Introduction
During the first six months of the coronavirus disease 2019 (COVID-19) pandemic, the U.S. Food and Drug Administration (FDA) and the Federal Trade Commission (FTC) issued warning letters to seven companies for selling fraudulent COVID-19-focused products. These products included teas, essential oils, tinctures and colloidal silver – all of which are utilized by many dietary supplement manufactures. The companies were asserting that their products treat, cure or prevent COVID-19, a serious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (FDA, 2020). U.S. federal regulations provide the ability for dietary supplement manufacturers to make structure/function claims, that is, statements with respect to the supplement’s effects on the body’s structure or function. They may not, however, claim their products “…diagnose, mitigate, treat, cure, or prevent a specific disease or class of diseases” (21 U.S.C. 343(r)(6)). This is because dietary supplements that bear such claim may cause consumers to delay or stop appropriate medical treatment, leading to serious and life-threatening harm (FDA, 2020). Depending on the phrasing, or the context in which it is presented, a statement about the effect of a product on the structure or function of the body may lead consumers to believe that the product is beneficial for the treatment or prevention of a disease. The following demystifies the line of what is and is not a structure/function claim for a dietary supplement product by describing (1) the meaning of a structure/function claim (and related claims); (2) the regulatory framework and history; and (3) non-acceptable versus acceptable claims.
What is a structure/function claim?
A structure/function (S/F) claim is a statement addressing the role of a specific substance in maintaining normal healthy structure or function of the human body. This should not be confused with a health claim, which is a statement describing a relationship between a substance and reduced risk of a disease or health-related condition, such as “adequate calcium throughout life may reduce the risk of osteoporosis” (FDA, 2018). S/F claims (1) describe the role of a nutrient or dietary ingredient on the structure or function in humans (e.g., “calcium builds strong bones”); or (2) characterize the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function (e.g., “fiber maintains bowel regularity” or “antioxidants maintain cell integrity”) (FDA, 2018; 21 CFR § 101.93(f)).
There are two types of dietary supplements claims related to S/F claims, described below.
General well-being claims: These describe general well-being from consumption of a nutrient or dietary ingredient (g., “zinc will help you feel healthy”).
Nutrient-deficiency disease claims: These describe a benefit related to a nutrient deficiency disease like vitamin C and scurvy. Such claims are only allowed if the claim also states how widespread the stated disease is in the United States (FDA, 2018).
Regulatory framework
Since the enactment of the Dietary Supplement Health and Education Act (DSHEA) of 1994, FDA has lacked authority to approve structure/function claims (and related general well-being and nutrient-deficiency disease claims) before the dietary supplement products enter the market. However, a manufacturer must submit a notification with the text of the claim to FDA no later than 30 days after putting the dietary supplement product on the market. Manufacturers must also have competent and reliable scientific evidence to show that the claim is truthful and not misleading, but they do not have to submit the substantiation to FDA. The product label must include a disclaimer stating that FDA has not reviewed the claim and that the product is not intended to “diagnose, treat, cure, or prevent any disease,” because only a drug can legally assert such a claim (FDA, 2018; 21 CFR § 101.93). FDA has the authority to protect consumers from companies selling unapproved products and making false or misleading claims, including, issuing warning letters, product seizures, injunctions or criminal prosecutions against products and firms or individuals that violate the law (FDA, 2021).
Regulatory history
DSHEA set forth a regulatory framework for dietary supplements that previously did not exist, and was a response by the U.S. Congress to FDA’s aggressive approach to regulating dietary supplements (Kaczka, 2000). Before the enactment of DSHEA, dietary supplement products (including vitamins and minerals) were subject to be regulated as a drug: (1) if “disease claims” were made (i.e., claims to diagnose, treat, cure, or prevent disease); (2) if claims were made to affect the structure or function of the body through a non-nutritive mechanism; or (3) if there was other evidence that the intended use of the product was as a drug. Dietary supplements with such claims had to meet the rigorous drug safety and efficacy requirements of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including in nearly all cases, pre-market approval (FDA, 1999).
