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Herbal Medicine and Aristolochic Acid Nephropathy

It has been a stunning triumph of marketing and propaganda that many people believe that treatments that are “natural” are somehow magically safe and effective (an error in logic known as the naturalistic fallacy). There is now widespread belief that herbal remedies are not drugs or chemicals because they are natural. The allies in Congress of those who sell such products have even passed laws that embody this fallacy – taking herbal remedies away from FDA oversight and regulating them more like food than drugs.

The other major fallacy spread by the “natural remedy” industry is that if a product has been used for a long time (hundreds or thousands of years), then it must also be safe and effective because it has stood the test of time (this fallacy is referred to as the argument from antiquity).  This fallacy even has a specific regulatory term to invoke it – GRAS or “generally recognized as safe.” With food and food ingredients the FDA does not require evidence of safety if the ingredient is generally recognized as safe. This might make sense when referring to foods that have be eaten by humans for a long time. Although the logic is still dubious, it’s just practical – the FDA could not take upon itself the task of proving that every food eaten by humans has no significant negative health consequences. It is more a recognition of practicality than reality.

The GRAS principle, however, is misplaced when referring to herbal remedies, as is the naturalistic fallacy. Herbal remedies are drugs, plain and simple. They contain chemicals that are ingested on a regular basis for their pharmacological effects. The fact that they derive from plants is irrelevant. The fact that individual chemicals are not purified and given is precise amounts does not mean they are not pharmacologically active chemicals – it just means that when taking an herbal remedy you are getting a mixture of many chemicals in unknown doses.

Every now and then the public needs to be reminded of this fact. Recent studies of the effects of aristolochic acid on the renal system are a good opportunity to do so. Aristolochia is an herb that has been used for thousands of years in many cultures for many indications, such as child birth, weight loss, and joint pain. It is both “natural” and ancient. It is also a powerful nephrotoxin – it causes kidney damage.

This first came to world-wide attention in the 1990s when a group of Belgian women who were taking Chinese herbs as part of a weight loss regimen developed end-stage kidney failure. The syndrome became known as Chinese Herbs Nephropathy, and it was soon discovered that aristolochic acid was likely the culprit. It was later discovered that Endemic Balkan Nephropathy was also likely due to aristolochic acid – aristolochia seeds were being baked into bread and therefore consumed on a regular basis. Now some researchers are recommending that these two entities be combined into one – aristolochic acid nephropathy.

This latest research just published finds that use of aristolochia is linked to the high incidence of urinary tract cancer in Taiwan. The rate of urinary tract and renal cancer in Taiwan is about four times higher than in Western countries. This led the study authors to suspect there was an environmental cause, and they quickly suspected that aristolochia might be the culprit. Although use of aristolochia was banned in Taiwan in 2003, its use is still widespread. The study found that 60% of the 151 subjects with renal cancer studied had specific mutations that previous research has linked to aristolochia.

There is now extensive research demonstrating that aristolochic acid causes kidney damage and increases the risk for urinary tract cancers. This latest study adds to that growing evidence. And yet this connection was entirely unknown prior to the 1990s, despite thousands of years of use of aristolochia. This example just highlights the fact that widespread use of an herbal product, or any treatment, is not sufficient to ensure that it is safe, or even that it is effective. Common use may be enough to detect immediate or obvious effects, but not increased risk of developing disease over time. That requires careful epidemiology or specific clinical studies. We know about the risks of prescription drugs only because they are studied, and then tracked once they are on the market. Without similar study and tracking there is simply no way to know about the risks of herbal products. Relying upon “generally recognized as safe” is folly.

It is also interesting to consider how aristolochia came to be used to aid in the birthing process – one of its most popular uses and the source of its name, which means “noble birth” in Greek. As with the traditional use of many herbs, it appears to be based entirely on sympathetic magic – the belief that a plant will be useful for an indication based upon what the plant looks like. In this case the flower of many aristolochia species looks like a birthing womb. The rest is anecdote, placebo effect, and confirmation bias – but no science.

We cannot know how many people over the centuries have been harmed by the use of aristolochia, for indications for which there is no evidence or good reason to believe that the herb is effective. In short, aristolochia is both unsafe and ineffective. This has not stopped it from being a popular herbal remedy for thousands of years. So much for the naturalistic fallacy and the argument from antiquity.

Posted in: Herbs & Supplements

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50 thoughts on “Herbal Medicine and Aristolochic Acid Nephropathy

  1. Jan Willem Nienhuys says:

    For Balkan nephropathy a better source is maybe http://www.pnas.org/content/104/29/12129.full .

    The phrase ‘aristolochia seeds were being baked into bread’ suggests some kind of deliberate action, but it seems that in these regions Aristolochia clematitis grows as a weed in the wheat fields.

    The case of the Belgian women highlights another point. Part of their weightloss program was that they were supposed to drik teas made of Stephania tetranda (in Chinese: fangji) but the shop where they obtained this gave them Guan Fang Chi (Artistolochia fangchi), which is still being advertised on the internet :
    http://www.naturalmedicinalherbs.net/herbs/a/aristolochia-fangchi=guan-fang-chi.php

    Another moral of the story is that one never can be sure what is in a Chinese herbal preparations. Somewhere between the place where the plants grow and the consumer someone may have thought that plants with a similar appearance or a similar name or both can be substituted for each other. Even if there is no mixup about plants, it may be that the plant used contains a lot more or a lot less active ingredients, depending on the soil and on the wheather during its growth.

  2. Jan – you are correct, and thanks for the additional details.

    I would add, however, that the final point about not ever being sure what is in a Chinese herbal preparation may lead some to believe and argue that all that is needed, therefore, is better regulation (and to be clear, I am not suggesting you are making this claim).

    However, simply regulating herbal products for accuracy and purity, while certainly better than no regulation, would not solve the problems I discussed above. We would still not know the real risks and benefits, or drug-drug interactions, of herbal drugs unless they are required to have adequate scientific evidence – just like other drugs.

    Specifically, I think we need to dispense with GRAS as applied to herbal remedies.

    We need to repeal DSHEA and dispense with the entire concept of “structure function” claims.

