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European Union “Ban” On Herbal Products

Regulations have just gone into effect in the EU regarding the sale of herbal products. The regulations seem reasonable, but they have sparked near hysteria on the part of herbal sellers and advocates of “natural” medicine. They are calling the regulation a “ban” on herbal products, which much of the media has parroted, but it is not a true ban, just a requirement for registration.

The law was sparked by cases of toxicity from over-the-counter herbal products. For example, aristolochia is a toxic plant species that is either used deliberately or can be accidentally or carelessly substituted for other plant species. It is known to cause kidney damage – even leading to kidney failure is some cases. Another herb, kava, has been linked to liver damage.

The new EU law, which went into effect May 1, 2011, will require herbal products to be licensed, or prescribed by a licensed herbal practitioner. In order to be licensed evidence for safety of the product must be presented. It is estimated that it will cost between 80,000 and 120,000 British pounds to get an individual herbal product licensed.

I find it interesting, and completely predictable, that sellers of herbal products are wailing that this is all a conspiracy by “Big Pharma” to crush the little guy and steal all the herbal profits for themselves, or to ban herbal products to protect their drug profits. But this is a straw man. The real question here is the balance between marketing freedom and quality control – but those who want to defend their right to sell herbs don’t want to discuss the real issues, apparently.

Dr Rob Verkerk from a trade organization, the ANH, is quoted as saying:

“Thousands of people across Europe rely on herbal medicines to improve their quality of life. They don’t take them because they are sick – they take them to keep healthy. If these medicines are taken off the market, people will try and find them elsewhere, such as from the internet, where there is a genuine risk they will get low quality products, that either don’t work or are adulterated.”

First, he begs the question that the use of herbs improves anyone’s quality of life. That is, in fact, the entire question – are the risks worth the alleged benefits. The legislation is simply an attempt to provide a better risk/benefit for the consumer by putting into play better assurances of safety.

His next point if the same point that is always made against regulation – if you make X illegal then people will just obtain X illegally or from less regulated sources. This is not specific to herbal products. There is a point there – regulation is not easy, especially with a global market and the internet. But that does not mean we should abandon all efforts at quality control and honesty in marketing.

He concludes with an assumption that herbal products under the current scheme work for anything and have adequate quality control – but again, that is the very issue. In fact regulations are generally not adequate to assure quality control in terms of dose and purity. And there is virtually no regulation about the claims that can be made for herbal products.

In the US the 1994 DSHEA essentially allows herbal manufacturers to make a host of pseudo-health claims without any oversight. The same is and will continue to be true in the EU. One could argue that this legislation does not go far enough to protect the public against false claims and useless products.

Others argue that this legislation will put the small producers out of business. This is exactly what patent medicine sellers complained about when the FDA was proposed. In fact all of the objections are identical to those raised against regulation of drugs. Of course, the point of the FDA was to put the mom and pop patent medicine sellers out of business – because they were largely selling snake oil and did not have the resources to perform proper safety and efficacy testing.

Here the claims are even less relevant – because herbal remedies are a multi-billion dollar industry, and the relative cost to get licensing is much less than getting a drug through the FDA.

What we really have here is an industry that wants to continue selling poorly regulated products with health claims and without any burden of having to prove that their products are safe or that their health claims are based upon science.

I acknowledge that there is a real political debate here, and that some people might want to favor freedom and risk over government regulation. But I object to the way the debate is often framed by opponents to regulation. Even for those who would prefer to have a free market for herbal products would likely agree that the consumer deserves accurate information in order to make informed decisions. Right now, in most markets, the consumer does not have that.

Most people I talk to about this assume that herbs are more regulated than they currently are. People want both freedom and protection, and are not always aware of the degree to which the two are at cross purposes. So if you ask them if they want freedom in the market, they say yes. And if you ask them if they want assurance of safety and honesty, they also say yes. They want the freedom to choose, but only among products that are safe and effective.

With respect to herbal remedies, however, the evidence is largely against the efficacy that is being claimed for many products. If you look at the big sellers, like echinacea and Gingko biloba, the large well-controlled studies are largely negative – they don’t appear to work for the indications for which they are commonly marketed.

The industry has largely failed to self-regulate, and to use their profits to generate good science to back up their claims. And they consistently fight against regulation to force them to do so, and try to make it seem like they are on the side of the little guy against big corporate interests. But this is just spin – they are just another big industry protecting their interests. If they really cared about the little guy or the consumer they would be producing good science, and keeping their claims within the evidence, rather than fighting against attempts to make them do just that.

Under most current regulatory schemes, there is a disincentive to conduct good efficacy research. Such research is a lose-lose proposition for industry. They have to spend the money to do the research. If it’s positive, it is unclear how that will benefit them since they already can make health claims (or pseudo-health claims, like the so-called “structure function” claims under DSHEA). But if it’s negative, then they risk losing market share. The risk/benefit of doing efficacy research is simply not there, and that is probably why there is so little such industry-sponsored research into supplements. The only way to get the industry to spend some of their profits doing quality research is to make such research a requirement for entry into the marketplace.

In the end we should remember that herbs are drugs – they have pharmacological activity, they have toxicity, an they have drug-drug interactions. How much regulation and quality assurance do we want for our drug industries (no matter what they are called)?

Posted in: Herbs & Supplements, Politics and Regulation

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105 thoughts on “European Union “Ban” On Herbal Products

  1. windriven says:

    “He concludes with an assumption that herbal products under the current scheme work for anything and have adequate quality control – but again, that is the very issue. In fact regulations are generally not adequate to assure quality control in terms of dose and purity. ”

    This raises the question of whether this herbal stuff is, in fact, safe. I cannot recall ever hearing of OTC herbals causing serious health issues. On the other hand it is fairly common to see FDA actions where herbals are contaminated with undeclared substances (sometimes pharmaceuticals).

    Is anyone aware of an herbal or OTC supplement causing widespread morbidity? (And please, I’m not suggesting that absent such an instance the OTC supplements people should be unregulated).

  2. Jan Willem Nienhuys says:

    One can read the details on
    http://europa.eu/rapid/pressReleasesAction.do?reference=IP/11/510&format=HTML&aged=0&language=EN&guiLanguage=en

    an longer explanation is here:

    http://europa.eu/rapid/pressReleasesAction.do?reference=MEMO/11/71&format=HTML&aged=0&language=EN&guiLanguage=en

    See also
    http://ec.europa.eu/health/human-use/herbal-medicines/index_en.htm
    with links to official regulations.

    As a matter of fact this ‘ban’ already went into effect in 2004. Anyone wanting to sell herbal products must provide proofs of at least safety. However if one already has been selling such products for 30 years and at least 15 years in the EU, then one can simply register them without many questions asked. Only the safety has to be proved (if in those 30 years serious accidents have happened with your herb then you have a problem of course). A kind of grandfather clause. What has expired on May 1, 2011, is the seven years deadline for this type of registration.

    So any company that has been selling herbal preparations for a long time already, that hasn’t applied for this kind of grandfathering, will have to register their stuff under the new and tougher rules for either ‘medicinal preparations’ or ‘foodstuffs’ (for which medical claims are not allowed).

    This detail, namely that it is the expiry date of a grandfather registration, is missing from the article in The Independent.

  3. marcalbe says:

    Ephedra comes to mind, windriven. FDA had 155 deaths on record (according to at least one charge) prior to the ban.

  4. Scott says:

    Monitoring to find rare side effects is also much less robust than for pharmaceuticals. It is virtually certain that there are some significant problems out there which simply haven’t had the data collected to identify them.

  5. tmac57 says:

    windriven-See this article about the Consumer Reports supplements to avoid (in Medscape):
    http://www.medscape.com/viewarticle/472871

  6. Mojo says:

    The EU directive in question actually dates from 2004. In the UK, the legislation implementing it came into force in late 2005. April 30th 2011 was just the end of the transitional period during which manufacturers were permitted to carry on selling the products while going through the process of getting them registered.

  7. majkinetor says:

    “In the end we should remember that herbs are drugs”

    The most obvious difference between herbs and drugs is that herbs are occurring in nature while drugs are usually not.

    I don’t want to say that the fact that something is natural means it should a priory thought as beneficial with few side effects, however, the probability that the body encountered various levels of this substance during human existence is big including the probability that the body evolved to deal with or attenuate its negative effects.

    Contrary to that, many artificially made drug molecules are never encountered in nature and there is no way you can tell about possible effects that such molecule might have in the body in chronically exposed people.

    More on topic, I think this regulation is good thing – it will hopefully lead to more controlled products. You will surely be able to find unregulated herbs anyway, and you can eventually grow some yourself. One of the problems with herbal remedies and vitamins are that doses are often inadequate (i.e. something that is more suitable for maintenance is considered therapeutic) and that quality of substrate and array of supportive chemicals are not adequate.