Congress passed DSHEA with the intent “…to strike the right balance between providing consumers access to both products and truthful information about the products while retaining authority for FDA to take action against products that present safety problems or are improperly labeled” (FDA, 1999). DSHEA not only created a broad comprehensive definition of “dietary supplements,” but also allowed retailers to sell third-party books and other educational materials concerning dietary supplements (Kaczka, 2000). Increasing information on dietary supplements to the public was considered by Congress as an inexpensive way to promote public health (Kaczka, 2000); a decision that was possibly motivated by President Clinton’s health care plan of 1993.
Additionally, DSHEA amended the FD&C Act to allow for certain types of claims for dietary supplements that formerly would have made them drugs, including claims concerning the supplement’s effects on the body’s structure or function through a non-nutritive mechanism (FDA, 1999). Dietary supplements may bear authorized health claims, but Congress prohibited dietary supplements to be intended to treat, prevent, mitigate, cure, or diagnose disease. Congress recognized that if dietary supplements were allowed to make disease treatment and prevention claims without pre-market review, the burden would be on consumers to evaluate the validity of countless claims about products marketed for serious and life-threatening conditions. Through the lack of pre-market review, dietary supplements would also be given an unfair advantage in the marketplace of prescription and over-the-counter (OTC) drugs (FDA, 1999).
What a structure/function claim is not
As mentioned before, a S/F claim is not a statement that claims, explicitly or implicitly, to diagnose, mitigate, treat, cure, or prevent disease. Such statements are described as “disease claims.” However, under DSHEA, the distinction between a S/F claim and a disease claim was not clear. This resulted in FDA drawing a line between the two types of claims. On January 6, 2000, FDA published a final rule in the Federal Register (65 FR 1000), defining the types of statements that can be made concerning the effect of a dietary supplement on the structure or function of the body. The regulations establish criteria for determining when a statement about a dietary supplement is a claim to diagnose, cure, mitigate, treat, or prevent disease. This action was intended to clarify the types of claims that may be made for dietary supplements without prior review by FDA and the types of claims that require prior authorization as health claims or prior approval as drug claims (FDA, 2000).
According to the final rule, in recognizing what is and is not an acceptable S/F claim for dietary supplements, it is first important to identify what constitutes a disease claim. Under 21 CFR § 101.93(g)(1), “disease” is defined as:
“…damage to an organ, part, structure, or system of the body such that it does not function properly (e.g., cardiovascular disease), or a state of health leading to such dysfunctioning (e.g., hypertension); except that diseases resulting from essential nutrient deficiencies (e.g., scurvy, pellagra) are not included in this definition.”
The definition of disease does not refer to signs or symptoms but claims that mention them will still be considered disease claims (21 CFR § 101.93(g)(2)(ii)). A test to make it easier to recognize what will be considered a sign or symptom is to ask oneself, “…whether the labeling suggests that the product will produce a change in the characteristic signs or symptoms of a specific disease or class of diseases” (FDA, 2000). Examples of statements that refer (explicitly or implicitly) to an effect on a specific disease or the characteristic signs or symptoms of such disease include “improves joint mobility and reduces inflammation” (characteristic symptoms of rheumatoid arthritis) and “lowers cholesterol” (characteristic symptom associated with stroke and heart disease) (FDA, 2000). It is the specificity of the signs or symptoms that prohibits these claims on dietary supplement. Examples of acceptable S/F statements include “promotes joint health and flexibility” and “helps maintain cholesterol levels that are already in the normal range” (FDA, 2000), which are not specific enough to imply reference to a specific disease or class of diseases.
This distinction between a S/F claim under 21 CFR § 101.93(g)(2)(i–ii), however, can be ambiguous and dependent on interpretation. For example, should the claim ‘‘maintains healthy cholesterol levels’’ be an acceptable S/F claim, while ‘‘lowers cholesterol’’ be treated as a non-acceptable (disease claim) for a dietary supplement product? As stated by a major trade association, “what is healthy cholesterol, but a lower cholesterol level?” According to FDA, references to ‘‘healthy’’ cholesterol may be misleading to consumers because the phrase ‘‘healthy cholesterol’’ is frequently used to refer to high density lipoproteins (HDL), a specific cholesterol fraction believed to be beneficial. To avoid this confusion, FDA determined that an appropriate S/F claim for maintaining cholesterol would be ‘‘helps to maintain cholesterol levels that are already within the normal range.” Maintaining cholesterol levels within the normal range is essential to the structure and function of the body for reasons besides prevention of heart disease (FDA, 2000).
