Dietary supplement

Last updated

As a pill (iodine) Iodine pills.jpg
As a pill (iodine)
As a capsule (spirulina) Spirulina Capsules.jpg
As a capsule (spirulina)
As a tablet (B vitamins) B vitamin supplement tablets.jpg
As a tablet (B vitamins)
As a softgel capsule (cod liver oil) Codliveroilcapsules.jpg
As a softgel capsule (cod liver oil)
Production of cod liver oil, one of the first dietary supplement products manufactured in the 18th century A Chemist Carries On- the work of Allen and Hanburys in the Production of Cod Liver Oil, 1942 D6761.jpg
Production of cod liver oil, one of the first dietary supplement products manufactured in the 18th century

A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill, capsule, tablet, powder, or liquid. [2] A supplement can provide nutrients either extracted from food sources, or that are synthetic (in order to increase the quantity of their consumption). The classes of nutrient compounds in supplements include vitamins, minerals, fiber, fatty acids, and amino acids. Dietary supplements can also contain substances that have not been confirmed as being essential to life, and so are not nutrients per se, but are marketed as having a beneficial biological effect, such as plant pigments or polyphenols. Animals can also be a source of supplement ingredients, such as collagen from chickens or fish for example. These are also sold individually and in combination, and may be combined with nutrient ingredients. The European Commission has also established harmonized rules to help insure that food supplements are safe and appropriately labeled. [3]

Contents

Creating an industry estimated to have a value of $151.9 billion in 2021, [4] there are more than 50,000 dietary supplement products marketed in the United States, [5] where about 50% of the American adult population consumes dietary supplements. Multivitamins are the most commonly used product among types of dietary supplements. [6] The United States National Institutes of Health states that supplements "may be of value" for those who are nutrient deficient from their diet and receive approval from their medical provider. [7]

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. [8] 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. [8] 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).

Definition

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." [9]

Per DSHEA, dietary supplements are consumed orally, and are mainly defined by what they are not: conventional foods (including meal replacements), medical foods, [10] 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 (for example: melatonin). All products with these ingredients are required to be labeled as dietary supplements. [11] 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. [11]

Types

Vitamins

Pharmacies and supermarkets in the U.S. sell a large variety of vitamin dietary supplements. VitaminSupplementPills.jpg
Pharmacies and supermarkets in the U.S. sell a large variety of vitamin dietary supplements.

A vitamin is an organic compound required by an organism as a vital nutrient in limited amounts. [12] 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 they synthesize vitamin D in skin. [13] 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 vitamins are consumed as a dietary supplement by those who are healthy and have a nutritionally adequate diet. [14]

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), [15] but products are available without prescription at 10,000 IU.

Minerals

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 that 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 must contain at least 20% of the Reference Dietary Intake, which for calcium means at least 260 mg/serving. [16]

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. [17] The U.S. FDA also approved Qualified Health Claims (QHCs) for various health conditions for calcium, selenium and chromium picolinate. [18] 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." [19]

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, [20] [21] to athletes who believe that strenuous physical activity increases protein requirements, [22] to people hoping to lose weight while minimizing muscle loss, i.e., conducting a protein-sparing modified fast, [23] and to people who want to increase muscle size for performance and appearance. Whey protein is a popular ingredient, [21] [24] [25] but products may also incorporate casein, soy, pea, hemp or rice protein. A meta-analysis found a moderate degree of evidence in favor of whey protein supplements use as a safe and effective adjunct to an athlete's training and recovery, including benefits for endurance, average power, muscle mass, and reduced perceived exercise intensity. [26]

According to US and 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. [27] [28] [29] Scientific reviews can conclude that a high protein diet, when combined with exercise, will increase muscle mass and strength, [30] [31] [32] or conclude the opposite. [33] 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. [22] One review proposed a maximum daily protein intake of approximately 25% of energy requirements, i.e., approximately 2.0 to 2.5 g/kg. [28]

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". [34] 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. [35] [10] Liquid medical food products – for 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. [27] 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. [36] In elderly people, supplementation with just leucine resulted in a modest (0.99 kg) increase in lean body mass. [37] 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. [38] 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. [39]

Bodybuilding supplements

This section is an excerpt from Bodybuilding supplement.[ edit ]
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. Bodybuilding supplements may contain ingredients that are advertised to increase a person's muscle, body weight, athletic performance, and decrease a person's percent body fat for desired muscle definition. Among the most widely used are high protein drinks, pre-workout blends, branched-chain amino acids (BCAA), glutamine, arginine, essential fatty acids, creatine, HMB, whey protein, ZMA, and weight loss products. [40] [41] Supplements are sold either as single ingredient preparations or in the form of "stacks" – proprietary blends of various supplements marketed as offering synergistic advantages.

Essential fatty acids

Fish oil is a commonly used fatty acid supplement because it is a source of omega-3 fatty acids. [42] 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. [42] [43] 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. [42] 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. [44] 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. [45]

Supplementation with EPA and/or DHA does not appear to affect the risk of death, cancer or heart disease. [46] [47] Furthermore, studies of fish oil supplements have failed to support claims of preventing heart attacks or strokes. [48] 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. [49]

Manufacturers have begun to include long chain polyunsaturated fatty acids DHA and arachidonic acid (AA) into their formula milk for newborns, however, a 2017 review found that supplementation with DHA and AA does not appear to be harmful or beneficial to formula-fed infants. [50]

Natural products

St. John's wort petals used in natural product supplements Springtime St. John's Wort (12610079565).jpg
St. John's wort petals used in natural product supplements

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. [51] [52] [53] 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. [52] 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. [54] [55] [56] Canada has published a manufacturer and consumer guide describing quality, licensing, standards, identities, and common contaminants of natural products. [57]

In 2019, sales of herbal supplements just in the United States alone were $9.6 billion, with the market growing at approximately 8.6% per year, [58] with cannabidiol and mushroom product sales as the highest. [59] 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. [60]

Probiotics

Claimed benefits of using probiotic supplements are not supported by sufficient clinical evidence. [61] [62] [63] Meta-analysis studies have reported a modest reduction of antibiotic-associated diarrhea and acute diarrhea in children taking probiotics. [64] There is limited evidence in support of adults using mono-strain and multi-strain containing probiotics for the alleviation of symptoms associated with irritable bowel syndrome. [65] Probiotic supplements are generally regarded as safe. [66]

Fertility

A meta-analysis provided preliminary evidence that men treated with supplements containing selenium, zinc, omega-3 fatty acids, coenzyme Q10 or carnitines reported improvements in total sperm count, concentration, motility, and morphology. [67] A review concluded that omega-3 taken through supplements and diet might improve semen quality in infertile men. [68] A 2021 review also supported selenium, zinc, omega-3 fatty acids, coenzyme Q10 or carnitines, but warned that "excessive use of antioxidants may be detrimental to the spermatic function and many of the over-the-counter supplements are not scientifically proven to improve fertility." [69]

There is low quality and insufficient evidence for the use of oral antioxidant supplements as a viable treatment for subfertile woman. [70] A review provided evidence that taking dehydroepiandrosterone before starting an in vitro fertilization series may increase pregnancy rates and decrease miscarriage likelihood. [71]