    I personally use Ehinacea along with Acetyl-L-Cystein and Vitamin C megadoses on first sign of viral disease and in my case results are amazing. My typical dosage regimen is around 1 g of purified Ehinacea extract, 1.2g of AC and 10-20 g of Vit. C taken according to “dynamic flow hypothesis” depending on severity of symptoms (all in powder forms without any fillers). Results – I killed any common cold growing in me in past 3 years in 1 day only. The timing, however is absolutely crucial. It has to be on first signs of illness.

  8. jyesselm says:

    @majkinetor

    I feel you are falling into

  9. DTR says:

    Here’s a fun article on the “dynamic flow hypothesis”:
    http://www.medicalnewstoday.com/articles/10022.php

  10. Harriet Hall says:

    @majkinetor,

    “I killed any common cold growing in me in past 3 years in 1 day only.”

    You have no way of documenting that you actually were infected with a cold virus or that your symptoms wouldn’t have resolved just as fast without treatment.

    I’ve told this anecdote before but I’ll tell it again. When she feels the first signs of a cold coming on, my friend takes echinacea, and she hasn’t had a cold in 7 years. When I feel the first signs of a cold coming on, I do nothing, and I haven’t had a cold in 7 years either. So if she is correct to assume on the basis of her experience that taking echinacea prevents colds, I would be equally correct to assume that avoiding echinacea prevents colds. We can’t both be right.

  11. Jan Willem Nienhuys says:

    @majkinetor

    You may want to look at

    http://www.annals.org/site/collections/rct_pdf/0000605-201012210-00003.pdf

    The same test as what you did has been done with over 700 people and there was no real difference between the ones that got Echinacea and the others. I realize that you won’t be impressed but others may be, especially the ones that like to see experiments with comparisons.

  12. majkinetor says:

    “You have no way of documenting that you actually were infected with a cold virus or that your symptoms wouldn’t have resolved just as fast without treatment.”

    Sort of… my medical record is not useless tho.
    Prior to my free of common cold 3 years I was suffering CC around 3 times per year for at least 5 years, the symptoms were nasty and sometimes bacterial infection followed. I was sort of sick constantly actually, especially during a winter. During that time I was treated only using ‘conventional’ medicine. At final point my doctor told me that I should look for the ways to boost my immune system using diet and/or supplements like Ehinacea, Vitamin C, fish oil, green tea and similar as it was obvious that ‘standard’ treatment is not helpful in my case.

    The other indicative way is that my tolerance to Vitamin C rise in stressful states – I tolerate 10-15 g daily without any GI discomfort, when I feel sick, however, I can tolerate several times more until the disease is resolved.

    Now, you are right, I have no way to know if one particular case would turn out to be virus or not. For that reason, I used to hang out with already sick people from time to time to expose myself to virus to test this hypothesis – I share a glass with sick or cigarette or similar. So far, the protocol works (for me) and I don’t get sick or if I catch something, it lasts for a day or two and symptoms are not of the kind that would prevent me to do my job.

    2 DTR
    The correct place to learn more is paper “Dynamic Flow – A New Model for Ascorbate” by D.S. Hickey, Ph.D. H.J. Roberts, Ph.D.; R.F. Cathcart, M.D. or better, highly recommended book “Ascorbate: the science of Vitamin C”.

  13. zeno says:

    Mojo said:

    The EU directive in question actually dates from 2004. In the UK, the legislation implementing it came into force in late 2005. April 30th 2011 was just the end of the transitional period during which manufacturers were permitted to carry on selling the products while going through the process of getting them registered.

    Quite.

    One thing Steven didn’t mention is that Verkerk’s organisation, the ANH, has raised £90,000 to mount a legal challenge to the EU Directive. I suspect that’s £90,000 down the drain.

    Herbalists should be asking their trade bodies what they’ve been doing for the last seven years rather than an eleventh-hour panic.

    Big Herbal now has just over 100 registered products and the Nightingale Collaboration will be keeping a close eye on what sellers do. Unfortunately, sellers are allowed to sell products that were ‘placed on the market’ before 1 April – ie stocks in the supply chain can be used up, so it’s difficult at the moment to be sure any unregistered product for sale is, in fact, illegal.

    If anyone’s interested, the complete list of THR registered products is here and it’s worth looking at one of the Public Assessment Reports to see how sparse of information they are. No evidence of efficacy is required, of course.

    For further information, see this EU information sheet and our last Campaign News.

  14. majkinetor says:

    2 Jan Willem Nienhuys
    That research is irrelevant for me as I don’t use Ehinacea alone which was one of the exclusion criteria in this research. I use whole array of vitamins and minerals when I feel sick with special attention to some of them. I will read complete research when I find time, however, by quick reading I can see that:

    - Placebo pill content is not specified, its only stated that fillers are of the same proportion.
    - The authors acknowledge that research is not without flaws:

    “We also made no attempt to base inclusion on viral cause; some of the illnesses represented here may have been caused by influenza or other viruses. In addition, this trial may have been underpowered. We also note that our results were obtained with only 1 of many possible types of echinacea formulations. A substantively different formulation could give substantially different results.”

    That is, they don’t know if people had influenca at all, As H Hall already noted. Prospective participants were required to answer “yes” to either, “Do you think that you have a cold?” or “Do you
    think you are coming down with a cold?”. ” Symptoms had
    to start within 36 hours before enrollment.

    So, the disease was left untreated for 36 hours.

    The research conclusion is: Individual choices about whether to use echinacea to treat the common cold should be guided by personal health values and preferences, as well as by the limited evidence available.

    While I don’t say this research is invaluable, it is hardly proof to not use ehinacea as concluded by authors.

  15. majkinetor says:

    “So if she is correct to assume on the basis of her experience that taking echinacea prevents colds, I would be equally correct to assume that avoiding echinacea prevents colds. We can’t both be right.”
    Actually you can. Nutrigenomics.

  16. Harriet Hall says:

    Nutrigenomics might possibly be an explanation for one individual responding to a echinacea and another not. (Although there is no evidence to support this, just speculation). But it doesn’t justify the general conclusion that echinacea prevents colds or that avoiding it prevents colds.

    And the research shows that if some individuals respond to echinacea it could only be a tiny minority too small to affect the statistical outcome of the studies.

  17. WilliamLawrenceUtridge says:

    @majkinetoron 04 May 2011 at 10:40 am

    The most obvious difference between herbs and drugs is that herbs are occurring in nature while drugs are usually not.

    I don’t want to say that the fact that something is natural means it should a priory thought as beneficial with few side effects, however, the probability that the body encountered various levels of this substance during human existence is big including the probability that the body evolved to deal with or attenuate its negative effects.

    There are lots of things encountered in nature that can kill us, both plant and animal. They are only relevant on evolutionary time scales where selection pressure forces the poison or human to adapt. For instance, smallpox is still quite deadly, but was far, far worse for Native Americans than Europeans because of selection pressure. We only evolve to deal with negative effects when those who did not deal with these effects failed to breed. There’s lots of cases where substances have little selection pressure but are still quite dangerous – snake venom, cyanide, and you may want to look up favism. If something is “beneficial” to humans, it’s because of a chance configuration of molecules, not because nature loves us. And “beneficial” is always relative – salicylic acid is good at relieving pain and reducing blood clotting, which are great so long as you are careful to always clean any cuts you get and don’t have a bleeding disorder. Drugs being “good” or “bad” for us is again due to a chance configuration of the molecule interacting with our bodies and have a much, much higher chance of being effective than random chemicals in nature because they are tailored and there is a rational effort to try to identify useful molecules.

    You have no idea of the effects of any human chronically exposed to a molecule until you study it. For all we know, chronic exposure to high-dose vitamin C could have significant side effects, or be completely benign. Your anecdotes are useless because of the multitude of other possible explanations. Perhaps you had allergies that waned. Perhaps it was simple conincidence. Perhaps the influenza strain you were exposed to was recirculated from previous years and you had developed immunity. Perhaps when you became more aware of vitamin C you altered other habits at the same time – more sleep, more exercise, better diet, change in job, etc.

    The assumption that nature is beneficent (the naturalistic fallacy) is unwarranted. Nature doesn’t love us, it isn’t our pharmacy, and the only parts that are “designed” for us are fruits, specifically evolved to appeal to our senses in order to scatter seeds – but often containing toxic compounds that will either make us sick or kill us, thus neatly depositing these toxic seeds in a healthy stew of feces, vomit or a decomposing corpse. One “natural” strategy to increase evolutionary success (the only type of success that nature actually “values”) is to covertly rape as many women as possible. A multitude of species do just this – ducks, geese, beetles, spiders to start.

    Nature hates all of us.

    Incidentally – your medical record is useless unless it includes viral titres indicating active infection that remained asymptomatic. Most doctors don’t bother for colds and coughs.

  18. Jeff says:

    In the US the 1994 DSHEA essentially allows herbal manufacturers to make a host of pseudo-health claims without any oversight.

