Feb 10 2015

Regulating Supplements

While I try to stick in these articles to science and critical thinking, and try to minimize any expression of my personal ideology or political opinion, I make no secret of the fact that I support fair and effective government regulation of all aspects of healthcare. This is partly because I feel the evidence strongly supports this position, but also I am a physician so it is my additional duty to advocate for the health of my patients and society.

The inadequate regulation of the supplement industry has recently been in the news and possibly (hopefully) this issue is coming to a head, perhaps sufficiently to garner the political will to revise current regulations.

First let me point out that I consider the pharmaceutical industry and the supplement industry to be essentially the same thing, the only real difference being the different rules for their regulation. They are different regulatory categories, but the companies making drugs and supplements have significant overlap. Further, the market forces are largely the same, the major difference being that for non-over-the-counter drugs a doctor’s prescription is needed.

I am often accused by defenders of supplements, homeopathy, and “natural” medicine of favoring the pharmaceutical industry, or at least giving them a pass. This is simply not true. I favor strong regulation of the pharmaceutical industry. I have specifically advocated reforms, such as registering clinical trials so drug companies cannot hide data. I favor recent reforms limiting conflicts of interest between physicians and pharmaceutical companies, and the full disclosure of any potential conflicts when they occur. I am against pharmaceutical industry practices, such as ghost authoring white papers to promote their products. There have been numerous multi-billion dollar settlements for pharmaceutical companies breaking the rules that govern the marketing of their products.

The core regulations of pharmaceuticals, however, work. Drug companies must provide high quality evidence of safety and efficacy for their products and can only make claims that are specifically approved by the FDA. Quality control is also high. When I prescribe 25mg of drug X to my patients I can be highly confident that the tablets they take will consistently contain 25mg of drug X and have sufficient bioavailability. Adverse effects are tracked and reported. The system is not perfect, but it basically works, and largely just needs to be tweaked and monitored.

Supplements, however, are a different story entirely. Since the Dietary Supplement Health and Education Act of 1994 (DSHEA) supplements have been largely deregulated. Companies can market products to the public without submitting any evidence for safety, and they can make pseudo-health claims (so-called structure/function claims) without any oversight either. Quality control is essentially voluntary.

The only real regulation in place is generic post-marketing monitoring for fraud, through agencies like the FTC, which is a hopeless game of whack-a-mole.

The history of the supplement industry (which is really the history of snake oil) is the main reason I support effective regulations for health products. We don’t have to speculate – we know what an unregulated health-product industry will look like. Market forces seem to favor hyped claims and slick marketing, but not quality control. It is simply too difficult for individuals to detect for themselves the quality of a product they are taking, due to placebo effects and the natural variability in illnesses. Further, many products are promoted for vague benefits such as overall health, which are nearly impossible for an individual to track.

Again we know from history that worthless and even harmful products with slick health claims can be extremely popular (such as radioactive tonics).

There has been a recent slew of studies showing how poor the quality control in the supplement industry is.  I reviewed many of these studies here: Supplements often contain contaminants, unlisted fillers, and even use fillers to substitute for the alleged active ingredients. You may think you are getting Gingko, but in fact you’re getting alfalfa. Some of those substitutes may cause allergies. Supplements often have drug-drug interactions. Ingredient levels vary incredibly. Bioavailability is anyone’s guess. Supplements also often illegally and secretly contain real drugs.

The FDA will sometimes respond, when it detects such problems, with a sternly worded letter requesting the company to voluntarily fix the problem, which they often don’t.  The FDA can only pull a product from the market if it contains a regulated drug, or if the FDA meets their burden of proof demonstrating that the product has already caused harm.

Recently the New York State attorney general’s office, after an investigation, filed a cease-and-desist order against GNC, Target, Walgreens and Wal-Mart, ordering them to stop selling a number of herbal supplements that were found not to contain the ingredients on the label, and some of which contained unlisted fillers that were potential allergens.

How did the supplement industry respond?

“These actions today by the New York State Attorney General’s (AG) office smack of a self-serving publicity stunt under the guise of protecting public health.”

They simply deny the DNA barcoding technique that was used in the investigation, and swears that the industry is following best practices. However, there have been validation studies of DNA barcoding for herbal supplements. Is this enough? I don’t know, and certainly further validation studies would be welcome. I don’t think we can so casually dismiss the DNA barcoding evidence, however, as the supplement industry does.

