Terra Sigillata

Alexa Ray Joel, the daughter of Billy Joel and Christie Brinkley, was hospitalized Saturday with what I originally thought was an overdose of some type of sedative.

However, today’s Newsday and MTV are reporting that the family is calling this an overdose of a homeopathic medication called Traumeel. Traumeel is manufacturer by an Albuquerque-based company called Heel USA, a company founded by a German physician in the 1920s.

If Traumeel is truly homeopathic, there is absolutely no way this product could have caused Joel’s hospitalization.

If you are new to our blog, you may not know the different between herbal medicines and homeopathic remedies. Herbal folk remedies are actually the source of some commonly used pharmaceuticals. And like drugs, herbs have the potential to have a therapeutic effect in direct proportion to the dose given. The more herb, the more likely a benefit – or side effects – may be observed.

Homeopathic remedies, however, have nothing to do with herbal medicines. In fact, the basic principles underlying their use are diametrically opposed to everything we know about physics, chemistry, and biology. They are the remnants of a pseudoscientific practice developed in the 1800s whereby it was deemed that a substance which produces effects similar to an illness can be diluted out (or “potentized”) to create a remedy that might treat that illness. Hence, extremely dilute ipecac (which is used to induce vomiting) might be used homeopathically to treat disorders that involve vomiting.

The primary reason people get confused between herbal/botanical medicines and homeopathic remedies is that both are often derived from similar plant materials.

However, homeopathics differ in one critical respect: they are often so dilute that they contain not a single molecule of the original starting material. Homeopathic remedies are essentially water that is sold at even more exorbitant prices than bottled drinking water.

An excellent and approachable overview of homeopathy can be found in this 1996 article (free PDF) in the American Journal of Pharmaceutical Education by Dr W Steven Pray of Southwestern Oklahoma State University’s School of Pharmacy. I have used it for over 10 years in teaching students and educating the public.

So let’s look at the composition of Traumeel, purported for used as an anti-inflammatory agent for musculoskeletal injuries. Traumeel comes in several dosage forms, including one for injection, but let’s look at the tablets, especially since the New York Daily News reported reports a 911 call that Joel “had taken some pills”:

Each 300 mg tablet contains: Aconitum napellus 3X (Reduces pain after injury) 30 mg; Arnica montana, radix 3X (Reduces swelling and bruising) 40 mg; Belladonna 4X (Reduces swelling and pain) 75 mg; Bellis perennis 2X (Treats bruises) 6 mg; Calendula officinalis 2X (Stimulates healing process) 15 mg; Chamomilla 3X (Soothing pain relief) 24 mg; Echinacea 2X (Immune support) 6 mg; Echinacea purpurea 2X (Stimulates healing process) 6 mg; Hamamelis virginiana 2X (Relieves bruised soreness) 15 mg; Hepar sulphuris calcareum 8X (Stimulates injury healing) 15 mg; Hypericum perforatum 3X (Relieves pain) 8 mg; Mercurius solubilis 8X (Reduces swelling) 15 mg; Millefolium 3X (Treats minor bleeding) 15 mg; Symphytum officinale 8X (Relieves joint pain) 24 mg. Inactive ingredients: Lactose, Magnesium stearate.

I need to describe the nomenclature for those readers used to working with science-based medicine. Homeopathic remedies are defined by the magnitude of dilution from the original product or plant extract with terms like 12X or 20C. X refers to a 10-fold dilution and C refers to a 100-fold dilution and the number denotes how many times each dilution was made. Therefore, a 12X remedy would be a 1012 dilution; a 20C remedy would be a 10020 dilution.

However, some of the plant products used in this homeopathic remedy are only of modest dilution. These 2X and 3X remedies are, by definition, only 100-fold and 1000-fold dilutions of the starting material. These concentrations are probably too dilute to have any positive or negative biological effect but I can’t be certain.

There are a couple of very, very toxic components in the remedy but, again, are even more dilute so as to be unlikely to have any harmful effect. For example, the toxic belladonna alkaloids are 10,000-fold diluted and Symphytum officinale (also known as comfrey) is diluted 108-fold. Conventional concentrations of comfrey extract contain well-documented hepatotoxins called pyrrolizidine alkaloids, which are converted into highly-reactive metabolites by hepatic cytochrome P450 enzymes.

As you can see, this is going to be a confusing issue as the lay press sifts through the facts and fallacies associated with homeopathic remedies.