    Those who might disagree with this statement include the owners of websites marketing Acai as a miracle weight-loss aid:
    http://www.nutraingredients-usa.com/Industry/It-s-about-time-says-acai-expert-as-FTC-cracks-down-on-bogus-weight-loss-claims

    The FDA does have clear rules for what claims can be made – the rules just need enforcing. See article on FDA’s website: Claims That Can Be Made for Conventional Foods and Dietary Supplements

  19. vicki says:

    Or maybe the particular cold viruses majkinetor has been exposed to recently have evolved to be less virulent. William Utridge mentioned smallpox. Around 1900 doctors introduced the term “variola minor” to specify a new, less harmful form of smallpox. (Not benign: a case fatality rate of 1% is reassuring only when you’d been dealing with 30%. But less harmful than what is now called variola major.) That may have been an accidental mutation in the virus, and then selected for because people with that form of smallpox were more likely to be healthy enough to travel, mix with other people, and thus spread the virus than people with the more dangerous form.

  20. ConspicuousCarl says:

    > majkinetor on 04 May 2011 at 10:40 am
    > the probability that the body encountered various
    > levels of this substance during human existence is
    > big including the probability that the body evolved
    > to deal with or attenuate its negative effects.

    Lactose? Peanuts? Gluten?

    Your argument doesn’t even work for many common foods. Then what about ephedra? Naturopaths and medical researchers alike both scour the Earth for rare and unusual plants, so it makes no sense to say that such things were likely to be encountered in the past often enough to cause us to develop tolerance.

    We have also not evolved the ability to consume all encountered things safely. Our primary defense against toxic substances is disgust. Most plants taste and/or smell awful, as does moldy food and poop. You can’t extract substances from those things, put them in a pill to bypass your primary food differentiators, and then assume that your natural defenses will protect you.

    > Contrary to that, many artificially made drug molecules
    > are never encountered in nature and there is no way
    > you can tell about possible effects that such molecule
    > might have in the body in chronically exposed people.

    Most of your “nature” chemicals aren’t encountered in nature in the same concentrations as they are offered in bottles, so this isn’t a rational distinction. Humans do not have a long history of evolving in the presence of highly-concentrated supplements of any sort.

    > I personally use Ehinacea along with Acetyl-L-Cystein
    > and Vitamin C megadoses on first sign of viral disease
    > and in my case results are amazing. [....] The timing,
    > however is absolutely crucial. It has to be on first
    > signs of illness.

    This is a perfect setup for self delusion. The quicker you are to self-diagnose a cold after every little throat tickle or chill, the more likely you are to falsely credit your favorite drug with the cure of a non-illness. “[sneeze] Uh oh, I’m sick, better take a drug! Wow, it went away instantly, what a great drug!”

  21. S.C. former shruggie says:

    Majikinetor

    [T]he probability that the body encountered various levels of this substance during human existence is big including the probability that the body evolved to deal with or attenuate its negative effects.

    Sure. For example, it’s possible anyone who ate that particular plant species died, cautious apes were selectively favoured, and we evolved not to just swallow any old plant we saw, no questions asked.

    And then there’s that evolved ability of the body to expell at least some poisonous plants back out the way they came in.

    No sir, age-old possible exposure does not inspire confidence in me.

    @Windriven
    I could provide a poorly remembered personal anecodte, but the links above are better.

    I’m glad to see some regulation is in place in Europe. I would prefer that herbal remedies and supplements were governed by the very same laws that regulate pharmaceutical products, however. A body of scientific research showing safety and efficacy should be a necessary pre-requisite to market any drug or supplement.

  22. ConspicuousCarl says:

    I should add that roughly from 2007-2009, I had a horrible week-long flu twice per year. In 2010 and so far in 2011, I have had nothing but a couple mild 1-day viral infections.

    I did ABSOLUTELY NOTHING DIFFERENT to avoid illness. I already washed my hands carefully my whole life. I took no supplements and no flu vaccines. I did not change jobs or social habits. Had I begun taking some pill at the right time, I might be tempted to interpret my personal anecdote as evidence.

    So consider me your control group. You took a bunch of stuff and stopped getting sick. I took nothing, and I also stopped getting sick.

  23. Trod says:

    What majkinetoron is trying to say is that his handful of isolated incidents that were in no way documented on his medical record, that had no verification of his symptoms or their cause, wherein he took an unspecified cocktail of herbal remedies, somehow amounts to a statistically significant exercise in showcasing the power of an herb well-proven to have no more healing power than the cardboard it’s packaged in.

    This is science based medicine, motto “the plural of anecdote is not data.” You don’t even have more than one anecdote. You just have some bizarre story where we have to take your word for not having been sick for some time. What you’re saying isn’t right. What’s worse, it’s not even wrong.

  24. Harriet Hall says:

    No, majkinetor is really trying to say that he’s special. He designs his own suite of treatments so that none of the research can apply to him and anyway his personal nutrigenomics makes him unique. He somehow knows to take exactly what his unique genome requires. And there is no other possible observation for what he thinks he has observed. It’s sort of like an audience member saying the magician really did saw that woman in half: I saw it happen with my own eyes!

  25. majkinetor says:

    2 WilliamLawrenceUtridgeon

    Hello there and thanks for nice observations.

    I never claimed nature loves us nor that there is no chance that humans can’t create better molecule then, as you say, nature randomly creates (if that is true). I understand that plants will protect themselves from extinction using various chemicals and if something on the Earth knowns how to make chemicals, its the plants. To claim otherwise, that plants are made to be food/medicine for humans and other species is to resort to divine intervention.
    Universe couldn’t care less for our fate.

    Of all of your other assumptions the only one that isn’t purely theoretical is that by learning about Vitamin C (or whatever else, I actually learned about C the last) is the one about general awareness once a man decides to take care of its own health. For instance, I doubt that its coincidence that I had gingivitis for 15 years which never occurred again after supplementation. Or that 5++ years of constant illness just like that stops without changing the environment, food or exercise habits or pretty much anything else. One thing might be coincidence, several things not so much. I am sure that it isn’t some specific strain of virus that is responsible as I judge my progress by looking at indirect evidence too – I was always the sickest one of all people close to me (what took 2-3 days to my my wife, friends and majority of colleagues took 2-3 weeks for me). Now I am on the other side of the line – I am the one that never gets sick or gets sick for a day while trends of others are the same as before or worse (i.e. aging). Placebo might be another explanation, if we imagine that it exists. Deficiency of some sort is most probable, and although I never did eat junk food nor had any of those problems in family, we now know better (i.e. epi/nutri/meta genomics).

    Also, I don’t claim that any specific nutrient is responsible for my well being. Its most probable that synergy is responsible. I don’t take C alone, I use adequate doses of B,D3,E,Mg,K2,Q10,w-3. ‘Adequate’ is something i learned over longer period of time, I judge over my daily food intake or current psychophysical state – for instance if I don’t eat vegetables for a day or I am nervous without any reason or heave a mild headache I will boost Mg intake or if I don’t see a Sun for few days, I will boost D3 intake; during sickness I will use higher doses of most of them, some more then the others due to the fact that acute disease brings acute vitamin deficiencies (1 ref: “Blood vitamin concentrations during the acute-phase response”).

    2 ConspicuousCarlon
    Lactose ? What about it, its well known that ability of part of human population to process lactose is recent evolutionary benefit. Some poeple dont have the gene and some others induced lactose intolerance because it is highly dependend on dairy consuption.
    About rare and unusual plants, there are different forms of exposure – you can for instance eat animal that eats ‘rare’ forms of plants.

    I never said that we evolved to handle everything problematic.

    “Our primary defense against toxic substances is disgust. Most plants taste and/or smell awful, as does moldy food and poop”

    This is also learned according to environment and culture. People from one part of the planet are usually disgust by the food from other parts of the planet. Infants need time eat specific foods for brain to associate specific sensory information to nutrient ratios.

    “You can’t extract substances from those things, put them in a pill to bypass your primary food differentiators, and then assume that your natural defenses will protect you.”

    I don’t assume. I get avialable evidence then I put my faith to one side of the argument. Its all about faith at the end, science is not mathematics where you can prove things. Also your argument doesn’t hold water for many drugs, as they are modified versions of naturally occurred molecules (Vitamin D analogues etc…).

    “Most of your “nature” chemicals aren’t encountered in nature in the same concentrations as they are offered in bottles, so this isn’t a rational distinction. ”
    Yes, indeed, however food contains less nutrients now then before and bunch is lost with cooking. Also, the issue is concentration. With drugs, the issue is both concentration and existance.

    “The quicker you are to self-diagnose a cold after every little throat tickle or chill, the more likely you are to falsely credit your favorite drug with the cure of a non-illness”
    You need to monitor your body all the time. During certain periods I tend to keep complete logs of all my inputs/outputs/sympthoms which sometimes I pass to pattern recognition software :P
    Anyway, if I am not sure, its better to be safe then sorry.

    I also don’t see a point crossing our anecdotal evidences. First, your evidence is too short and can’t be compared to mine which lasted entire decade. I said it works for me and I suspect its about supplements (at least, they don’t make me worst which is also kewl) and better diet and general higher awerness. Whats going on in your camp I don’t know. Also, people who actually have chronic problem, like I did, will probalby not follow your advise to do nothing at all about it and hope that it will resolve next year when nature gives rise to happy and benign strein of influenca.