    Herbal drugs need to be regulated like drugs (perhaps not exactly, but at least there needs to be a requirement for evidence for safety and efficacy with similar information on pharmacology that is available for drugs.

  3. Jeff says:

    It’s not quite true to say the FDA can’t regulate herbal preparations. In 2000 the agency banned the importation of products containing aristolochic acid:

    http://www.fda.gov/Food/DietarySupplements/Alerts/ucm096374.htm

    These were two of the FFDCA laws cited in the import ban:

    “The product is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a dietary supplement or contain a dietary ingredient that presents a significant or unreasonable risk of illness or injury under the conditions of use set out in the labeling or, if none are set out in the labeling, under customary conditions of use [Adulteration, Section 402(f)(1)(A)."

    and/or

    "The product is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to bear or contain a poisonous or deleterious substance which may render it injurious to health [Adulteration, Section 402(a)(1)].”

    I could not find any website currently selling Aristolochia as a supplement.

  4. Jeff,

    You are correct – they can ban importation. But they cannot ban the use of aristolochia, not without a long process where the burden of proof of harm is on them. So far, since 1994, they have only done this for one substance – ephedra. I think it’s a good indication of the ineffectiveness of the current FDA powers to regulate herbs that a proven toxin and carcinogen like aristolochia cannot be outright banned by the FDA.

  5. Also, regarding finding it for sale, you have to look under its common names, like birthwort: http://www.alibaba.com/product-gs/218804592/Birthwort.html

    There are also plenty of CAM sites that list its traditional uses but make scant mention of the toxicity: http://www.altmeds.com/birthwort/description

  6. Jan Willem Nienhuys says:

    Herbal drugs need to be regulated like drugs

    Hear hear!

    More specifically, anyone offering such stuff for sale should be able to back up medical claims for it, and anyone selling aristolochia with even a whiff of suggestion that you should consume it should be prosecuted for attempted murder or attempted aggravated battery, just as would happen to anyone who would sell cyanide as a cure for the common cold.

  7. n8jaynes says:

    It’s surprising how pervasive the naturalistic fallacy is in so called “natural medicine”. The same logic is used to describe even the most dangerous plants as “strong medicine” rather than poisonous or toxic.

  8. lizditz says:

    (link-free to avoid moderation; you should be able to search & find the references pretty easily)

    I was confused by the reference to “aristolochia”. As far as I can tell, Aristolochiaceae is the family,aristolocia is the genus name, and there are a number of species.

    According to “The Poison Garden” (a UK website) aristolocia clematitis is birthwort; it’s the only one that’s listed as poisonous (perhaps because that’s the only species commonly grown in UK gardens?) According to the Kew Gardens website, “There are around 120 species of Aristolochia from the tropics and subtropics, most of which are woody vines or herbaceous perennials with heart-shaped leaves.”

    There’s a monograph available from WHO’s Interagency Research on Cancer, “ARISTOLOCHIA SPECIES AND ARISTOLOCHIC ACIDS” that lists the various aristolocia species used in TCM:

    Aristolochia fangchi Root Guang Fang Ji

    Aristolochia manshuriensis Stem Guan Mu Tong

    Aristolochia contorta Fruit Ma Dou Ling

    Aristolochia debilis Fruit Ma Dou Ling

    Aristolochia contorta Herb Tian Xian Teng

    Aristolochia debilis Herb Tian Xian Teng

    Aristolochia debilis Root Qing Mu Xiang

    There are native-to-North America species of Aristolochia, including Virginia Snakeroot (Aristolochia serpentaria) and Duchman’s Pipe (Aristolochia tomentosa). Both have traditional uses, including uses as medicines by Native Americans and early settlers. Of the four “herbal medicines” sites I accessed, two contained warnings about aristolochic acid, and two did not

    It turns out that Asarum species also contain aristolochic acid, including Asarum canadense (wild ginger) and Asarum caudatum (western wild ginger). Asarum species also have traditional uses, including uses as medicines by Native Americans and early settlers. None of the four “herbal medicines” sites I accessed contained warnings about aristolochic acid.

  9. Jan Willem Nienhuys says:

    If you look on http://alternativehealing.org/fang_ji.htm

    you can see that there are many herbs whose Chinese name is something or other fangji .
    Now fangji (the last two characters in all these names) means ‘self defense’ and doesn’t denote any specific plant, maybe like ‘wort’ in birthwort and mugwort etc.

    The reason the Latin name contains fangchi is that in the old time the sound ‘ji’ (=gee) was rendered as ‘chi’, notably in the Wade-Giles transcription.

    So Stephania tetranda and >i>Aristolochia clematitis are in a sense ‘the same’. The prefix ‘guan’ in the latter means something like ‘extended’. It is quite possible that for a Chinese herbalist they are quite alike, just like the various ‘christmas trees’ on sale in December.

  10. rokujolady says:

    I think that it’s also important to remember that people in the past were not stupid. It would have been impossible without modern science to make this connection. It was only made by looking for specific mutations in DNA in the kidneys that are a signature for this chemical. So, if people took this for hundreds of years without noticing effects, it’s probably that the lifespans of Humans in the past were such that a toxin with an up to 40 year latency wasn’t an issue for them.
    Altes and some scientists alike tend to forget sometimes that cancers and other diseases with a latency period of decades have always been a problem in humans. We have for example, found evidence of tumors in many ancient Egyptian mummies. It’s just that in the past, something else usually got you before the tumor did. Like a dental abscess or massive parasitism or pox.

  11. michaelangelica says:

    This is very old news, renal toxicity from Aristolochia species was reported in China in 1964 possibly due to confusion with han fang ji (Stephania tetrandra) and guang fang ji (Aristolochia spp).

    I would be surprised and disappointed to see Aristolochia still in use.
    However I suspect this is just a recycling of old news to assist the herb scare campaign. Thus diverting attention to the massive ADRs and deaths caused by prescription drugs.

    While we are looking at what causes cancer another question to ask is- Why is prostate cancer, the third biggest killer cancer in the west, rare in China japan and some other Asian countries?
    What are we poisoning ourselves with?

