Terra Sigillata

The Dietary Supplement Health and Education Act of 1994 (DSHEA) allows herbal and non-herbal supplements to be sold in the US without demonstration of effectiveness or safety. Despite recent improvements in Good Manufacturing Practices required of supplement manufacturers, these products still pose significant risks to the population simply because the hands of regulatory authorities are tied – products cannot be removed from the market until there is evidence for lack of safety, meaning that consumers must first be harmed before FDA is authorized to intervene.

After cautions a couple weeks ago from FDA, we learned today why a popular liquid dietary supplement has been causing adverse reactions – selenium poisoning:

The FDA notified healthcare professionals and patients that it has found hazardous levels of selenium in samples of certain flavors of the dietary supplement products “Total Body Formula” and “Total Body Mega Formula.” Analyses of samples by FDA have found most of the samples contain extremely high levels of selenium — up to 200 times the amount of selenium indicated on the labels of the products. The FDA has received 43 reports of persons from nine states who experienced serious adverse reactions using these products. The adverse reactions generally occurred after five to 10 days of daily ingestion of the product, and included significant hair loss, muscle cramps, diarrhea, joint pain, deformed fingernails, and fatigue. Consumers should stop taking the products and consult their healthcare professional if they experience any adverse events associated with the use of the products.

Yes, 200 times the labeled amounts of selenium:

Analyses of samples of the products by FDA laboratories have now found most of the samples contain extremely high levels of selenium–up to 40,800 micrograms per recommended serving, or more than 200 times the amount of selenium per serving (i.e., 200 micrograms) indicated on the labels of the products.


The LD50 for selenium in rodents and rabbits is on the order of 2 to 2.5 mg/kg body weight, meaning that the average 70 kg adult could take a potentially lethal dose of selenium with only four servings of this product. We’re not talking here about the hysterical rantings about “toxins” that would have deleterious effects if one drank a hundred cans of soda. Enthusiastic supplement users commonly use a few times more than the recommended amounts of “health products” – this product could have killed people.

Selenium is a relatively safe nutrient and most dietary supplement manufacturers have reasonable quality controls in place to be in the ballpark of labeled content. But one really has to screw up royally to release a product with 200 times the intended amount of any constituent. I can’t even think of how a mistake of this magnitude might have occurred – mixing up milligrams and micrograms would’ve caused a 1000-fold error, a mistake that would have certainly resulted in deaths.

What would be the harm in requiring supplement companies to confirm even the content of their products before they leave the factory. You don’t need weeks of optimizing an HPLC-MS method to measure selenium. Contract labs can do the measurements quickly for a couple hundred bucks.

But as long as DSHEA is on the books, supplement manufacturers have such wide latitude relative to any other facet of the food, drug, and cosmetics industries that a product like this can get out the door.

Even if our legislative leaders fail to find it important to require that supplements are proven effective for any health condition, we at least deserve to know that the products aren’t deadly.

However, the Coalition to Preserve DSHEA argues instead that:

Congress may soon consider new legislation that would trump DSHEA and put consumer access to dietary supplements at risk.

The Coalition is described as, “a non-profit coalition comprised of major suppliers of dietary supplement products and services, as well as leading industry trade associations and other supporters.” This organization is also behind the website, SaveOurSupplements.org, to “protect your access to safe, effective, & affordable dietary supplements.”

Safe? Effective? Neither of these attributes are required by current legislation. So please don’t insult us by implying this is the case.

Affordable? Now I see. Preventing any requirements for prospective demonstration of safety or confirmation of supplement content would certain cut into profit margins.

For anyone who ever thought that dietary supplements are made by altruistic hippies frolicking in nature, think again – it is just another business trying to get by with minimal regulatory oversight.

Comments

  1. #1 PalMD
    April 10, 2008

    Thank you for this excellent post. I’m not sure how much the non-medical public understands that supplements are essentially unregulated, as opposed to actual drugs which are heavily regulated.