The makers of Traumeel, you might expect, are on the defensive.

They don’t exactly come out and declare it specifically but I can practically sense they want to say, “There’s really nothing in our product so how can you claim it is dangerous?”

As this story continues to develop, be sure to pay attention to discussion of Traumeel. I’ve seen one report via Twitter that declares it to be a herbal medicine.

Let me just add another very serious note about this case: I truly hope that Ms Joel gets the assistance she needs, given new reports that she called 911 and said that she wished to die. She is very fortunate that she took what appears to be a homeopathic remedy rather than some other kind of pill. Some types of mental disorders first rear their heads in a person’s early 20s, even those without the stress of a new musical career or coming from a high-profile family. My warmest wishes go to all involved.

If you are a journalist looking for comment or interpretation of this story, please feel free to e-mail me at the address under “Contact” and I will be happy to provide background under my real name and credentials.

Comments

  1. #1 Dave X
    December 7, 2009

    So, how do they get from the dilution form to pill form? There’s probably not enough energy in the world to evaporate a 20C potency down to 6mg

    If I add up the components, 30+40+75+6+15+24+6+6+15+15+8+15+15+24=294 it leaves room for only 6mg of the “inactive” ingredients.

    Of course if they make the pills by running some asprin through a homeopathic mister/humidifier, then who knows?

  2. #2 Karen James
    December 7, 2009

    Maybe she’s allergic to lactose or magnesium stearate, or one of the 2X or even 3X ingredients. I like that you took the time to remind readers of the difference between herbal folk remedies and homeopathics – some may be new to the discussion.

  3. #3 Tsu Dho Nimh
    December 7, 2009

    Mercurius solubilis 8X (Reduces swelling) 15 mg

    That’s MERCURY! Specifically what you get when you react mercury with nitric acid.
    http://chestofbooks.com/health/materia-medica-drugs/British-Homoeopathic-Pharmacopoeia/Mercurius-Solubilis.html

    The herbals, even the belladonna, are way more diluted than old pharmacy book formulas have. However, taking a handful of the things might get you to toxic levels.

  4. #4 Tsu Dho Nimh
    December 7, 2009

    Dave- You add “X” of the solution to a certain amount of lactose, triturate (grind up real good), and make higher dilutions with the lactose.

    Like cutting cocaine or heroin.

  5. #5 Raka
    December 7, 2009

    Dave, you are trying to apply useful principles to… well, let’s call it a “less useful” methodology. No evaporation is necessary.

    Take one unit of Whatever. Mix it with ten units of water. That water, no evaporation involved, is now a 1X solution of Whatever. Take one unit of that solution. Mix it with ten parts pure water to get a 2X solution. Any quantity of that solution is 2X. One glass of it, one microliter of it, it’s all a 2X solution. So any quantity of it included in a dose still qualifies as (however many milligrams) of 2X.

    I believe the capsules are generally suspensions of the “active” solutions in an inert gel or other excipient, no evaporation involved. But I’m not 100% on that and don’t see a solid source at the moment. Regardless, they are certainly not taking 6mg of the evaporate of (effectively) pure water; the mass refers to the actual water involved at the listed concentration.

  6. #6 Sam C
    December 7, 2009

    Remember the manufacturers and practitioners are quacks. They lie. Their business is lying. Why assume that the bottle contains what the label says? I recall that some manufacturers got into trouble because what were labeled as homeopathic remedies actually contained active ingredients that might actually have a real effect.

    So even if it is not possible to have a reaction to “pure” Nonsensicalium 10C or Drivellium 20X, it is certainly possible to have an adverse reaction to something in a bottle with that label on it.

  7. #7 jre
    December 7, 2009

    Interestingly, FDA does inspect makers of homeopathic remedies, and issues warning letters when one is found to be falsely claiming its product to be homeopathic. The criteria for being a properly labeled homeopathic remedy are all derived from Hahnemann’s original philosophy, including the “proving” of new remedies — a kind of pseudoscientific drug discovery process. Go to fda.gov and search for “CPG 7132.15″ to learn more.

    In essence, then, FDA is on the lookout for homeopaths whose remedies actually do something, and when it finds them punishes them severely.