  12. Jan Willem Nienhuys says:

    a toxin with an up to 40 year latency wasn’t an issue

    The 100 Belgian women whose kidneys were destroyed didn’t have to wait 40 years. And that Aristolochia was the culprit became clear long before the precise mechanism of the poison was elucidated. (Why exactly arsenic, cyanide or hemlock or various mushrooms and snakes are poisonous is only recently discovered, but the fact that they were poisonous was known.)

    As a matter of fact, even nowadays people will not make the connection between a treatment received and an adverse event a little later. The victims of chiropractic-induced strokes usually don’t collapse in the chiropractor’s office, and hence don’t make the connection. In Ayurveda it is common that substantial amounts of heavy metals like lead are put into the drugs. The lead is ‘detoxified’ by cooking it with cow dung or similar procedures, and in all the centuries that this practice has been going on, the link between poisoning an Ayurveda was never made. Lead poisoning really doesn’t have a 40 years latency periode.

    Similarly the copious bloodletting as a remedy against very many diseases must have killed many more people than that the odd American president. For about 2000 years nobody noticed how bad it was, even though the victims must have succumbed rather quickly and not with a 40 year latency period.

    People in the past were just as stupid as the chiropractic client who gets a stroke after a neck manipulation and only finds out the reason because a neurologist has the idea of asking whether he recently saw a chiropractor. When Louis started his ‘numerical method’ (around 1835) doctors tought this a repulsive idea.

  13. jtfische says:

    I am a natural products researcher whose main focus is in finding useful compounds (drugs etc) from various natural sources. I know full well the dangers and benefits of various natural compounds. I fully agree that natural does not automatically equal better or safe. In certain cases a synthetic derivative can be better or safer it depends on the chemical(s) and how they are being used.

    Anyway a student in the laboratory I work in is actually doing research on this compound. Specifically looking at if the compound aristolochic acid is found in related species. Despite the ban on the Chinese species in certain countries there are other species being used and no one really has looked into whether or not the compound is there. So it is a public health concern.

    However the point is that just banning herbs is not the answer. The public needs to be better educated on drugs in general. Of course with herbs this is a major problem because there is a perception that natural is safe. Which is a naive perception. The solution is not just to ban herbs. This just creates a black market for those herbs. It also makes it more difficult to engage the public about the risks versus benefits of any particular herb or complex concoction. It makes it impossible to control in any legit way.

    I attended a conference whose point was to try to encourage the development of good practices for Chinese medicine. Things like quality control clinical research safety etc. However anti quackery organizations jumped on the conference like it was some kind of promotion of quackery when it clearly was not. Of course companies will try and advertise their products at these conferences. But big deal? Most scientists and people attending know the difference between advertising and science.

    Also I heard an insane comment by one of these anti quackery people. This clinician thought the solution is to ban all herbs from China until they are proven to work or be safe. This is crazy. Your talking literally about hundreds of species of plants being banned. Its an impossible task for law enforcement and it would involve gross violations of human rights to accomplish it (much like the drug war).

    Its appropriate to make it illegal to false advertise herbs as medicine without evidence. But just banning hundreds of plants because some people are stupid enough to take them despite warnings about their safety and efficacy is absurd. There has to be some aspect of personal responsibility in the regulation of this market.

    Education is the solution. So lets improve the dialogue a bit instead of just pointing fingers at anyone and everyone who might be a quack. Of course real quacks deserve to be bashed but when people can’t tell the difference it gets a bit redundant these discussions.

  14. Scott says:

    @ jtfische:

    A very important point is that banning the false advertising is generally presented as banning the herb, by the sellers themselves. This is simply because the lies are all they have to say! There isn’t some sharp dividing line like you’re implying.

  15. jtfische says:

    Re: Scott,

    Whenever discussing false advertising you always get into complicated issues about freedom of speech and issues about what you can and can’t claim. So I understand it isn’t something that’s easy to draw a line and say whats acceptable and whats not. It can be very difficult to define legally.

    However I am not sure its fair to characterize all herbal drug suppliers as liars. Depending on a countries regulatory framework you can have very professional suppliers of these kinds of products who do have to demonstrate various kinds of safety and efficacy as well adhere to quality control. Of course you have pure snake oil salesman and this is a problem. Telling the difference can be difficult for an uninformed consumer and even among doctors or scientists.

    I think the problems begin when you have companies under no regulatory framework who can sell products with no research into active components, dose response, safety, clinical effectiveness and efficacy. This is basically situation in the U.S. with regards to dietary supplements as I am sure anyone who reads this blog knows. Of course some companies make the argument that history already proves the safety/effectiveness and in some cases this is true. Certain herbs that are widely used in food or that have been studied in detail with scientific methods don’t need to be regulated so heavily. What I mean is it would be absurd to require every one at a farmers market to put disclaimers or warning labels on bags of rosemary. However if a company is going to sell a herb with a known medical risk that company should most certainly be restricted from doing so without proper warnings. In the case of a highly dangerous plant banning the commercial sale may be necessary and indeed can be an entirely appropriate response.

    For plants that little to nothing is known I think you have to restrict what companies can say about it if being sold for medicine.

    These problems have solutions. Unfortunately due to scientific ignorance on the part of policy makers and greed / ability to manipulate policy by certain companies is the reason this problem has not been solved in the United States.

  16. Scott says:

    I have yet to encounter a case where an herb was being sold as medicine which WASN’T based on falsehood, and there’s good reason to doubt such cases exist. If the necessary science to demonstrate safety and efficacy has been done, then the active ingredient has presumably been isolated. And it is then far superior to purify the active ingredient and sell it in known dosages… at which point you’re no longer selling the actual herb.

    Selling the actual herb is hence an almost certain indication that any claims of safety or efficacy are unfounded, and without claims of safety and efficacy there’s no reason anyone would buy it. And even if the claims being made ARE founded, the product is distinctly suboptimal because it’s still an impure drug of variable (and unknown) dosage.

    The “farmers selling bags of rosemary” is an entirely unrelated point, unless you’re suggesting that said farmers are making drug claims for their rosemary. In which case they absolutely should also be required to have the necessary science before making the claim.