Conclusion

There are serious concerns about the quality of herbal supplements, and therefore the adequacy of current regulations. Even if, however, good manufacturing practices were fully enforced, ensuring that products contained what was on the label and only what was on the label, we are still left with a much bigger question – do herbal supplements work as claimed?

The evidence is not promising. For the most popular supplements the answer ranges from “probably not” to “unknown.” Gingko, glucosamine, echinacea, milk thistle, black cohosh, and saw palmetto all do not work for their marketed indications.

We have also been given a peek at the dark underbelly of the supplement industry with the recent Dr. Oz green, coffee bean hoax.

It seems clear we need more effective regulations. However, attempts at updating DSHEA have been blocked in the senate, largely by the supplement industry’s champion, Orin Hatch. We need to muster sufficient political will to overcome the industry’s powerful bulldogs.

 

11 responses so far

11 Responses to “Regulating Supplements”

  1. carbonUniton 10 Feb 2015 at 9:49 am

    On my list of things to do: write my representatives about killing DSHEA. Also, if they need a target for budget cuts, how about the National Center for Complementary and Alternative Medicine?

  2. BBBlueon 10 Feb 2015 at 12:29 pm

    Here’s another recently whacked mole, POM Wonderful: http://1.usa.gov/1CQDXRE

  3. skeptic15on 10 Feb 2015 at 3:22 pm

    “Recently the New York State attorney general’s office, after an investigation, filed a cease-and-desist order against GNC, Target, Walgreens and Wal-Mart, ordering them to stop selling a number of herbal supplements that were found not to contain the ingredients on the label, and some of which contained unlisted fillers that were potential allergens.”

    Because they did not find the DNA, that doesn’t necessarily mean it’s not a processed extract of the actual substance (DNA may be destroyed in processing – if you look at papers related to the specific DNA testing used for the NY investigation, they specifically comment that the DNA may have been destroyed in processing and thus not detected by the methodology). If we’re going to actually study this, chemical analysis of expected active ingredients probably needs to be done.
    Besides the technical aspects of whether DNA or active ingredients are the target of ingredient investigations, whether these things actually have any efficacy is just as important – as I believe you’ve written about, most (if not all) supplements likely don’t have any good evidence of efficacy (for properly nourished adults) when subjected to properly designed studies.
    Personally, I am all for criticism of the supplement idustry and “cracking down” on the supplement industry. But if we’re going to be critical, we should probably get the science right – whether we’re determining the contents or the efficacy.

  4. skeptic15on 10 Feb 2015 at 4:21 pm

    I guess it’s more complicated- although the author of one paper stated “For the supplements in which I found no evidence of ginkgo, I cannot be sure if that is because the DNA was destroyed (for example by drying at very high temperatures) or if the samples simply do not contain any ginkgo,” another paper related to the minibarcoded DNA technique states that the drying process for ginko does not sufficiently degrade the DNA.
    Perhaps it’s enough that these things simply don’t do what they are claimed to do.

  5. Steven Novellaon 10 Feb 2015 at 4:38 pm

    15 – from the study I cited:

    “DNA amenable to PCR could be extracted from 37 (92.5%) of the 40 herbal dietary supplements. Usable DNA was extracted from seven of the eight (87.5%) samples labeled as containing ginkgo leaves and 30 (93.8%) of the 32 samples labeled as containing leaf extract. The DNA extraction success rate is similar to that reported for dried herbal supplements (77.3%–92.0%; Baker et al. 2012; Little and Jeanson 2013; Newmaster et al. 2013). Thus, the process used to produce G. biloba leaf extract is not a notable source of DNA degradation.”

    Of course I agree with using good science. I think this qualifies, but as I said more validation to remove any doubt would be welcome.

  6. Steven Novellaon 10 Feb 2015 at 4:41 pm

    Here is another study:
    http://www.ncbi.nlm.nih.gov/pubmed/?term=DNA+barcode+identification+of+black+cohosh+herbal+dietary+supplements

    You will note that in 100% of the samples they were able to extract and identify DNA from the herbal preparations. In 75% they contained black cohosh. In 25% they contained related species that are easy to confuse with black cohosh, some of which are toxic.