Prenatal

Prenatal vitamins are dietary supplements commonly given to pregnant women to supply nutrients that may reduce health complications for the mother and fetus. Although prenatal vitamins are not meant to substitute for dietary nutrition, prenatal supplementation may be beneficial for pregnant women at risk of nutrient deficiencies because of diet limitations or restrictions. The most common components in prenatal vitamins include vitamins B6, folate, B12, C, D, E, iron and calcium. [72]

Sufficient intake of vitamin B6 can lower the risk of early pregnancy loss and relieve symptoms of morning sickness. [73] [74] Folate is also an essential nutrient for pregnant women to prevent neural tube defects. [73] In 2006, the World Health Organization endorsed the recommendation for women of child-bearing age to consume 400 micrograms of folate through the diet daily if planning a pregnancy. [75] A 2013 review found folic acid supplementation during pregnancy did not affect the mother's health other than a risk reduction on low pre-delivery serum folate and megaloblastic anemia. [76] There is little evidence to suggest that vitamin D supplementation improves prenatal outcomes in hypertensive disorders and gestational diabetes. [77] [78] Evidence does not support the routine use of vitamin E supplementation during pregnancy to prevent adverse events, such as preterm birth, fetal or neonatal death, or maternal hypertensive disorders. [79] [80]

Iron supplementation can lower the risk of iron deficiency anemia for pregnant women. [81] [ needs update ] In 2020, the World Health Organization updated recommendations for adequate calcium levels during pregnancy to prevent hypertensive disorders. [82] [83]

Pharmacotherapy

Individuals with hypokalemic sensory overstimulation are sometimes diagnosed as having attention deficit hyperactivity disorder (ADHD), raising the possibility that a subtype of ADHD has a cause that can be understood mechanistically and treated in a novel way. The sensory overload is treatable with oral potassium gluconate.

Industry

In 2020, the American market for dietary supplements was valued at $140.3 billion, [4] with the economic impact in the United States for 2016 estimated at $122 billion, including employment wages and taxes. [84] A 2020 analysis projected that the global market for vitamins and dietary supplement products would reach $196.6 billion by 2028, where the growth in market size is largely attributed to recent technological advancements in product manufacturing, increased demand for products advertised as healthy, increased product availability, and population aging. [85]

Adulteration, contamination and mislabeling

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, [86] with 92% of tested herbal supplements containing lead and 80% containing other chemical contaminants. [87] 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. [87] Consumer Reports also reported unsafe levels of arsenic, cadmium, lead and mercury in several protein powder products. [88] The Canadian Broadcasting Corporation (CBC) reported that protein spiking, i.e., the addition of amino acids to manipulate protein content analysis, was common. [89] Many of the companies involved challenged CBC's claim. [90]

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. [55] In 2015, the New York Attorney General (NY-AG) 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. [91] According to the NY-AG, only about 20% of the herbal supplements tested contained the plants claimed. [91] The methodology used by the NY-AG was disputed. The test involves looking for DNA fragments from the plants named as the dietary supplement ingredients in the products. One scientist said that it was possible that the extraction process used to create the supplements removed or destroyed all DNA. This, however, would not explain the presence of DNA from plants such as rice or wheat, that were not listed as ingredients. [91]

A study of dietary supplements sold between 2007 and 2016 identified 776 that contained unlisted pharmaceutical drugs, many of which could interact with other medications and lead to hospitalization. [92] 86% of the adulterated supplements were marketed for weight loss and sexual performance, with many containing prescription erectile dysfunction medication. Muscle building supplements were contaminated with anabolic steroids that can lead to health complications affecting the kidney, the heart, and cause gynecomastia. [93] Multiple bodybuilding products also contained antidepressants and antihistamines. Despite these findings, fewer than half of the adulterated supplements were recalled. [92]

Regulatory compliance

The European Commission has published harmonized rules on supplement products to assure consumers have minimal health risks from using dietary supplements and are not misled by advertising. [94]

In the United States and Canada, dietary supplements are considered a subset of foods, and are regulated accordingly. The U.S. Food and Drug Administration (FDA) monitors supplement products for accuracy in advertising and labeling. Dietary supplements are regulated by the FDA as food products subject to compliance with current Good Manufacturing Practices (CGMP) and labeling with science-based ingredient descriptions and advertising. [95] [96] When finding CGMP or advertising violations, FDA warning letters are used to notify manufacturers of impending enforcement action, including search and seizure, injunction, and financial penalties. [97] Examples between 2016 and 2018 of CGMP and advertising violations by dietary supplement manufacturers included several with illegal compositions or advertising of vitamins and minerals. [98] [99] [100]

The U.S. Federal Trade Commission, which litigates against deceptive advertising in marketed products, [101] established a consumer center to assist reports of false health claims in product advertising for dietary supplements. [102] In 2017, the FTC successfully sued nine manufacturers for deceptive advertising of dietary supplements. [103]

Adverse effects

In the United States, manufacturers of dietary supplements are required to demonstrate safety of their products before approval is granted for commerce. [104] Despite this caution, numerous adverse effects have been reported, [86] 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. [86] The potential for adverse effects also occurs when individuals consume more than the necessary daily amount of vitamins or minerals that are needed to maintain normal body processes and functions. [105] The incidence of adverse effects reported to the FDA were due to "combination products" that contain multiple ingredients, whereas dietary supplements containing a single vitamin, mineral, lipid product, and herbal product were less likely to cause adverse effects related to excess supplementation. [86]

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. [56] 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. [106] 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. [106] Weight loss supplements have also had adverse psychiatric effects. [107] Some dietary supplements may also have adverse interactions with prescription medications that may enhance side effects or decrease therapeutic effects of medications. [108]

Society and culture

Public health

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. [109]

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. [110] [111] 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. [112] [113]

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 ultra-processed food, salt and sugar and to get exercise daily, and to abandon Western pattern diets and a sedentary lifestyle. [114] [115] : 10 

United States

The regulation of food and dietary supplements by the U.S. Food and Drug Administration (FDA) is governed by various statutes enacted by the United States Congress. Pursuant to the Federal Food, Drug, and Cosmetic 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 [99] if not in compliance with GMPs, stop production, and if there is a health risk, require that the company conduct a recall. [116] Only after a dietary supplement product is marketed, may the FDA's Center for Food Safety and Applied Nutrition (CFSAN) review the products for safety and effectiveness. [117]

European Union

The European Union's (EU) Food Supplements Directive of 2002 requires that supplements be demonstrated to be safe, both in dosages and in purity. [118] 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. [119]

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. [120] In 2004, along with two British trade associations, the Alliance for Natural Health (ANH) had a legal challenge to the Food Supplements Directive [121] referred to the European Court of Justice by the High Court in London. [122]

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, [123] 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. [124] 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. [125]