  17. Jan Willem Nienhuys says:

    a case where an herb was being sold as medicine which WASN’T based on falsehood, and there’s good reason to doubt such cases exist.

    What about Hypericum perforatum (Saint John’s wort)?

  18. Scott says:

    What I tend to see there are still claims that it’s magical because of being an “herb” instead of a “drug.” Red Yeast Rice is another example in the same category – reasonable to good evidence of efficacy, but still refusal to admit that they’re impure drugs of variable dosage.

    In hindsight “almost certain indication” was too strong a phrasing in my second paragraph; apologies for any confusion due to that error.

  19. jtfische says:

    Scott,

    I think stating that you have never heard of any cases of herbs being sold which had scientific evidence to back up the claim is more an indication of ignorance then a scientific or factual claim. Please don’t take offense because that is not the intention. There are many examples so I will not go into a citation war because the information is most certainly available. An easy place to look for such examples is the system in place for herbal drugs in countries like Germany and Switzerland.

    The claim that herbs or preparation thereof are always of variable dosage is also untrue. It is most certainly possible to prepare standardized extracts of herbs and it is possible to produce homogenous batches of plant material with known levels of active constituents. Does that mean that companies always do this? No. But it doesn’t mean all companies don’t and in some countries companies must adhere to such rules which are themselves based on scientific evidence. If your only perspective on this issue is from America I’d recommend taking a look elsewhere because the complete lack of regulation in the U.S. distorts the entire discussion.

    Your argument about impurity is most certainly true. But that doesn’t mean all impurities in any given product are necessarily harmful. Food is an impure way to get various nutrients. Should we all just eat purified carbohydrates, amino acids, and vitamins? Of course not. Most food crops are safe that’s why we eat them. But I could make the argument that no ones knows the health effect of all secondary metabolites in food thus make a similar sensationalist claim as you are making about herbal drugs. The same goes for any synthetic chemical that manages to get into our bodies at similar levels as minor compounds in herbs.

    Of course none of what I am stating in the previous paragraph is meant to imply that just because we don’t know the safety of all possible chemicals being consumed by humans doesn’t mean we shouldn’t require companies or governments to investigate safety of any product being ingested for medicine. It should be a requirement to have scientific evidence concerning safety. Although you can’t make the safety regulations grossly disproportionate between cost and what scientific evidence is actually needed. Otherwise such legislation is not really about safety but about wiping out competition.

    Furthermore the argument that if you know the active constituent you should just purity it and sell it in that form neglects to take in some rather important facts. One of those is cost. As a natural product chemist I can attest to the fact that purifying a compound can be a very time consuming and expensive process. For many people in the developing world cost is still a major issue in their health care and they have no choice but to use plants or plant preparations for their health. I’m not stupid enough to believe that the pharmaceutical industry is going to magically lower their prices to include these people.

    Finally there are examples of mixtures of compounds working better then purified components. If you will claim that you’ve never heard of any that’s just going to be a statement based out of ignorance. I’m not saying that all herbs are better because of things like synergy. That’s a broad claim that can’t be made. But there are some examples of compounds that have better bio-availability when taken in a mixture. There are also instances when development of resistance to a drug is weakened by consuming more then 1 substance. There are cases where taking two cancer drugs with different mechanisms of action is better then 1. These kinds of examples are not just true for certain natural products but synthetic compounds as well.

    Really the entire point of me making this discussion is to try and get people in science based medicine blogs and such kinds of public awareness to stop being so blatantly ignorant about natural products research and chemistry.

  20. Scott says:

    First up, yes, I am referring to the US. Precisely because it’s so screwed up. It may help if I clarify that I am not claiming there is no possible way for herbal medicine to be done legitimately; I am claiming that the industry as it actually exists in the US is so profoundly fraudulent that it cannot be said to have a single redeeming value. Other regulatory systems may be different, but I am not opining about them. My apologies if my prior posts were confusing.

    I think stating that you have never heard of any cases of herbs being sold which had scientific evidence to back up the claim is more an indication of ignorance then a scientific or factual claim.

    Given how pervasively we are bombarded by ads for herbal medicines, not having seen a single one of them that’s legitimate is not “an indication of ignorance.” It is a damning indictment of the entire industry. Might there be a few paragons out there? Maybe. If so, it’s impossible to find them through the noise, and therefore fails to redeem the industry in any meaningful way.

    Your second and third paragraphs rather miss the point I’m making. That point being that a preparation which is a purified active ingredient, at a carefully defined dosage, is superior to a preparation that is impure and contains variable dose. Do I mean to claim that those impurities and variations are necessarily harmful? No. Do I mean to claim that they might well be, and therefore you’d have to be out of your mind to pick the impure variable preparation (all else being equal)? Yes.

    Furthermore the argument that if you know the active constituent you should just purity it and sell it in that form neglects to take in some rather important facts. One of those is cost.

    And if a case is made that an herbal product is a good option because of cost, then that can be a reasonable argument. The proponents of herbal medicine here do not make that case; instead they claim magic.

    Finally there are examples of mixtures of compounds working better then purified components.

    Certainly. Indeed, I’d go so far as to say it’s common – arguably even the norm. (One could credibly suggest that it’s quite likely that even with those single compounds where we don’t KNOW of anything that make them work better, that’s just saying we haven’t yet figured out what it is.) But that’s not the claim at hand. The claim I’m talking about is the standard one that (a) all herbs have such synergy and (b) the exact mixture of compounds in the herb is always optimal. This is complete and utter nonsense.

    It’s also true that in such cases, a mixture of purified compounds is still superior to an effectively random mix of whatever else the plant happened to grow along with the active ingredients. Especially since you can then tweak the proportions, or substitute a different form of one of the ingredients, etc. to see whether you can improve the result.

    As for the food vs. drug distinction, I assert that there’s a pretty clear dividing line between selling something as a food and selling it as a drug. Specifically, in the latter case it comes with specific health claims. (Even if they’re disguised under wink-wink-nudge-nudge “structure/function” claims or otherwise obfuscated.) If specific health claims are to be made, scientific evidence of safety and efficacy should be required. And the extent of that evidence should be independent of whether the product in question came out of a field or was synthesized in a lab.

