Will the government ever regulate dietary supplements?

Advocates of so-called “complementary and alternative medicine” (CAM) frequently make the claim that they are the victims of a “double standard,” in which (or so they claim) they are subjected to harsher standards than what they often refer to as “conventional” or “orthodox” medicine, usually because, don’t you know, big pharma controls everything and rigs the game. Whatever the sins of big pharma (and they are legion), this claim is, of course, a whole lot of hooey. If there is a double standard (and, indeed there is), it favors CAM. Indeed, CAM itself is a “wedge strategy” to apply a favorable double standard to modalities that are either ineffective or, although strictly speaking unproven, highly unlikely to be effective based on our understanding of science and prior probability alone. Scientific medicine has to jump through many hoops, including scientific plausibility, biochemical and cell culture studies, animal models, and, finally, randomized clinical trials; in contrast, we are told that we should “respect” CAM modalities and that they should be permitted by “tradition,” regardless of whether there’s any science whatsoever.

One area where this double standard is glaringly apparent is in the regulation of supplements by the Food and Drug Administration. Among the hodge-podge mish-mash of divergent and sometimes mutually contradictory modalities that have found a home under the “big tent” of CAM, there are two areas that come to mind that might actually produce more than placebo effects. The first are herbal medicines, which, being raw plant extracts, are in reality nothing more than impure drugs with variable purity and activity–if drug there is in them. It’s basically the way medicine was practiced a couple of hundred years or more ago, and there really is nothing “alternative” about medicines derived from natural products. Indeed, there is a whole perfectly scientifically respectable field of pharmacology devoted to natural products known as pharmacognosy, whose cooptation as “alternative” by the woo that is CAM is one of the biggest crimes against science ever committed. This second area of CAM that might produce actual effects is the area of dietary supplements, for the same reasons, given that many of them are based on plant extracts. Others, of course, are simply vitamins, all too often taken in much higher doses than ever recommended.

Here’s where the double standard comes in. Since 1994, dietary supplements have been almost immune from regulation by the FDA, thanks to the Dietary Supplement Health and Education Act of 1994 (DSHEA), which created a new class of regulated entities known as dietary supplements and liberalized the sorts of information that supplement manufacturers could transmit to the public. The end result was:

It [the DSHEA] also expanded the types of products that could be marketed as “supplements.” The most logical definition of “dietary supplement” would be something that supplies one or more essential nutrients missing from the diet. DSHEA went far beyond this to include vitamins; minerals; herbs or other botanicals; amino acids; other dietary substances to supplement the diet by increasing dietary intake; and any concentrate, metabolite, constituent, extract, or combination of any such ingredients. Although many such products (particularly herbs) are marketed for their alleged preventive or therapeutic effects, the 1994 law has made it difficult or impossible for the FDA to regulate them as drugs. Since its passage, even hormones, such as DHEA and melatonin, are being hawked as supplements.

Indeed, the DSHEA largely allows the use of the “Quack Miranda warning” to avoid FDA scrutiny. It in essence neutered the FDA, making it very hard for it to regulate so-called dietary supplements, even when potentially dangerous. In brief, it (mostly) exempts from regulation compounds “generally recognized as safe” if they were in widespread use before 1994. While this is reasonable for true foods, such as corn, wheat, or other ingredients, a lot of supplements are have pharmacologically active ingredients. Worse, the DSHEA allows manufacturers to make “structure/function” claims. Specifically, the law allows dietary supplements to bear “statements of support” for (a) a benefit for classical nutrient deficiency disease; (b) a description of how ingredients affect the structure or function of the body, organs, or cells; (c) the documented mechanism by which the ingredients act to maintain structure or function; and (d) general well-being from consumption of the ingredients. As Quackwatch points out, the statement “calcium builds strong bones and teeth” is a classic example of an allowable structure/function statement for a food.

Unfortunately, supplement manufacturers often go far beyond such uncontroversial statements claims of curing all sorts of disease, albeit usually in the form of postulated vague benefits, all communciated with a “nudge, nudge, wink, wink” that lets the people buying them know what the real health claims are. For science- and evidence-based medicine, the DSHEA has been an unmitigated disaster, although the quacks sure do like it because before a supplement can be removed from the market the burden of proof is on the FDA to show that the supplement is dangerous, not on the manufacturer to show that it’s safe, as is the case for drugs. That’s one reason why it was so difficult to get ephedra off the market; indeed, it was a decade after the first advisory before the FDA could finally pull ephedra from the market–and then only after thousands of adverse events and several deaths. Can you imagine the reaction that would have occurred if such a delay had occurred for a pharmaceutical product with exactly the same number of adverse events?

In fact, the DSHEA is so much of a problem that even under the Bush Administration, the Government Accoountability Office (GAO) commissioned a report on dietary supplements, which was released in January of this year. The report, entitled Dietary Supplements: The FDA Should Take Further Actions to Improve Oversight and Consumer Understanding presents evidence of a real problem.

The report begins by pointing out that, since the passage of the DSHEA, dietary supplements have become big business:

Dietary supplements and foods containing added dietary ingredients, such as vitamins and herbs, constitute growing multibillion dollar industries. Sales of dietary supplements alone reached approximately $23.7 billion in 2007, and data from the 2007 National Health Interview Survey show that over half of all U.S. adults consume dietary supplements. In 1994, there were approximately 4,000 dietary supplement products on the market, whereas an industry source estimated that, in 2008, about 75,000 dietary supplement products were available to consumers. Similarly, food products–such as fortified cereals and energy drinks–that contain added dietary ingredients are in the marketplace in unprecedented numbers, and consumers are expected to spend increasing amounts on these products over the next several years.