Fraudulent products during the COVID-19 outbreak

During the COVID-19 pandemic in the United States, the FDA and Federal Trade Commission (FTC) warned consumers about marketing scams of fraudulent supplement products, including homeopathic remedies, cannabidiol products, teas, essential oils, tinctures and colloidal silver, among others. [126] [127] By August 2020, the FDA and FTC had issued warning letters to dozens of companies advertising scam products, which were purported "to be drugs, medical devices or vaccines. Products that claim to cure, mitigate, treat, diagnose or prevent disease, but are not proven safe and effective for those purposes, defraud consumers of money and can place consumers at risk for serious harm" [126] [128] [129]

Research

Examples of ongoing government research organizations to better understand the potential health properties and safety of dietary supplements are the European Food Safety Authority, [3] the Office of Dietary Supplements of the United States National Institutes of Health, [7] [130] the Natural and Non-prescription Health Products Directorate of Canada, [131] and the Therapeutic Goods Administration of Australia. [132] 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. [130]

Databases

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, [5] Dietary Supplement Ingredient Database, [133] and Dietary Supplement Facts Sheets of the United States. [134] 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. [135] The European Food Safety Authority maintains a compendium of botanical ingredients used in manufacturing of dietary supplements. [136]

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. [137] 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. [138] 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. [139]

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. [136] [140] High-dose products have received research attention, [130] [141] especially for emergency situations such as vitamin A deficiency in malnutrition of children, [142] and for women taking folate supplements to reduce the risk of breast cancer. [143]

Population monitoring

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. [130] 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. [144] Particular attention has been given to use of folate supplements by young women to reduce the risk of fetal neural tube defects. [145] [146]

Clinical studies

Limited human research has been conducted on the potential for dietary supplementation to affect disease risk. Examples:

A 2017 academic review indicated a rising incidence of liver injury from use of herbal and dietary supplements, particularly those with steroids, green tea extract, or multiple ingredients. [106]

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 HIV, [154] or tuberculosis. [155]

Reporting bias

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. [156] 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. [156] [157] One review reported that fewer than half of the registered clinical trials resulted in publication in peer-reviewed journals. [158]

Future

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. [159] 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). [130]

See also

Related Research Articles

<span class="mw-page-title-main">Fat</span> Esters of fatty acid or triglycerides

In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.

Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or n−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure. They are widely distributed in nature, being important constituents of animal lipid metabolism, and they play an important role in the human diet and in human physiology. The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA can be found in plants, while DHA and EPA are found in algae and fish. Marine algae and phytoplankton are primary sources of omega−3 fatty acids. DHA and EPA accumulate in fish that eat these algae. Common sources of plant oils containing ALA include walnuts, edible seeds, and flaxseeds as well as hempseed oil, while sources of EPA and DHA include fish and fish oils, and algae oil.

<span class="mw-page-title-main">Vitamin C</span> Essential nutrient found in citrus fruits and other foods

Vitamin C is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription dietary supplement. As a therapy, it is used to prevent and treat scurvy, a disease caused by vitamin C deficiency.

Vitamin E is classified as an essential nutrient for humans that is found naturally in some types of food and is also widely available as a nutritional supplement. It exists as a group of eight molecular-structure related compounds that include four tocopherols and four tocotrienols. Vitamin E functions as a fat-soluble antioxidant which may help protect cell membranes from reactive oxygen species. Various government organizations recommend that adults consume between 3 and 15 mg per day, whereas a worldwide review reported a median dietary intake of 6.2 mg per day. Foods rich in vitamin E include seeds, nuts, seed oils, peanut butter, and vitamin E-fortified foods. Symptomatic vitamin E deficiency is rare, is usually caused by an underlying problem with digesting dietary fat rather than from a diet low in vitamin E. Deficiency can cause neurological disorders.

Vitamin B<sub>6</sub> Class of chemically related vitamins

Vitamin B6 is one of the B vitamins, and is an essential nutrient for humans. The term essential nutrient refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.

<span class="mw-page-title-main">Folate</span> Vitamin B9; nutrient essential for DNA synthesis

Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division and maturation of blood cells. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.

<span class="mw-page-title-main">Dietary fiber</span> Portion of plant-derived food that cannot be completely digested

Dietary fiber or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition and can be grouped generally by their solubility, viscosity and fermentability which affect how fibers are processed in the body. Dietary fiber has two main subtypes: soluble fiber and insoluble fiber which are components of plant-based foods such as legumes, whole grains, cereals, vegetables, fruits, and nuts or seeds. A diet high in regular fiber consumption is generally associated with supporting health and lowering the risk of several diseases. Dietary fiber consists of non-starch polysaccharides and other plant components such as cellulose, resistant starch, resistant dextrins, inulin, lignins, chitins, pectins, beta-glucans, and oligosaccharides.

A nutrient is a substance used by an organism to survive, grow and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi and protists. Nutrients can be incorporated into cells for metabolic purposes or excreted by cells to create non-cellular structures such as hair, scales, feathers, or exoskeletons. Some nutrients can be metabolically converted into smaller molecules in the process of releasing energy such as for carbohydrates, lipids, proteins and fermentation products leading to end-products of water and carbon dioxide. All organisms require water. Essential nutrients for animals are the energy sources, some of the amino acids that are combined to create proteins, a subset of fatty acids, vitamins and certain minerals. Plants require more diverse minerals absorbed through roots, plus carbon dioxide and oxygen absorbed through leaves. Fungi live on dead or living organic matter and meet nutrient needs from their host.

<span class="mw-page-title-main">Multivitamin</span> Dietary supplement containing vitamins

A multivitamin is a preparation intended to serve as a dietary supplement with vitamins, dietary minerals, and other nutritional elements. Such preparations are available in the form of tablets, capsules, pastilles, powders, liquids, or injectable formulations. Other than injectable formulations, which are only available and administered under medical supervision, multivitamins are recognized by the Codex Alimentarius Commission as a category of food.

<span class="mw-page-title-main">Nootropic</span> Compound intended to improve cognitive function

Nootropics, colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.

Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega−3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body and improve hypertriglyceridemia. There has been a great deal of controversy in the 21st century about the role of fish oil in cardiovascular disease, with recent meta-analyses reaching different conclusions about its potential impact.

<span class="mw-page-title-main">Vegetarian nutrition</span> Nutritional and human health aspects of vegetarian diets

Vegetarian nutrition is the set of health-related challenges and advantages of vegetarian diets.

<span class="mw-page-title-main">Cat food</span> Food for consumption by cats

Cat food is food specifically formulated and designed for consumption by cats. As obligate carnivores, cats have specific requirements for their dietary nutrients, namely nutrients found only in meat or synthesized, such as taurine and Vitamin A. Certain nutrients, including many vitamins and amino acids, are degraded by the temperatures, pressures and chemical treatments used during manufacture, and hence must be added after manufacture to avoid nutritional deficiency. Cat food is typically sold as dry kibble, or as wet food in cans and pouches.

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. Bodybuilding supplements may contain ingredients that are advertised to increase a person's muscle, body weight, athletic performance, and decrease a person's percent body fat for desired muscle definition. Among the most widely used are high protein drinks, pre-workout blends, branched-chain amino acids (BCAA), glutamine, arginine, essential fatty acids, creatine, HMB, whey protein, ZMA, 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.