  26. majkinetor says:

    “No, majkinetor is really trying to say that he’s special. He designs his own suite of treatments so that none of the research can apply to him and anyway his personal nutrigenomics makes him unique. He somehow knows to take exactly what his unique genome requires. And there is no other possible observation for what he thinks he has observed. ”

    LOL :). No need to be sarcastic Hall, there are times when people will not agree with you. I never offended you although you articles on this site are in my opinion not much different then pseudo science you try to fight against. I shared my experience just like many other people here did.

    I don’t ‘somehow’ know to take ‘exactly’ what my unique genome requires. I clearly stated that its about experimentation, monitoring and correction using the least sensational substance.

    Also, I clearly stated I don’t know which is it, or is it any at all (placebo, remember?). I say it appears to work here and some stuff work like other scientists said it would work. It might help some people decide about their treatment.

    Again, maybe its all in my bad imagination, who knows… I don’t pretend that there is actually ‘proof’ in science like you do.

  27. Scott says:

    Science has evidence. You have random speculation, confirmation bias, regression to the mean, and quite a few other problems.

    Your account has no reliability. If you were honest with yourself, you’d recognize that you really haven’t the faintest idea whether a single pill you’ve popped had any effect whatsoever.

    The first principle is that you must not fool yourself – and you are the easiest person to fool.

  28. EKrumbeck says:

    The idea that natural medicine is unscientific is blatantly false. Yes, there are many negative studies for some herbal medicines like Ginkgo and Echinacea. However, Echinacea and Ginkgo were never traditionally used for colds/flu’s or Alzheimer’s, so perhaps the issue is not with the herb, but the indication. I always find it interesting that writers who are critical of CAM neglect to mention the large positive studies – St. John’s wort (Hypericum perfoliatum) for mild to moderate depression (look at the Cochrane review), Glucosamine sulfate for osteoarthritic pain, and many more.

    I have two much longer posts on my own blog discussing this: http://naturalmedicineisthebestmedicine.blogspot.com/2010/05/is-naturopathic-medicine-science-based.html; and http://naturalmedicineisthebestmedicine.blogspot.com/2010/10/evidence-based-naturopathic-medicine.html

    Furthermore, DSHEA actually DOES regulate herbal products, but it is my understanding that there was never any funding appropriated and therefore the legislation is completely ineffective.

    Can you imagine if every single supplement had to go through the same rigors of pharmaceuticals? Prenatal vitamins, chamomile tea, herbal cough drops – these would be completely unaffordable to the general public. Imagine requiring a prescription for a $30 single packet of EmergenC…

  29. Harriet Hall says:

    I was going to respond to maj again, but I remembered Rule 14 just in time.

  30. nybgrus says:

    indeed, rule 14 is coming into play here quite strongly. Especially since ekrumbeck came in to toss in a l’il bait ‘n’ switch with pharmacognosy. It was a nice progression too – St. johns to glucosamine to big pharma keepin’ down the EmergenC. Which of course all proves maj’s points and anecdotes (or at least lends support). Because maj has an extra 5-10 years of anecdote which suddenly makes the claims go from complete piffle to robust. But wait, lets toss in a l’il quack miranda warning (it may be my own imagination but… but… it works for me!!).

    I’m sold. Gimme some of that sweet herbal awesomeness so I can be like Wolverine and Aquaman rolled into one (cuz we know Aquaman had awesome teeth, after his gingivits calmed down too).

    /end sarcastic rant

  31. windriven says:

    “I was going to respond to maj again, but I remembered Rule 14 just in time”

    Good on you, Dr. Hall. S/he seems to be channeling Th1Th2.

  32. Rule 14?

    Is that one of the long lost amendments to the ten commandments?

    Thou shalt neither feedeth the troll nor befriendeth the troll nor harbor false hopes of bringing forth reason in the mind of the troll. For the troll shall first consume (th) your time, then your patience and, verily, you will sink into a well of despair…or possibly beer (the tablet got chipped there.)

  33. nybgrus says:

    lol… close enough. Rule 14 is one of the “100 rules of the internet” and you have summed it up quite nicely

  34. JPZ says:

    *wipes away a tear*

    I mentioned Rule 14 and people are already killing trolls. I officially love this blog now. :)

    @ EKurmbeck

    Thank you for raising some very valid points. Dietary supplements are regulated but these rules are not enforced adequately due to funding. Thankfully, the FTC is filling in the gap, and they are well funded thanks to their role with the SEC. And I agree that ingredients in dietary supplements are not the same as new chemical entities (I blogged about it too on Monday), but it depends on if we are talking about cinnamon or something from obscure folklore. Testing and science are the main points. My favorite comedian, Dara O’Briein, said it best when he pointed out that herbal medicine was tested long ago and things that work became medicine and all the rest was potporri and a nice bowl of soup. Pardon the self-promotion, but I posted his hilarious clip on my blog too (NSFW btw).

  35. Mark P says:

    Can you imagine if every single supplement had to go through the same rigors of pharmaceuticals?

    Yes I can. It would be fantastic!

    The herbalists want it both ways. They want their herbals to have effects – just like drugs. They want their herbals to regulated differently from things known to have effects.

    I say that is unacceptable. Everything intended for consumption should clearly be labelled as one of a food, condiment, confectionery or medicine. If herbals are marketed to have a non-food effect then they should be treated as medicines in every respect.

  36. GLaDOS says:

    Along with safety data regarding herbal products, it would be nice to know what’s actually in the bottle.

  37. JPZ says:

    @ Mark P

    Easter egg dye? Coffee? Dough conditioners? I am not even sure what a “food effect” might be. Oversimplification leads to black-and-white thinking, so I would urge some caution in your analysis. Somebody might revoke your skeptic license. ;)

    If scientists studying cinnamon and insulin resistance could get a 20 year patent and the legal right to tell patients the clinically-proven benefits, then I think our points of view might be much closer. Right now, getting patents on natural products is very complicated (i.e. less protection) compared to new chemical entities, and the FDA forbids truthful health claims on nutritional products (with a few exceptions). Although, I believe some of these extracts of obscure herbs definately should be subject to additional testing and possibly be required to go down the drug route (which may be where you are coming from – and I would agree up to a point). That is more of a case-by-case basis. Write to Congress if you don’t like it – they are the only ones who can do anything about your concerns (I too am rather irked about the current legislative situation). Until then, I prefer to work on improving the situation in the here and now.

    @ GLaDOS

    Agreed! Testing standards need to be established for saying what constitutes “ginkgo,” e.g. ginkgoside content. Some of the more responsible companies are already doing this, but I would love to see standards in place.

  38. Scott says:

    the FDA forbids truthful health claims on nutritional products

    Please provide evidence to support this assertion. Each time I’ve seen it previously, the ACTUAL objection is that the FDA forbids made-up health claims. If they can actually be demonstrated to be true, they are permitted. Keep in mind that in typical cases, it’s impossible to determine whether such claims are in fact true without large placebo-controlled trials.

  39. JPZ says:

    @ Scott

    Claims That Can Be Made for Conventional Foods and Dietary Supplements:

    http://www.fda.gov/Food/LabelingNutrition/LabelClaims/ucm111447.htm

    It is a lot of regulatory language, but it boils down to three kinds of allowed nutrient-disease “health claims”:

    1) health claims based on significant scientific agreement (two well-controlled RCTs will get a drug claim but do not constitute significant scientific agreement)

    2) claims made by government agencies (e.g. NAS, USDA, etc.)

    3) qualified health claims (the FDA lost so many lawsuits about these claims that they are now nearly incomprehensible to consumers)

    Structure-function claims are not nutrient-disease claims.

    I tried to translate some of the issues here: http://nutrition-industry.blogspot.com/2011/03/health-claims-part-ii-food-and-drug.html

  40. EKrumbeck – you misunderstand. No one said that “natural” medicine is unscientific, or that no herb works for anything. Rather – “natural” is meaningless, and whether or not herbs work for any specific indication needs to be studies scientifically. Currently there is a huge disconnect between the evidence and the marketing claims. The most popular herbs do not work for the indications for which they are marketed.

    You mention St. John’s Wort – there is mild effect for mild to moderate depression (not severe depression) but the evidence is actually quite weak. Also, St. John’s Wort contains an MAO inhibitor – a known anti-depressant. So it’s a drug.

    Glucosamine doesn’t work: http://www.ncbi.nlm.nih.gov/pubmed/21403067 and http://www.ncbi.nlm.nih.gov/pubmed/20847017

  41. Scott says:

    Well, gee, that’s kind of exactly what I said. If there’s good evidence they’re allowed, but without actual science to back them up they’re not. In other words, they can’t simply be made up.

  42. JPZ says:

    @ Scott

    Two positive, well-controlled RCTs are sufficient (with FDA approval) to market a drug as efficacious for a disease condition.

    If I do two positive, well-controlled RCTs on cinnamon and insulin resistance and then market a cinnamon-based product to diabetics, the FDA comes after me for selling a misbranded drug.