    Whereas if no specific health claims are made (and people are interested in buying it without), then a decreased level of scrutiny is in order. Partially for the practical reason that safety testing of watermelons to the same extent as, say, Nexium is not feasible. Whereas it’s perfectly practical for anything being sold as a drug, regardless of “field” vs. “lab” status. Partially for the reason that if there’s no health claim made, the question of efficacy is irrelevant. And partially because, if you’re going to make the claim, you HAVE to do the science before you know the claim is legitimate… so allowing shortcuts in demonstrating efficacy is precisely the same as allowing fraud. (IOW, evidence that will convince the FDA is what a manufacturer should require in order to convince THEMSELVES.)

    And yes, this means that labeling a box of cereal as “lowers cholesterol” should mean that said cereal is now subject to the drug standard for demonstrating that it does indeed do that, and does so safely. If Kellogg’s wants to say that, they need to put up or shut up.

  21. michaelangelica says:

    Some good points being made here by jtfische and scott about herbal medicine in general rather than Aristolochia specifically.
    It would be nice if some compromise could be cobbled together as neither herbal medicine or ‘Big Pharma’ are going to go away. (There are many intelligent attempts to do this around the world today.) Neither are 100% safe, but ADRs from herbs are minuscule by comparison with drugs.

    I agree about herbal medicines in the US Scott, the situation is sad; but then so is the whole Yank medical system. The US is a county with one of the worst infant mortality and lowest ‘average age of death’ of any western nation. Unfortunately some of your statements border on the extremism that you decry;(“proponents of herbal medicine claim magic”. “not having seen a single one of them that’s legitimate”). Some of your arguments are unsubstantiated by science. Perhaps a course in pharmacy esp herbal pharmacy would help you? Most of the modern drugs we all rely on have been developed from herbs.

    A search of Medline or Embase (that includes European research)will give you thosands of papers on herbs. (unfortunately Japanese and Chinese reseach is harder to access). Even limiting that search to ”double blind clinical trials” will still give you thousands ; but then there are probably more than 40,000+ medical plants to be studied and a lot of work to do. In the last 10 years that research has exploded particularly in developing countries (India, Brazil for example). Part of the reason for that may be the growing disenchantment with the US ‘magic bullet’ approach, or perhaps the many successes with developing new drugs for cancer etc from herbs

    Your point scott about “Given how pervasively we are bombarded by ads for herbal medicines” ignores the fact that while a drug may cost a billion dollars to be registrable by the FDA, an extra half a billion $ is also allocated to promotion. (Sadly, also, despite billions of dollars in research 50% of new drugs approved by the FDA as “safe and efficacious” are withdrawn from the market within 10 years because they are shown to be neither).

    Jan Willem Nienhuys a little study of medical history will show you that blood-letting and treatment with mercury was the conventional doctors treatment; while in the US ‘herbalists’ like Thomson were being put in jail for treating patients with herbs such as chilli and goldenseal. (Doctors were called “quacks” because the used quick(quack)silver (mercury). Nowadays the AMA has other uses for the word)

  22. Chris says:

    michaelangelica:

    . The US is a county with one of the worst infant mortality and lowest ‘average age of death’ of any western nation.

    Some additional reading for you:

    It’s ironic that Bernadine Healy, who’s associated herself so heavily with the anti-vaccine movement, to the point of having been named Age of Autism’s Person of the Year in 2008, provided such a nice, concise explanation about why it’s so problematic to compare infant mortality rates between nations.

    I see no reason to believe herbal medicine should not be given the same scrutiny as any other medicinal produce like those produced by pharmaceutical companies. Just because it has been used for a while does not make it good. There is a reason that we no longer have certain medications (like mercury laced teething powders) is because real medicine learns from it mistakes and moves on. Those who were prescribing aristolochic acid now have reason to stop using it.

  23. michaelangelica says:

    Yes agreed Chris However I am not arguing for the anti vaccine movement (or chiropractors). To lump these into an argument about herbal medicine is not logical. Many countries mange to regualte the safety and efficacy of herbs (Japan, France, Germany etc) The fact that it is a mess in USA is not the fault of the herbs
    Further aristolochia is only used rarely in the Chinese system and it seems this occurred from an unfortunate confusion of names. The Belgian tragedy was isolated to a doggy weight loss clinic. I wonder if the conventional use of metherdine for weight loss is any better an option?
    While I agree the fact that a herb has been used for a thousand or even tens of thousands of years does not automatically make it good. However that does give a longer time frame for toxicity problems to become apparent.
    Herbal medicine needs to be studied within the scientific culture of the time, there is much to learn, and many problems (as there are with drugs) but an open mind is needed.

  24. Chris says:

    If you mention infant mortality, you have to understand that it is defined differently in many countries. You only brought it up in an attempt to “poison the well.”

    You say:

    Further aristolochia is only used rarely in the Chinese system and it seems this occurred from an unfortunate confusion of names.

    Please read the article more carefully:

    This latest research just published finds that use of aristolochia is linked to the high incidence of urinary tract cancer in Taiwan. The rate of urinary tract and renal cancer in Taiwan is about four times higher than in Western countries. This led the study authors to suspect there was an environmental cause, and they quickly suspected that aristolochia might be the culprit. Although use of aristolochia was banned in Taiwan in 2003, its use is still widespread. The study found that 60% of the 151 subjects with renal cancer studied had specific mutations that previous research has linked to aristolochia.

    It was still used enough to cause a noticeable blip in the epidemiological data. Trying to dismiss it with excuses like “confusion of names” is not a defense.

    Herbal medicine needs to be studied within the scientific culture of the time, there is much to learn, and many problems (as there are with drugs) but an open mind is needed.

    And it is, which is what Dr. Novella wrote about above. This is also something that one of the contributors to this blog does: David Kroll. I suggest you open your mind and read his articles here and on his blog: http://cenblog.org/terra-sigillata/ .

  25. michaelangelica says:

    So we resort to ad hominem arguments.(‘I suggest you open your mind’ “You only brought it up in an attempt to “poison the well.”) I am sorry you thought this last. I was merely trying to say that the USA model for regulating herbs is not necessarily the best one to follow.