Chromium deficiency is described as the consequence of an insufficient dietary intake of the mineral chromium. Chromium was first proposed as an essential element for normal glucose metabolism in 1959, but its biological function has not been identified. Cases of deficiency were described in people who received all of their nutrition intravenously for long periods of time.

<span class="mw-page-title-main">Nutrition and pregnancy</span> Nutrient intake and dietary planning undertaken before, during and after pregnancy

Nutrition and pregnancy refers to the nutrient intake, and dietary planning that is undertaken before, during and after pregnancy. Nutrition of the fetus begins at conception. For this reason, the nutrition of the mother is important from before conception as well as throughout pregnancy and breastfeeding. An ever-increasing number of studies have shown that the nutrition of the mother will have an effect on the child, up to and including the risk for cancer, cardiovascular disease, hypertension and diabetes throughout life.

<span class="mw-page-title-main">Vitamin D</span> Group of fat-soluble secosteroids

Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most significant compounds within this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).

<span class="mw-page-title-main">Vegan nutrition</span> Nutritional and human health aspects of vegan diets

Vegan nutrition refers to the nutritional and human health aspects of vegan diets. A well-planned vegan diet is suitable to meet all recommendations for nutrients in every stage of human life. Vegan diets tend to be higher in dietary fiber, magnesium, folic acid, vitamin C, vitamin E, and phytochemicals; and lower in calories, saturated fat, iron, cholesterol, long-chain omega-3 fatty acids, vitamin D, calcium, zinc, and vitamin B12.

<span class="mw-page-title-main">Vegetarian and vegan dog diet</span> Adequate meat-free or animal-free nutrition

As in the human practice of veganism, vegan dog foods are those formulated with the exclusion of ingredients that contain or were processed with any part of an animal, or any animal byproduct. Vegan dog food may incorporate the use of fruits, vegetables, cereals, legumes including soya, nuts, vegetable oils, as well as any other non-animal based foods.

Pre-workout is a generic term for a range of bodybuilding supplement products used by athletes and weightlifters to enhance athletic performance. Supplements are taken to increase endurance, energy, and focus during a workout. Pre-workout supplements contain a variety of ingredients such as caffeine and creatine, differing by capsule or powder products. The first pre-workout product entered the market in 1982, and since then the category has grown in use. Some pre-workout products contain ingredients linked to adverse effects. Although these products are not regulated, the Food and Drug Administration (FDA) warns consumers to be cautious when consuming them.