    The stuff you buy at, say, GNC, is no required to prove that what they say is in the bottle is in the bottle, and are not required to prove it is safe.

    The prescription your doctor writes you has had to prove both its content and its safety and efficacy.

  2. #2 Hank Roberts
    April 10, 2008

    I know some of these things are prescription medicines in the EU, but not in the USA
    Example: http://www.drugdigest.org/DD/DVH/HerbsTake/0,3927,4058%7CS%252Dadenosyl%2Bmethionine%2B%2528SAM%252De%2529,00.html

    Is there _any_ way to know whether an EU-approved and prescription-grade product is for sale, to distinguish it from the floor sweepings being hyped by the woo merchants to the US suckers?

  3. #3 Albion Tourgee
    April 11, 2008

    Excellent points — the 1994 legislation was one of a typical Republican deregulation scheme. Now you see shelves in health food stores crowded with all kinds of awful stuff, from steroids to herbal concoctions many having very dangerous side effects. Interestingly, the other side of this coin is, herbal medicines are pretty much ignored by the drug industry because they cannot be patented. The cost of proving a drug safe and effective is now so enormous that if a drug cannot be patented, no one is willing to make the investment. So we have untested herbal supplements and patent medicines. The public interest in the best, most cost effective remedies, be damned. would anyone sane run their health care system like this?

  4. #4 Ahcuah
    April 11, 2008

    I was struck by a basic disconnect between your description of the DSHEA and the description of the problem here.

    First, you described the DSHEA as “allow[ing] herbal and non-herbal supplements to be sold in the US without demonstration of effectiveness or safety.” But then you go and tell us about a problem unrelated to either of effectiveness or safety, but a question of proper labeling.

    If you buy a product that claims it has certain ingredients in certain dosages, that should be what you are getting, and the dosages you describe are fraud and the government should definitely get involved.

    But that is an entirely different issue than the one of whether people (the plebes) should be able to do their own research and be able to buy properly labeled supplements.

    [By the way, as I write this, the right-hand column of this page is showing a bunch of "Related Ads" for selenium supplements!]

  5. #5 andy
    April 11, 2008

    Agree w Ahcuah – this is not a problem of supplements as much as it is a problem with labelling. Let people make informed decisions so long as the information is accurate.

  6. #6 Abel Pharmboy
    April 11, 2008

    Ahcuah and andy, let me say at the outset that you’ll be hardpressed to find another conventionally-trained scientist more willing to support dietary supplements that are proven safe and effective. Safety should be easy; effectiveness is where the vast majority of supplements fail.

    But to the point that my argument is simply about labeling – that is not true. My primary point was one of safety; the consumer, no matter how well-educated or well-researched on a supplement, cannot be guaranteed of supplement safety under DSHEA. There is no possible way in which a consumer could have known that this supplement would cause selenium poisoning. Why? Prospective demonstration of safety is not required by DSHEA. Prospective demonstration of product content relative to labeling is not required.

    I didn’t even bother getting into the issue of whether Total Body Formula was effective since their website is currently dead so I couldn’t accurately assess their claims. In citing DSHEA, I wanted to impress upon the reader the larger issue that the legislation doesn’t require proof of efficacy.

    To the point of Albion Tourgee, some of the more reputable botanical manufacturers such as Germany’s Madaus have actually applied for and were granted US patents for their extraction procedure to make the EGb 761 formulation of Ginkgo biloba extract and have supported clinical trials of their products; however, this is more the exception than the rule. Conventional drug companies have ventured into botanicals, such as GlaxoSmithKline whose consumer products division sold Remifemin brand of black cohosh for menopausal issues. I cannot speak for them but the product may have not generated enough revenue or the company was scared off because of hepatotoxicity reports for the supplement, running away like Bill Murray in Caddyshack after the minister gets struck by lightning (Remifemin is now sold by Enzymatic Therapy, Inc.).