Additionally, common conditions associated with natural states or processes (e.g., menopause, pregnancy, aging) that do not cause significant or permanent harm are acceptable S/F claims (FDA, 2000). For example, hot flashes, common symptoms associated with the menstrual cycle, ordinary morning sickness associated with pregnancy, mild memory problems associated with aging, hair loss associated with aging, and noncystic acne are not diseases under 21 CFR § 101.93(g)(2)(iii). Therefore, the claim “morning sickness associated with pregnancy” is identified as a S/F claim. However, abnormal conditions that are uncommon or can cause significant or permanent harm like senile dementia, toxemia of pregnancy, severe depression associated with the menstrual cycle, and cystic acne are treated as diseases under 21 CFR § 101.93(g)(2)(iii) (FDA, 2000). Therefore, the claims “toxemia of pregnancy” and “severe depression associated with the menstrual cycle” are identified as disease claims.
Under 21 CFR § 101.93(g)(2)(iv), other aspects of the labeling of a dietary supplement product may also constitute a disease claim. This includes explicit or implicit disease claims made in a product’s name, formulation, or reference of a publication title (refer to Table 1 for examples). The “use of pictures, vignettes, symbols, or other means” that portray an effect on a disease or diseases is also considered a disease claim. For example, an image of a woman wearing a mask may imply a claim that promotes the product’s ability to protect consumers against COVID-19 (National Advertising Division (NAD), 2020); this is a non-acceptable claim for a dietary supplement product.
Some product class names are so strongly associated with use to treat or prevent a specific disease or class of diseases that claiming membership in the product class implies disease treatment or prevention. The following examples of product class names imply disease treatment or prevention under 21 CFR § 101.93(g)(2)(v): claims that the product is an ‘‘antibiotic,’’ an ‘‘analgesic,’’ an ‘‘antiviral,’’ an ‘‘antimicrobial,’’ an ‘‘antidepressant,’’ or a ‘‘vaccine” (FDA, 2000). An acceptable S/F claim would state that a product is in a class that is not recognizable to health care professionals or consumers as intended for use to diagnose, mitigate, treat, cure or prevent disease, for instance, claims that the product is an ‘‘energizer,’’ a ‘‘rejuvenative,’’ a ‘‘revitalizer,” or an “adaptogen.” Although obesity is a disease, being overweight is not; therefore, ‘‘appetite suppressant’’ is also an acceptable S/F claim in the context where it does not imply use for obesity (FDA, 2000).
S/F claims do not suggest that the product has a role in the body’s response to a disease or to a vector of disease. A general reference to an effect on a body system that does not imply prevention or treatment of a disease state is an acceptable S/F claim. For example, “supports the immune system” is a S/F claim, whereas “supports the body’s antiviral capabilities’’ is a disease claim (FDA, 2000). The distinction between the two claims is one of specificity and an understanding of the immune system. The immune system has several functions other than fighting disease in the body; for example, the white blood cells of the immune system play an essential role in the phagocytosis and disposal of aging red blood cells or otherwise damaged cells. Therefore, the statement, “supports the immune system”, by itself, conveys no specific reference to the disease-fighting function of the immune system. In contrast, the claim that a product ‘‘supports the body’s antiviral capabilities’’ specifies a role in the body’s response to a specific class of diseases, those caused by viruses (e.g., colds, hepatitis, or HIV infection) (FDA, 2000).