References

  1. ↑ "Cod liver oil". Encyclopædia Britannica. 2018. Retrieved 18 February 2018.
  2. ↑ "Dietary Supplements: Background Information". Office of Dietary Supplements, US National Institutes of Health. 24 June 2011. Archived from the original on 14 August 2020. Retrieved 2 February 2018.
  3. 1 2 "Food Supplements". European Food Safety Authority, European Commission. 2009.
  4. 1 2 "Dietary Supplements Market Size & Trends Report, 2021–2028". Grand View Research. San Francisco, CA. Retrieved 2021-07-30.
  5. 1 2 "Dietary Supplement Label Database". Office of Dietary Supplements, US National Institutes of Health. 2017.
  6. ↑ Park M. "Half of Americans use supplements". CNN. Retrieved 3 October 2013.
  7. 1 2 "FAQs on Dietary Supplements". Office of Dietary Supplements, US National Institutes of Health.
  8. 1 2 "Structure/Function Claims". Office of Dietary Supplement Programs, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration. 14 December 2017.
  9. ↑ Office of Inspector General (2003). "Dietary Supplement Labels: Key Elements" (PDF). U.S. Department of Health and Human Services. Archived from the original (PDF) on 18 November 2004.
  10. 1 2 "Guidance for Industry: Frequently Asked Questions About Medical Foods" (PDF) (Second ed.). U.S. Food and Drug Administration. May 2016.
  11. 1 2 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. pp. ES-1–ES-3. ISBN   978-0-309-09206-7.{{cite book}}: CS1 maint: multiple names: authors list (link)
  12. ↑ Lieberman, S and Bruning, N (1990). The Real Vitamin & Mineral Book. NY: Avery Group, 3, ISBN   0-89529-769-8.
  13. ↑ Drouin G, Godin JR, Pagé B (August 2011). "The genetics of vitamin C loss in vertebrates". Current Genomics. 12 (5): 371–78. doi:10.2174/138920211796429736. PMC   3145266 . PMID   22294879.
  14. ↑ Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP (December 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): 824–34. doi: 10.7326/0003-4819-159-12-201312170-00729 . PMID   24217421.
  15. ↑ Dietary Reference Intakes (DRIs): Recommended Intakes for Individuals, Food and Nutrition Board, Institute of Medicine, National Academies, 2004, archived from the original on January 18, 2017, retrieved 2009-06-09
  16. ↑ "Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis". U.S. Food and Drug Administration. 29 September 2008.
  17. ↑ "Scientific Opinion in relation to the authorisation procedure for health claims on calcium and vitamin D and the reduction of the risk of osteoporotic fractures by reducing bone loss pursuant to Article 14 of Regulation (EC) No 1924/2006". EFSA Journal. 8 (5): 1609. 2010. doi: 10.2903/j.efsa.2010.1609 .
  18. ↑ "Qualified Health Claims: Letters of Enforcement Discretion". U.S. Food and Drug Administration. Archived from the original on 26 November 2013.
  19. ↑ "Selenium and a Reduced Risk of Site-specific Cancers". U.S. Food and Drug Administration. 19 June 2009. FDA-2008-Q-0323. Archived from the original on 2017-11-14.
  20. ↑ Liao CD, Tsauo JY, Wu YT, Cheng CP, Chen HC, Huang YC, et al. (October 2017). "Effects of protein supplementation combined with resistance exercise on body composition and physical function in older adults: a systematic review and meta-analysis". The American Journal of Clinical Nutrition. 106 (4): 1078–91. doi: 10.3945/ajcn.116.143594 . PMID   28814401.
  21. 1 2 Colonetti T, Grande AJ, Milton K, Foster C, Alexandre MC, Uggioni ML, Rosa MI (May 2017). "Effects of whey protein supplement in the elderly submitted to resistance training: systematic review and meta-analysis" (PDF). International Journal of Food Sciences and Nutrition. 68 (3): 257–64. doi:10.1080/09637486.2016.1232702. PMID   27653283. S2CID   205659209.
  22. 1 2 Nutrition Working Group of the Medical and Scientific Commission of the International Olympic Committee (June 2016). "Nutrition for Athletes" (PDF). International Olympic Committee. Archived from the original (PDF) on 2018-01-22.
  23. ↑ Stonehouse W, Wycherley T, Luscombe-Marsh N, Taylor P, Brinkworth G, Riley M (July 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.
  24. ↑ Naclerio F, Larumbe-Zabala E (January 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" (PDF). Sports Medicine. 46 (1): 125–37. doi:10.1007/s40279-015-0403-y. PMID   26403469. S2CID   31140351.
  25. ↑ Miller PE, Alexander DD, Perez V (2014). "Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials". Journal of the American College of Nutrition. 33 (2): 163–75. doi:10.1080/07315724.2013.875365. PMID   24724774. S2CID   19434136.
  26. ↑ Lam FC, Bukhsh A, Rehman H, Waqas MK, Shahid N, Khaliel AM, et al. (April 2019). "Efficacy and Safety of Whey Protein Supplements on Vital Sign and Physical Performance Among Athletes: A Network Meta-Analysis". Frontiers in Pharmacology. 10: 317. doi: 10.3389/fphar.2019.00317 . PMC   6491698 . PMID   31068804.
  27. 1 2 Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids . Institute of Medicine. National Academy Press. 2005. doi:10.17226/10490. ISBN   978-0-309-08525-0.
  28. 1 2 Bilsborough S, Mann N (April 2006). "A review of issues of dietary protein intake in humans". International Journal of Sport Nutrition and Exercise Metabolism. 16 (2): 129–52. doi: 10.1123/ijsnem.16.2.129 . PMID   16779921. S2CID   10339366.
  29. ↑ Tarnopolsky MA, Atkinson SA, MacDougall JD, Chesley A, Phillips S, Schwarcz HP (November 1992). "Evaluation of protein requirements for trained strength athletes". Journal of Applied Physiology. 73 (5): 1986–95. doi:10.1152/jappl.1992.73.5.1986. PMID   1474076. S2CID   46188182.
  30. ↑ Lemon, PW (June 1995). "Do athletes need more dietary protein and amino acids?". International Journal of Sport Nutrition. 5 (Suppl): S39–61. doi:10.1123/ijsn.5.s1.s39. PMID   7550257. S2CID   27679614.
  31. ↑ Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, et al. (March 2018). "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". British Journal of Sports Medicine. 52 (6): 376–84. doi:10.1136/bjsports-2017-097608. PMC   5867436 . PMID   28698222.
  32. ↑ Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ (December 2012). "Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis". The American Journal of Clinical Nutrition. 96 (6): 1454–64. doi: 10.3945/ajcn.112.037556 . PMID   23134885.
  33. ↑ Finger D, Goltz FR, Umpierre D, Meyer E, Rosa LH, Schneider CD (February 2015). "Effects of protein supplementation in older adults undergoing resistance training: a systematic review and meta-analysis". Sports Medicine. 45 (2): 245–55. doi:10.1007/s40279-014-0269-4. PMID   25355074. S2CID   31362761.
  34. ↑ "Regulatory Issues: Meal Replacements – Convenience or Compromise?". Food Processing. Archived from the original on 2013-08-15. Retrieved 2018-01-22.
  35. ↑ "Medical Foods Guidance Documents & Regulatory Information". U.S. Food and Drug Administration. 6 December 2017.
  36. ↑ Charles EJ, Johnston LE, Herbert MA, Mehaffey JH, Yount KW, Likosky DS, et al. (October 2017). "Impact of Medicaid Expansion on Cardiac Surgery Volume and Outcomes". The Annals of Thoracic Surgery. 104 (4): 1251–58. doi:10.1016/j.athoracsur.2017.03.079. PMC   5610068 . PMID   28552372.
  37. ↑ Komar B, Schwingshackl L, Hoffmann G (April 2015). "Effects of leucine-rich protein supplements on anthropometric parameter and muscle strength in the elderly: a systematic review and meta-analysis". The Journal of Nutrition, Health & Aging. 19 (4): 437–46. doi: 10.1007/s12603-014-0559-4 . PMID   25809808. S2CID   24759289.
