, Office of Dietary Supplements. 2 November 2016. Retrieved 5 April 2017.
- Whitney Ellie; Rolfes SR (2008). Understanding Nutrition (11th ed.). California: Thomson Wadsworth. p. 154.
- "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017. Archived (PDF) from the original on August 28, 2017.
- Dietary Reference Intakes (DRIs) Food and Nutrition Board, Institute of Medicine, National Academies
- Rizos, EC; Elisaf, MS (June 2017). "Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?". Current cardiology reports. 19 (6): 47. doi:10.1007/s11886-017-0856-8. PMID 28432658.
- MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC (2006-01-25). "Effects of omega−3 fatty acids on cancer risk: a systematic review". JAMA: The Journal of the American Medical Association. 295 (4): 403–415. doi:10.1001/jama.295.4.403. PMID 16434631. Retrieved 2006-07-07.
- Grey, Andrew; Bolland, Mark (March 2014). "Clinical Trial Evidence and Use of Fish Oil Supplements". JAMA Internal Medicine. 174 (3): 460–462. doi:10.1001/jamainternmed.2013.12765. PMID 24352849.
- Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D (2017). "Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association". Circulation. 135 (15): e867–e884. doi:10.1161/CIR.0000000000000482. PMID 28289069.
- "Botanicals". European Food Safety Authority. 2018. Retrieved 1 February 2018.
- Prince, Jennifer (13 September 2017). "U.S. Herbal Supplement Sales Up 7.7% in 2016". Nutritional Outlook. Retrieved 1 February 2018.
- "Natural and Non-prescription Health Products". Government of Canada. 2018. Retrieved 1 February 2018.
- Barrett, Stephen (23 November 2013). "The herbal minefield". Quackwatch. Retrieved 1 February 2018.
- Zhang, J; Wider, B; Shang, H; Li, X; Ernst, E (2012). "Quality of herbal medicines: Challenges and solutions". Complementary Therapies in Medicine. 20 (1–2): 100–106. doi:10.1016/j.ctim.2011.09.004. PMID 22305255.
- Coghlan, M. L.; Haile, J; Houston, J; Murray, D. C.; White, N. E.; Moolhuijzen, P; Bellgard, M. I.; Bunce, M (2012). "Deep Sequencing of Plant and Animal DNA Contained within Traditional Chinese Medicines Reveals Legality Issues and Health Safety Concerns". PLoS Genetics. 8 (4): e1002657. doi:10.1371/journal.pgen.1002657. PMC 3325194
. PMID 22511890.
- "Quality of Natural Health Products Guide". Government of Canada. 1 May 2015. Retrieved 1 February 2018.
- Becker, Mark (8 March 2016). "Dietary Supplements in Europe Poised for Profound Growth". Natural Products Insider. Retrieved 1 February 2018.
- Thursby E, Juge N (2017). "Introduction to the human gut microbiota". Biochem. J. 474 (11): 1823–1836. doi:10.1042/BCJ20160510. PMC 5433529
. PMID 28512250.
- "Probiotic Health Claims". Food Safety Authority of Ireland. 5 May 2017. Retrieved 4 February 2018.
- Rijkers GT, de Vos WM, Brummer RJ, Morelli L, Corthier G, Marteau P (2011). "Health benefits and health claims of probiotics: Bridging science and marketing". British Journal of Nutrition. 106 (9): 1291–1296. doi:10.1017/S000711451100287X. PMID 21861940.
- Slashinski MJ, McCurdy SA, Achenbaum LS, Whitney SN, McGuire AL (2012). ""Snake-oil," "quack medicine," and "industrially cultured organisms:" biovalue and the commercialization of human microbiome research". BMC Medical Ethics. 13: 28. doi:10.1186/1472-6939-13-28. PMC 3512494
. PMID 23110633.
- Crane, Michael (14 October 2015). "Crackdown on Probiotic Health Claims Costs Billions for EU Yogurt Industry". Nutritional Outlook. Retrieved 1 February 2018.
- Grebow, Jennifer (1 November 2016). "Probiotic Supplements Will Be the #1 Fastest-Growing Supplement in North America through 2021, Says Euromonitor at SupplySide West". Nutritional Outlook. Retrieved 4 February 2018.
- UAS Warning Letter, May 13, 2005 US Food and Drug Administration
- FDA News Release, June 7, 2011 US Food and Drug Administration
- "Dannon Agrees to Drop Exaggerated Health Claims for Activia Yogurt and DanActive Dairy Drink FTC Charges that Evidence Supporting Benefits of Probiotics Falls Short". Federal Trade Commission, US Government. 15 December 2010. Retrieved 9 May 2017.
