Learn more about how dietary supplements are regulated here. All prescription and non-prescription drugs are regulated in the United States by the Food and Drug Administration (FDA). But dietary But since they became widely available in , the FDA and some . Imagine a world free from cancer. Some freely available resources and tools that ODS has developed for advancing . FDA Food and Drug Administration Dietary Supplements. A dietary supplement is a manufactured product intended to supplement the diet when taken by From Wikipedia, the free encyclopedia . Liquid medical food products - example Ensure - are available in regular and high protein versions. .. The regulation of food and dietary supplements by the U.S. Food and Drug.
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Federal Food, Drug and Cosmetic Act that establishes a regulatory framework for dietary supplements. It effectively excludes manufacturers of these products from virtually all regulations that are in place for prescription and over-the-counter drugs.
Generally, manufacturers do not need to register their products with FDA nor get FDA approval before producing or selling dietary supplements. Manufacturers must make sure that product label information is truthful and not misleading. The Federal Trade Commission regulates dietary supplement advertising.
The main concerns with the Act can be summarized as:. Until several years ago, Canadian natural health products fell into a regulatory grey zone.
Products were treated either as drugs, or as foods. Rather than fully regulating these products as drugs, or leaving them virtually unregulated, the NHP regulations were a regulatory compromise: Health Canada assures Canadians of the following:.
Through the Natural Health Products Directorate, Health Canada ensures that all Canadians have ready access to natural health products that are safe, effective and of high quality, while respecting freedom of choice and philosophical and cultural diversity. Does it set a science-based example? The two most common types of traditional use claims are provings , and references to homeopathic materia medica , which are essentially compilations of provings. There is no objective evaluation of efficacy in provings or in materia medica.
Consider the popular remedy Oscilliococcinum , sold as an influenza treatment. Wikipedia notes that that in order to obtain even a single molecule of the original fermented duck, a volume of tablets greater that the mass of the entire universe would need to be consumed. This is one consequence of Canadian regulation: Yet the product Dr. Again, the evidence bar is far lower than a critical appraisal of the evidence would suggest is accurate. Statements based on questionable evidence gain a regulatory stamp of approval.
The NHP Directorate establishes manufacturing standards and issues site licenses. Setting aside the labelling accuracy of homeopathic remedies, the licensure should provide consumers and health professionals with more assurance that what is on the label is actually in the product.
In the United States, dietary supplements are considered as food products under the Dietary Supplements Health Education Act DSHEA and, as such, claims may not be made about the use of a dietary supplement to diagnose, prevent, mitigate, treat, or cure a specific disease. These products are not subject to mandatory review, approval or quality requirements, including appropriate testing for identity, purity or potency of active ingredients.
The NHP Directorate has created a series of monographs about dozens of single-ingredient products which are intended to provide more standardization of product labeling, dosing and constituents.
All of this is worthwhile. In contrast, the current Health Canada-approved monograph for glucosamine selectively cites the positive trials, and labels it effective for osteoarthritis pain. One of most important elements of the NHP regulations is the implementation of pre-marketing registration requirements. That is, only products reviewed and deemed to meet minimal standards of product quality, safety, and the relaxed standard for efficacy claims are permitted to be sold.
These experiences led publishers and funders to demand better product characterization and funders to demand more mechanistic evidence of bioactivity. Once mechanistic plausibility is established, animal and small phase 1 and phase 2 trials should precede the launch of large phase 3 studies of efficacy. Health outcomes such as changes in validated surrogate markers for performance, functions, morbidity, and mortality from diseases or conditions are required rather than changes in biochemical measures in blood with unvalidated surrogate markers.
The question of the use of evidence from traditional forms of health and healing such as Traditional Chinese Medicine TCM makes the question of efficacy often more complex. This is briefly explored in the regulatory section below. Widespread consensus exists on the need to translate the scientific evidence on supplements into appropriate recommendations, regulations, and policies that ensure the public health.
Population-based prevalence estimates of supplement use are needed to estimate total exposures to nutrients or other bioactives that can be related to health outcomes [ 14 ]. Monitoring is especially important when supplementation is used as a public health strategy to fill nutrient gaps in deficient populations. It is also needed in other countries such as the USA where use of certain supplements is high, and where substantial proportions of total intakes of nutrients such as vitamin D and calcium come from supplements, especially among older adults [ 15 ].
As with other categories of regulated goods such as foods and drugs, the development of regulations is a balancing act where many different factors need to be taken into account. Notable among these are ensuring that products are of high quality and safe, that any claims made are truthful and not misleading, and that there is reasonable and appropriate access to the marketplace.