  38. ↑ Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W (December 2011). "Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials". American Heart Journal. 162 (6): 959–65. doi:10.1016/j.ahj.2011.09.012. PMID   22137067.
  39. ↑ "the definition of amino acid". Dictionary.com. Retrieved 2017-02-22.
  40. ↑ Cruz-Jentoft, Alfonso J. (2018). "Beta-Hydroxy-Beta-Methyl Butyrate (HMB): From Experimental Data to Clinical Evidence in Sarcopenia". Current Protein & Peptide Science. 19 (7): 668–672. doi:10.2174/1389203718666170529105026. ISSN   1875-5550. PMID   28554316. Archived from the original on 2021-07-29. Retrieved 2021-07-29.
  41. ↑ Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH (January 2017). "Liver injury from herbal and dietary supplements". Hepatology. 65 (1): 363–373. doi:10.1002/hep.28813. PMC   5502701 . PMID   27677775.
  42. 1 2 3 "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.
  43. ↑ Whitney E, Rolfes SR (2008). "Chapter 5: The Lipids: Triglyerides, Phospholipids, and Sterols". Understanding Nutrition (11th ed.). California: Thomson Wadsworth. p. 154. ISBN   978-0-495-11669-1.
  44. ↑ Food and Nutrition Board. "Dietary Reference Intakes (DRIs)" (PDF). Institute of Medicine, National Academies. Archived from the original (PDF) on 2018-09-11.
  45. ↑ 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. S2CID   23585060.
  46. ↑ MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, et al. (January 2006). "Effects of omega-3 fatty acids on cancer risk: a systematic review". JAMA. 295 (4): 403–15. doi:10.1001/jama.295.4.403. hdl: 10919/79706 . PMID   16434631.
  47. ↑ Grey A, Bolland M (March 2014). "Clinical trial evidence and use of fish oil supplements". JAMA Internal Medicine. 174 (3): 460–52. doi: 10.1001/jamainternmed.2013.12765 . PMID   24352849.
  48. ↑ Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, et al. (April 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. PMC   6903779 . PMID   28289069.
  49. ↑ Jasani B, Simmer K, Patole SK, Rao SC, et al. (Cochrane Neonatal Group) (March 2017). "Long chain polyunsaturated fatty acid supplementation in infants born at term". The Cochrane Database of Systematic Reviews. 2017 (3): CD000376. doi:10.1002/14651858.CD000376.pub4. PMC   6464574 . PMID   28281303.
  50. ↑ "Botanicals". European Food Safety Authority. 2018. Retrieved 1 February 2018.
  51. 1 2 Prince J (13 September 2017). "U.S. Herbal Supplement Sales Up 7.7% in 2016". Nutritional Outlook. Retrieved 1 February 2018.
  52. ↑ "Natural and Non-prescription Health Products". Government of Canada. 2018. Retrieved 1 February 2018.
  53. ↑ Barrett S (23 November 2013). "The herbal minefield". Quackwatch. Archived from the original on 18 August 2018. Retrieved 1 February 2018.
  54. 1 2 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): 100–06. doi:10.1016/j.ctim.2011.09.004. PMID   22305255.
  55. 1 2 Coghlan ML, Haile J, Houston J, Murray DC, White NE, Moolhuijzen P, et al. (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.
  56. ↑ "Quality of Natural Health Products Guide". Government of Canada. 1 May 2015. Retrieved 1 February 2018.
  57. ↑ "US Sales of Herbal Supplements Increase by 8.6% in 2019 –American Botanical Council". www.herbalgram.org. Retrieved 2021-07-30.
  58. ↑ "Herbal Supplements Post Strongest Sales Growth in Two Decades". Nutraceuticals World. 23 September 2019. Retrieved 25 September 2019.
  59. ↑ Becker M (8 March 2016). "Dietary Supplements in Europe Poised for Profound Growth". Natural Products Insider. Retrieved 1 February 2018.
  60. ↑ "Probiotic Health Claims". Food Safety Authority of Ireland. 5 May 2017. Archived from the original on 10 July 2017. Retrieved 4 February 2018.
  61. ↑ Rijkers GT, de Vos WM, Brummer RJ, Morelli L, Corthier G, Marteau P (November 2011). "Health benefits and health claims of probiotics: bridging science and marketing". The British Journal of Nutrition. 106 (9): 1291–96. doi: 10.1017/S000711451100287X . PMID   21861940.
  62. ↑ Slashinski MJ, McCurdy SA, Achenbaum LS, Whitney SN, McGuire AL (October 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.
  63. ↑ Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC, et al. (Cochrane IBD Group) (April 2019). "Probiotics for the prevention of pediatric antibiotic-associated diarrhea". The Cochrane Database of Systematic Reviews. 4 (4): CD004827. doi:10.1002/14651858.CD004827.pub5. PMC   6490796 . PMID   31039287.
  64. ↑ Dale, HF; Rasmussen, SH; Asiller, ÖÖ; Lied, GA (September 2019). "Probiotics in Irritable Bowel Syndrome: An Up-to-Date Systematic Review". Nutrients. 11 (9): 2048. doi: 10.3390/nu11092048 . ISSN   2072-6643. PMC   6769995 . PMID   31480656.
  65. ↑ Doron S, Snydman DR (May 2015). "Risk and safety of probiotics". Clinical Infectious Diseases. 60 (Suppl 2): S129–34. doi:10.1093/cid/civ085. PMC   4490230 . PMID   25922398.
  66. ↑ Salas-Huetos A, Rosique-Esteban N, Becerra-Tomás N, Vizmanos B, Bulló M, Salas-Salvadó J (November 2018). "The Effect of Nutrients and Dietary Supplements on Sperm Quality Parameters: A Systematic Review and Meta-Analysis of Randomized Clinical Trials". Advances in Nutrition. 9 (6): 833–48. doi:10.1093/advances/nmy057. PMC   6247182 . PMID   30462179.
  67. ↑ Falsig AL, Gleerup CS, Knudsen UB (November 2019). "The influence of omega-3 fatty acids on semen quality markers: a systematic PRISMA review". Andrology. 7 (6): 794–803. doi: 10.1111/andr.12649 . PMID   31116515.
  68. ↑ Torres-Arce E, Vizmanos B, Babio N, Márquez-Sandoval F, Salas-Huetos A (March 2021). "Dietary Antioxidants in the Treatment of Male Infertility: Counteracting Oxidative Stress". Biology. 10 (3): 241. doi: 10.3390/biology10030241 . PMC   8003818 . PMID   33804600.
  69. ↑ Showell MG, Mackenzie-Proctor R, Jordan V, Hart RJ, et al. (Cochrane Gynaecology and Fertility Group) (August 2020). "Antioxidants for female subfertility". The Cochrane Database of Systematic Reviews. 8 (11): CD007807. doi:10.1002/14651858.CD007807.pub4. PMC   8094745 . PMID   32851663.
  70. ↑ Schwarze JE, Canales J, Crosby J, Ortega-Hrepich C, Villa S, Pommer R (November 2018). "DHEA use to improve likelihood of IVF/ICSI success in patients with diminished ovarian reserve: A systematic review and meta-analysis". JBRA Assisted Reproduction. 22 (4): 369–74. doi:10.5935/1518-0557.20180046. PMC   6210617 . PMID   30125071.
  71. ↑ Brown B, Wright C (October 2020). "Safety and efficacy of supplements in pregnancy". Nutrition Reviews. 78 (10): 813–26. doi:10.1093/nutrit/nuz101. PMC   7558284 . PMID   31925443.
  72. 1 2 De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P, et al. (Cochrane Pregnancy and Childbirth Group) (December 2015). "Effects and safety of periconceptional oral folate supplementation for preventing birth defects". The Cochrane Database of Systematic Reviews. 2015 (12): CD007950. doi:10.1002/14651858.CD007950.pub3. PMC   8783750 . PMID   26662928.
  73. ↑ Matthews A, Haas DM, O'Mathúna DP, Dowswell T, et al. (Cochrane Pregnancy and Childbirth Group) (September 2015). "Interventions for nausea and vomiting in early pregnancy". The Cochrane Database of Systematic Reviews. 2015 (9): CD007575. doi:10.1002/14651858.CD007575.pub4. PMC   7196889 . PMID   26348534.
  74. ↑ McStay CL, Prescott SL, Bower C, Palmer DJ (February 2017). "Maternal Folic Acid Supplementation during Pregnancy and Childhood Allergic Disease Outcomes: A Question of Timing?". Nutrients. 9 (2): 123. doi: 10.3390/nu9020123 . PMC   5331554 . PMID   28208798.
