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Economically-Motivated Herb Adulteration

As early as 2006, I used to be able to write monthly about US FDA warnings on erectile dysfunction supplements being found adulterated with prescription drugs such as sildenafil, the phosphodiesterase-5 inhibitor found in Viagra. These adulteration episodes raised the question of how many anecdotal reports of herbal products “working” had to do with them containing approved medicines.

So common was this practice that FDA created a site in 2008 that was dedicated to this problem: Hidden Risks of Erectile Dysfunction “Treatments” Sold Online. Indeed, these products were more commonly encountered from online retailers and not in health food stores. Other similar practices include bodybuilding supplement being spiked with anabolic steroids and weight loss supplements being adulterated with sibutramine (formerly Meridia), an anorectant removed from the market last year after showing increased incidence of heart attacks and stroke in patients with preexisting cardiovascular disease.

The herbal industry, led by the American Herbal Products Association (AHPA), aimed to clean up this problem and launched an initiative called, KeepSupplementsClean.org. Spurred by an FDA letter to the industry on 15 December 2010 of increased scrutiny on the adulteration problem, AHPA actually encouraged FDA to root out manufacturers who adulterated their products or failed to qualify suppliers of their raw materials.

AHPA has publicly expressed its support for FDA actions against marketers of products that masquerade as dietary supplements but contain illegal ingredients. AHPA encourages FDA to use its regulatory authority to hold accountable those who violate the law and jeopardize the public confidence, including all legal means to enforce the law.

The initiative seems to have been effective. This week, the independent testing organization ConsumerLab.com reported that testing of 11 “sexual enhancement” products revealed no adulteration with prescription drugs. On the other hand, the organization showed that, “[f]our products contained less of a key ingredient than claimed on the label, one product was contaminated with an unacceptable level of lead, and two products lacked FDA-required information on their labeling.”

Economically-Motivated Adulteration

This week also saw increased attention on another problem: herbal supplements containing less-expensive plant materials, some of which can cause liver damage. A US Department of Agriculture group has published an analytical method to detect adulteration of Scutellaria lateriflora L. (American skullcap) with two species of germander, a plant well known to contain compounds bioactivated by cytochrome P450 to reactive chemicals that damage the liver. The group of Vanderbilt University biochemist Larry Marnett showed in an elegant 2007 Chemical Research in Toxicology paper how the germander compound teucrin A is activated and identified key proteins in the liver that are chemically attacked by the reactive metabolite.

Skullcap supplements are normally taken to relieve anxiety and do indeed contain flavone compounds that bind to the benzodiazepine site on GABAA receptors like some prescription drugs. However, the herb hasn’t fared well in clinical trials for anti-anxiety activity.

Well, how’s this for increasing anxiety: In the current USDA study, 13 Scutellaria lateriflora products were tested using the new method and four were found to contain teucrin A, indicating that the products contained germander.

But this is apparently old news. In a NutraIngredients USA article that discussed the paper’s findings, American Botanical Council founder and Executive Director Mark Blumenthal called the finding, “disappointing, but by no means surprising,” noting that,

Many experts in the herb community have known about this misidentification for many years, he said. “ABC published an article by botanist Steven Foster about this problem in HerbalGram in the fall of 1985! Foster cited this problem as having been around for decades.

Indeed, one can find on the ABC website a nice monograph by Gayle Engles on the history of skullcap use and the cases of human hepatotoxicity from the 1980s.

The use of cheaper materials in drug and supplement products came to light with melamine used to artificially boost apparent protein content in pet food and infant formula products in China. In 2009, the Council for Responsible Nutrition released a statement on the problem of economically-motivated adulteration in the supplement industry. While the new Good Manufacturing Practice guidelines for the industry were intended to address this issue, the current USDA analytical paper tells us that more stringent enforcement of the rules is necessary.

Until then, be careful when taking herbs for anxiety. Because that’s exactly what you might get.