  26. michaelangelica says:

    Epidemiology as applied to human events is more descriptive than a hard science.
    “Despite the differences in data sources, study subjects and definition of CKD, the prevalence of CKD (9.8–11.9%) in Taiwan was slightly lower than 13.1% in United States,”
    http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1797.2010.01304.x/pdf

  27. Chris says:

    I did not use an “ad hominem.” I did not say your argument was invalid due to something you are or have done. Actually, I was describing your tactic of using the American statistics, which was truthfully deflecting the discussion by “poisoning the well.” The subject was not on a health issue in the USA, but one particular herbal medical practice in Taiwan. There are so many reasons that effect average lifespan, that it is pointless. Especially between Taiwan and the USA (which are almost the same).

    Why are you upset over using something you said first? From your comment: “but an open mind is needed.” You are the one who has trouble with the above article which is doing exactly what you said should be done: “Herbal medicine needs to be studied within the scientific culture of the time, there is much to learn…” I merely pointed out that this is being done, both by the researchers in Taiwan and the USA in the paper discussed above by Dr. Novella, and by Dr. Kroll’s research.

    The epidemiology was only on the one thing, urinary tract cancer. Just like the epidemiology showed that Catholic nuns had less cervical cancer than other women, which pointed to a sexually transmitted virus, HPV, as a possible cause. There is a vast difference between kidneys disease and urinary tract cancer, so there is no reason to change the subject.

    Now if you have an objection to the actual paper, “Aristolochic acid-associated urothelial cancer in Taiwan” by Chung-Hsin Chena, please present them. Since I linked to the full paper, I will assume you can quote from the parts that you will discuss.

  28. michaelangelica says:

    I am not sure you are reading all my posts Chris
    I fist commented that the toxicity of aristolocia has been know since 1964 and questioned why this was being raised now.
    Then I thought we had gone on to a discussion of herbal medicine generally; so what exactly do you want to talk about?

  29. Chris says:

    It was being raised now because it was still being used, even though it was illegal. No, it was not a discussion of herbal medicine generally. The point was that people think just because it is “natural” it is good, which is known as the “Naturalistic Fallacy”, which is the title of the most recent 5X5 podcast that includes Dr. Novella.

    The hint on the subject is in the first sentence:

    It has been a stunning triumph of marketing and propaganda that many people believe that treatments that are “natural” are somehow magically safe and effective (an error in logic known as the naturalistic fallacy).

    Anyone who has done any gardening knows that just because it is a plant does not mean it is safe and healthy. One reason why I got into edible landscaping was to avoid some of the more toxic plants like castor bean, elephant ears, foxglove and daphne. I have grown the herb angelica, which is very similar to poison hemlock. Locally people have died by thinking poison hemlock is wild carrot. So it helps to know what is dangerous and what is not.

    You claimed that herbal medicine should be studied. It is being studied, and it has been studied. That is one reason why one plant I will not put into my garden, foxglove, has been a useful source of a heart medication (digitalis). It is also why there are lots of other pharmaceuticals, and why there are researchers like Dr. Kroll looking into more herbal based medicines that work. Sometimes that research shows that the herbal medicine is not good or useful, so then it is time to let it go and move on.

  30. michaelangelica says:

    Still confused but. . .
    the toxicity of most plants in my view has been overstated, usually by crime writers.(banned drugs and herbs excepted). Death by drugs is a far more common event than death by herbs, which is rare, and usually results from misguided attempts at suicide.To not grow foxglove because it can be poisonous is paranoia or even ‘plant- phobia’ in my view.
    (BTW foxglove and herbs containing alkaloids taste revoltingly bitter.)

    You are obviously a fan of Dr. Novella, I did visit his site but found little of relevance to this discussion, perhaps I need a more specific link

    If “people think just because it is “natural” it is good” that thought is obviously misguided.
    Perhaps they have been influenced by the number of killer drugs (eg vioxx ) and chemicals (eg CHCs) created since WW2?

  31. Jan Willem Nienhuys says:

    Lots of quite common plants are very poisonous, even indoor plants. Nobody here talks about ‘not growing’ such plants. The case of foxglove is interesting. Digitalis derives from foxglove. The problem with ‘herbs’ is that it is very hard to monitor the contents of herbs. The amount of active drugs they contain depends strongly on the way they are grown, the amount of sunshine and rain they had, and the quality of the soil. So in the old times (about 50 years ago, I guess) pharmaceutical companies had to test each batch of plant derived digitalis on rabbits in order to find out the strength of that batch.

    I won’t comment much on the remark that it was already known in 1964 that aristolochia was poisonous (in what dosis, and how quickly?). Fact is that aristolochic acid was found in quite a few ‘Chinese Medicines’ after the Belgian drama had alerted the medical community to the dangers of Aristolochia. But even then, at least one Belgian purveyor of TCM claimed that Aristolochia was harmless and that he had had good results with it.

    A bit off-topic: the idea that only natural herbs are good is very old. The founder of homeopathy, Samuel Hahnemann wrote in the 6th edition of his book Organon in the footnote to section 273:

    extracts obtained by means of acids of the so-called alkaloids of plants, are exposed to great variety in their preparation (for instance, chinin, strychnine, morphine), and can, therefore, not be accepted by the homœopathic physician as simple medicines, always the same, especially as he possesses, in the plants themselves, in their natural state (Peruvian bark, nux vomica, opium) every quality necessary for healing. Moreover, the alkaloids are not the only constituents of the plants.

    and then (in section 274) he continues to extoll the virtues of ‘simple drugs’:

    the true physician finds in simple medicines, administered singly and uncombined, all that he can possibly desire

    So there you have it. A total plant (or animal compound like honey bee, snake poison or Spanish Fly) is a ‘simple medicine’, and substances like alkaloids obtained by chemical means from them are complicated stuff. That idea goes back to the inventor of homeopathy and hence is a leftover of 19th century vitalism.