Moreover, S/F claims are not to mention a therapy for disease. For example, the statement ‘‘helps maintain intestinal flora’’ alone, without any reference to a disease, drug, drug action, or therapy, does not imply an effect on disease and would be considered a S/F claim about general health maintenance. However, the statement, ‘‘helps individuals using antibiotics to maintain normal intestinal flora” is an implied disease prevention claim. This is because certain antibiotics can suppress normal intestinal flora that are used to prevent infection in the intestinal tract, which may result in overgrowth in the gut of a pathogenic organism (FDA, 2000).
Under 21 CFR§ 101.93(g)(2)(x), a statement is considered a disease claim if it “otherwise” suggests an effect on a disease or a class of diseases. This provision is necessary to allow for implied disease claims that may not fit into the nine enumerated criteria (21 CFR § 101.93(g)(2)(i–ix). FDA developed the criteria of what constitutes a disease claim based on past experience and recognizes the possibility that other types of statements may also imply disease treatment or prevention (FDA, 2000). Does that mean FDA can classify any S/F claim as a disease claim? – no, it does not; to regulate a statement as a disease claim, FDA has to show that the statement implies an effect on disease.
The table below summarizes how to identify what is and is not an acceptable S/F claim for a dietary supplement product.
Table 1. Identifying non-acceptable and acceptable structure/function claims for dietary supplement products.)
Structure/function claims(a)… | Non-acceptable claim (disease claim) | Acceptable claim (structure/ function claim) |
1. Do not suggest an effect on a specific disease or class of disease. | “Improves joint mobility and reduces inflammation” (implies treatment for a disease, rheumatoid arthritis).(b) | “Promotes joint health and flexibility.” |
2. Do not suggest that the product will produce a change in the characteristic signs or symptoms of a specific disease or class of diseases. | “Lowers cholesterol” (characteristic signs or symptoms associated with stroke and cardiovascular disease).(b) | “Helps maintain cholesterol levels that are already in the normal range” (maintaining normal function, not a disease).(c) |
3. May refer to a natural state (e.g., aging, pregnancy) generally but may not mention an abnormal condition that is uncommon or can cause significant or permanent harm. | “Toxemia of pregnancy” (toxemia is an abnormal condition that is uncommon and can cause significant or permanent harm).(c) | “Morning sickness associated with pregnancy” (morning sickness is a common, mild abnormality associated with pregnancy).(c) |
4. Do not suggest an effect on a disease or diseases through: | | |
A) product name; | ‘‘CircuCure’’; ‘‘Soothing Sleep’’(c) | “HeartHealth”; “MoodSupport”(c) |
B) product formulation; | Products that contain aspirin, digoxin, or laetrile (drugs that are known for its use in preventing or treating a disease).(c) | — |
C) citation of publication titles; | “The Role of Zinc in Antiviral Immunity.” Adv Nutr. 2019;10(4):696-710. (title refers to specific class of diseases, those caused by viruses) | “Zinc and its importance for human health: An integrative review.” J Res Med Sci. 2013;18(2):144-157. |
D) the use of the term “disease” or “diseased”; or | ‘‘Promotes good health and prevents the onset of disease’’ (product itself will achieve the intended effect).(c) | ‘‘A good diet promotes good health and prevents the onset of disease.”(c) |
E) the use of pictures, vignettes, symbols, or other means. | Picture of an abnormal tissue or organ.(b) | Pictures of healthy organs (Exception: symbols, like the heart symbol, that are widely associated with disease treatment and prevention). (b) |
5. Do not suggest membership to a class of products that are strongly associated with use to treat or prevent a specific disease or class of diseases. | Claims that the product is an ‘‘antibiotic,’’ an ‘‘analgesic,’’ an ‘‘antiviral,’’ an ‘‘antimicrobial,’’ an ‘‘antidepressant,’’ or a ‘‘vaccine.”(c) | Claims that the product is an ‘‘energizer,’’ a ‘‘rejuvenative,’’ a ‘‘revitalizer,’’ or an ‘‘adaptogen.’’(c) |