  7. Ekkoon 10 Feb 2015 at 10:33 pm

    If DNA barcoding is a reliable test for identification of all herb-based dietary supplements, then it should be accepted and adopted as part of the FDA/USP standards. It hasn’t been accepted that way at this point though. For the black cohosh example, it doesn’t specify if it was a standardized extract or just the raw botanical and from my understanding, there is a very big difference between the two – just as you wouldn’t expect to find any yew plant DNA in Taxol.
    David Kroll has a good piece on Forbes covering this: http://www.forbes.com/sites/davidkroll/2015/02/03/cease-and-desist-orders-hit-walmart-walgreens-and-others-for-herbal-supplement-sales/

    I’m all for pre-market approval personally, but I think DNA barcoding on standardized extracts, as opposed to raw botanicals, has not proven itself useful. It’s not the right tool for the job.

    Also, this part “Quality control is essentially voluntary.” is false. Dietary supplements manufacturers are required by law to follow specific GMP guidelines. The fact that murders still happen in our society does not mean there are no laws against it. The FDA can take and has taken action to stop companies sales if they are not in compliance. Maybe their powers and funding need increasing?

  8. LDoBeon 11 Feb 2015 at 12:15 am

    Ekko, as mentioned above, these studies were able to detect DNA at a high rate in their samples. That’s a good baseline to show that the method works. Why is it that often the plants claimed don’t show up among the rest of the preparation? Is it because they aren’t there? Is it because the “active” ingredients are heavily processed, but the rest of the stuff is raw? Or is it because this technique is invalid?

    For a lot of herbal crap, they don’t specifically identify the active chemical anyway, so what would we be searching for? Magical-Life-Force-Chi? We can only look for what the label says should be there and a set of expected adulterants, we can’t look for everything.

    And hey whaddya know, really often we find the DNA of adulterants in these pills and extracts, but don’t find the DNA of any of the claimed plant. Or we find DNA of adulterants AND the plant. Neither of these are acceptable circumstances if the dietary supplement industry wants to claim it has medical validity.

    Imagine going into an auto parts store, buying a bottle of 10W-40, but when you start funneling it into your engine turns out to be steering fluid and water mixed with 5W-30?

    You don’t say “well, 5W-30 works pretty well in most climates”. You go sue DuPont or whoever for selling you a shoddy bill of goods. Just keep in mind, people don’t get sick or have potentially fatal allergic reactions to the wrong kind of engine oil.

  9. Steven Novellaon 11 Feb 2015 at 8:21 am

    Ekko – you did not address this specific conclusion of the study, “Thus, the process used to produce G. biloba leaf extract is not a notable source of DNA degradation.”

    This was on extract, not raw botanical.

    I agree the DNA barcoding needs further study, but the evidence so far suggests it is the right tool for the job.

    I agree that the FDA technically has the authority to issue sanctions, but in practice they don’t. Their burden is too high. They typically just issue letters of warning, and ask companies to come into compliance, which they often don’t.

  10. Bronze Dogon 11 Feb 2015 at 10:41 am

    I am often accused by defenders of supplements, homeopathy, and “natural” medicine of favoring the pharmaceutical industry, or at least giving them a pass. This is simply not true. I favor strong regulation of the pharmaceutical industry…

    I’m often irritated by the pharma shill gambit because the people who use it just can’t seem to understand that I’m in favor of strong regulation like you are. But I suppose the accusation serves its real purpose: Distracting from the point that we want to strip quackery of its privileges. The pharmaceutical industries had to earn the level of trust we give them, and they undermine that trust whenever they pull the shenanigans you mentioned after the above quote. The worst parts of the pharmaceutical industry still look better to me than the typical quacks who have special privileges and keep demanding more.

  11. Ekkoon 11 Feb 2015 at 12:26 pm

    Steven,
    In the conclusion of that Ginkgo study, they state:

    “The matK mini-barcode assay cannot distinguish between samples that do not contain any G. biloba and samples that contain G. biloba processed in a way that rendered the G. biloba DNA incompatible
    with PCR (e.g., prolonged high temperature treatment). Thus, the assay cannot determine if the six samples (16.2%) without trace of G. biloba DNA do not in fact contain any G. biloba.”

    The best thing to do at this point would be to test all those samples with the standard Gas Chromatography/Mass Spectrometry methods and then compare. Because different herbal extracts are prepared with different methods, DNA barcode tests may be suitable for some but not for others. We just don’t know enough about it yet.

Trackback URI | Comments RSS

Leave a Reply

You must be logged in to post a comment.