All regulatory scientists want to both protect consumers from harm and support them in making informed choices about the products they include—or as importantly do not include—in their healthcare options. Appropriate regulatory oversight of this category is very challenging, and requires that scientists and regulators work together, as the former director general of the World Health Organization, Margaret Chan, MD urged [ 16 ].
This section provides a concise overview of how these regulations have been developed, and common themes as well as challenges faced in a global market.
Although the definition of dietary supplement within a specific jurisdiction such as the USA is quite precise [ 17 , 18 ], a fundamental challenge to any discussion on regulation is that there is no global consensus on either what falls within this category or even what the category is called.
Intuitively many equate a dietary supplement in the USA with a NHP in Canada or a traditional herbal medicine in the European Union or a complementary medicine in Australia, but this is not the case. For example, while melatonin is regulated in the USA as a dietary supplement and in Canada as a NHP, in Australia it is considered as a prescription medicine [ 19 , 20 , 21 ].
Dehydroepiandrosterone DHEA is readily available as a dietary supplement in the US, while in many other jurisdictions it is regulated as a controlled substance and is subject to significant regulatory oversight [ 22 ]. For this reason, we must differentiate between the manner in which nations regulate the practice of medicine and the manner in which they regulate marketed products used in medical practice or as foods.
Approaches and regulatory frameworks in many parts of the world, notably in Asia, reflect this fact with terminology and categories developed accordingly [ 23 ]. Although this classification does have significant limitations, it recognizes the fact that definitions for this category vary significantly globally. While it would be easy just to consider that the substance itself is the defining factor in determining whether or not a product is a dietary supplement, this is not the case.
Two other important factors considered are the claim that the product is making and how the product is supplied or recommended intended use. In many jurisdictions such as the USA, Canada and Australia, dietary supplements are considered suitable for self-selection without the need for the intervention of a practitioner or prescription. Here the claims that can be made are limited to minor conditions and to the support of health and wellness depending on the jurisdiction [ 24 , 25 ].
In other jurisdictions, notably those where a traditional form of health and healing is recognized, traditional and complementary medicine products are often prescribed, and in some cases supply is limited only to trained practitioners. As with the definition of the products themselves, there is no consistent global approach to regulation, with many different frameworks developed that largely reflecting national and regional priorities and needs.
That being said, there are a number of common themes and approaches that have been taken internationally. With a few exceptions, notably where traditional forms of health and healing exist, most countries do not regulate dietary supplements as a stand-alone category. Rather, they include them as a subset of existing legislation [ 17 , 18 ].
In the past, this was largely a question of whether these products should be considered a subset of drugs or foods; increasingly though, a third option is to capture them under existing regulations for biologics. It is important to note that overarching legislation is often one of the most important factors impacting the type of claim that can be made and what level of scrutiny and oversight will exist.
For example, countries that regulate these products as a subset of drugs or therapeutic goods such as Australia, Canada and the European Union EU for traditional herbal medicines allow far more specific clinical claims to be made than in a jurisdiction such as the USA, where dietary supplements are captured in regulations under the existing food legislation, with their advertising regulated by trade regulations [ 20 , 25 , 26 ].
As noted above in many jurisdictions dietary supplements are simply captured under the existing food or drug regulations and legislation with no specific consideration for these products, in some cases specific regulations have developed to reflect the category. In these cases, two different regulatory models have typically been adopted that reflect their domestic use, national priorities and public health needs.
In many jurisdictions, the first model applies. Dietary supplements are simply captured under the existing food or drug regulations and legislation. In that model, a wide range of products typically herbal medicines, traditional medicines and dietary or nutritional supplements reside under an umbrella term such as dietary supplements in the USA, complementary medicines in Australia or NHP in Canada [ 20 , 24 , 25 ].
In the second model, specific regulations are developed to deal with these products. This is particularly the case in countries with a strong traditional form of health and healing such as Chinese proprietary medicines in China TCM , Ayurvedic medicines in India and Kampo medicines in Japan [ 23 ].
Irrespective of the approach taken, it is rare that one set of regulations will encompass all products commonly considered to be dietary supplement-like.
Typical examples of this are guidelines and legislation related to advertising that apply irrespective of whether or not a product is considered to be a dietary supplement. As with other forms of regulations, independent and irrespective of the approach taken, frameworks that deal with dietary supplements may contain a number of common elements, in this case often specifically developed to reflect the challenges and nature of the products.
