Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-19T06:04:26.877Z Has data issue: false hasContentIssue false

Dietary Supplements: Reports Reviewed by Tia Powell and Barbara A. Noah

Institute of Medicine, Dietary Supplements: A Framework for Evaluating Safety (Washington, D.C., 2005)

Published online by Cambridge University Press:  01 January 2021

Extract

The Institute of Medicine’s 2005 publication, Dietary Supplements: A Framework for Evaluating Safety, is authoritative and thorough, and thus representative of other reports by the Institute of Medicine (IOM). What makes this report particularly interesting, however, is the rich political subtext that exists in the interstices of the report, popping up here and there in brief comments and barely suppressed yelps of exasperation. To understand this context, it is useful to reflect for a moment on the special nature of the IOM and its relationship to government.

IOM is part of the National Academy of Sciences, and is a private, non-governmental organization that does not receive direct federal funding for its work. Rather, IOM studies are often funded by contract with governmental entities that request reports on particular topics. As a case in point, the dietary supplement study was requested and paid for by the FDA.

Type
Reviews in Medical Ethics
Copyright
Copyright © American Society of Law, Medicine and Ethics 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Gillis, J., “Herbal Remedies Turn Deadly for Patients,” Washington Post, September 5, 2004, at A1.Google Scholar
FDA, Advance Notice of Proposed Rulemaking on Dietary Supplements, 58 Fed. Reg. 33,690 (1993) (recommending that the FDA establish safe levels for use of vitamins and minerals, that it regulate drugs amino acid-containing dietary supplements as drugs, and that various other types of supplements be evaluated under the food provisions of the statute in order to determine whether they are generally recognized as safe [GRAS]).Google Scholar
Pub. L. No. 103–417, 108 Stat. 4325 (1994) (codified in scattered sections of 21 U.S.C.).Google Scholar
“Definition of certain foods as dietary supplements, 21 U.S.C. § 321, is amended by adding at the end the following: The term dietary supplement: (1) means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E).” 21 U.S.C. § 321 ff 2000. The statute further defines dietary supplements as products that are labeled as “dietary supplements” and are not represented for use as a conventional food or as a sole item of a meal or the diet. See 21 U.S.C. § 321(ff).Google Scholar
21 U.S.C. § 321(s)(6). The FDCA subjects food additives to pre-market review in order to determine whether such substances are safe for use. See id. § 348(a)-(c). The FDA has, however, exempted from pre-market approval requirements substances added to food that are generally recognized as safe (“GRAS”). See 21 C.F.R. § 170.30(a) (2004); also see generally Noah, L. and Merrill, R. A., “Starting from Scratch? Reinventing the Food Additive Approval Process,” Boston University Law Review 78 (1998): 329–95, at 392–95.Google Scholar
21 U.S.C. § 321(g)(C). The definition provisions specifically exempt foods and dietary supplements from regulation as drugs, even if their labeling contains certain types of health claims permitted under DSHEA. See id. § 321(g)(1)(D).Google Scholar
21 U.S.C. § 355 (pre-market review provisions of the FDCA).Google Scholar
A company wishing to sell a supplement containing a “new dietary ingredient,” (defined as one not marketed before October 15, 1994) however, must file a notification with the FDA at least 75 days prior to market introduction, which provides the basis for the manufacturer's conclusion that the supplement will “reasonably be expected to be safe” and must demonstrate only that “[t]here is a history of use or other evidence of safety.” 21 U.S.C. § 350b(2). If the agency finds the notification inadequate, it can prevent marketing only by initiating formal enforcement proceedings, under the provisions of DSHEA.Google Scholar
New York State Task Force on Life and the Law, Dietary Supplements: Balancing Consumer Choice & Safety (2005) [hereinafter Task Force Report] available at <http://www.health.state.ny.us/nysdoh/taskfce/index.htm> (last visited September 22, 2005).+(last+visited+September+22,+2005).>Google Scholar
Task Force Report, supra note 9, at 16.Google Scholar
Gugliotta, G., “Lawsuits Show Big Increase: Stimulant's Critics Try New Forum,” Washington Post, July 23, 2000, at A1 (noting that a lawsuit involving the 20-year-old college student's death settled for $2.5 million, that 33 other lawsuits involving ephedra side effects settled between 1994 and 2000, and that another 42 cases were pending at the time). See also Vecsey, G., “Baseball Has Failed to Confront Drugs,” New York Times, February 19, 2003, at D1; also “As Backlash Against Ephedra Mounts, Congress Drags Feet,” USA Today, July 17, 2003, at A12 (listing several other deaths apparently related to ephedra use).Google Scholar