  75. ↑ Lassi ZS, Salam RA, Haider BA, Bhutta ZA (March 2013). "Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes". The Cochrane Database of Systematic Reviews. 2013 (3): CD006896. doi:10.1002/14651858.cd006896.pub2. PMC   10069458 . PMID   23543547.
  76. ↑ Palacios C, Trak-Fellermeier MA, Martinez RX, Lopez-Perez L, Lips P, Salisi JA, et al. (October 2019). "Regimens of vitamin D supplementation for women during pregnancy". The Cochrane Database of Systematic Reviews. 2019 (10): CD013446. doi:10.1002/14651858.CD013446. PMC   6776191 . PMID   31581312.
  77. ↑ "Vitamin D supplementation during pregnancy". WHO. Archived from the original on March 30, 2014. Retrieved 2021-07-30.
  78. ↑ Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA (September 2015). "Vitamin E supplementation in pregnancy". The Cochrane Database of Systematic Reviews. 2016 (9): CD004069. doi:10.1002/14651858.CD004069.pub3. PMC   8406700 . PMID   26343254.
  79. ↑ "Vitamin E supplementation in pregnancy". WHO. Archived from the original on July 30, 2021. Retrieved 2021-07-30.
  80. ↑ Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T, et al. (Cochrane Pregnancy and Childbirth Group) (July 2015). "Daily oral iron supplementation during pregnancy". The Cochrane Database of Systematic Reviews. 2015 (7): CD004736. doi:10.1002/14651858.CD004736.pub5. PMC   8918165 . PMID   26198451.
  81. ↑ Hofmeyr GJ, Manyame S, Medley N, Williams MJ, et al. (Cochrane Pregnancy and Childbirth Group) (September 2019). "Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy". The Cochrane Database of Systematic Reviews. 2019 (9): CD011192. doi:10.1002/14651858.CD011192.pub3. PMC   6745517 . PMID   31523806.
  82. ↑ "Calcium supplementation during pregnancy to reduce the risk of pre-eclampsia". WHO. Archived from the original on January 2, 2015. Retrieved 2021-07-30.
  83. ↑ "Supplement Industry Contributes $122 Billion To U.S. Economy". Nutraceuticals World. 10 June 2016. Retrieved 1 February 2018.
  84. ↑ "Vitamins and Supplements Market Size & Industry Report [2028]". www.fortunebusinessinsights.com. 2021. Retrieved 2021-07-30.
  85. 1 2 3 4 U. S. Government Accountability Office (18 March 2013). Dietary Supplements: FDA May Have Opportunities to Expand Its Use of Reported Health Problems to Oversee Products (Report). Government Accountability Office, US Government. Retrieved 2 February 2018.
  86. 1 2 Harmon, K (28 May 2010). "Herbal Supplement Sellers Dispense Dangerous Advice, False Claims". Scientific American. Retrieved 2 February 2018.
  87. ↑ McGinn D (26 March 2017). "Are protein shakes the weight-loss magic bullet?". The Globe and Mail (Toronto). Retrieved 2 February 2018.
  88. ↑ Griffith-Greene M (November 13, 2015). "Marketplace: Some protein powders fail fitness test". CBC News . Retrieved December 11, 2015.
  89. ↑ "Supplements: Company statements". CBC News. November 13, 2015. Retrieved December 11, 2015.
  90. 1 2 3 O'Connor A (3 February 2015). "New York Attorney General Targets Supplements at Major Retailers". The New York Times. Retrieved 1 February 2018.
  91. 1 2 Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M (October 2018). "Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings". JAMA Network Open. 1 (6): e183337. doi:10.1001/jamanetworkopen.2018.3337. ISSN   2574-3805. PMC   6324457 . PMID   30646238.
  92. ↑ Mathews NM (2018). "Prohibited Contaminants in Dietary Supplements". Sports Health. 10 (1): 19–30. doi:10.1177/1941738117727736. PMC   5753965 . PMID   28850291.
  93. ↑ "Food supplements". European Commission. 2019. Retrieved 31 January 2019.
  94. ↑ "Dietary Supplements". US Food and Drug Administration. 12 December 2017. Retrieved 31 January 2019.
  95. ↑ "Dietary Supplement Labeling Guide: Chapter I. General Dietary Supplement Labeling". US Food and Drug Administration. 21 March 2018. Retrieved 31 January 2019.
  96. ↑ "FDA Warning Letters, 2018". US Food and Drug Administration. 29 January 2019. Retrieved 31 January 2019.
  97. ↑ Porter SE (20 June 2016). "Warning letter: Vitalife Inc". Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved 31 January 2019.
  98. 1 2 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.
  99. ↑ Burbach MR (31 August 2018). "Warning letter: Independent Nutrition Inc". Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved 31 January 2019.
  100. ↑ "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.
  101. ↑ "Dietary supplement concerns? Tell the FTC and FDA". Federal Trade Commission, US Government. 25 July 2017. Archived from the original on 23 January 2018. Retrieved 2 February 2018.
  102. ↑ "Three Dietary Supplement Marketers Settle FTC, Maine AG Charges". Federal Trade Commission, US Government. 23 August 2017. Retrieved 2 February 2018.
  103. ↑ "New Dietary Ingredients in Dietary Supplements - Background for Industry". US Food and Drug Administration. August 2016. Retrieved 2 February 2018.
  104. ↑ Ronis MJ, Pedersen KB, Watt J (January 2018). "Adverse Effects of Nutraceuticals and Dietary Supplements". Annual Review of Pharmacology and Toxicology. 58 (1): 583–601. doi:10.1146/annurev-pharmtox-010617-052844. PMC   6380172 . PMID   28992429.
  105. 1 2 3 Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH (January 2017). "Liver injury from herbal and dietary supplements". Hepatology. 65 (1): 363–373. doi:10.1002/hep.28813. PMC   5502701 . PMID   27677775.
  106. ↑ Bersani FS, Coviello M, Imperatori C, Francesconi M, Hough CM, Valeriani G, et al. (2015). "Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products". BioMed Research International. 2015: 120679. doi: 10.1155/2015/120679 . PMC   4589574 . PMID   26457296.
  107. ↑ "Herbal and Dietary Supplement Interactions with Drugs", Handbook of Food-Drug Interactions, CRC Press, pp. 273–308, 2003, doi:10.1201/9780203490242-17, ISBN   978-0-429-20832-4 , retrieved 2021-07-29
  108. ↑ Lichtenstein AH, Russell RM (July 2005). "Essential nutrients: food or supplements? Where should the emphasis be?". JAMA. 294 (3): 351–58. doi:10.1001/jama.294.3.351. PMID   16030280. S2CID   2896499.
  109. ↑ "Vitamin E – Health Professional Fact Sheet". dietary-supplements.info.nih.gov. Archived from the original on 13 August 2009. Retrieved 5 February 2015.
  110. ↑ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (March 2012). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". The Cochrane Database of Systematic Reviews. 2012 (3): CD007176. doi:10.1002/14651858.CD007176.pub2. hdl: 10138/136201 . PMC   8407395 . PMID   22419320.
  111. ↑ Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER (December 2013). "Enough is enough: Stop wasting money on vitamin and mineral supplements". Annals of Internal Medicine (Editorial). 159 (12): 850–51. CiteSeerX   10.1.1.668.4335 . doi:10.7326/0003-4819-159-12-201312170-00011. PMID   24490268. S2CID   8623113.
  112. ↑ Rautiainen S, Manson JE, Lichtenstein AH, Sesso HD (July 2016). "Dietary supplements and disease prevention – a global overview". Nature Reviews. Endocrinology. 12 (7): 407–20. doi:10.1038/nrendo.2016.54. PMID   27150288. S2CID   8722286.
  113. ↑ Katz DL, Meller S (2014). "Can we say what diet is best for health?". Annual Review of Public Health. 35: 83–103. doi: 10.1146/annurev-publhealth-032013-182351 . PMID   24641555.
  114. ↑ 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.
  115. ↑ "Current Good Manufacturing Practices (CGMPs) for Dietary Supplements". U.S. Food and Drug Administration. 2007.
  116. ↑ Center for Food Safety and Applied Nutrition (16 August 2019). "Information for Consumers on Using Dietary Supplements". FDA.