These common elements include: Again, the number and nature of these elements applied are determined by the specific regulations in place. Operationally, the regulation of dietary supplements faces a number of issues and challenges not shared with conventional drugs or even food products.
Notable amongst these are the sheer number of individual dietary supplements on the domestic markets, often numbering in the tens of thousands, and the fact that the sector contains many different types of products often posing very different risks that are grouped together often by the fact that they do not fit under any other regulatory regime. In particular, considerable challenges are posed especially by herbal and traditional medicine products that contain crude botanicals and a complex milieu of potentially active moieties, unlike conventional allopathic pharmaceuticals.
This has led to the development of regulatory frameworks that increasingly blend elements looking at products and sites both before they come to market as well as once they are available to consumers, or post-market. Examples of post-market regulatory approaches i. The determining factor on which approach is applied is largely determined by risk posed to the consumer.
Since most dietary supplements when appropriately manufactured are considered to be inherently low risk, increasingly regulatory frameworks are increasingly focused more on post-market review than pre-market licensure. Even in countries that are in many ways socially, economically and legally similar, different approaches to the definition and regulation of dietary supplement health products are evident although they contain some common elements.
Illustrative examples of this are evident in the different regulatory frameworks in place in the United States, Australia and Canada. This approach is primarily post-market in nature. However, it does contain pre-market elements. For example, manufacturers must hold evidence to support their claims and they cannot make specific disease treatment claims but only claims related to nutritional support which includes physiological structure and function [ 20 ].
Provisions also include a post-market site audit process for manufacturing sites for Good Manufacturing Practice compliance and mandatory reporting of serious adverse effects by manufacturers. Companies must notify the Food and Drug Administration before marketing products with new dietary ingredients NDI [ 27 ].
There is at present no indication that DSHEA will be substantially changed or modified by Congress, in recent years the regulatory authority has given more attention to the notification and classification of NDIs as well as the importance of Good Manufacturing Practices GMP [ 20 ]. In Australia, although a small number of these products are captured by a food standard, most are regulated as therapeutic goods under the Australian Therapeutic Goods Act. Products are referred to as complementary medicines and are legally defined as being a listed therapeutic good or a registered therapeutic good.
The legislation itself does not define these terms, but a comprehensive set of guidelines describes how they are considered. Most complementary medicines are listed medicines and are managed through an online portal called the Electronic Listing Facility ELF.
Permitted claims are limited to minor, self-limited considerations and those traditional forms of health and healing such as traditional Chinese medicine. Evidence for efficacy is assured through a random and targeted post-market audit system and new listable substances are evaluated pre-market. As with all registered therapeutic goods, registered complementary medicines are evaluated pre-market for safety, quality and efficacy. Manufacturers of either finished listed or registered complementary medicines must undergo an on-site audit to ensure GMP [ 28 ].
In , complementary medicines were included within a comprehensive review of regulations for all therapeutic goods and medical devices to be conducted by an external expert panel [ 29 ]. The Commonwealth government accepted the majority of the recommendations from the panel and preliminary draft legislation was made public in September Although one of the recommendations was to keep complementary medicines as a distinct category, some significant changes are proposed, allowing mid-level claims through a new third regulatory route between the listed and registered therapeutic goods process as well as changes to how advertising is approved and compliance management [ 25 , 30 ].
In Canada, the majority of these dietary supplement products are referred to as natural health products NHPs and are considered a subset of drugs under a specific set of regulations—the Natural Health Products Regulations. Products must undergo a premarket assessment for safety, quality and efficacy. This is done in part through an online submission process with permissible claims supported by Health Canada monographs.
Producers of NHPs who wish to make novel claims not supported through the monograph process must submit a full dossier of evidence for review. The products can make therapeutic claims, but their use is limited to self-care situations. While manufacturers are required to have a valid site license following approved GMP guidelines, no pre-market site audit is needed; the process being primarily paper based [ 24 ].
The category does allow for some health claims, but they are limited reflecting the nature of the products [ 31 ]. Unlike Australia, Canada is proposing to take different approach and rather than keeping NHPs as a distinct category, will include them in a self-care health product category together with non-prescription medicines and cosmetics. The intent of this initiative is to support informed consumer choice through a more consistent regulatory approach to these product categories that is based on risk.
Key questions being explored deal with topics including evidence needed to support claims, provisions ensuring safety and quality and introduction of cost recovery framework [ 32 ]. The overviews above are brief and concise with more detailed information on these country specific approaches to be found through the list of resources in Table 1.