Ephedra can cause a variety of serious adverse events, including irregular heartbeat, sleeplessness, anxiety, tremors, headache, seizures, heart attack, and stroke. See Task Force Report, supra note 9, at 16.Google Scholar
Task Force Report, supra note 9, at 16–17; see also Hampton, T., “More Scrutiny for Dietary Supplements?” JAMA 293 (2005): 2728, at 28 (noting that critics argue that the FDA waited too long to act, promulgating the final rule declaring ephedra products adulterated only after reports of at least 155 deaths associated with the product's use).Google Scholar
Task Force Report, supra note 9, at 18.Google Scholar
FDA, Proposed Rule, 62 Fed. Reg. 30,678 (1997) (proposing new rules that would render dietary supplements containing ephedra adulterated if they contain more than 8 mg. of ephedrine alkaloids or if the product's label suggests dosing that would result in an intake of more than 8 mg. in a six-hour period or more than 24 mg. in 24 hours and that requires the labeling to contain warnings against using the product for more than 7 days or in combination with any other stimulant).Google Scholar
Additional evidence of ephedrine's dangers continues to accumulate. One recent meta-analysis of published and unpublished trials of ephedra products found that such products create a 2.2 – 3.6-fold increased risk of psychiatric, autonomic, gastrointestinal, or coronary symptoms, including 2 deaths, 3 myocardial infarctions, 9 strokes, and 3 seizures. See Shekelle, P. et al, “Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects,” JAMA 289 (2003): 1537–44, at 1543–44.Google Scholar
FDA, Ephedrine Final Rule, 69 Fed. Reg. 6788 (2004). Several dietary supplement firms that manufacture ephedra-containing products challenged the ban, alleging that the FDA's rule is arbitrary and capricious. See Wallace, P., “Utah Firms File Lawsuit Challenging Ephedra Ban,” Food Chemical News, May 10, 2004, available at 2004 WL 67505224 (describing several legal challenges).Google Scholar
Nutraceutical Corp. v. Crawford, 364 F. Supp. 2d 1310 (D. Utah 2005).Google Scholar
Id. at 1319. The court also objected to the FDA rule because it considered all ephedrine-containing supplements to pose an unreasonable risk despite wide variations among products in amounts of active ingredients and recommended dosages. Another industry challenge to the Ephedrine Final Rule remains unresolved. See NVE, Inc. v. HHS, No. 04-CV-999 (D.N.J. 2004).Google Scholar
Task Force Report, supra note 9, at 18–19.Google Scholar
Id. at 19.Google Scholar
Id. at 26–27. The U.S. Centers for Disease Control and Prevention are working to collect more comprehensive data on supplement use.Google Scholar
Id. at 30.Google Scholar
Task Force Report, supra note 9, at 27–30.Google Scholar
Id. at 30–31.Google Scholar
The Report Task Force Report also contains an Appendix listing commonly used dietary supplements, their indications, evidence of efficacy, if any, associated side effects, contraindications, evidence of contamination problems, if any, recommended dosages, and information about supplement-drug interactions. See Task Force Report, supra note 9, at 85 (App. A).Google Scholar
See id. at 36 (explaining that “methodological flaws in the available literature includ[e] insufficient statistical power, sampling errors, absence of control groups, and incomplete reporting” and adding that meta-analyses of the available research add little to the safety or efficacy picture because the primary data is so flawed).Google Scholar
See John Ioannidis, P. A., Lau, J., “Completeness of Safety Reporting in Randomized Trials,” JAMA 285 (2001): at 437 (“[S]afety reporting is often inadequate and neglected. Key information that would take minimal space to report is often missing”) On the various flaws associated with premarket evaluation and postmarket safety surveillance of prescription drugs more generally, including problems with the detection of adverse drug interactions, see Noah, B. A., “Adverse Drug Reactions: Harnessing Experiential Data to Promote Patient Welfare,” Catholic Law Review 49 (2000): 449-504.Google Scholar
See Task Force Report, supra note 9, at 36.Google Scholar
See id. at 35 (observing that such assumptions ignore the fact that herbal products in particular vary in their concentration and potency of active ingredients and that modern consumers lack the knowledge and experience of traditional healers). DSHEA itself reinforces this misconception-the statute only requires premarket submission of safety data for supplements containing a “new dietary ingredient.” For these products, manufacturers must submit evidence to FDA 75 days prior to marketing that demonstrates that “[t]here is a history of use or other evidence of safety.” 21 U.S.C. § 350b(2).Google Scholar
See id. at 37.Google Scholar
See id. at 38–39.Google Scholar
The FDCA's food safety standard renders a food product adulterated if it “bears or contains any poisonous or deleterious substance which may render it injurious to health.” 21 U.S.C. § 342(a).Google Scholar