- Doron S, Snydman DR (2015). "Risk and safety of probiotics". Clin Infect Dis (Review). 60 Suppl 2: S129–S134. doi:10.1093/cid/civ085. PMC 4490230
. PMID 25922398.
- Durchschein F, Petritsch W, Hammer HF (2016). "Diet therapy for inflammatory bowel diseases: The established and the new". World J Gastroenterol (Review). 22 (7): 2179–2194. doi:10.3748/wjg.v22.i7.2179. PMC 4734995
. PMID 26900283.
- "Supplement Industry Contributes $122 Billion To U.S. Economy". Nutraceuticals World. 10 June 2016. Retrieved 1 February 2018.
- "Report Forecasts Supplement Market to Reach $278 Billion by 2024". Nutraceuticals World. 1 July 2016. Retrieved 1 February 2018.
- "Dietary Supplements: FDA May Have Opportunities to Expand Its Use of Reported Health Problems to Oversee Products". Government Accountability Office, US Government. 18 March 2013. Retrieved 2 February 2018.
- Harmon, Katherine (28 May 2010). "Herbal Supplement Sellers Dispense Dangerous Advice, False Claims". Scientific American. Retrieved 2 February 2018.
- McGinn, Dave (26 March 2017). "Are protein shakes the weight-loss magic bullet?". The Globe and Mail (Toronto). Retrieved 2 February 2018.
- Griffith-Greene, Megan (November 13, 2015). "Marketplace: Some protein powders fail fitness test". CBC News. Retrieved December 11, 2015.
- "Supplements: Company statements". CBC News. November 13, 2015. Retrieved December 11, 2015.
- Newmaster, Steven G; Grguric, Meghan; Shanmughanandhan, Dhivya; Ramalingam, Sathishkumar; Ragupathy, Subramanyam (2013). "DNA barcoding detects contamination and substitution in North American herbal products". BMC Medicine. 11: 222. doi:10.1186/1741-7015-11-222. PMC 3851815
. PMID 24120035.
- O'Connor, Anahad (3 February 2015). "New York Attorney General Targets Supplements at Major Retailers". The New York Times. Retrieved 1 February 2018.
- Pace, RM (18 December 2017). "Warning letter: Maine Natural Health, Inc". Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved 3 February 2018.
- "Dietary supplement concerns? Tell the FTC and FDA". Federal Trade Commission, US Government. 25 July 2017. Retrieved 2 February 2018.
- "Three Dietary Supplement Marketers Settle FTC, Maine AG Charges". Federal Trade Commission, US Government. 23 August 2017. Retrieved 2 February 2018.
- "New Dietary Ingredients in Dietary Supplements - Background for Industry". US Food and Drug Administration. August 2016. Retrieved 2 February 2018.
- Bersani, F. S; Coviello, M; Imperatori, C; Francesconi, M; Hough, C. M; Valeriani, G; De Stefano, G; Bolzan Mariotti Posocco, F; Santacroce, R; Minichino, A; Corazza, O (2015). "Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products". BioMed Research International. 2015: 120679. doi:10.1155/2015/120679. PMC 4589574
- Lichtenstein, Alice H.; Russell, Robert M. (2005). "Essential Nutrients: Food or Supplements?". JAMA. 294 (3): 351–8. doi:10.1001/jama.294.3.351. PMID 16030280.
- "Vitamin E — Health Professional Fact Sheet". dietary-supplements.info.nih.gov. Retrieved 5 February 2015.
- Bjelakovic, G; Nikolova, D; Gluud, LL; Simonetti, RG; Gluud, C (14 March 2012). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". The Cochrane Database of Systematic Reviews. 3 (3): CD007176. doi:10.1002/14651858.CD007176.pub2. PMID 22419320.
- Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER (December 2013). "Enough is enough: Stop wasting money on vitamin and mineral supplements". Ann. Intern. Med. (Editorial). 159 (12): 850–851. doi:10.7326/0003-4819-159-12-201312170-00011. PMID 24490268.
- Rautiainen, S; Manson, JE; Lichtenstein, AH; Sesso, HD (July 2016). "Dietary supplements and disease prevention – a global overview". Nature Reviews. Endocrinology. 12 (7): 407–420. doi:10.1038/nrendo.2016.54. PMID 27150288.
- Katz DL, Meller S (2014). "Can we say what diet is best for health?". Annu Rev Public Health. 35: 83–103. doi:10.1146/annurev-publhealth-032013-182351. PMID 24641555.