While it is clear that high quality scientific evidence is always required to support the quality of a dietary supplement, from a regulatory perspective the same may not always be true with regard the type and nature of the evidence required to support a product claim. Given the nature of the dietary supplement sector and the fact that it often encompasses traditional medicines with a long history of use, the question faced by regulators is how to balance the need for robust scientific evidence with a respect for diverse forms of health and healing.
Globally, no consistent approach has been taken in answering this question. In some jurisdictions such as Canada and Australia, the approach has been to link the form of evidence, whether it be traditional or evidence based from scientific research, to the level and type of claim that can be made. For products making higher level, clinical claims, in a way similar to that for conventional pharmaceuticals, companies must supply a full dossier with appropriate supporting evidence such as that from randomized controlled trials RCTs [ 24 , 28 ].
In many countries such as the United States with no pre-market approval framework system, claims that can be made are more limited [ 17 , 18 ]. In countries with long-established traditional forms of medicines such as in China, India, and Japan, specific regulatory frameworks have been developed for these types of products with the type of claim that can be made and the evidence required to reflect this approach [ 23 ]. As the dietary supplement sector matures and develops and the market for raw ingredients becomes more global, establishing a balance between evidence generated by scientific research and that coming from traditional forms of health and healing is becoming increasingly demanding.
This will be discussed later. International regulatory frameworks are still considered by many to be a new and novel sector, although many of them are now more than two decades old.
They were developed to reflect a time when the sector and nature of the market, not to mention the needs and demands of the consumer, were very different. This has meant that some decisions made in the past around policies and regulatory decisions may need to be revisited. Table 1 provides links to some of the regulatory frameworks of different countries that provide insights into the ways issues are dealt with in them.
As the market for dietary supplements has increased, so has the amount and diversity of scientific evidence and research to support, or not support, their use.
This market is made more complex when there are conflicting evidence bases and conflicting ways for evaluating them.
For example, how, or should, traditional evidence be evaluated within the framework of traditional healing theories or those of allopathic evidence based medicine; what should be done when evidence from traditional forms of health and healing are not supported by more conventional evaluation mechanisms such as randomized clinical trials; and how can consumers, often wanting to explore both conventional and traditional medicine, be supported in making informed choices about including, or not including, these products in their health care options.
The challenge faced by the regulator is to ensure that these are in play and to support consumers in making informed choices that are often made in a self-care setting. It has never been easy to distinguish between a dietary supplement and other categories such as conventional foods, drugs and biologics. As all these sectors have evolved, this question of product classification has become even more complex. Two of the main questions at the regulatory interface are: As the popularity of dietary supplements available in a food-like format such as a pre-prepared drink or bar has increased, the line between what a consumer would understand to be a food as compared to a dietary supplement has become increasingly blurred.
In essence, how does the regulator provide for appropriate regulatory oversight? This has been particularly challenging for those jurisdictions that consider these products as a sub-set of drugs with regulation and often legislation governing them that is very different from that for foods. In these cases, the regulatory frameworks are more specific to such dosage forms as capsules, tablets and tinctures.
The challenge is one primarily of balance in providing a regulatory approach that is appropriate and not unnecessarily restrictive with the need to ensure that consumers are aware that these food-like dietary supplements that they are considering are not typical foods.
This lack of clarity is also challenging for the private sector in determining what regulatory framework applies to a product, either food or drug, that they wish to develop and bring to market. In other jurisdictions such as Australia, authority has been given to the respective regulators to deem something to be either a therapeutic good or a food based a specific set of criteria [ 34 ].
A number of herbal medicines with a long history of use within the conventional health care model, such as senna and cascara, are regulated in most countries as OTC drugs rather than dietary supplements. As described above, Health Canada is proposing to address this issue in part by considering both NHPs and OTC drugs within a single regulatory approach for self-care products [ 32 ]. Although science and research may be global, regulations are still made primarily to reflect domestic needs and pressures.
In spite of calls for regulatory harmonization, examples of true harmonization are limited to regions such as countries in the Association of South East Asian Nations ASEAN with the lack of a coherent and consistent regulatory approach prohibiting this globally [ 35 ].
Even if regulatory harmonization is not possible, regulatory cooperation is often a viable option, taking into account inputs from stakeholder groups such as industry and not just governments. IRCH now has over twenty members and provides a forum and mechanism for regulators to share information on safety issues and common challenges they all face [ 36 ].