    So, even if I do good science to support the product, I am not allowed to make a truthful claim.

    This is what irks me about the current regulatory situation, it does not reward companies for doing good science – and yet, many companies still go out and do good science.

  43. Scott says:

    Well, if your claim is that herbs are held to a higher standard of evidence than pharmaceuticals (your use of “drug” is inappropriate since any herb that does anything IS a drug) then you need to provide evidence for THAT claim.

    And since when does a pharmaceutical get approved with two RCTs anyway?

  44. JPZ says:

    @ Scott

    The significant scientific agreement standard on the FDA site I posted discusses the process and expectations (some of it is linked there). It is closer to a Cochrane review plus support from most experts in the field than a drug application review process.

    I tend to go with what the FDA calls a “drug,” “The FD&C Act defines drugs, in part, by their intended use, as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals” [FD&C Act, sec. 201(g)(1)].” FDA definitions in this area are based on intended use not efficacy.

    The drug approval process only requires two studies (only one in some circumstances), but, in practice, I imagine that companies submit more.

  45. Scott says:

    The drug approval process only requires two studies (only one in some circumstances), but, in practice, I imagine that companies submit more.

    See, this is why I don’t even begin to buy your argument. The approval process is VERY long and VERY expensive. When you try to claim that it’s only one or two studies, either you’re not saying what it sounds like you’re saying, or you’re grossly wrong.

    Also, even IF you managed to provide some sort of documentation of that, then all you’d have managed to prove would be that THAT approval process would be lax.

    I tend to go with what the FDA calls a “drug,”

    By the quoted definition, herbs are most certainly drugs. Unless they’re just salad without any interesting pharmacological effects.

  46. JPZ says:

    @ Scott

    http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064981.htm

    Under the heading, “Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products”

    page 3: “With regard to quantity, it has been FDA’s position that Congress generally intended to require at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness.”

    Exceptions for single study approvals begin on page 6.

    I am not in for any word games about “drug.” It is not really a good use of anyone’s time. If you want to call air a drug because it keeps you alive, that is entirely up to you. You would have to ask the FDA if they agree with you. I just want first dibs on the patent! ;)

    I am only engaging in this discussion to provide evidence countering misconceptions based on beliefs about the nutritional product regulatory process. Saying that dietary supplements should be regulated as drugs is easier said than done (call your representatives in Congress). My point of view is that nutritional products should be safe and any claim of effectiveness must be supported by sufficient amounts of good quality science (which is a little closer to current regulations and has a legislative and practicality gap that is easier to close).

  47. GLaDOS says:

    I thought the FDA approval process relied upon two independent controlled trials, as JPZ says. And I thought the billion dollar figure was an “as much as” value. Some trials involve complex testing and follow up for each patient, but not all trials must be so complex.

    WRT “truthful” claims: if the maker of a cinnamon product has two controlled trials proving safety and efficacy, the maker should submit a new drug app. Otherwise, he can’t truthfully make drug-type claims, as “drug” has a legal meaning.

  48. Scott says:

    Ah, you’re referring only to the efficacy part not the entire process. That was my misunderstanding; thanks for clearing it up.

  49. qetzal says:

    JPZ, you wrote:

    Two positive, well-controlled RCTs are sufficient (with FDA approval) to market a drug as efficacious for a disease condition.

    That’s not correct. Two positive well-controlled RCTs are sufficient to establish effectiveness. They are not sufficient to market.

    If I do two positive, well-controlled RCTs on cinnamon and insulin resistance and then market a cinnamon-based product to diabetics, the FDA comes after me for selling a misbranded drug.

    Yes, because you haven’t submitted those studies for FDA review. Plus, those studies don’t address any of the tox concerns, and may not be adequate to address safety concerns either.

    The significant scientific agreement standard on the FDA site I posted discusses the process and expectations (some of it is linked there). It is closer to a Cochrane review plus support from most experts in the field than a drug application review process.

    I suspect the rationale here is this. If you want to market a drug whose effectiveness is supported by only two RCTs – especially ones that you conducted in anticipation of profit – then those RCTs need to be reviewed by FDA to be sure they were properly designed, executed, analyzed, etc., and that all appropriate safety and tox concerns have been addressed. If you want to bypass that level of direct FDA scrutiny, then you need to make up for it by showing a substantially higher level of support from the research/medical community.

  50. JPZ, if you think two studies showing efficacy for cinnamon should be sufficient to market cinnamon as a drug, then you are saying that two studies showing efficacy should be sufficient for marketing a drug.

    Really? Do you really trust Big Pharma that much? If you don’t need to establish safety or toxicity, then why should Pfizer have to?

  51. tmac57 says:

    Wait! Does this mean that I might need to get a prescription for my next Cinnabon?

  52. JPZ says:

    The big difference between nutritional products and new chemical entities is “history of use.” Based on history of use of the product, you can make a case to the FDA that the product should be “Generally Recognized as Safe” (GRAS), i.e. experts in the field have looked at all the evidence and say the product is safe at recommended use levels. When I worked on a New Dietary Ingredient (NDI) application for zeaxanthin to the FDA, I made the case that the recommended level of use of our product was equal to one glass of orange juice and half a cup of corn. We also filed nine tox studies.

    This difference is another reason I feel the drug approval process is inappropriate for many (but not all) nutritional products. Most do not need to go through phase I trials. (http://nutrition-industry.blogspot.com/2011/05/phase-i-clinical-trials-on-nutritional.html)

    Caveat – If someone is marketing something from a food like cinnamon that has been concentrated several thousand fold over normal exposure – tox studies are probably essential. Also, substances derived from herbs or foods with a un- or poorly documented history of use should probably be subject to safety testing.

    @ all replies

    Thank you for spotting that error! When I said “market AS efficacious” (emphasis added) what I meant was “claim that the drug is efficacious.” I am sorry about creating the confusion.

    @GLaDOS

    Exactly, “drug” has a specific legal meaning at the FDA. So does “disease.”

    @quetzal

    The FDA conducts all reviews for approved “health claims” relating to a “disease” claim on dietary supplements and foods. And, as you can guess, “health claim” has a specific legal meaning too. The standards for efficacy are different for drugs and nutritional products – and the standard is lower for drugs.

    @Alison Cummins

    Hopefully I cleared up that I was focused on the efficacy portion of the health claim, not the safety package. Sorry about that.

    :( I think I wore out my quotes key LOL

  53. JPZ says:

    @tmac57

    Only if it is a statin! LOL

    The classic version is something like 700 calories each. The fancy ones are higher!

  54. JPZ,

    If the recommended level of something is that which is obtained by eating a diet containing whole grains and lots of coloured fruits and vegetables, then why make a dietary additive out of it? Just eat the standard recommended diet, the diet your doctor nags you about.

    It seems to me it only needs to be provided in pills if you’re aiming for more than can be provided by diet, in which case you can’t rely on “it’s part of a normal diet so it must be ok” anymore… because now it’s a drug.

  55. weing says:

    “The drug approval process only requires two studies (only one in some circumstances), but, in practice, I imagine that companies submit more.”

    Not sure I understand this. What kind of studies are you talking about? I thought phase 2 trials were to see if a treatment is effective. It takes about 100-300 subjects for this. Phase 2 trials are used to confirm effectiveness and take about 1000-3000 subjects. Am I wrong?

  56. weing says:

    The last “phase 2″ should be “phase 3″

  57. JPZ says:

    @Alison Cummins

    You make a fair point. The amount of the dietary component needed to reach the efficacy threshold for benefit may be attainable in the diet but over time would likely imbalance the mix of foods consumed and the supply of other nutrients. Some of the essential vitamins and minerals can do this as well, e.g. calcium in people who are lactose intolerant.

    As an aside, I think (I am not positive) the “colorful foods” message was started by the nutritional ingredient companies to promote consumption of carotenoid supplements, e.g. “If you are concerned that you are not getting enough colorful fruits and vegetables in your diet, you may want to consider supplements containing…” I thought the dietetics field picked it up in a food-only context as a means to encourage dietary variety – with health benefits still focused on carotenoid content. I could be wrong.

  58. qetzal says:

    JPZ,

    The standards for efficacy are different for drugs and nutritional products – and the standard is lower for drugs.

    With all due respect, I think you’re mistaken. The standards are basically the same: significant scientific agreement that the product is effective. If the amount of data or number of trials required to establish that is more for nutrutional products, I submit that’s because the quality or conclusiveness of the individual trials is weaker.

  59. JPZ says:

    @qetzal

    Humor me. If the two efficacy trials are of equal quality/conclusiveness, the drug passes and the nutritional product doesn’t – by law. I have no problem agreeing that the quality of many nutritional product clinical trials should be improved, but my point is that, if they did improve the trials to GCP/ICH standards (and I have done many of those trials – oh gods the documentation!), nutritional products could not make the same claims as drugs. The standards are lower for the drug I would want to treat my septicemia. The supplement proven to reduce muscle pain after exercise in clinical trials needs far more evidence.

    Is this really “Science Based Medicine” in this forum? My impression was that people were open to wherever science was developed, as long as it was good quality science and scientifically/medically sound.

