11. However, the following guidance document from FDA on substantiation of claims for dietary supplements is included here for comparison with the requirements required to make health claims. In particular, a scientific evidence‐based review is fundamental to the substantiation of both structure/function claims and health claims. The nature of evidence and weight of various types of evidence remain the same across all types of claims. The only distinction is the amount of evidence that is sufficient and whether FDA advance approval is required.
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Guidance for Industry Substantiation for Dietary Supplement Claims Made Under Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act
CFSAN, FDA (December 2008)
… Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 343(r)(6)) requires that a manufacturer of a dietary supplement making a nutritional deficiency, structure/function, or general well‐being claim have substantiation that the claim is truthful and not misleading.
This guidance document is intended to describe the amount, type, and quality of evidence FDA recommends a manufacturer have to substantiate a claim under section 403(r)(6) of the Act. This guidance document is limited to issues pertaining to substantiation under section 403(r)(6) of the Act; it does not extend to substantiation issues that may exist in other sections of the Act….
The Act, as amended by the Dietary Supplement Health and Education Act of 1994 (DSHEA) and the legislative history accompanying DSHEA do not define “substantiation.” …
Under the Act, FDA has exclusive jurisdiction over the safety, and primary jurisdiction over the labeling, of dietary supplements. The FTC has primary jurisdiction over advertisements for dietary supplements. Given these jurisdictional assignments, we and the FTC share an interest in providing guidance on what “substantiation” means. In April 2001, FTC issued a guidance document entitled, “Dietary Supplements: An Advertising Guide for Industry.”63 Our guidance document is modeled on, and complements, the FTC guidance document….
The FTC has typically applied a substantiation standard of “competent and reliable scientific evidence” to claims about the benefits and safety of dietary supplements and other health‐related products. FDA intends to apply a standard for the substantiation of dietary supplement claims that is consistent with the FTC approach….
The FTC standard of competent and reliable scientific evidence has been defined in FTC case law as “tests, analyses, research, studies, or other evidence based on the expertise of professionals in the relevant area, that has been conducted and evaluated in an objective manner by persons qualified to do so, using procedures generally accepted in the profession to yield accurate and reliable results.”
Although there is no preestablished formula as to how many or what type of studies are needed to substantiate a claim, we, like the FTC, will consider what the accepted norms are in the relevant research fields and consult experts from various disciplines. If there is an existing standard for substantiation developed by a government agency or other authoritative body, we may accord some deference to that standard.
In determining whether the substantiation standard has been met with competent and reliable scientific evidence, we recommend that firms consider the following issues in their assessment:
The meaning of the claim(s) being made;
The relationship of the evidence to the claim;
The quality of the evidence; and
The totality of the evidence… .
The first step in determining what information is needed to substantiate a claim for a dietary supplement is to understand the meaning of the claim and to clearly identify each implied and express claim. When a claim may have more than one reasonable interpretation, we recommend that a firm have substantiation for each interpretation. Consumer testing may be useful to determine consumer understanding of each claim, in context. We recommend that firms not only focus on individual statements or phrases, but also on what expected effect or benefit are being promoted when all of the statements being made for the product are considered together. Although it is important that individual statements be substantiated, it is equally important to substantiate the overall “message” contained when the claims are considered together.
Example 1:
The label of a dietary supplement containing “X” uses the following claims: “The amino acid ‘X’ is the chemical precursor to nitric oxide. Blood vessel cells contain enzymes that produce nitric oxide. Nitric oxide is important in maintaining blood vessel tone.” Assuming this statement were supported by sound science so that each individual statement was substantiated, the “message” conveyed by the claims, when considered together, is that taking oral “X” will affect nitric oxide production and blood vessel tone. Therefore, we recommend in this case that the dietary supplement manufacturer have substantiation that taking the amount of “X” provided by the product affect nitric oxide production and blood vessel tone under the product’s recommended conditions of use.
The firm’s clear understanding of the meaning of the claim is useful in ensuring that the evidentiary basis for substantiation is appropriate for the claim. Understanding the claim’s meaning will help identify the appropriate study hypotheses and measurable endpoints, which can be used to ensure that the firm has appropriate studies to substantiate the claim. For example, a firm making a claim that a dietary supplement “helps maintain blood vessel tone” or “supports healthy immune system” should have a clear understanding of the claim’s meaning to develop endpoints that could be measured and replicated in studies used as a basis for substantiation.
Example 2:
The labeling of a dietary supplement includes the statement “promotes weight loss.” The dietary supplement contains various vitamins and minerals and a botanical extract. The manufacturer relies on a randomized controlled double blind clinical study showing that subjects who took the botanical extract had a small but significant increase in metabolism over subjects taking a placebo over a 24 hour period. The study did not examine the effect of the extract on subjects’ weight and there is no research showing that a short term increase in metabolism will translate into any measurable weight loss. The weight loss claim would likely not be adequately substantiated.
Example 3:
The labeling for a dietary supplement contains a statement saying, “Recommended by Scientists,” in connection with the product’s claim. The statement gives consumers the impression that there is a body of scientists, qualified experts, who believe that the claim being made is supported by evidence. Consumers might also reasonably interpret the statement as meaning that there is general scientific agreement or consensus regarding the claim. If the manufacturer does not possess evidence to demonstrate such a consensus, the claim may not be substantiated. The opinion of a single scientist or small group of scientists is probably not adequate substantiation for such a claim.
Example 4:
The labeling states, in connection with the product’s claim, that the dietary supplement has been “studied for years” in a particular country or region and is the subject of clinical or “university” research. Here, the labeling conveys the impression that the product has been studied and also conveys the impression that there is a substantial body of competently conducted scientific research supporting the claim. We recommend that manufacturers possess evidence to substantiate both the express statements and their implied meaning….
We recommend that the studies being used as substantiation for dietary supplement claims identify a specific dietary supplement or ingredient and serving size and that the conditions of use in the studies are similar to