- Fitzgerald M (2014). Diet Cults: The Surprising Fallacy at the Core of Nutrition Fads and a Guide to Healthy Eating for the Rest of US. Pegasus Books. ISBN 978-1-60598-560-2.
- Current Good Manufacturing Practices (CGMPs) for Dietary Supplements U.S. Food and Drug Administration (2007).
- "Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements". Eur-lex.europa.eu. Retrieved 2012-12-05.
- "European Commission website: Food Safety – Labelling & Nutrition – Health & Nutrition Claims". Ec.europa.eu. Retrieved 2012-12-05.
- Knight, Sam (2005-07-12). "Controversial EU vitamins ban to go ahead". The Times Online. Retrieved 2012-12-05.
- "Food supplements - Food Safety - European Commission". Food Safety.
- "'Court victory for vitamin firms'". BBC News. 2004-01-30. Retrieved 2012-12-05.
- "'EU health foods crackdown 'wrong''". BBC News. 2005-04-05. Retrieved 2012-12-05.
- "'Vitamin controls backed by Europe'". BBC News. 2005-07-12. Retrieved 2012-12-05.
- "'EU court backs health supplements ban'". Guardian. 2005-07-12. Retrieved 2012-12-05.
- Dwyer, J. T; Coates, P. M; Smith, M. J (2018). "Dietary Supplements: Regulatory Challenges and Research Resources". Nutrients. 10 (1): 41. doi:10.3390/nu10010041. PMID 29300341.
- "About Natural Health Products". Natural and Non-prescription Health Products Directorate, Government of Canada. 14 March 2013. Retrieved 3 February 2018.
- "Complementary medicines". Therapeutic Goods Administration, Australian Government. 2018. Retrieved 3 February 2018.
- "Dietary Supplement Ingredient Database". Office of Dietary Supplements, US National Institutes of Health and US Department of Agriculture, National Nutrient Database. 14 August 2017. Retrieved 3 February 2018.
- "Dietary Supplement Fact Sheets". Office of Dietary Supplements, US National Institutes of Health. 2018. Retrieved 3 February 2018.
- "Licensed Natural Health Products Database". Natural and Non-prescription Health Products Directorate, Government of Canada. 4 May 2015. Retrieved 3 February 2018.
- European Food Safety Authority (2012). "Compendium of botanicals reported to contain naturally occuring [sic] substances of possible concern for human health when used in food and food supplements". EFSA Journal. 10 (5): 2663. doi:10.2903/j.efsa.2012.2663.
- Baggoley C (2015). "Review of the Australian Government Rebate on Natural Therapies for Private Health Insurance" (PDF). Australian Government – Department of Health. Lay summary – Gavura, S. Australian review finds no benefit to 17 natural therapies. Science-Based Medicine. (19 November 2015).
- "Assessment of clinical safety and efficacy in the preparation of Community herbal monographs for well-established and of Community herbal monographs/entries to the Community list for traditional herbal medicinal products/substances/preparations". European Medicines Agency. 2017. Retrieved 25 February 2017.
- "Herbs at a Glance". National Center for Complementary and Integrative Health, US National Institutes of Health. 21 November 2016. Retrieved 24 February 2017.
- "Measurements and Standards for Botanical Dietary Supplements". US National Institute of Standards and Technology. 21 September 2016. Retrieved 3 February 2018.
- Dwyer, J. T; Wiemer, K. L; Dary, O; Keen, C. L; King, J. C; Miller, K. B; Philbert, M. A; Tarasuk, V; Taylor, C. L; Gaine, P. C; Jarvis, A. B; Bailey, R. L (2015). "Fortification and Health: Challenges and Opportunities". Advances in Nutrition: an International Review Journal. 6 (1): 124–131. doi:10.3945/an.114.007443. PMC 4288271
- Iannotti, L. L; Trehan, I; Manary, M. J (2013). "Review of the safety and efficacy of vitamin a supplementation in the treatment of children with severe acute malnutrition". Nutrition Journal. 12: 125. doi:10.1186/1475-2891-12-125. PMC 3850897
. PMID 24028603.
- Chen, P; Li, C; Li, X; Li, J; Chu, R; Wang, H (2014). "Higher dietary folate intake reduces the breast cancer risk: A systematic review and meta-analysis". British Journal of Cancer. 110 (9): 2327–2338. doi:10.1038/bjc.2014.155. PMC 4007237
- Kantor, E. D; Rehm, C. D; Du, M; White, E; Giovannucci, E. L (2016). "Trends in Dietary Supplement Use among US Adults from 1999–2012". JAMA. 316 (14): 1464–1474. doi:10.1001/jama.2016.14403. PMC 5540241
. PMID 27727382.