Posted in: Herbs & Supplements

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24 thoughts on “Economically-Motivated Herb Adulteration

  1. TsuDhoNimh says:

    It’s been around for centuries! Look at any of the Materia Medica books. They explain how to look for the most common adulterants.

    Housekeeping books from the 1600s explain how to detect adulterated spices and other ingredients.

    And vanilla has long been adulterated with Tonka bean because of its strong vanilla-like flavor.

  2. Kenneth says:

    I lost my grandfather five years ago yesterday after he’d been taking a string of herbal medicines who knows how many names long for who knows how long (I know the latter is measured in years). Ever since first reading of various consumer reports of issues with adulteration and impurities with regard to herbal medicines, I’ve been convinced that what my grandfather was taking had to have been what slowly killed him. Unfortunately my suspicions could never be confirmed as no post-mortem or toxicology screening was ever performed.

    The last time I saw him, I noticed he had red splotches, almost like bruises, on his legs and on some parts of his arms. Could that have been a result of any impurities or adulterations — or possibly the combination of herbals he was taking? I don’t know. I can’t know.

    My grandfather also started getting my dad into taking some of these herbals as well. And after my grandfather died, thankfully my father completely ended that regimen.

    I’m trying to avoid confirmation bias on this, but I know how much we don’t know about conflicts, interactions, and actual efficacy with regard to these herbals. Yet I see friends of mine on Facebook talking about herbals. A friend of mine from high school confers with a naturopathic “physician” and has even said that she’ll readily trust the naturopath’s judgment over any medical doctor. Some people just won’t listen to reason, it seems.

    I know my mother and I both were a little anxious about my father taking the herbals my grandfather was recommending, mainly because it seemed like every couple months my dad was ordering something new. He wasn’t on them nearly as long as my grandfather was, so hopefully he hasn’t come to any ill effects and that the last five years have allowed his body to clean everything out of him… I’ve wondered if my father had continued with the herbals if I would’ve been burying him sometime in the last couple years.

    Sorry for the rant, but I just can’t get the link out of my mind. Again, I’m trying to avoid confirmation bias on this…. but when you have something like that sitting on your mind, it’s painfully difficult.

  3. Jann Bellamy says:

    The New York Times recently had a good article on this subject, “Ingredients of Shady Origins, Posing as Supplements,” by Natasha Singer (8/27/11). It quoted Pieter Cohen, M.D., an internist and assistant professor of medicine at Harvard, whose patients have been harmed by taking tainted supplements (kidney failure, heart problems, depression, addiction):

    “ ‘In the current regulatory framework, is it possible to ensure the safety of what we purchase?’ Dr. Cohen asks. ‘To me, the answer is no.’ ”

    But the supplement industry disagrees:

    “The supplement industry argues that existing regulations work perfectly well. It blames the F.D.A. as failing to institute mandatory recalls and seize tainted goods. . . .”
    “ ‘We are concerned that if we alert consumers, we may unnecessarily drive them away from the marketplace,’ [Steve Mister of the Council for Responsible Nutrition] says. ‘We could make them afraid to take legitimate dietary supplements.’ ”

    In other words, the supplement industry can’t warn people about tainted supplements because it would cost them money. Plus, it’s the FDA’s fault for not doing its job, even though the industry, with help from its friends in Congress, made it pretty much impossible for the FDA to effectively regulate dietary supplements.

  4. Jeff says:

    @Jann Bellamy: The NY Times has a long history of portraying supplements and the supplement industry in the worst possible light. Actually the law is quite clear: Once a product is identified as containing a drug (like sibutramine), it is not a legal dietary supplement; it is a misbranded or unnaproved drug. The Federal Food, Drug, and Cosmetic Act gives the FDA strong enforcement options against these adulterated products: Product seizure, injunctions, fines, and criminal charges against company executives. The Times article gives the impression that the FDA’s hands are tied, and much stronger supplement regulation is needed. Of course this is also the FDA’s public position; the agency has always wanted total control over supplements.