  60. JPZ,

    So which is it?

    1) Available from a glass of orange juice and half a cup of corn, which is why you feel that a low threshold for testing is sufficient… and also why pills are unnecessary?

    2) Only theoretically achievable through diet, and then only by eating a seriously unbalanced diet, making pills necessary… meaning it’s a drug and should have the testing requirements of any other drug?

  61. JPZ says:

    @Alison Cummings

    Assumption: Anything you can’t get in a well-balanced diet is a drug? Start picketing the calcium, iron and vitamin K supplement manufacturers.

    Point: People are exposed to the recommended use frequently. In fact, we quoted data from a South Pacific islander study showing habitual consumption of 30 times our recommended use. The point was to say we were not exposing the public to outrageous amounts.

    Caution and Second Point: New Chemical Entities are chemicals humans have never been exposed to before. If humans have been exposed to a compound frequently (via orange juice or corn), then it is different from exposure to a New Chemical Entity. Several fold higher levels of exposure to a frequent dietary exposure compound are a different story.

  62. weing says:

    “If the two efficacy trials are of equal quality/conclusiveness, the drug passes and the nutritional product doesn’t – by law.”

    Example, please.

  63. TTZ says:

    @Majkinetor and others

    “my doctor told me that I should look for the ways to boost my immune system”

    I remember reading about how an over-enthusiastic immune system is to blame for the common cold. Yes, a rhinovirus is the cause strictly speaking, but someone with a not-so-boosted immune system would feel perfectly healthy even if infected, because they would show no symptoms. Remember, all the cold symptoms are basically our body’s defences swelling up our nose and throat tissues, producing mucous and inflammation to oust/fry the intruder. The article said that rhinoviruses are basically harmless so our immune system really does us no favour by causing us so much misery. Can any of the doctors here come up with the references?

    If I’m correct, Majkinetor, maybe you have somehow impaired your immune system? This would also explain your findings…

  64. JPZ,

    As you agreed upthread, yes. (That is, if it does anything.)

    You can indeed get calcium, iron and vitamin K eating an ordinary diet, though there are people who don’t. Supplements prescribed to people who don’t, for whatever reason, are to replace missing nutrients.

    If it’s not a nutrient, and it has an effect, it’s a drug.

    If it is a nutrient, but pills are used to obtain it in amounts that bear no resemblance to nutritional requirements, then it’s being used as a drug.

    Even nutrients can be dangerous. See the recent post on heart attacks and calcium supplementation. http://www.sciencebasedmedicine.org/?p=12240 See also the disappointing results from studies of supplementation with antioxidant vitamins: sometimes they promote cancer.

  65. qetzal says:

    Ditto weing’s request. I’m happy to change my mind based on evidence, but not just to humor you. Please show me where the law (or FDA’s interpretation of it) says that two well-designed, well-controlled, positive RCTs conducted under GCP are inadequate to establish a health claim.

  66. JPZ says:

    @weing and qetzal

    FDA guidance on approved health claims for foods and supplements:

    http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm073332.htm

    Its closer to a Cochrane review. By “humor me” I meant “consider this in the hypothetical” since no New Drug Application (NDA) efficacy section nor Petition for Approved Health Claim is going to consist solely of two efficacy studies. I am approaching this comparison from what is allowed. Please pardon the gruff tone of “humor me.”

  67. JPZ says:

    @Alison Cummings

    As I discussed with @Scott, “drug” has a specific definition as far as the FDA is concerned, and it is not based on dose. As soon as the FDA allows us to define drug differently, I am so filing that patent on air for “maintenance of lung volume.” :)

    @humor

    To steal a line from Dr. McCoy, “Dammit Jim, I’m a scientist not a FDA expert!”

  68. JPZ,

    I don’t know anything about the FDA and I’m not speaking to it. You want to be able to extract and concentrate substances that exist in a foodstuff somewhere and sell it in pills as a treatment for disease… and you don’t want to be asked to establish that it’s both safe and effective.

    It’s a pill to treat a disease, but you don’t want to call it a drug? Because drugs need to be safe, but your pills don’t?

    Your pills are drugs. You get no sympathy from me with your complaints about the FDA.

    Unless of course you are fine with Merck and Pfizer being held to the same standards you want to be held to. I might disagree, but your complaints would at least make sense.

  69. JPZ says:

    Perhaps I diluted my main point with all of these comments, questions and answers. I believe that health claims must be supported by sufficient scientific evidence whether they appear on drugs or nutritional products. I believe products must be safe whether they are drugs or nutritional products. Nutritional products and new chemical entities can vastly differ in their history of use. I believe that history of use should be factored in and weighed when determining the safety of both nutritional products and new chemical entities. FDA requirement for proving efficacy in a disease are lower for drugs than for nutritional products. I believe that if a company does the research to establish a disease claim, they should be able to make the actual claim whether it is on a drug or a nutritional product. I believe consumers should be able to get accurate information about the efficacy of the products they use, e.g. throw out the structure-function claim.

    Even if a company does the research on a nutritional product, the current regulatory environment only allows minimal benefit to the company compared to a drug company doing the same work (as Steven noted in his penultimate paragraph in this post). I disagree with Steven about making the research requirement a “stick” at registration (although he does make a fair point). I believe “carrots” can be built into the system to reward good science behind a product – and “sticks” for having no science or fake science.

    Trying to call nutritional products “drugs” is an oversimplification of the spectrum of their sources, effects and regulatory status – kind of like using the term CAM to lump together unrelated topics. I am starting to wonder if much of the disagreement here is just over the semantics of the word “drug.” I’ll go by the definition provided by the FDA because it is authoritative and citable. All of the other fascinating and intelligent people on this board can use whatever definition they prefer – just define your terms so I know what you mean.

  70. JPZ says:

    Oops, I forgot to post what I mean by “history of use.”

    We use national dietary intake surveys and other epidemiological studies to determine the frequency and amount consumed of the nutritional product under study. The distribution of quantity and frequency curves is then compared to the intended use level. If there is time-course data available, we can note if the trend is going up or down.

    I do NOT mean “history” in the sense of “used for 1000 years.”

  71. JPZ,

    Are the national dietary intake surveys you use powerful enough to detect effects like Vioxx raising the risk of heart attack or stroke?

  72. JPZ says:

    @Alison Cummins

    Dietary intake surveys are not designed like clinical trials. One can test the correlation between intake and health outcome but not causation. The n= is something like 20,000 depending on the variable set. The intent is to test intake, not safety.

    Do efficacy trials for new pharmaceuticals have a high enough sample size to detect those differences?

  73. JPZ says:

    Oops, I meant “measure intake” not “test intake”

  74. JPZ,

    According to you:

    1) It takes an n of 20,000 to find out whether your drug is as safe as Vioxx.
    2) Your drug and Vioxx both need to be safe.
    3) Dietary intake surveys cannot determine that your drug is safe.

    And yet you want to be able to market your drug as being safe and effective without testing for safety?

    But you still think that Vioxx should have to be tested for safety?

    I don’t get it.

  75. Oooh, am I a troll now?

    Kewl!

  76. Alison, and it only took you a few years of consistently posting reasonable comments on the blog to be labeled as such.

    JPZ, if you think Alison is a troll, then you just took up residence in Modor. Beware, the trolls are all around you…

    wahaha, waaahaha…

    ahem.

    Sorry, don’t know what came over me.

  77. Nate Dogg says:

    “FDA guidance on approved health claims for foods and supplements:

    http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm073332.htm

    Its closer to a Cochrane review.”

    You seem to be confused about what is actually being communicated in that guidance.

    Firstly, sponsors of novel drugs and biologics are required to perform a thorough literature review. It happens at the initial IND stage, before the product even reaches clinical use.

    Secondly, that guidance is not giving the literature review as an additional onus on top of RCTs. It is allowing literature review ALONE as a possible basis for food claims.

    This is not an avenue available for sponsors of novel drugs and biologics. For them it is a series of (very expensive) prospective RCTs or nothing.

    In summary, I guarantee you that if a food or supplement can demonstrate safety and efficacy in a particular disease indication to same degree as a drug or biologic, FDA will allow the claim.

  78. Nate Dogg says:

    @weing

    “Not sure I understand this. What kind of studies are you talking about? I thought phase 2 trials were to see if a treatment is effective. It takes about 100-300 subjects for this. Phase 2 trials are used to confirm effectiveness and take about 1000-3000 subjects. Am I wrong?”

    The “two” refers to number of phase 3 studies. One of them will be the “pivotal” on which the efficacy determination will be most heavily based.

    The phase 2 study also looks at efficacy, but it is really a “proof of concept” for the sponsor’s benefit, to decide that if the compound is worth the investment of initiating phase 3 studies. The patients from the ph2 will go into the overall ITT database but the study itself is too small and underpowered to serve as one of the two required by FDA.

    The two studies requirement may be waived in cases like orphan drug, where enrollment is difficult and medical demand is high. In that case you will often see only one phase 3.