Increasingly governments are working together as well as with other stakeholders such as industry and consumers to address common problems and in some cases to provide regulatory decisions in one jurisdiction that can be used as a basis for action in another.
As the dietary supplement market has become more global and lucrative, so have the importance of ensuring product quality and the challenges in doing so. There are increasing numbers of cases of adverse reactions and some fatalities due to contaminants or adulterants in the product rather than in the dietary supplement ingredients themselves.
In some cases this has been due to intentional fraud by producers of these poor quality products who have developed sophisticated methods for overcoming existing regulations and oversight. This situation is explored in greater depth elsewhere in this paper. Irrespective of whether the goal is to support production of high quality products or to develop, apply or modify methods for evaluation of evidence in support of claims, the need for robust and relevant science and research on dietary supplements has never been more necessary.
As regulatory frameworks evolve, many of the questions posed above will need to be addressed, balancing the need for robust science with a respect for traditional forms of health and healing. Scientists often disagree about definitions of human requirements for bioactives and the implications for supplements. They differ on whether some non-nutrient bioactives are required for certain population subgroups and also on the health effects associated with the use of non-nutrient bioactives.
It has been known for over years that inborn errors of nutrient metabolism exist that can be remediated by supplying the lacking nutrient that has become conditionally essential. However, it is not clear that such a model based on single gene defects is useful for the amelioration of multigenic complex diseases. It is unclear that there are large numbers of individuals with common diseases and conditions such as type 2 diabetes or depression whose unique genetic characteristics cause them to have special nutritional requirements requiring supplements or medical foods [ 37 ].
Discoveries of genetic polymorphisms and the advent of inexpensive genetic tests that are widely available to consumers have nutritional implications. The extent to which such supplements are efficacious in reducing chronic degenerative disease remains to be determined. Challenges remain on the appropriate means for assuring supplement quality, safety and efficacy.
Regulators, health professionals and manufacturers often disagree on how much quality testing is necessary for supplements. Botanical extracts and blends present particular challenges for detecting misidentification and contamination. The presence of adulterants and contaminants of both a biological and chemical nature in supplements is also challenging.
Purity is a special problem for individuals with inborn errors of metabolism for specific nutrients such as vitamin B-6 or choline who require reliable, high quality sources of the nutrient. In countries that do not require that added nutrients be pharmaceutical grade or provide nutrients free to such patients, afflicted individuals must buy products that vary greatly in their quality on the open market.
The scientific challenges involved in all of the problems cited above depend in part on the adequacy and application of analytical methods. Analytical methods and reference standards are lacking for many of the thousands of different bioactive ingredients in dietary supplements.
There is still disagreement about whether only a single officially endorsed method of analysis is acceptable. Any analytical method that is appropriately calibrated to a recognized reference standard should suffice but the onus is on the user of the method to demonstrate that affirmative requirements are met and that the method is suitable for its intended use and yields results that are accurate and precise. Methods that are suitable for foods may not be so for dietary supplements.
Opinions also differ on whether government or the private sector is responsible for developing reference standards and analytical methods, and, if the private sector develops them, how they can be both kept independent and objective and made publicly available to avoid duplication of effort while preserving the marketing advantage of the developer.
Tension also exists between researchers who desire ever more precise analytical methods for ingredients in dietary supplements and manufacturers who are concerned about the expertise and monetary costs required to apply some of the methods.
A balance needs to be struck between the two. Apart from concerns related to product quality, the safety of dietary supplements depends largely on dose. High doses of some nutrients are more likely to pose problems than others, although there is disagreement about the levels at which problems arise. For example, some dialysis patients who are receiving very large doses of calcium and the active form of vitamin D on a chronic basis may exceed the Tolerable Upper Level UL and incur adverse effects on health, including calcification of the soft tissues [ 40 ].
Very high doses of vitamin D may also cause adverse effects in people with normal kidney function [ 41 ]. There is little evidence that usual doses and forms of these nutrients give rise to health problems [ 42 ]. The possibilities of excessive intakes of nutrients from dietary supplements are greater in countries with programs to fortify their food supplies than in others, and therefore they must also be evaluated [ 43 , 44 , 45 , 46 ].
Dose-response data for establishing safe levels of intakes of non-nutrient bioactives in supplements is frequently lacking [ 47 , 48 ]. Some dietary supplements containing non-target herbs added intentionally like germander as an adulterant for skullcap , or others such as black cohosh, kava extract, green tea and others have been associated with liver injures of various types even after taking into account concomitant use with acetaminophen and alcohol and consumption while fasting [ 49 ].