    Look it up: http://www.homeopathyhome.com/reference/organon/organon.html

  32. Chris says:

    Mr. Angelica:

    the toxicity of most plants in my view has been overstated, usually by crime writers

    This is something you need to provide a citation for. Because it is obvious you are falling for the naturalistic fallacy. I am really curious how the relative of parsley, dill and angelica, poison hemlock, has had its toxicity overstated. Or that of foxglove, and especially the product of the castor bean plant: ricin.

    I mentioned Dr. Novella and his podcast because at the top of this page under the article’s title it says: “Published by Steven Novella.” The podcast on naturalistic fallacy is the most recent one, you actually have to listen to it. I figured you might want to hear how he interprets the naturalistic fallacy.

    Here is another book for you, written at a level you might actually understand: Wicked Plants: The Weed That Killed Lincoln’s Mother and Other Botanical Atrocities.

    Over twenty years ago I took a class on herbal medicine taught by a naturapath. At least she was truthful about the toxicity of the plants, especially since an elderly couple had recently died by drinking tea from what they thought was comfrey (which they had gathered in the woods). It turned out to be foxglove. The last part of the class included a tour through this pharmaceutical garden.

    It is what prompted me make sure the my garden plants were not toxic when I had kids. As I designed my garden I attended a landscaping seminar, and I did a face palm when shown a slide of elephant next to castor bean as an example of a good looking pairing. As the kids got older I did plant delphiniums (belladonna), but I can’t keep them alive. Plus I have an apricot tree that has cyanide in its seeds and leaves. Kids don’t gnaw of the wood, and don’t think the pits are almonds. The only thing is to not give the apricot branches and leaves to their pet hamsters, or burn them in the barbecue.

  33. Chris says:

    Oops. missed an essential word: “elephant next to castor bean” should be “elephant ear next to castor bean.”

    Elephant ear is a plant:

    Within the Aracae, genera such as Alocasia, Arisaema, Caladium, Colocasia, Dieffenbachia and Philodendron contain calcium oxalate crystals in the form of raphides. When consumed, these may cause edema, vesicle formation and dysphagia accompanied by painful stinging and burning to the mouth and throat, the symptoms occurring for up to two weeks.

    Castor bean plant:

    The toxicity of raw castor beans due to the presence of ricin is well-known. Although the lethal dose in adults is considered to be four to eight seeds, reports of actual poisoning are relatively rare.

    … though it continues:

    Poisoning occurs when animals, including humans, ingest broken seeds or break the seed by chewing: intact seeds may pass through the digestive tract without releasing the toxin.[16] Toxicity varies among animal species: four seeds will kill a rabbit, five a sheep, six an ox or horse, seven a pig, and eleven a dog.

    So, yes, it is not easy to get pure ricin. But it is still one of many plants that protect themselves from insects by creating poisonous compounds inside their leaves and/or seeds. There is a reason that squirrels will munch on tulip bulbs, but leave daffodil bulbs alone (they are poisonous). Also, I grow fall blooming saffron crocus, but not the other fall blooming crocus: Colchicum autumnale (which is toxic).

    I’ll say one way to not get fooled by the naturalistic fallacy is to become a gardener. Learning what plants do what (some of them will cause rashes, like giant hogweed a relative to celery, so don’t plant those), aphids prefer some over others, and others become invasive (sweet cicily, thimbleberry, lemon balm, etc) and the constant battle with the squirrels, bugs, raccoons and birds over the edibles.

    Nature is not good, nor is it bad: it just doesn’t care.

  34. michaelangelica says:

    Chris what part of “in my view” don’t you understand?
    The relative risks of being killed by poisonous plants as against prescribed drugs is extremely low.
    (see Krenzelok EP, Mrvos R.,”Friends and foes in the plant world: A profile of plant ingestions and fatalities.” Clin Toxicol (Phila). 2011 Mar;49(3):142-9)
    I am sure you can Google the stats for plant verses drug ADRs and deaths in your country.
    None of the plants you mention are used by herbalists. in fact their use would be illegal. Digoxin, from Foxglove, has a very small therapeutic window.

    I have a large toxicology and plant library thanks and have read the book you mention. I have also grown most of the plants you mentioned and even nibbled some like foxglove
    I have also studied PG plant toxicology/pharmacy (where they taught us about Aristolochia);
    but of course those who want to push the myth that herbalism is not science, want such studies excluded from Universities.
    How that will help make herbalism safer is beyond me.

  35. Jan Willem Nienhuys says:

    The relative risks of being killed by poisonous plants

    This all besides the point. The point is that the dangers of Aristolochia are quite well known (to the point that in Europe anything that contains detectible amounts of aristolochic acid is outlawed), the benefits are zilch, and that notwithstanding this fact this herb is sold in Taiwan on a considerable scale, even though the herb was banned there in 2003.

    And from a wider perspective it is the fact that this herb has been used for many centuries even though it contains just about the most potent carcinogen known to mankind. So ”generally recognized as safe” is nonsense. Anything used as drug should be considered ‘guilty until proven innocent’, and ‘proven’ in the sense of scientific proof, not the accumulated superstitions of herb gatherers in Farfaraway.

  36. michaelangelica says:

    What exactly is the point?
    It seems to keep changing
    Has anyone suggested that aristolochia is not toxic?
    many things cause renal toxicity including drugs (eg COX-2 inhibitors, cisplatin, aminoglycoside ), heavy metals, industrial chemicals, elevated ambient temperatures, and infections
    Drugs cause approximately 20 percent of community-and hospital-acquired episodes of acute renal failure
    http://www.aafp.org/afp/2008/0915/p743.html

    Though, just because a plant is poisonous does not mean it does not have drug development potential
    Phytochemical and pharmacological potential of Aristolochia indica: A review.
    Sati H., Sati B., Saklani S., Bhatt P.C., Mishra A.P.
    Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2 (4) (pp 647-654), 2011.

  37. Chris says:

    What is your point? Yes, we have mentioned several plants that have drug development potential, hence the reference to Dr. Kroll who does exactly that.

    Perhaps you need a short version:

    1. Some people believe that because it is a plant that it is always good: the naturalistic fallacy.

    2. Plants have chemicals.

    3. Some are good and some are bad.

    4. The bad ones can be helpful in a proper dose.

    5. The plants need to be studied.

    6. The herb medicine aristolochia was studied.

    7. It was found to be bad.

  38. michaelangelica says:

    “Some people believe that because it is a plant that it is always good: the naturalistic fallacy”
    Some people believe they were abducted by aliens so?