    The supplement industry has long complained, justifiably, of lax enforcement against these illegal products. Most of the time the FDA merely asks for voluntary recalls, which is the regulatory equivalent of a slap on the wrist. The problem is lax FDA enforcement, not weak regulation.

    The FDA knows it can’t credibly question the safety of legal dietary supplements, which are responsible for few adverse events and virtually no deaths. The agency publicizes the genuine problem of illegal, adulterated products in order to build public support for stronger supplement regulation (with the enthusiastic cooperation of media outlets like the NY Times).

  5. daedalus2u says:

    No one has said it yet, but I am Shocked, Shocked I tell you that Big Supplement would put adulterated, or misbranded, or synthetic, or untested drugs into their pure and totally wholesome natural supplements.

  6. DU2 – hehe, good one.

  7. nybgrus says:

    As I was reading this I was thinking “Hmmm… I wonder how long it will take Jeff to comment.”

    JPZ I’m curious as to your commentary. I’m personally tired of “discourse” with Jeff.

    Although I do find it interesting that the discussion of adulterants in supplements exist – no, not the known pharmaceuticals but the skullcap vs germander adulteration. I mean, how can one reasonably “adulter” a supplement, which can contain absolutely anything that grew out of the ground but hasn’t yet been demonstrated to be an active pharmaceutical and used by physicians or a scheduled (illegal) drug, with another completely natural plant?

    Oh right, just because it is a plant and has existed as a supplement on some random “ancient” formulary (or if even just invented wholesale) doesn’t mean it isn’t toxic. Well, at least those Vanderbilt boys figured out exactly how germander causes liver damage so we can remove it from supplements. Because that was almost certainly the only “natural supplement” ingredient out there that caused slow, insidious damage of any kind. So at least now we know that the rest of the supplements out there are safe because we got rid of germander. Phew. I was worried there for a minute.

  8. nybgrus says:

    lol, and apparently I am lysdexic:

    “Hmmm… I wonder how long will it take Jeff to comment.”

  9. GLaDOS says:

    “Once a product is identified as containing a drug (like sibutramine), it is not a legal dietary supplement…”

    Okay, but how do I get someone to analyze what’s in a supplement?

  10. kathy says:

    There are still some websites that advertise germander as a supplement, eg. http://www.naturesherbal.com/Germander.htm, which came up third in the list when I googled the two species mentioned in this article. It includes a recipe for germander tea, and gives a long list of things it is supposedly good for. It appears to be an American site, though this is not stated. I haven’t looked for any more sites, but presumably it is OK for germander to be advertised for sale without any mention that it may have negative effects.

  11. The systematic review on herbal anxiety treatments was kind of confusing.

    what does this mean?
    “Anxiety is a prominent indication for herbal medicine.”

    and why did they say at the end that “only kava has been shown beyond reasonable doubt to have anxiolytic effects in humans.”

    Isn’t “beyond reasonable doubt” a legal statement rather than a scientific one? Shouldn’t they be mentioning statistical significance instead?

  12. Calli Arcale says:

    kathy — you can do a “whois” search on any domain name (just google “whois” to get a variety of whois servers). I looked up that one, and it is indeed an American website. The company is located in Tennesee, at least according to their registration information, with the actual site hosted by a website hosting provider in Florida.

  13. JPZ says:

    @nybgrus

    Sorry, I was working on a big project.

    I’m with David Kroll (mostly) on this. But, substitutions for economic gain happen in most any area of industry where you can get away with it. Years ago, I was speaking with a Mexican regulator from their equivalent of the FDA. She had students taking her classes to learn HOW to adulterate milk and other food products so that they could dilute them or otherwise cut costs and still pass QC testing. Melamine was to meet nitrogen specs for pet food and get rid of industrial waste (I am sure someone thought – “Win, win!” in Chinese) Below spec auto parts too (was that Toyota?) – you name it! Are there irresponsible herbal product manufacturers who substitute other herbs or other junk – absolutely!

