We advocate for Science-Based Medicine partly because science incorporates various generic intellectual virtues to which everyone should aspire. These include logical and clear thinking, unambiguous definitions, and internal consistency. In fact it is demonstrably true that opposing science often equates to promoting muddied and sloppy thinking, ambiguous language, and self-contradiction.
Last week I wrote about that latter virtue – consistency – and its lack when dealing with regulating physicians vs regulating so-called complementary and alternative medicine (CAM). In fact CAM exists, in my opinion, specifically to create a double-standard to disguise contradictory standards. It is institutionalized compartmentalization to minimize public cognitive dissonance.
This week, as promised, I will discuss how the same double standard has been made to apply to the regulation of supplements vs pharmaceuticals. The recently published Government Accountability Office (GAO) report on supplement regulation by the FDA brings this to light.
DSHEA
In the US, supplement regulation is primarily determined by the Dietary Supplement Health and Education Act of 1994 (DSHEA), which is an amendment of the Federal Food, Drug and Cosmetic Act. The purpose of DSHEA was to limit FDA power to regulate supplements and to expand the definition of “supplement.” Here we see the first internal contradiction. The GAO report states:
DSHEA defines dietary supplements as products that, among other things, are intended for ingestion to supplement the diet, labeled as a dietary supplement, and not represented as a conventional food or as a sole item of a meal or diet. They must also contain one or more dietary ingredients.
DSHEA also states that herbs and other botanical are to be considered supplements. Botanicals, however, are not dietary supplements. They are taken not for their nutritional value but for their pharmacological effects. Herbs and botanicals are simply one form of drugs. Vitamins and minerals are nutritional supplements; echinacea is a collection of chemicals, some of which may be pharmacologically active, but with no or trivial nutritional value.
The GRAS Is Always Greener
The justification for regulating herbal drugs as nutritional supplements derives, it seems, from the concept of GRAS – which stands for “generally recognized as safe.” FDA regulations state that for supplements and food additives companies do not have to prove safety if the ingredient is GRAS and if it was in use prior to 1994. Any totally new ingredient must be studied for safety (which makes sense as a new ingredient has not been around long enough to be considered GRAS).
The argument is that herbs that have been around for a long time are generally recognized as safe and therefore should not suffer the burden of having to prove safety prior to marketing. However, it is not always true that herbal supplements have been in use for very long, especially not as they are currently marketed. And even for those that have been around for centuries, subtle risks and toxicity would not be necessarily generally recognized without controlled trials.
The example I think is very relevant is that of VIOXX, which was pulled from the market because studies showed that it significantly increased heart attacks in those at risk. This was enough to generate a scandal. And yet, without large post-marketing clinical trials this increased statistical risk would never have come to light. We cannot say with any confidence that any herbal supplement does not carry a similar risk – the GRAS standard is simply not sufficient for this.
GRAS is reasonable when it comes to food and true supplements. Companies should not have to conduct clinical trials prior to adding salt, corn oil, chocolate, or other common ingredients to their food products. The GRAS standard is sufficient for this. But I do not think it properly applies to taking an botanical drug for a medical condition.
The GAO report also noted that companies are responsible for determining whether or not an ingredient falls under GRAS, and they are under no obligation to report this to the FDA (although some do voluntarily). This means the FDA may not even hear about food or supplement ingredients if the companies themselves felt they were GRAS.
Safety, Efficacy, and the GAO Report
The GAO report looks at current FDA effectiveness in regulating the safety and educating the public about the science of supplements under DSHEA. It is interesting to note that the GAO report does not question a central fact of DSHEA – that the FDA has no role in regulating the claims made for supplement products. This, in my opinion, is a major failure of DSHEA. Regulating marketing claims has been left entirely to regulatory agencies like the Federal Trade Commision (FTC), which can go after supplement marketers for commercial fraud. However, FTC fines have been little more than a slap on the wrist, and they have no authority to pull products themselves from the market.
FDA regulation of claims was reduced with another double-standard contradiction – so-called structure/function claims. Under DSHEA companies are free to make whatever structure/function claims they wish. These are claims that a supplement or ingredient improves a structure or function of the body. Companies are not allowed to claim that their product treats or cures a disease. However, it did not take long for companies to figure out that they could restate disease claims as structure/function claims to skirt the FDA. For example, a company may claim that their product promotes a positive mood, but they cannot say it treats depression. Or they may say it boosts the immune system (which is important for fighting cancer -wink, wink, nod, nod), but they may not say it cures cancer.
The result has been an explosion of unregulated supplement claims, and a growing supplement market. The GAO report says the supplement industry grew to 23.7 billion dollars in 2007.
The GAO report does not question or recommend changes to this basic structure, which I think is fatally flawed. Rather their recommended solution is to increase FDA efforts to educate the public about the science of supplements. I am very much in support of efforts to educate the public. However, I do not hold out much hope that such efforts will have a significant effect. The supplement industry has billions of dollars with which to market their claims. The FDA is not likely to significantly impact upon this. It is also much easier to make claims that people want to believe rather than patiently explain that science does not support those claims.
Regarding safety the GAO report makes a number of observations and conclusions. At present companies are required to report to the FDA severe adverse reactions to their products. They are not required to report mild or moderate adverse reactions, which are voluntary.
The FDA cannot require safety testing prior to marketing. The FDA primarily uses after-marketing monitoring for safety, and the burden of proof is on them to show that a product is unsafe before they can pull it from the market. The only product so removed was ephedra, and that was 10 years after the FDA issued it first warning about the product and after thousands of people were harmed.
Conclusion
The GAO report brings to light many of the current shortcomings of FDA regulations of supplements. The FDA is underfunded and does not have the authority to properly regulate supplements and as a result, the GAO concludes, the public is insufficiently protected.
In order to improve safety regulation they recommend:
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
Recommendations for Executive Action• 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.
To better regulate claims of efficacy for supplements they recommend:
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.
While I think these are all reasonable measures, my sense is that they do not go nearly far enough. Perhaps they consider this a baby-step, making the best of the current regulations. However, there are core problems with DSHEA that need to be addressed.
Structure/function claims are a fiction – a manufactured loop-hole for supplement marketers. It should be done away with. Instead, any health claims made for supplements or food ingredients should be subjected to some form of FDA review prior to allowing the claims. Opponents of this typically appeal to a false dichotomy – pharmaceutical level regulation or no regulation. However, a middle-level of regulation is also an option. Existing scientific evidence can be reviewed and only claims that are sufficiently backed by evidence should be allowed in the marketplace.
In terms of safety, I do not think the GRAS standard should apply to herbals and botanicals. They should, in fact, not be categorized as supplements at all. This would eliminate the problem of having companies classify their food additives as supplements to evade regulation. Rather, it makes more sense to create another category for botanical drugs. Evidence of both safety and efficacy should be required, but the same level of procedures for pharmaceuticals is not realistic. An appropriate level of evidence can be mandated, but perhaps, for example, the FDA can allow use of prior research to establish their claims.
Further, even though DSHEA and the GAO report do not deal with this issue, while I am making recommendations to alter FDA regulation, I would eliminate approval for homeopathic substances. Their inclusion under FDA approval is anachronistic (not that it was ever justified) and is another glaring contradiction. Homeopathic substances are not supplements or drugs – they are nothing but water, lies, and pseudoscience. It is time FDA regulations reflected this demonstrable scientific fact.
While the GAO recommendations would be a few baby steps in the right direction, much more substantive changes to FDA regulations are required to bring them into line with science-based medicine.