  117. ↑ "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 5 December 2012.
  118. ↑ "European Commission website: Food Safety – Labelling & Nutrition – Health & Nutrition Claims". Ec.europa.eu. Retrieved 5 December 2012.
  119. ↑ Knight, S (12 July 2005). "Controversial EU vitamins ban to go ahead". The Times Online . Archived from the original on 2015-05-10. Retrieved 5 December 2012.
  120. ↑ "Food supplements – Food Safety – European Commission". Food Safety. 2016-10-17.
  121. ↑ "Court victory for vitamin firms". BBC News. 30 January 2004. Retrieved 5 December 2012.
  122. ↑ "EU health foods crackdown 'wrong'". BBC News. 5 April 2005. Retrieved 5 December 2012.
  123. ↑ "Vitamin controls backed by Europe". BBC News. 12 July 2005. Retrieved 5 December 2012.
  124. ↑ "EU court backs health supplements ban". Guardian. 12 July 2005. Retrieved 5 December 2012.
  125. 1 2 "Fraudulent coronavirus disease 2019 (COVID-19) products". US Food and Drug Administration. 7 April 2020. Retrieved 8 April 2020.
  126. ↑ "Coronavirus: Scammers follow the headlines". US Federal Trade Commission. 10 February 2020. Retrieved 1 March 2020.
  127. ↑ "FTC coronavirus warning letters to companies". US Federal Trade Commission. 29 July 2020. Retrieved 15 August 2020.
  128. ↑ Masterson D (17 August 2020). "FTC to marketers: Stop making unsupported COVID treatment claims". NutraIngredients.com – USA, William Reed, Inc. Retrieved 18 August 2020.
  129. 1 2 3 4 5 Dwyer JT, Coates PM, Smith MJ (January 2018). "Dietary Supplements: Regulatory Challenges and Research Resources". Nutrients. 10 (1): 41. doi: 10.3390/nu10010041 . PMC   5793269 . PMID   29300341.
  130. ↑ "About Natural Health Products". Natural and Non-prescription Health Products Directorate, Government of Canada. 14 March 2013. Retrieved 3 February 2018.
  131. ↑ "Complementary medicines". Therapeutic Goods Administration, Australian Government. 2018. Retrieved 3 February 2018.
  132. ↑ "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.
  133. ↑ "Dietary Supplement Fact Sheets". Office of Dietary Supplements, US National Institutes of Health. 2018. Retrieved 3 February 2018.
  134. ↑ "Licensed Natural Health Products Database". Natural and Non-prescription Health Products Directorate, Government of Canada. 4 May 2015. Retrieved 3 February 2018.
  135. 1 2 European Food Safety Authority (May 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 .
  136. ↑ Baggoley C (November 2015). "Review of the Australian Government Rebate on Natural Therapies for Private Health Insurance" (PDF). Australian Government – Department of Health. Archived from the original (PDF) on 26 June 2016. Retrieved 3 February 2018.
  137. ↑ "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. Archived from the original on 26 February 2017. Retrieved 25 February 2017.
  138. ↑ "Herbs at a Glance". National Center for Complementary and Integrative Health, US National Institutes of Health. 21 November 2016. Retrieved 24 February 2017.
  139. ↑ "Measurements and Standards for Botanical Dietary Supplements". NIST. US National Institute of Standards and Technology. 21 September 2016. Retrieved 3 February 2018.
  140. ↑ Dwyer JT, Wiemer KL, Dary O, Keen CL, King JC, Miller KB, et al. (January 2015). "Fortification and health: challenges and opportunities". Advances in Nutrition. 6 (1): 124–31. doi:10.3945/an.114.007443. PMC   4288271 . PMID   25593151.
  141. ↑ Iannotti LL, Trehan I, Manary MJ (September 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.
  142. ↑ Chen P, Li C, Li X, Li J, Chu R, Wang H (April 2014). "Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis". British Journal of Cancer. 110 (9): 2327–38. doi:10.1038/bjc.2014.155. PMC   4007237 . PMID   24667649.
  143. ↑ Kantor ED, Rehm CD, Du M, White E, Giovannucci EL (October 2016). "Trends in Dietary Supplement Use Among US Adults From 1999-2012". JAMA. 316 (14): 1464–74. doi:10.1001/jama.2016.14403. PMC   5540241 . PMID   27727382.
  144. ↑ Obeid R, Koletzko B, Pietrzik K (April 2014). "Critical evaluation of lowering the recommended dietary intake of folate". Clinical Nutrition. 33 (2): 252–59. doi:10.1016/j.clnu.2013.12.013. PMID   24503418.
  145. ↑ Wilson RD, Wilson RD, Audibert F, Brock JA, Carroll J, Cartier L, et al. (June 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". Journal of Obstetrics and Gynaecology Canada. 37 (6): 534–52. doi: 10.1016/S1701-2163(15)30230-9 . PMID   26334606.
  146. ↑ Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. (February 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.
  147. ↑ O'Brien KO, Ru Y (December 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–54S. doi:10.3945/ajcn.117.155986. PMC   5701721 . PMID   29070557.
  148. ↑ Schwingshackl L, Boeing H, Stelmach-Mardas M, Gottschald M, Dietrich S, Hoffmann G, Chaimani A (January 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. 8 (1): 27–39. doi:10.3945/an.116.013516. PMC   5227980 . PMID   28096125.
  149. ↑ Bagheri, Amir; Naghshi, Sina; Sadeghi, Omid; Larijani, Bagher; Esmaillzadeh, Ahmad (2021-03-03). "Total, Dietary, and Supplemental Magnesium Intakes and Risk of All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies". Advances in Nutrition. 12 (4). Oxford University Press (OUP): 1196–1210. doi:10.1093/advances/nmab001. ISSN   2161-8313. PMC   8321838 . PMID   33684200.
  150. ↑ Veronese N, Dominguez LJ, Pizzol D, Demurtas J, Smith L, Barbagallo M (November 2021). "Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials". Nutrients. 13 (11): 4074. doi: 10.3390/nu13114074 . PMC   8619199 . PMID   34836329.
  151. ↑ Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB (August 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.
  152. ↑ Ingles, David Perez; Cruz Rodriguez, Jose B.; Garcia, Hernando (2020-02-14). "Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment". Current Cardiology Reports. 22 (4). Springer Science and Business Media LLC: 22. doi:10.1007/s11886-020-1270-1. ISSN   1523-3782. PMID   32067177. S2CID   211139054.
  153. ↑ Visser ME, Durao S, Sinclair D, Irlam JH, Siegfried N (May 2017). "Micronutrient supplementation in adults with HIV infection". The Cochrane Database of Systematic Reviews. 2017 (5): CD003650. doi:10.1002/14651858.CD003650.pub4. PMC   5458097 . PMID   28518221.
  154. ↑ Grobler L, Nagpal S, Sudarsanam TD, Sinclair D (June 2016). "Nutritional supplements for people being treated for active tuberculosis". The Cochrane Database of Systematic Reviews. 2016 (6): CD006086. doi:10.1002/14651858.CD006086.pub4. PMC   4981643 . PMID   27355911.
  155. 1 2 Dunn AG, Coiera E (July 2014). "Should comparative effectiveness research ignore industry-funded data?". Journal of Comparative Effectiveness Research. 3 (4): 317–20. doi: 10.2217/cer.14.31 . PMID   25275226.
  156. ↑ Knottnerus JA, Tugwell P (October 2013). "The potential impact of unpublished results". Journal of Clinical Epidemiology. 66 (10): 1061–63. doi: 10.1016/j.jclinepi.2013.08.001 . PMID   23993310.
  157. ↑ Zarin DA, Tse T, Sheehan J (January 2015). "The proposed rule for U.S. clinical trial registration and results submission". The New England Journal of Medicine. 372 (2): 174–80. doi:10.1056/NEJMsr1414226. PMC   4344313 . PMID   25539444.
  158. ↑ "ODS Strategic Plan 2017-2021". Office of Dietary Supplements, US National Institutes of Health. December 2017. Retrieved 3 February 2018.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.