    As for the selenium ads to the right sponsored by Proximic, I am disgusted and ashamed that these ads appear – the right sidebar is owned by Seed Media Group and I have no control over what the Proximic search engine puts up as advertising.

  7. #7 Nomen Nescio
    April 11, 2008

    herbal medicines are pretty much ignored by the drug industry because they cannot be patented.

    what on earth do you mean they can’t be patented? identify the active ingredient in a herb, prove it safe and effective, and patent a medicine containing X% of that active molecule when used to treat W, Y and Z medical conditions. how would that be different from any other medical patent? and why should the patent office or the FDA, either one, care if the resulting product was an herbal extract so long as the product on the shelf actually consisted of what it said on the label?

    the U.S. patent office is, if anything, notoriously lax in what it allows to be patented — computer software algorithms, perpetual motion machines (until recently, at least), all manner of nonsense. where’s the rule says you can’t patent herbals, and who got that passed?

  8. #8 Ahcuah
    April 11, 2008

    Abel Pharmboy wrote:

    Why? Prospective demonstration of safety is not required by DSHEA. Prospective demonstration of product content relative to labeling is not required.

    Let me re-iterate that my only issue was the disconnect in your initial statement. I agree with you that the DSHEA is horribly weak.

    I would have no problem with requirements of accurate labeling of content (and actually find it hard to believe that the dosages involved here would not be actionable). Well, I go beyond “no problem” and think, like you do, that it should be positively required.

    I would also have no problem with requiring statements of well-known (or even possible) toxicity on the labels. I would want those statements to be pretty accurate, though. Selenium toxicity is well known, and a statement to the effect that daily doses above [fill-in-the-blank] are inherently dangerous would be a good idea. But, I would also be aware that both the government (via lobbyists) and industry might try to manipulate that information (particularly the dosage level).

    The trouble with invoking “effectiveness” is that, for so many of these, the science (and anecdotes!) is often a mish-mash. Something works in animal models, then it doesn’t in human. But then there’s another study that shows it does work in humans. Or not. Does Beta Carotene cause cancer? Or is it in smokers only? What other confounding factors are there? Are there other supplements that it works in conjunction with that turn it into a net positive? And that’s just one example.

    My view is that reasonably informed persons ought to be able to make those decisions for themselves. The rub, of course, is what happens when the labeling and manufacturing are heavily biased, as you note, away from that.

    Bottom line: I agree DSHEA really needs to be strengthened, but not to the point of being a straightjacket (as the situation was, if I recall correctly, before it was passed).

  9. #9 Orac
    April 11, 2008

    As for the selenium ads to the right sponsored by Proximic, I am disgusted and ashamed that these ads appear – the right sidebar is owned by Seed Media Group and I have no control over what the Proximic search engine puts up as advertising.

    As well you should be. If I see something like this happening on my blog, you can be sure that I’ll dish out a heapin’ helpin’ of my nastiest not-so-Respectful Insolence. In fact, I might do it over this, even though it’s not my blog.

  10. #10 Anonymoustache
    April 11, 2008

    AP, I agree. The discussion of whether this particular case was a QC problem etc is rather semantic—The act and what it allows is pretty ridiculous. I don’t know what a practical solution to this can be. How difficult is it (in real DC lobby-fighting terms) to have the act repealed? Is it feasible to bring any meaningful regulation to what is now a big industry? Is it at least possible to get something enacted that would require all stores carrying such products to boldly advertise over the respective sections that “These products have never been tested for their safety of effectiveness. Take them at risk to your health”?—sorta like cigarette warnings, I guess.

  11. #11 Julie Stahlhut
    April 11, 2008

    Proper labeling is a safety concern. Would you take an over-the-counter pain medicine like aspirin or acetaminophen if you didn’t know whether the dosage was misstated by a factor of 200 in either direction? (Hint: Overdoses of either drug can be fatal.)

    On a brighter note: I’ve noticed that soft-drink bottlers have started to list caffeine content on their product labels. My own main concern is usually over whether the caffeine content of my drink is too low :-), but this is going to be a big benefit to anyone who wants to monitor their own caffeine consumption.