    So, the Congress/FDA passed the Good Manufacturing Practices rules for dietary supplements. It is a BIG step in the right direction and it is endorsed by most of the industry. Do they still mess up? Sure they do – but a lot less often. Even the amazing cGMP system for drugs messes up (albeit rarely). Our libertarian friend can hopefully explain to me why those regulations take away consumer freedom.

    Analytically, it is a piece of cake to tell two herbs (skullcap vs. germander) apart if you know the indicator molecules – GC/MS. I still remember the Italians developing a GC/MS method to tell the amount of buffalo mozzerella in a mixture of cow’s and buffalo sources. If a company WANTS to ensure purity and potency (and many, many do), they can.

  14. JPZ says:

    @GLaDOS

    I may have said this a few times, but, if you want to get a sample analyzed, contact ConsumerLabs.com. They regulary grab headlines by analyzing many dietary supplements and pointing out that a small minority don’t pass. I guess companies have to advertise somehow.

  15. nybgrus says:

    @JPZ:

    Ah, you had been missed here (well, at least I did).

    I absolutely agree that substitution, no matter how deleterious, can and will be made for economic gain. Anti-freeze in your wine, anyone?

    And I wasn’t aware of the specific legislation (or what kind of teeth it may or may not have) but I expected that there would be something stating that if an herbal supplement says one thing on the bottle and is found to have something else in it, that would be grounds for recourse. And of course that would extend to actual pharmaceuticals and herbs that are known to be deleterious to health (germander). And that there would be ways to test for it, assuming one wanted to.

    The question I had though is broader – lets say germander wasn’t on some “no fly list” of herbs. What is to stop a manufacturer from just changing the label post-hoc and still call it a supplement legal for sale? My understanding is that the newest (proposed) legislation – which Jeff is vehemently against – is the only thing that could stop it (forgive me for blanking on the name – it is 7am and I have been dragging ass since I woke from a nightmare over an hour ago). So if ingredients aren’t locked in place (well, with pre-1994 ingredients getting grandfathered in), then wouldn’t there be literally nothing from such post-hoc changing?

  16. JPZ says:

    @nybgrus

    “Ah, you had been missed here” – Aw, thanks man.

    If the bottle says one thing and there is something else in it – then the product is ” misbranded” at a minimum and likely “adulterated” and the FDA can confiscate the material, burn it all AND go after the company. The FDA does testing like this regularly on food and supplements. They have teeth in that enforcement case, just not enough hands to find the stuff. Imported food must take an amazing amount of their limited resources.

    You don’t get to relabel product that is already labeled – the consumer might peel it off. If what’s in the bottle doesn’t match what’s on the label or doesn’t match what is in the regulations – then you are in trouble. If all three match, you are golden – whether it is efficacious or not. The new proposed rule making (which was just extended) says that if you want to put something totally new on the market, you have to prove it is safe (in essence). And there are some crazy things in the proposed rules, but hopefully those will get fixed.

  17. “I’m with David Kroll (mostly) on this.”

    My work is done here.

    But, substitutions for economic gain happen in most any area of industry where you can get away with it.

    Thank you, good sir, also with pointing out the caveats that any industry will have folks willing to do what it takes to get around regs.

    I do worry about cases like Kenneth’s where, despite his concerns about confirmation bias, the quality of supplements five years ago could have at least generated a hypothesis for causation in the case of his grandfather.

  18. nybgrus says:

    @JPZ:

    Thanks for the info. So am I correct to say that currently the biggest issue regarding adulteration (or substitution of any kind) is simply manpower of the FDA? Any thoughts on how that may be best rectified?