6. Do not suggest that the product is a substitute for a product that is a therapy for a disease. | ‘‘Herbal Prozac’’ (makes a direct connection with an approved drug)(c) | ‘‘Use as part of your weight loss plan’’ (not specific enough; obesity is a disease but overweight is not)(c) |
7. Do not suggest that the product augments a particular therapy or drug action that is intended to diagnose, mitigate, treat, cure, or prevent a disease or class of diseases. | ‘‘Use as part of your diet when taking insulin to help maintain a healthy blood sugar level.’’(c) | “Use as part of a healthy diet to help maintain healthy blood sugar levels.”(c) |
8. Do not suggest that the product has a role in the body’s response to a disease or to a vector of disease. | ‘‘Supports the body’s antiviral capabilities.’’(c) | “Supports the immune system.”(c) |
9. Do not suggest that the product treats, prevents, or mitigates adverse events associated with a therapy for a disease, if the adverse events constitute diseases. | ‘‘Helps individuals using antibiotics to maintain normal intestinal flora.’’(c) | ‘‘Helps maintain healthy intestinal flora.’’(c) |
10. Do not “otherwise” suggests a disease or disease condition. This does not mean FDA can classify any structure/ function claim as a disease claim. | To regulate a statement as a disease claim, FDA would have to show that the statement implied an effect on disease.(c) | ‘‘Provides nutritional support for women during premenstruation by promoting proper fluid balances and breast health” (not a disease claim, despite the critics who thought it would be under this criterion).(c) |
(a)Based on 21 CFR § 101.93(g)(2)(i–x); (b)Example/ explanation from FDA (2002); (c)Example/ explanation from FDA (2000).
Conclusion
On first review, statement for a dietary supplement may look like a structure/function claim, but in fact it is possible that FDA would likely view the claim as a disease claim. The distinction between the two claims is largely based on specificity, context, and interpretation. Burdock Group can work with dietary supplement manufacturers to assess whether a claim or claims is acceptable for their product(s) and to assist with submitting the claim(s) to the proper regulatory authority or governmental bodies.
References
FDA (1999) Statement of Jane E. Henney, Commissioner, Food and Drug Administration In: Dietary Supplement Health and Education Act: Is the FDA Trying to Change the Intent of Congress?: Hearing Before the House Comm. On Government Reform, 106th Congr., 1st Sess. U.S. Government Printing Office, Washington, D.C., pp. 33–50.
FDA (2000) 65 FR 1000 – Regulations on Statements Made for Dietary Supplements Concerning the Effect of the Product on the Structure or Function of the Body. Federal Register. 65(4):1000–1050.
FDA (2002) Small Entity Compliance Guide on Structure/Function Claims. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/small-entity-compliance-guide-structurefunction-claims#N_1_ (site accessed 14Sep2021).
FDA (2018) Label Claims for Conventional Foods and Dietary Supplements . https://www.fda.gov/food/food-labeling-nutrition/label-claims-conventional-foods-and-dietary-supplements (site accessed 29Sep2021).
FDA (2020) Coronavirus Update: FDA and FTC Warn Seven Companies Selling Fraudulent Products that Claim to Treat or Prevent COVID-19. https://www.fda.gov/news-events/press-announcements/coronavirus-update-fda-and-ftc-warn-seven-companies-selling-fraudulent-products-claim-treat-or (site accessed 2Oct2021).
FDA (2021) Fraudulent Coronavirus Disease 2019 (COVID-19) Products. https://www.fda.gov/consumers/health-fraud-scams/fraudulent-coronavirus-disease-2019-covid-19-products (site accessed 2Oct2021).
Kaczka, K.A. (2000) From Herbal Prozac to Mark McGwire’s Tonic: How the Dietary Supplement Health and Education Act Changed the Regulatory Landscape for Health Products. Journal of Contemporary Health Law and Policy. 16(2):463–499.
National Advertising Division (NAD) (2020) Social Media Post Implying Continual-G Glutathione Enhancer Protects Against COVID-19 is Discontinued Following NAD Inquiry. https://bbbprograms.org/media-center/newsroom/social-media-post-implying-continual-g-glutathione-enhancer-protects-against-covid-19-is-discontinued-following-nad-inquiry (site accessed 2Oct2021).