    If your point is there is that TOO MANY (a value judgement) “people who people believe that because it is a plant that it is always good: the naturalistic fallacy” I am not sure if this is supported by scientific research eg
    “Orthodox medicine was clearly seen, by the great majority of subjects, as being more effective in the treatment of most complaints, especially in the treatment of major, life-threatening conditions. Complementary medicine was seen as more effective in the treatment of minor and chronic conditions, though generally not superior to orthodox medicine. For some specific conditions complementary medicine was seen as the most effective treatment”
    Vincent C., Furnham A.The perceived efficacy of complementary and orthodox medicine: Preliminary findings and the development of a questionnaire.Complementary Therapies in Medicine. 2 (3) (pp 128-134), 199

    I am just curious how one old, banned, nephrotoxic herb, who’s toxicity has been known for near 50 years can get produce so much hysteria while there are dozens of drugs that do the same, and are commonly prescribed, and are not banned. Is that a balanced point of view?

  39. JPZ says:

    Steve,

    I have personally filed two GRAS applications – how many have you filed? You are misleading your audience on a scale I find unsettling. Herbal compounds were approved under DHSEA and have no GRAS status. Please consider, the obhvious fact that they are not GRAS – unless they went through the approval process post-1994. Do you really want to give your audience the impression that the GRAS process leads to misdeads? Are you aware of the GRAS process?

    Having gone through that approval process, I have to say it looks nothing like your ill informed viewpoint. The FDA asks a lot of questions during that process. I found myself scrambling for answers many times during the process because their questions were so insightful. But, in each case, I provided efficacy for each claim.

    I will consider your lack of response as acceptance of my points,
    JPZ

  40. michaelangelica says:

    BTW Some may be interested in this article. The Chinese do occasionally use herbs that would not be used in the West but they are used in decocted formulas with herbs that seem somehow to reduce toxicity In the Belgian case large does of the pure powder of an incorrect herb was used ( rather than a traditional formulae) .Perhaps this was due to the Wests’ magic bullet fallacy?
    “It is clear from the Chinese National Pharmacopoeia that fang ji is the root of the S. tetrandra plant, whereas guang fang ji is from a totally different plant, A. fangchi. 1 Since fang ji does not have a renal toxic component, the tragedy would never have occurred if the correct herbs had been used in the Belgian dietary clinic.
    Guang fang ji and related herbs have antiarthritis and diuretic effects and are often used together with other herbs to optimize efficacy and reduce toxicity.
    None of these herbs have been used in traditional Chinese medicine for weight control. They have a low level of toxicity and should be used with caution; they should never be used during pregnancy. The proper dose is 3 to 9 g of the decocted herb per day, and the herbs should be used for only a short period of time. The patient’s renal function should also be monitored regularly. In the Belgian cases, the physicians apparently did not follow these guidelines of traditional medicine.
    http://www.nejm.org/doi/full/10.1056/NEJM200010263431713

  41. Jeff says:

    I am just curious how one old, banned, nephrotoxic herb, who’s toxicity has been known for near 50 years can get produce so much hysteria while there are dozens of drugs that do the same, and are commonly prescribed, and are not banned. Is that a balanced point of view?

    Excellent question. It makes one wonder why some doctors, pharma researchers, and FDA bureaucrats have such an intense dislike of all dietary supplements. Perhaps too much freedom of consumer choice means a loss of control and authority by the medical and regulatory establishments. According to Bill Sardi a financial motive could be involved:

    http://knowledgeofhealth.com/drugs-versus-supplements-unproven-versus-disproven/

  42. Harriet Hall says:

    Aristolochia is being singled out not because it is being misused but because its use in the East according to TCM tradition has been killing people, even after bans tried to protect the public.

    Pharmaceuticals are approved for marketing based on evidence of safety, but post-marketing surveillance can reveal problems. Similarly, evidence can arise that a GRAS product is unsafe even after centuries of use. East or West, we must be responsive to new evidence.

  43. Chris says:

    Actually, Mr. Angelica, the question is why you are reacting so vehemently that a product that was banned, but still being used, was formally tested to find out why it was dangerous. It does not if the Belgium cases were not “traditional Chinese medicine”, aristolochia use was killing people in Taiwan. That caught the attention of Chung-Hsin Chen, who practices in the Dept. of Urology in both a university and hospital in Taiwan. Hence the resulting study which is linked to above.

    You remind me of the defenders (and sellers) of laetrile. It was studied and found to be dangerous, yet its advocates keep trying to sell it. They even renamed it “Vitamin B-17.” And so there are occasional case reports of cyanide poisoning from these “supplements.” Well, after all, it is assumed that apricot pits are perfectly safe because they are natural (really, they are not).

  44. Chris says:

    Actually, it just occurred to me: since aristolochia was already banned in Taiwan, how could it be “GRAS”? And even now after it was shown to be dangerous, including the mechanism, why would you want it to be “Generally Regarded As Safe”?

  45. michaelangelica says:

    O dear chris you remind me of people who use “science” to support GW denial
    Is that the best you can do?

    One factor that may be interesting is the high use of acetaminophen in Taiwan .
    It is possible that there is a synergistic effect with AA
    http://ndt.oxfordjournals.org/content/26/6/1916.short

  46. Chris says:

    The point of this article was an illustration of naturalistic fallacy. It is a simple thing, explaining that just because something is “natural” and used for a long time (the antiquity fallacy) it is safe. But that is wrong.

    Mr. Angelica, you seem to have a bit of trouble grasping that concept. You complain about the “hysteria”, when it is only you who seem to be hysterical about the fact that an herbal medicine was studied and found to be dangerous. You said that “they should be studied”, but when it is pointed out that the studies were done and that particular plant was dangerous you have a conniption fit. This is emphasized when you try to deflect the issue by bringing up GW denial (huh?) and acetaminophen usage.

    It was a simple message: just because it was a plant is used for a long time does not mean it is safe.

    Get over it. Move on.

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