Indeed, so lucrative are supplements, and, thanks to the DSHEA, so free from regulation (at least compared to drugs) that increasingly large pharmaceutical companies are muscling in on the action to claim their share of the lucre. In response to the ephedra debacle, as the GAO report points out, a new law was passed called the Dietary Supplement and Nonprescription Drug Consumer Protection Act, which requires companies that receive a serious adverse event report to submit information about the event to FDA beginning in December 2007. This GAO report thus examines such adverse event reports (AERs) from 2007 to January 2009 and was initiated at the request of Representatives Henry A. Waxman, Chairman, and John D. Dingell, Chairman Emeritus, Committee on Energy and Commerce House of Representatives; Represenatative Bart Stupak, Chairman, Subcommittee on Oversight and Investigations Committee on Energy and Commerce; and Senator Richard Durbin. This is the CliffsNotes version of the findings:

Since mandatory reporting requirements went into effect, the agency has seen a threefold increase in the number of all adverse events reported compared with the previous year. For example, from January through October 2008, FDA received 948 adverse event reports, compared with 298 received over the same time period in 2007. Of the 948 adverse event reports, 596 were mandatory reports of serious adverse events submitted by industry; the remaining 352 were voluntary reports, which include all moderate and mild adverse events reported and any serious adverse events reported by health care practitioners and consumers directly to FDA. However, FDA recently estimated that the actual number of total adverse events–including mild, moderate, and serious–related to dietary supplements per year is over 50,000, which suggests that underreporting of adverse events limits the amount of information FDA receives. To facilitate adverse event reporting for all FDA-regulated products, FDA is currently developing MedWatchPlus, an interactive Web-based portal intended to simplify the reporting process and reduce the time and cost associated with reviewing paper reports.

Moreover, nearly 32% of supplement-related AERs resulted in hospitalization between 2003-2008; 13% were life-threatening; and 4% resulted in death. Possible reasons for the underreporting are described thusly:

Experts have cited several possible reasons for underreporting related to dietary supplements, including reduced attribution of adverse effects to supplements due to the assumption that all dietary supplements are safe, the reluctance of consumers to report dietary supplement use to physicians, the failure to recognize chronic or cumulative toxic effects from their use, and a cumbersome reporting process

In other words, people assume supplements are safe, and therefore do not routinely associate adverse events that they might have with the supplements. The report also cites a number of problems that hamper the FDA, including limited information about supplements and their manufacturers (or even how many manufacturers there were ; the identity of ingredients in the various supplements; and the mild and moderate AERs made to companies. But the worst problem hampering the the FDA’s ability to protect the public from dubious supplements is that it lacks mandatory recall authority. That’s right. The FDA can recall drugs if it decides there is evidence that they are unsafe, but for supplements it has to prove they’re unsafe before recalling them–yet another double standard favoring CAM. Meanwhile resources for regulating potentially dangerous supplements are tight; the FDA devoted only 1% of its field resources to dietary supplement programs from fiscal years 2006 through 2007.

So what does the GAO recommend? Do you have to ask? There were four recommendations for executive action:

1. To improve the information available to FDA for identifying safety concerns and better enable FDA to meet its responsibility to protect the public health, we recommend that the Secretary of the Department of Health and Human Services direct the Commissioner of FDA to request authority to require dietary supplement companies to
   • identify themselves as a dietary supplement company as part of the existing registration requirements and update this information annually,
   • provide a list of all dietary supplement products they sell and a copy of the labels and update this information annually, and
   • report all adverse events related to dietary supplements.
2. To better enable FDA to meet its responsibility to regulate dietary supplements that contain new dietary ingredients, we recommend that the Secretary of the Department of Health and Human Services direct the Commissioner of FDA to issue guidance to clarify when an ingredient is considered a new dietary ingredient, the evidence needed to document the safety of new dietary ingredients, and appropriate methods for establishing ingredient identity.
3. To help ensure that companies follow the appropriate laws and regulations and to renew a recommendation we made in July 2000, we recommend that the Secretary of the Department of Health and Human Services direct the Commissioner of FDA to provide guidance to industry to clarify when products should be marketed as either dietary supplements or conventional foods formulated with added dietary ingredients.
4. To improve consumer understanding about dietary supplements and better leverage existing resources, we recommend that the Secretary of the Department of Health and Human Services direct the Commissioner of FDA to coordinate with stakeholder groups involved in consumer outreach to (1) identify additional mechanisms–such as the recent WebMD partnership–for educating consumers about the safety, efficacy, and labeling of dietary supplements; (2) implement these mechanisms; and (3) assess their effectiveness.

These are all reasonable sounding enough, but they are mere Band-Aids on a sucking chest wound. What all this bureaucratese represents is nothing more than an admission that, as along as the DSHEA is in effect, all the FDA can do is whittle around the edges and try to increase consumer outreach efforts to educate the public, clarify what is and is not considered a “supplement,” and improve reporting mechanisms to monitor adverse events. The reason, of course, is that that is all the FDA can do as long as the DSHEA is law and the bogus construct of vague “structure/function” claims acts as shield to protect manufacturers from oversight. Regulations need to be based on science and designed so that the level of evidence required for each type of medicine under consideration is reasonable, based on existing science. It does not have to be “total regulation” (as for new drugs) versus no regulation. Intermediate levels of regulation are possible and would make sense for certain classes of herbal remedies.

Of course, the real answer to the problem is to repeal the DSHEA and replace it with a law that clearly defines what is and is not “food” and eliminates the loophole that allow manufacturers of dubious herbal remedies to add a bit of this amino acid or that vitamin, label their concoction as “food” or a dietary supplement, and thereby hide under the mantle of incredibly weak regulation The law as it’s currently constructed, as they say, is an ass.