  79. nybgrus says:

    I’ve been casually following along and I too am confused. As far as I am concerned, the FDA definition is not particularly interesting for the discussion – after all government definitions of things can be rather, well, stupid.

    Even JPZs own definitions start to fall apart – you say “nutrionational product” (NP) and “new chemical entity” (NCE) and base that upon whether human beings ingest said NP on a historical basis.

    So lets consider mold – a NP that is ingested by humans regularly. I myself love a nice hung of Roqeufort. However, certain mold has been isolated and the by products of it concentrated and made into a pill and called penicillin. This is also an NP made into pill form. It is also a drug and needs to be held to a high standard of efficacy and safety.

    Now lets consider red yeast rice. Also an NP – eaten historically in China for many years. It happens to also be able to lower cholesterol because its byproduct is a chemical quite similar to a statin. It is marketed in the US with the health claim that it can lower cholesterol and that it is all natural. It is sold in pills that eschew the rice and pack the yeast into a pill. Granted, they do not isolate the statin like chemical and concentrate that, however, it is certainly more than would be consumed in a “normal” diet of the stuff and much more easily. It is intended for “natural” treatment of hypercholesterolemia. Yet it is not considered a drug and via the DSHEA needs only to show marginal proof of safety and none of efficacy.

    What is the discepenancy here?

    It can be argued that neither of these are vital nutrients – the body can go on quite well without ever ingesting either product. Of course, if you argue that, then you dig another hole. You could also argue beef, or broccoli, or whatever other individual thing can be completely eschewed and not necessary for survival. And since broccoli is a rather recent invention of human artificial selection you can argue that it does not meet the criteria for NP and is more like a NCE. But what if you are low in protein in your diet? Or low in vitamin C and other nutrients? Then beef or broccoli would be a good thing to add to your diet. Well, what if you have a bacterial infection or hypercholesterolemia? Then penicillin or red yeast rice would also be good to add to your diet.

    In all cases, an argument can be made that each individual item is not necessary, not part of a “normal” diet, but yet can still be seen as “natural” or “unnatural” depending on the POV you decide to take.

    Should you accept my argumentation above? Of course not. It is intellectually dishonest. It is absolutely clear that beef and broccoli are merely parts of a diet that would be a healthy one and that penicillin is a drug that should have safety and efficacy trials. Red yeast rice, too, in my opinion since you are once again taking a biologically active substance but you don’t know the dose, purity, and make up of each pill from manufacturer to manufacturer or even bottle to bottle! Even in the case of beef and broccoli we need not express efficacy for obvious reasons, but safety and quality are still a requirement – one that is distinctly lax in “supplements” or NPs that sneak by the DSHEA. NCE’s are obviously not able to sneak in under the DSHEA since there can, by definition, be not established historical intake.

    Furthermore, in giving a quick read to the FDA link you provided above, I see no evidence of your mythical “two good trials” chestnut. From what I was able to gleen (and I’ll admit I didn’t dissect it in detail) that page describes what the FDA would view as adequate scientific consensus for a health claim. Since we can get consensus from more than just an RCT, it outlines all the various types of studies, all the other evidence that can be garnered, how the FDA weighs the evidence and rejects or accepts it, and then states that “significant scientific agreement” is needed to market a health claim. It even further states that if the SSA is not in concordance with the claim, then the claim must be adjusted to match the SSA. There is no mention that an NP must have X, Y, or Z to be marketed – it simply states that the health claim made by the NP must be in concordance with the level of SSA.

    In sum, I feel that the “two trials” idea has not been offered proper evidence and I reject that hypothesis. I also assert that the argument of NP vs NCE is easily nitpicked in any number of ways and has thus far been disingenuous. And lastly, that i still feel that NP vs NCE should only be a distinction in name only and that all such things should be under the same standards of efficacy and safety – the DSHEA should be done away with. And yes, I know that will drop the numbers of supplements on the shelves in pharmacies drastically and I am quite happy with that. And I’ll attempt to head off a potential critique here – no, the vast majority of people, especially in America are not vitamin or nutrient deficient and will not suffer ill health for lack of access to these “supplements.” If there is a genuine deficiency, they can still obtain them from their physician, just as the can obtain penicillin should they have a “deficiency” in that.

    Oh, and I find discussions with Allison to be quite stimulating and a good way for me to be sure of my facts and temper my zeal. So I call Rule 12 and Rule 15.

  80. Jeff says:

    @Alison Cummins:

    It’s a pill to treat a disease, but you don’t want to call it a drug? Because drugs need to be safe, but your pills don’t?.

    According to FDA rules, 99% of dietary supplements are not allowed to make health claims. Most people take supplements to stay healthy, not for treating a disease.

    If it is a nutrient, but pills are used to obtain it in amounts that bear no resemblance to nutritional requirements, then it’s being used as a drug.

    My nutritional requirements may be higher than yours. In the U.S. individual consumers are allowed to decide that for themselves. The proposed EU limits on nutrient levels for dietary supplements are ridiculously low (based on the German model). Proposed nutient levels are intended not to exceed the amount which would produce a measurable biological effect on the body: 2 mg beta-carotene per capsule, 4 mg. B1 per capsule, etc.. This establishes the primacy of pharmaceuticals to promote good health. Such tiny nutrient levels are supposed to ensure that supplements never interfere with the action of drugs. I fervently hope a European-style regulatory system never comes to the U.S.:

    http://www.anh-europe.org/campaigns/freedom-health-choice#EU_dumbing_down

    Supplements have an excellent record of safety, especially when compared to pharmaceuticals.

    2008 FDA Serious Adverse Event Reports for drugs: 320,000

    2008 FDA Serious Adverse Event Reports for supplements: 672

  81. Nate Dogg says:

    It might be worth pointing out that since 2008, supplements in the US have been required to be manufactured in accordance with cGMP, meaning manufactured consistently with regard to identity, purity, strength, and composition.

    When the new requirement was being debated, the airwaves were inundated with the exact same “BIG GUBMINT GUNNA TAKE YOUR VITAMINS” propaganda we’re seeing here.

    It’s 2011 and last I checked vitamins are still on the shelves.

  82. Nate Dogg says:

    @Jeff

    “2008 FDA Serious Adverse Event Reports for drugs: 320,000

    2008 FDA Serious Adverse Event Reports for supplements: 672″

    Active safety monitoring (in trials) versus passive safety monitoring (in consumer use). Very large apples compared to very tiny oranges.

    And as lots of people here will be happy to attest, most supplements have no toxicity because they don’t actually do anything.

  83. nybgrus “Oh, and I find discussions with Allison to be quite stimulating and a good way for me to be sure of my facts and temper my zeal. So I call Rule 12 and Rule 15.”

    If we’re talking rules of the internet still, can I just state ahead of time that I really don’t want to see the Morgellons application of rule 34.

  84. Jeff,

    JPZ wants to concentrate substances that are found in plants, supply them in pills and market them to treat disease. That’s the issue. He wants to be a drug manufacturer. But he thinks that he should be able to market drugs to treat disease without ever testing them for safety.

    Drugs have a risk/benefit profile. If you market them to treat disease then you need to be able to compare that benefit to the risk that they will harm you. JPZ wants to be able to tout benefits without ever addressing the possibility of risk, and he’s complaining that the FDA is being mean to him because they won’t let him.

    I think the FDA is being reasonable here and that JPZ is being inconsistent. That’s why he’s calling me a troll.

    Your nutritional requirements may be higher than mine — sure, but not that much higher. If you have your stomach surgically removed, you will need B12 injections. If you have your colon surgically removed you will need supplemental K. If you are a burn victim you will be constantly leaking protein through where your skin used to be and you’ll have huge nutritional requirements. Yes, way higher than mine. (You still won’t need 5 grams of ascorbic acid daily though.)

    But in general, your nutritional requirements are very close to mine. Government recommendations for nutrient intakes are guidelines for feeding populations. They aren’t your personal, individual requirement. Your personal, individual requirement is most likely to be lower than the recommended nutrient intake. When you’re feeding a population, you need to take into account that some individuals in the population have higher needs than others so you make sure that everyone gets that higher intake. More specifically, government recommendations are typically set to meet the needs of at least 97% of the population.

    If you want to be special, sure, put yourself in the high-needs 3%. But then talk to your doctor about your disease condition too, the one that is draining your nutrients, rather than simply exercising your American constitutional right to be special.

  85. micheleinmichigan and nybgrus,

    It doesn’t take much to send me running bashfully to my cave under the bridge. So if I disappear for a while… you folks are the best!

  86. Jeff says:

    Alison,
    I agree that drugs or supplements that are marketed to treat disease should undergo safety and efficacy testing.

    Actually there is considerable disagreement among researchers concerning appropriate nutrient intake levels. The IOM’s daily recommended allowance for vitamin D is 600 IU for adults. Another recent study found that 4000-8000 IU daily are required for optimum health:
    http://www.wellnessresources.com/studies/higher_vitamin_d_intake_recommended/

    There are also many supplements for which there are no daily requirement levels. No government agency recommends a particular daily intake of Acetyl-L-Carnitine or Lipoic Acid. I take them both anyway because of the documented health benefits. In Germany Lipoic Acid is obtainable only with a doctor’s prescription and only if one has a serious condition like diabetic neuropathy.