- Obeid, R; Koletzko, B; Pietrzik, K (2014). "Critical evaluation of lowering the recommended dietary intake of folate". Clinical Nutrition. 33 (2): 252–259. doi:10.1016/j.clnu.2013.12.013. PMID 24503418.
- Wilson, RD; Committee, Genetics; Wilson, RD; Audibert, F; Brock, JA; Carroll, J; Cartier, L; Gagnon, A; Johnson, J. A; Langlois, S; Murphy-Kaulbeck, L; Okun, N; Pastuck, M (2015). "Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies" (PDF). Journal of Obstetrics and Gynaecology Canada. 37 (6): 534–552. PMID 26334606.
- Martineau, A. R; Jolliffe, D. A; Hooper, R. L; Greenberg, L; Aloia, J. F; Bergman, P; Dubnov-Raz, G; Esposito, S; Ganmaa, D; Ginde, A. A; Goodall, E. C; Grant, C. C; Griffiths, C. J; Janssens, W; Laaksi, I; Manaseki-Holland, S; Mauger, D; Murdoch, D. R; Neale, R; Rees, J. R; Simpson Jr, S; Stelmach, I; Kumar, G. T; Urashima, M; Camargo Jr, C. A (2017). "Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data". BMJ. 356: i6583. doi:10.1136/bmj.i6583. PMC 5310969
. PMID 28202713.
- O'Brien, K. O; Ru, Y (2017). "Iron status of North American pregnant women: An update on longitudinal data and gaps in knowledge from the United States and Canada". The American Journal of Clinical Nutrition. 106 (Suppl 6): 1647S–1654S. doi:10.3945/ajcn.117.155986. PMC 5701721
. PMID 29070557.
- Li, Y; Huang, T; Zheng, Y; Muka, T; Troup, J; Hu, F. B (2016). "Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta‐Analysis of Randomized Controlled Trials". Journal of the American Heart Association. 5 (8): e003768. doi:10.1161/JAHA.116.003768. PMC 5015297
. PMID 27528407.
- Schwingshackl, L; Boeing, H; Stelmach-Mardas, M; Gottschald, M; Dietrich, S; Hoffmann, G; Chaimani, A (2017). "Dietary Supplements and Risk of Cause-Specific Death, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis of Primary Prevention Trials". Advances in Nutrition: an International Review Journal. 8 (1): 27–39. doi:10.3945/an.116.013516. PMC 5227980
- Navarro, V; Khan, I; Björnsson, E; Seeff, L. B; Serrano, J; Hoofnagle, J. H (2016). "Liver Injury from Herbal and Dietary Supplements". Hepatology. 65 (1): 363–373. doi:10.1002/hep.28813. PMC 5502701
. PMID 27677775.
- Visser, M. E; Durao, S; Sinclair, D; Irlam, J. H; Siegfried, N (2017). "Micronutrient supplementation in adults with HIV infection". Cochrane Database of Systematic Reviews (5): CD003650. doi:10.1002/14651858.CD003650.pub4. PMC 5458097
- Grobler, L; Nagpal, S; Sudarsanam, T. D; Sinclair, D (2016). "Nutritional supplements for people being treated for active tuberculosis". Cochrane Database of Systematic Reviews (6): 1–195. doi:10.1002/14651858.CD006086.pub4. PMC 4981643
- Dunn AG, Coiera E (2014). "Should comparative effectiveness research ignore industry-funded data?". J Comp Eff Res. 3 (4): 317–320. doi:10.2217/cer.14.31. PMID 25275226.
- Knottnerus JA, Tugwell P (2013). "The potential impact of unpublished results". J Clin Epidemiol. 66 (10): 1061–1063. doi:10.1016/j.jclinepi.2013.08.001. PMID 23993310.
- Zarin DA, Tse T, Sheehan J (2015). "The proposed rule for U.S. clinical trial registration and results submission". N. Engl. J. Med. 372 (2): 174–180. doi:10.1056/NEJMsr1414226. PMC 4344313
. PMID 25539444.
- "ODS Strategic Plan 2017-2021". Office of Dietary Supplements, US National Institutes of Health. December 2017. Retrieved 3 February 2018.
- Dietary Supplements: General Resources for Consumers (PDF|131 KB), Food and Nutrition Information Center, National Agricultural Library. List of resources that provides an overview of herbal and dietary supplements, including use, regulation, research, and cautionary information.
- Questions to Ask Before Taking Vitamin and Mineral Supplements, Nutrition.gov.
- Dietary Supplement Fact Sheets, NIH Office of Dietary Supplements.