Extracts that are used in bodybuilding and weight loss have also been linked to liver injury. This has led to studies of the composition of different supplements [ 50 , 51 ]. Causes of liver toxicity from supplements appear to be due to insufficient regulatory authority, inaccurate product labeling, adulterants and inconsistent sourcing of ingredients [ 52 ]. There is controversy about whether evidence of causality is sufficient for regulators to take action against supplements that seem to pose a hepatotoxic risk [ 53 ].
Adulterated or fraudulent tainted products sold as dietary supplements are already illegal and subject to recall [ 54 ]. Interactions of some ingredients in supplements with other dietary supplements, nutrients, prescription or over-the-counter drugs are well documented.
Of particular concern are adverse reactions occurring with commonly used medications, such as anti-hypertensive and cardiovascular preparations [ 55 ]. In addition, much interest focuses around concomitant use of herbal medicines such as St. Among the most hotly debated issues in supplement research is the type and amount of evidence needed to demonstrate the efficacy of dietary supplements.
Many of the issues involving efficacy include those common in testing of all medications such as study designs, significance testing, appropriate outcomes, effect sizes, acceptable biomarkers of effect, and the differences between statistical and clinical significance.
In order to be efficacious, dietary supplements must be bioavailable, and yet in some countries regulations do not require testing of supplements for disintegration and dissolution and some products on the market fail such tests. This is a matter of concern both to researchers and regulators since such results have a negative impact on studies of dietary supplement efficacy. In-vitro methods are available for testing disintegration and dissolution of drugs, and these are adaptable for use with dietary supplement products.
Regulators in some countries insist on changes in health outcomes or in validated surrogate biochemical markers of effect on the causal pathway to a health or performance outcome. Others accept changes in intermediary biochemical markers that may or may not be surrogates of health outcomes. These considerations have come to the fore because supplements on the market in some countries apparently have little or no demonstrated efficacy.
For example, one recent review of 63 randomized, placebo-controlled clinical trials of dietary supplements in Western adults found that in 45 of them no benefits were found, 10 showed a trend toward harm and 2 showed a trend toward benefit, while 4 reported actual harm, and 2 both harms and benefits; only vitamin D and omega 3 fatty acids had strong enough benefits and lack of harm to suggest possible efficacy [ 3 ].
This is an area of controversy that is highly polarized with questions being raised that depend on the type of dietary supplement being used, notably herbal medicines, the quality of the studies included in the review, and additional factors such as product quality of the supplement being evaluated that need to be taken into account [ 57 ].
Should usual standards for efficacy should apply to them when they are used in the traditional manner? Clearly such uses are quite different than the use of a single product or ingredient at much higher traditional doses and without such a cultural context. Although policy issues arise with all types of dietary supplements, the examples below will focus on nutrient-containing dietary supplements since these are particularly germane to discussions of nutritional status.
There are many strategies for filling nutrient gaps in dietary intakes. The supplements can be used selectively by those whose diets have gaps in them. However, supplements have disadvantages. Their use depends upon individual motivations. Because they provide concentrated sources of bioactives at relatively high levels, they may increase the risks that some individuals will ingest excessive quantities and suffer health risks. Moreover, since dietary supplements can contain ingredients that lack a history of safe use, their long-term health effects may be unknown.
The advantages and disadvantages of dietary supplements as a strategy to improve dietary intakes therefore must be carefully considered. The cost-effectiveness of using supplements to fill gaps in nutrient intakes as opposed to other means such as fortification or nutrition education varies from one nutrient to another and by country, and so each situation is unique and must be evaluated independently.
There are also questions about what the supplement should be, if supplementation is chosen. In countries where nutrient containing dietary supplements are common, the use of multivitamin-multi-mineral MVM supplements is often associated with a greater proportion of the population reaching the estimated average requirement EAR for nutrients [ 58 ].
However, for some of these nutrients, intakes are already adequate, so that the increased intakes may do little good, and in some cases supplements may increase the risk of exceeding the upper safe level UL of intakes.
Monitoring of supplement use is particularly important in countries where premarket approval is not required to detect potential adverse reactions. Dietary indicators are known to be imprecise and estimates of usual intake are lacking for many nutrients [ 59 ]. Biochemical indicators of deficiency are often not well linked with adverse health outcomes, underscoring the need for more attention to be paid to the development of agreed on measures of deficiency and excess [ 60 ].