See 69 Fed. Reg. 6788 at 6823 (2004) (discussing DSHEA's “unreasonable risk” standard and concluding that “the plain meaning of ‘unreasonable’ … connotes comparison of the risks and benefits of the product”)Google Scholar
Task Force Report, supra note 9, at 40–41 (noting that an estimated 18.4 percent of prescription drug uses take their medications concurrently with herbal supplements or high dose vitamins).Google Scholar
Id. at 40–41 (noting that 70 percent of patients do not disclose their herbal supplement use to their physicians).Google Scholar
Id. at 40–46 (including discussion of specific examples of herbal and other substances known to cause serious illness or death).Google Scholar
Task Force Report, supra note 9, at 53–55.Google Scholar
21 U.S.C. § 343(r)(6)(B); see also Task Force Report, supra note 9, at 56. Neither the statute nor its legislative history elaborate on the type or quantity of evidence sufficient to provide such substantiation and, as the Task Force Report points out, the FDA lacks the regulatory authority to require substantiating data from manufacturers. See id. at 56.Google Scholar
21 U.S.C. § 343(r)(6)(C).Google Scholar
21 U.S.C. § 321(g)(C) (“The term ‘drug’ means … articles (other than food) intended to affect the structure or function of the body of man …”); see also FDA, Structure/Function Claims Small Entity Compliance Guide, available at <http://www.cfsan.fda.gov/-dms/sclmguid.html> (last visited September 15, 2005) (providing examples of permissible claims and advice about divining the difference between structure and function claims and impermissible disease claims).+(last+visited+September+15,+2005)+(providing+examples+of+permissible+claims+and+advice+about+divining+the+difference+between+structure+and+function+claims+and+impermissible+disease+claims).>Google Scholar
21 U.S.C. § 343(r)(6)(C) (2000). As the Task Force Report elaborates in Chapter Four, the claim that “Calcium builds strong bones” is an example of a structure/function claim that would not require FDA approval on a dietary supplement label, whereas a claim that “Calcium prevents or reduces the effects of osteoporosis” would qualify as a specific disease claim requiring FDA approval. See Task Force Report, supra note 9, at 56.Google Scholar
Task Force Report, supra note 9, at 27–30.Google Scholar
Id. at 30. On a related note, chapter four also explains that DSHEA grants the FDA's authority to issue regulations concerning good manufacturing practices (“GMPs”) for supplement products, noting that the current GMPS, which have yet to become final, are modeled on food GMPs rather than those for pharmaceutical products. As the Task Force Report explains, the proposed GMPs fail to address two key issues-potential efficacy and toxicity of ingredients, focusing instead on reducing the risk of harm due to super-potency or contaminants. See id. at 40.Google Scholar
Id. at 60 (explaining that the FDA received only 10 adverse event reports from supplement manufacturers between 1994 and 1999 despite the fact that approximately 100 million U.S. consumers used these products).Google Scholar
Id. at 60–61 (describing information gaps in those adverse event reports that the FDA receives).Google Scholar
Id. at 63.Google Scholar
The Nutrition Labeling and Education Act (“NLEA”) sets out federal standards for permitted statements of nutritional support on food products. See Pub. L. No. 101–535, 104 Stat 2353 (1990) (codified as amended in scattered sections of 21 U.S.C).Google Scholar
Task Force Report, supra note 9, at 70.Google Scholar
Id. at 71–72.Google Scholar
Task Force Report, supra note 9, at 78.Google Scholar
Id. at 79–80.Google Scholar
Id. at 79–80 (recommending that the Expert Committee use federal regulatory standards for defining “serious adverse events” and urging voluntary reporting by consumers and health care professionals of less serious adverse events in order to facilitate identification of longer-latency toxicity problems).Google Scholar
Id. at 80–81.Google Scholar
Id. at 81.Google Scholar
Id. at 83.Google Scholar
The Task Force does not explicitly propose such a change in labeling policy but it does discuss the prospect of mandated labeling of specific risks for specific products and blanket labeling of risks to pregnant and lactating women. See Task Force Report, supra note 9, at 81.Google Scholar
Committee of Dental Amalgam Mfrs. v. Stratton, 92 F.3d 807 (9th Cir. 1996) (holding that California's Prop. 65 safety warning for carcinogenic products were not preempted by the federal statute).Google Scholar
Katz, J., “Informed Consent-Must It Remain a Fairy Tale?” Journal of Contemporary Health Law & Policy 10 (1994): 6991, at 81–85 (describing and discussing barriers to genuinely cooperative and informed decision making between physicians and patients); Merz, J. F. and Fischhoff, B., “Informed Consent Does Not Mean Rational Consent: Cognitive Limitations on Decision-Making,” Journal of Legal Medicine 11 (1990): 321-350, at 343-46 (discussing limitations on patient comprehension and decision-making ability in the healthcare setting).Google Scholar