  87. Jeff,

    You didn’t link to a study. This is a link to the study:
    http://ar.iiarjournals.org/content/31/2/607.long

  88. JPZ says:

    @Jeff

    I said, “I believe that health claims must be supported by sufficient scientific evidence whether they appear on drugs or nutritional products. I believe products must be safe whether they are drugs or nutritional products.”

    I am honestly baffled by the associated comments.

  89. JPZ says:

    @nybgrus

    I may have created some confusion. The “two maybe one” trial guidance for approval of a NCE is on the CDER/CBER “drug” side of the FDA. Since new chemical entities are only developed by one company up to the time of approval, then there is no other source of “significant scientific agreement.” On the CFSAN side of the FDA, nutritional products have a history from the moment they were discovered, and this history comes from many academic and government labs – eventually corporate labs too. This history should certainly be a part of the evidence for or against a product. Although, I have not yet encountered a nutritional product that was discovered at the same time as its health effects were demonstrated (but I always admit I could be wrong). So, a nutritional product that has been known for 100, 50 or 20 years has a longer history of use than a NCE. That history of use should be part of the safety package keeping in mind that I also said, “If someone is marketing something from a food like cinnamon that has been concentrated several thousand fold over normal exposure – tox studies are probably essential.” I would prefer that you react to my words and not the reaction to my words. In return, I welcome your comments.

  90. JPZ says:

    @GLaDOS

    I finally confirmed this with someone who worked many years at the FDA in this role. The status of a substance under regulatory guidelines is based on intended use. You want to put cinnamon in your food, it is a food. If you want to treat diabetes with cinnamon, it is a drug.

    Thanks for bringing up this point!

  91. JPZ- “I am honestly baffled by the associated comments.”

    I think you mentioned somewhere that you are new to the site.

    It might be helpful to understand that the supplement/drug safety efficiency discussion has been ongoing for a while. In a sense, you are starting kinda in the middle of the discussion. So when people ask you questions that don’t seem immediately relevant or directly related to your comment, they may be referencing previous arguments that have come up. It’s hard to know who has read what comments or articles.

    Yes, people do sometimes think you are saying something very similar to what the last ten proponents of a similar philosophy were saying.

    I’ve experience the same thing and I understand it can be a drag sometimes, but it’s sorta the nature of the beast.

    Unless there’s outright name calling, usually there is no offense intended.

  92. JPZ says:

    @micheleinmichigan

    I’m not offended at all – more puzzled. And I think you hit the nail on the head. I would say one thing and someone would follow up by putting words in my mouth to make their argument. It makes perfect sense that my arguments and somewhat similar arguments from others would tend to blend together over time. I’ll try to keep that in mind and add more statements of clarification when I can.

    @Alison Cummins

    As for saying “Rule 14,” I meant it in a much more cheeky context than it seems to have come across, as in “you aren’t turning into a troll on me, are you? ;)” I should have used some emoticons or something.

    @All

    I have a pretty good understanding of the nutritional supplement industry and its science. I promote quality science and responsible communications within that area. There are many examples of companies and products that are irresponsible and unscientific. I know this and I think the government could do more to protect consumers from harm. I share what I consider to be good quality science developed by responsible companies. I discuss ways of improving the regulatory situation. One way is by blogging and another is engaging in thoughtful discussion with a wide range of audiences.

    I enjoy discussions of this nature, and I believe I have a somewhat different but still fully science-based viewpoint to add to these discussions. I may challenge some of the commonly held views here, but, in a group of skeptics, the discussion may help you refine what you believe – or, maybe, change your mind.

  93. nybgrus says:

    JPZ – I apologize if you feel I put words in your mouth or that I was reacting to anything but your own words. I assure you I did not (intentionally) do so. I am not quite as motivated (nor do I have the time, really) to give fully researched and detailed responses. However, in general, I think Michele has indeed hit the nail on the head. The “regulars” over here are well versed in the debate about natural products and the DSHEA. It is my personal feeling that anything not clearly intended as “food” undergo the same level of scrutiny.

    If it is marketed as a nutritional supplement, then it must be shown to be safe to be sold OTC and it must be guaranteed to be pure and in the dosage on the bottle. If it is marketed for a specific purpose there must be rigorous scientific evidence/consensus to support it. The smaller the therapeutic window, the more rigorous and more controlled it should be.

    The problem we tend to have here is that numerous products go through with little to no scrutiny because of the DSHEA, only have voluntary reporting as oversight, and make health claims not in line with the evidence. Since the FDA doesn’t actively police such claims they get by. I also think the “quack miranda” warning should be removed and anything which would necessitate its use be removed from the label as well. In other words, no more QM warning needed because no more claims requiring it should ever be made.

    Sorry I don’t have the wherewithal at the moment to delve deeper, but that generally sums up what my views on the matter are. In short – the more regulation the better, because people do not need access to all the supplements and herbs and are most definitely getting harmed much more than helped by their availability (I also consider wasting your money on pills that do nothing to be a harm).

  94. JPZ says:

    @nybgrus

    Overall, I agree with you. That is a very cogent summary. The QM is probably by law or by FDA’s interpretation of the law or by the terms of some lawsuit. And the FDA should do a better job, but they need more money and they need upgraded laws.

    The line between food, supplement and drug has been blurring over time as more science becomes available. To say everything that is efficacious is a drug or everything humans have ever consumed before is food oversimplifies this blurring and is akin to politicians taking an absolutist stand as a means of discrediting their opponent (heh, heh – new Absolut vodka ad LOL). My point is that the various industries should all strive to make people healthier through proven, efficacious products. If it is concentrating a compound in artichokes many times over its natural concentration to treat the medical condition of persistent constipation (i.e. the food product FiberSure), or stopping companies who justify their product claims based solely on how long some culture has used it (too numerous to count), then I am all for it.

  95. Jeff says:

    @nybgrus:

    Adverse Event Reporting for dietary supplements is not voluntary. the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006 establishes a system of mandatory reporting of serious adverse events for OTC drugs and dietary supplements. Contact information must be listed on all supplement packaging:

    http://www.fdalawblog.com/2009/09/articles/miscellaneous/otc-drug-and-dietary-supplement-labeling-adverse-event-reporting-information/

  96. nybgrus says:

    @jeff:

    you either misunderstand me or the FDA rule. The rule states that there are “requirements for OTC drugs and dietary supplement labeling to include contact information for consumer reporting of a serious adverse event.” That is mandatory. There is nothing mandatory that then the consumer must report any adverse event, serious or not. And that is the entire point. When doing a trial for a drug, all adverse events are tracked and recorded. When a supplement goes to market under DSHEA the only “monitoring” is via voluntary end-consumer reporting to that mandatory number provided. Thus, when people make the claim that the adverse events for natural products and supplements is vastly lower than for prescription drugs, that is a misleading statement since the supplements have no method of ensuring all adverse effects are recorded – only the ones that are voluntarily called in.

    As such, minor adverse events are rarely (if ever) called in, and even major ones may not be called in since that actually takes effort to do and at least a good suspicion that the supplement caused it. Hence my statement that there is ” little to no scrutiny because of the DSHEA [with] only… voluntary reporting as oversight.”

  97. Jeff says:

    @nybgrus:

    I think you’re confusing drug trials with postmarketing surveillance. The AER figures released by the FDA relate directly to supplements and drugs after they have been approved by the FDA and marketed to consumers. Adverse events for drugs still under development are tracked in a completely different way. These are the rules:

    1. Manufacturers, packers or distributors of dietary supplements or OTC drugs are required to submit, through a MedWatch form, any serious adverse event they receive, along with a copy of the labeling for the product to the FDA within fifteen business days after the report is received.

    2. There is also mandatory reporting for prescription drugs – the only difference being that all adverse events, both serious and non-serious are tracked and recorded:

    http://uspharmacist.com/content/t/miscellaneous,otc_medications/c/20262/

    The U.S. Pharmacist article points out that “the FDA’s Adverse Event Reporting System is believed to capture only a small portion of ADEs that occur.”

    The FDA’s 2008 figures for drug and supplement serious adverse events reflect the fact that supplements are, on the whole, extremely safe compared to drugs.

  98. JPZ says:

    @nybgrus

    I had the impression that the reporting system for dietary supplement AEs was similar to the Consumer Product Safety Commission reporting system. The CPSC seems to do a reasonably good job of recalling cribs and infant car seats that are defective. Also, the Better Business Bureau has a similar system – passively collect complaints until you notice a disturbing trend.

    I don’t think the AE reporting frequency between two independent systems where physicians are trained to spot drug AEs but not supplement AEs are comparable. It is not a measure of the safety of dietary supplements. The 2006 law just requires dietary supplement companies to provide contact info for AEs, record complaints and share those calls with the FDA. What I don’t know about the 2006 law is whether it put a physician mandate on reporting dietary supplement AEs.

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