Recent work on key nutrient biomarkers is now available, facilitating the monitoring of high risk groups, such as pregnant women for folate status [ 61 , 62 ].
Health and nutrition experts differ on whether it is appropriate to include recommendations for nutrient containing dietary supplements in national health promotion and disease prevention recommendations.
Many countries opt to recommend that adequate nutrient intake for the general public be achieved solely from foods, and reserve recommendations of specific nutrient supplements for specific subgroups in the population. Others recommend only food alone with no recommendations for special populations.
There is pressure by industry to include MVM or other dietary supplements in food programs. However, there is little evidence that the target groups are deficient in the ingredients in the supplements, nor has it been demonstrated that provision of a supplement leads to better health outcomes. The development of new and more highly bioavailable forms of the nutrients, timed release, dosage forms, novel bioactive constituents and the appropriate application of new technologies such as nanotechnology are all important, but some pose new scientific and regulatory challenges.
This case study highlights some examples of dietary supplement research supported by or conducted at the ODS, and provides some research tools it has developed that may be useful resources for scientists both there and abroad. Since its establishment in as part of the implementation of the Dietary Supplement and Health Education Act [ 17 , 18 ] of , the ODS is the lead federal agency devoted to the scientific exploration of dietary supplements.
They include studies to clarify the implications for public health of omega-3 fatty acids [ 63 ], iodine [ 64 ], vitamin D [ 65 ], and iron [ 66 ]. This section provides the details on freely available research resources developed by ODS that are available for scientists to use to enhance the quality of dietary supplement research and meet public health priorities, with a focus on those that may be useful to scientists in other countries.
The rigorous assessment of dietary supplement ingredients requires accurate, precise and reliable analytical methods and matching reference materials. The ODS Analytical Methods and Reference Materials program accelerates the creation and dissemination of validated methods and reference materials.
It provides resources for characterization and verification of supplement product content that enhance the reliability and reproducibility of research using these products and supports product quality [ 67 ]. The genesis of the program was the paucity of publicly available methods for the analysis of supplement ingredients [ 68 , 69 ]. In , the US dietary supplement community tended to use proprietary or compendial methods for quality control operations, and scientists and laboratories often kept their proprietary methods to themselves.
Negative publicity about discrepancies between label claims and the results of product testing performed by third parties led to some unsuccessful efforts on the part of the industry to pay a laboratory to develop and validate methods through the Association of Official Analytical Chemists International AOACI.
The program was not successful for several reasons, including lack of expert technical guidance and conflicting sponsor priorities. In response to the need for such publicly available methods and to support efforts to validate methods used in biomedical research on dietary supplement ingredients, ODS established the Analytical Methods and Reference Materials AMRM program in ODS has been involved in sponsoring the creation of AOAC Official Methods of Analysis for dietary supplements and in the development and dissemination of numerous analytical methods and reference materials for 15 ingredients in dietary supplements in the USA, 32 botanical identification and documentation projects, and 45 studies determining contamination and adulterants.
It has also helped to develop guidance on the validation of identity methods for botanical ingredients [ 70 ] and the conduct of single-laboratory validation studies for dietary supplements, Appendix K, AOAC Official Methods of Analysis, and provided guidance to evaluation of the literature on botanical supplements [ 71 , 72 ]. The portion of the ODS website includes a searchable database of analytical methods; these can be accessed at: Exercises have included water and fat-soluble vitamins, nutritional and toxic elements, fatty acids, contaminants e.
A reference material is a material that is sufficiently homogeneous and stable with respect to one or more specified properties, which have been established to be fit for its intended use in a measurement process.
A certified reference material CRM is a reference material characterized by a metrologically valid procedure for one or more specified properties, accompanied by a certificate that provides the value of the specified property, its associated uncertainty, and a statement of metrological traceability. Certified reference materials can be used for laboratory proficiency studies, methods development, method verification, and method validation studies.
Calibration standards are the single chemical entities necessary for construction of calibration curves for quantitative analysis and for confirming analyte identity. Several processes are used to produce calibration standards. ODS provided funding to the U. The materials fall into one of the following categories: ODS is now expanding efforts to develop biomarkers of nutrient exposure and status in blood and other biological specimens in relation to chronic disease risk in individuals and populations.
ODS has worked with NIST to produce and make available reference materials for calibration of various laboratory methods. Supplementary Table S2 shows dietary supplement and nutritional assessment SRMs that are currently in progress. Two databases have been developed by ODS that are described elsewhere in detail [ 76 , 77 , 78 , 79 , 80 ].