    Starting with some assumptions I am about to make (which may be wrong so the whole thing could be wrong) I’d reckon that the new law requiring safety and efficacy testing prior to release of anything new would go a long way to that. My rationale being that every industry will always have such issues (as we established). However, the easier to entry it is and the more profit margin there is, then the easier and more likely it would be for unscrupulous people to act in such a manner. So making safety and efficacy testing will simply put the brakes on it and reduce the need for post-market surveillance and enforcement – maybe to a level commensurate with what the FDA can muster.

    What do you think?

  19. nybgrus says:

    oh, btw, I have an exam today on neuro, psych, and renal so my comments may not be as cohesive and well researched as I otherwise may like them to be, so my apologies for that

  20. Jeff says:

    I have no problem with GMPs for supplements. These regulations did not produce any noticeable reduction in consumer choice. The new NDI Guidance is an entirely different matter. It seems clear the precise intent of these new regs is a drastic reduction in the categories, numbers, and potencies of supplements available to consumers.

    To understand what a devastating impact the NDI Guidance would have on consumers and on industry, I strongly recommend the detailed analysis (22 pages) written by Joanna Shepherd-Bailey, economics professor at the Emory University School of Law. It is a pdf document and can be found by doing a search for this phrase: “docket no. fda-2011-n-0410 comments of alliance for natural health”.

  21. Jeff says:

    @Nybgrus: Postmarketing surveillance will always be important, just like it is for drugs. All the information is given the FDA by supplement manufacturers, consumers and healthcare professionals by way of the agency’s Medwatch program.

    According to Dr. Shepherd-Bailey’s figures, implementation of the NDI Guidance would substantially increase the FDA’s workload, not reduce it as you suggest. Note that these regs would apply to new supplements and new manufacturing methods introduced since 1994. If the NDI Guidance became law, about 50% of supplements currently on the market would have to be immediately withdrawn; NDI applications for all of them would be filed with the FDA. The agency woud be swamped with paperwork.

  22. JPZ says:

    @nybgrus

    In my opinion, pre-market regulations will do little to help reduce misbranding or adulteration. An irresponsible company can put anything in a bottle and put anything on the label and still be able to sell it until they are caught. The more outrageous the label or dangerous the contents, the more quickly they get caught. Catching something like skullcap vs. germander (I assume) would require the FDA to do more frequent testing of more finished lots, i.e. requiring more money and manpower. Alternatively, the government could mandate certain QA/QC tests for certain products and make them subject to inspections, but that process is still subject to adulteration downstream.

    Pre-market saftey and efficacy testing is more effective at keeping unproven supplements off the market (barring illegal activity) and increasing consumer confidence in the quality of their dietary supplements.

  23. JPZ says:

    @David Kroll

    About Kenneth’s grandfather, it is a very sad outcome. I empathize for his loss and his concerns about his father.

    I hope Kenneth will forgive me for lapsing into hard-nosed scientist for a moment. His grandfather’s death is a n=1 study (like physicians deal with each day). His heavy use of dietary supplement is one potential cause – maybe one of those supplements had a toxic contaminant (although that would still tend to get picked up in the news even five years ago since it would involve fatalities). Maybe he bought dinner plates in Mexico many years ago and the lead paint killed him over time. Maybe he had a taste for gamey meat from all his years as a hunter, and he always left his meat in the refrigerator to “cure” a few days. Maybe he couldn’t fight off some illness because he ate nothing but grape-nuts soaked in milk for an hour because his dentures hurt (that last one is an actual case report BTW). These are things equally hard to spot without an investigation, and, while not equally likely to be the cause, illustrate the complexity of making these assumptions.

    @Kenneth

    If you can get a list of herbal products your grandfather used the most (maybe from your father), perhaps you could do some internet research to see if there were recalls, case studies or news reports from that time period to see if any of them are suspect. Also, one very good point from this group, check if any of them are confused with or replaced by more toxic herbs by irresponsible manufacturers. This may help put your mind at ease and potentially get your father to stop taking any “bad actors” you find.

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