  12. #12 Michael Suttkus, II
    April 11, 2008

    Surely you mean, “Must MORE people die before DSHEA is repealed?” Ephedra, clearly, wasn’t enough.

  13. #13 N.B.
    April 11, 2008

    Very good points, Abel. The fact that the DSHEA is ultimately another Republican business deregulation maneuver is oddly overlooked by its most vehement supporters–New-Agers and conspiracy theorists distrustful of the “medical establishment” and “big pharma.”

  14. #14 Lab Cat
    April 11, 2008

    Another excellent post that I can use in teaching about this. At to the comment about labeling and safety I agree with Julie above.

    Additionally if food is wrongly labeled it is considered to be misbranding, which is illegal. Dietary supplements are not so heavily regulated and could contain anything as long as they do no harm. They do not even need to contain what is on the label.

    On a side note did you notice that I recently gave you an E rating. E for Excellent, that is.

    Great post. Thanks.

  15. #15 Joe
    April 11, 2008

    Lab Cat wrote “Dietary supplements are not so heavily regulated and could contain anything as long as ‘they do no harm’.”

    Who decides if they do no harm? Do you remember the congressional hearings in which the heads of tobacco companies swore, under oath, that cigarettes do not cause cancer!? That is the, inadequate, level of proof required by DSHEA.

    Abel, thanks for this post.

  16. #16 milkshake
    April 11, 2008

    There was a hillarious cased of selenium poisoning in NEJM: A guy suffering from a chronical fatigue for many yeas was told by alternative med “nutritionist” to use a particular brand of selenium supplement three times a day, triple dose, “until a diarrhoea develops” which he did. And sure enough he got the lose stool, and his nails and teeth also turned brown – at which point the patient luckily checked himself to the emergency room. He had acute selenium poisoning, known mainly from suicidal attempts from people working with selenic acid in metal finishing. Turns out the dietary supplement contained 10 000 times of the dose declared on the label. The patient survived, his nails and teeth color gradually turned to normal – and his chronic fatigue was cured too.

    I think there are some supplement quacks who ramp up the Se content in their supplement tablets to unsafe doses quite intentionaly.

  17. #17 Joe
    April 11, 2008

    Concerning Abel’s annoyance over quack links on the right-hand margin, Orac Wrote “As well you should be.”

    I never noticed those links till they were mentioned in the main text. Since then, I am amused that quacks are supporting the rational message.

  18. #18 Jim Lippard
    April 11, 2008

    I’ve never seen the ads on the right-hand margin, thanks to the AdBlock Plus plugin for Firefox.

  19. #19 Hank Roberts
    April 12, 2008

    This thread points up the reason that “country of origin” labeling isn’t required for these ‘supplements’ (or for any medicine for that matter).

    Consider where almost all this stuff is being made nowadays.

    Hasn’t anyone done an economic analysis of how easy it is to profit by adulterating what’s sold, in a globally anonymous economy?

  20. #20 Whacky Supplement User
    April 12, 2008

    While waiting for the government that you elected, or failed to prevent from getting elected, to get off its butt and save us, you can read Lyle MacWilliam’s “Comparative Guide to Nutritional Supplements,” then decide if his scientific methods and conclusions are valid, and, if you decide to the affirmative, buy from among supplements given the highest rating, if you are someone who thinks supplements are helpful.

    But maybe someone has already “debunked” the book? The only criticisms I know of for the book are those offered by the manufacturer’s whose products didn’t fare very well. If there have been others, from other scientists, We’d certainly like to know abut them.

    Please follow the URL link to let us know.

  21. #21 Mike
    April 12, 2008

    Obviously product labeling should be accurate but legislation can easily go to far in restricting what people can have access to. An adult consumer should be advised of risk but if they want to do something stupid it is ultimately their choice.

    I remember when ephedrine was taken off the OTC market despite it being effective in small doses for fat loss or a pre-workout energy boost. Some people overdosed and died but millions used the product safely for years. Is it right that now no one can use such products?