This provides all the information on the product label including composition, claims, and manufacturer contact information. It now contains over 72, dietary supplement labels, with new labels added at the rate of per month.
Used together with food composition databases it is possible to estimate total daily intakes of nutrients and other bioactive ingredients from both foods and dietary supplements.
A mobile version of DSLD is now available for use on smartphones to enhance consumer access to it [ 78 , 80 ]. It is primarily aimed at researchers and so contains information about products that are currently on the market, as well as those that have been removed from the market.
The Dietary Supplement Ingredient Database DSID provides analytically derived information on the amount of labeled ingredients of a representative sample of commonly used categories of supplement products sold in the USA, including adult, child and prenatal MVM supplements and omega-3 fatty acids.
DSID is now being expanded to examine botanicals and other ingredients in supplements that are of public health interest, such as green tea products. Calculators included with the DSID permit a consumer to examine how closely the labeled contents of a nutrient in a product compare to chemical analyses of all products in the category [ 79 ]. Systematic reviews of dietary supplements require special techniques. ODS has sponsored a series of technical reports on the application of review methodology to the field of nutrition and dietary supplements [ 81 , 82 , 83 , 84 , 85 , 86 ].
Staff have also collaborated in performing systematic reviews with other groups [ 87 , 88 ]. Several studies have focused on adults [ 89 ], children [ 90 , 91 ], and others in the population and their supplement use. Other studies have focused on the contributions to total intakes of nutrients made by dietary supplements. Investigators at ODS have been active in funding monitoring efforts on the links between intakes of folic acid and health [ 92 ].
They have devoted particular attention to blood levels of folic acid and dietary intake patterns that are associated with very low and very high intakes of the nutrient [ 93 , 94 , 95 ]. The survey methods used are well documented and they may be useful for those in other countries planning similar population-based surveys to consult [ 96 ].
The motivations for use of dietary supplements are also documented; they often differ from those specified in regulations. NHANES contains several items that are consumer tested and available for use in other surveys on motivations.
Knowledge of motivations can improve understanding of how people use these products and may provide clues for encouraging appropriate supplement use. ODS has produced and periodically updates a library of more than two dozen fact sheets on the ingredients in supplements such as vitamin D, magnesium, and special products such as MVM supplements and products marketed for weight loss. There is a detailed version for professionals that is complete with detailed references, as well as easy-to-read versions for consumers in both English and Spanish.
They can be accessed at https: ODS also hosts an intensive, free 3-day course on issues in dietary supplement research annually for researchers. Further information about these and other projects is accessible at: In order to foster the development of appropriate study methods for dietary supplement research, ODS sponsors workshops on the latest knowledge and emerging approaches to the study of dietary supplements.
It also supports the development of cutting—edge approaches to elucidate the mechanisms of action of complex botanical dietary supplements. These and other resources are announced as they become available on the ODS website. ODS has strengthened the scientific framework for developing dietary recommendations by encouraging the incorporation of systematic reviews into the development of the DRI. It has sponsored 18 systematic reviews on topics related to dietary supplements.
These include ephedra, B vitamins, MVM supplements, omega-3 fatty acids, soy, probiotics, and vitamin D. The ephedra systematic review was helpful to the US government in banning ephedra products from the US market. The systematic reviews of omega-3 fatty acids funded over a decade ago and more recent updates on their associations with cardiovascular disease and infant health outcomes have been useful for planning intervention programs as well as for regulatory purposes.
Attitudes toward safety, efficacy, and values about what is important in food and life will be important in determining future needs involving supplement science in the countries we have discussed and perhaps elsewhere in the world.
Dietary Supplements: Regulatory Challenges and Research Resources
Overview of dietary supplements and FDA's role in regulating them. FDA regulates dietary supplements under a different set of regulations than those covering "conventional" foods and drug Toll Free SAFEFOOD, Language Assistance Available: Español | 繁體中文 | Tiếng Việt. Dietary ingredients include vitamins, minerals, amino acids, and herbs or botanicals, as well as other These products are available in stores throughout the United States, as well as on the Internet. The Food and Drug Administration (FDA) suggests that you consult with a health care How Are Supplements Regulated?. No drug can be sold until the FDA has proof clear proof that it is safe 2) it is an FDA-regulated drug, and 3) when taken with heart drugs Related Information: Vitamins and Minerals: Choosing the nutrients take dietary supplements and the widespread availability of these . Our FREE E-Newsletter.