  22. #22 Spike
    April 12, 2008

    Hank,

    Good point, but don’t stop at drugs. To the extent that any product can be adulterated or copied, there are a large number of consumers willing to pick it up at the lower price, whihc privdes a reason for such manufacturing to happen. How about the economic analysis of the costs of regulating products from more and more manufacturing and distribution sources?

    People should be safe from contamination and deliberately shoddy design and manufacturing processes when using their meds and eating food and using the lawnmower. And, when they do their job as designed, regulatory agencies are the most efficient and effective way to ensure that safety.

    Are there curves that can be drawn showing costs and savings of regulation and savings and costs of overseas manufacturing where the intersection will provide economic and safety Nirvana?

  23. #23 Hank Roberts
    April 12, 2008

    Aha.

    And if you’ve got a surplus of a supplement (or maybe a supplement with too much sulfur, it’s hard to tell), what to do? What would the free market recommend?

    Well, apparently it passes the tests used to identify heparin. So — why not?

    “heparin made in China and distributed in the United States by Baxter International had been contaminated with inexpensive over-sulfated chondroitin, an altered version of a widely used dietary supplement…..”

    http://www.washingtonpost.com/wp-dyn/content/article/2008/04/12/AR2008041201662.html

  24. #25 fusilier
    April 14, 2008

    Post #3 ascribed DSHEA to a Republican congress, while correctly noting that it passed in 1994.

    DSHEA was passed and signed into law before the 1994 elections which replaced a Democratic Party-controlled Senate and House with Republican control. While it is true that Sen. Orin Hatch (R. Utah) and Rep. Dan Burton (R. Indiana) were sponsors, they were in the minority. One needs to ask just what Rep. Henry Waxman (D. California) was doing as chair of the committee which let it onto the House floor.

    President Clinton was a Democrat, last time I looked, and could have vetoed the bill.

    fusilier, who is embarassed to be in Burton’s district, and is supporting John McGoff, an ER doc, in the primary next month.
    James 2:24

  25. #26 Hank Roberts
    April 14, 2008

    I suspect there’s a real economics question here — one not dealt with at all right now.

    Think about it. The heparin problem was foreshadowed by a rapid change in the price paid for the material. That made it attractive to dump crap into the pipeline.

    Think about this: http://scienceblogs.com/terrasig/2008/04/you_got_lead_in_my_marijuana.php

    What happened? Well, lead was cheap and easily available so it could be used to adulterate a product sold by weight.

    How many other lead-contamination problems are due to the very same economic choice, to take cheap lead and put it into expensive products to sell more by weight?

    How fast did the value of lead change?

    How fast is the value of copper changing — note how many public and private property destruction reports are coming in because the raw metal scrap value is more, to the people going and ripping up the infrastructure, than their participation in the local community.

    Leaving aside the “difference in ethics” that lets some people reason that “passing the test is what matters, so what cheap crap can I add to this that will pass the test?”

    Is the problem all the vapormoney in the financial system, all the fake securities? Vapor lock. Need to cool the system down til the bubble collapses and fluid behavior resumes, eh?

    That would at least slow the rates of change that let one material become so pricey people will quickly start faking it with whatever crap is at hand — which is easy to do in a globalized anonymous trading system.

  26. #27 Lab Cat
    April 14, 2008

    Joe,

    I wrote about the regulation of dietary supplements back in 2006 with a particular emphasis on misbranding.

    It is still not clear who decides when something is causing harm. Unfortunately, this is something that some manufacturers are using to their advantage.

    There is lots more information at FDA’s dietary supplement website.

  27. #28 Melissa
    April 18, 2008

    Seems like this thing happens regardless of regulation. This wasn’t about not enough regulation…just mislabeling clear and simple, which is illegal already as far as I know. Same thing happened with the birth control patch and in that case the regulations are shielding Johnson & Johnson from liability.