  8. #8 ak@invariant.eu
    December 7, 2009

    Apparently this Traumeel isn’t your ordinary homeopathic product aftera all. The concentration of the ingredients is much higher than in regular homeopathic products. In fact (with the exception of mercury, calcium sulphide and Symphytum officinale, listed with an 8X dilution, or 1:10^8, and therefore irrelevant in context), it is tens of orders of magnitude higher than the usual 10^-14 (7C) to 10^-60 (30C) theoretical concentration of the most h. products. And it enters in the realms of not only measurable quantitities, but of “truly” active ingredients.

    Doing the math on their declared composition, each pill should contain about .60 mg of various plants. Out of this, .15 mg are known to be toxic (Aconitum napellus, Atropa belladona, Echinacea)– with Echinacea sp. and Echinacea purpurea leading, each with .06 mg.

    While this still means she should have taken literally hundreds of pills in order to ingest a few milligrams of these, the quantities are relevant. What I’m thinking of is not so much a “normal” toxic effect, as an allergic/anaphylactic reaction to one or several of the components.

    Of course, as I’m not an MD or pharmacologist, this is merely an educated guess, little more than speculation. I’d really appreciate input on this matter from our host or someone else knowledgeable of the subject.

  9. #9 T. Bruce McNeely
    December 7, 2009

    I suspect that Alexa Joel was hospitalized to protect her from further suicide attempts, rather than any effects of the drug.
    I hope that she will recover from whatever condition drove her to this attempt.
    BTW, her father has a history of depression, and attempted suicide at about the same age (from Wikipedia):

    Joel battled many years with depression. In 1970, a career downturn and personal problems aggravated his condition. He left a suicide note (which became the lyrics to “Tomorrow Is Today”) and attempted to commit suicide by drinking furniture polish, saying later, “I drank furniture polish. It looked tastier than bleach.”

  10. #10 Dagda
    December 8, 2009

    Isn’t it possible that she experienced a nocebo effect( kind of the only possible “homeopathic overdose”)? I don’t know anything about this story therefore I’m just guessing.

  11. #11 Armand K.
    December 8, 2009

    Hum… I looked up some of the Alexa Ray Joel news around the internet.

    “Suicide attempt” with 8 (eight!) homeopathic “sleeping pills”? Really, suicide attempt with roughly 2.4g (about half a teaspoon) of sugar? Containing as a very maximum 5mg of some random herbs, if the pills were indeed Traumeel?

    If she really had some genuine “breathing troubles,” I can’t see how they could relate to the pills.

    I call this a publicity stunt.

  12. #12 paraphen
    December 8, 2009

    My wife was so kind as to translate your post into German and we have incorporated it into our blog.

    http://www.unglauben.org/2657/uberdosis-dank-traumeel/

    We think her condition may have been caused by the nocebo-effect. It is sad to see such a young woman have such troubling condition and we surely hope she gets the assistance she needs.

  13. #13 T. Bruce McNeely
    December 8, 2009

    I call this a publicity stunt.

    Even a lame suicide attempt should be taken seriously. The next attempt could be successful. There is a high chance that the attempter has clinical depression, which carries a high risk of completed suicide. Also, effective treatment of clinical depression is available, so that identification of this condition is important.
    This viewpoint that it was an attempt at manipulation – “publicity stunt” – is cynical, and not supported by anything else I’ve read about Alexa.

  14. #14 DLC
    December 8, 2009

    So, she has a fit over her breakup, gobbles a handful of sugar pills, and then has an anxiety attack because she believed that the pills were a powerful pain killer. Blammo! instant trip to the Emergency Dpt, where hopefully some gastric lavage or some ipecac made her night a winner.
    thanks for posting on this Abel.

  15. #15 Armand K.
    December 8, 2009

    This viewpoint that it was an attempt at manipulation – “publicity stunt” – is cynical, and not supported by anything else I’ve read about Alexa.

    Might be… yes, a bit cynical maybe; “realistic” would be, however, much more appropriate.

    We’re talking about a person so desperately depressed that she apparently changes her mind about suicide, and calls 911 herself, right after ingesting an insignificant amount (8 pills, ca. 2.5g) of a harmless drug (Traumeel), accusing some way too easy to fake symptoms (“difficult” breathing).

    Not convincing at all as an attempted suicide story. In fact, the least convincing I ever heard of. And I’m one who regularly overestimates people’s sincerity and bona fide.

    Also, it would be a great insult to her to take this story at face value, wouldn’t it? It’d require a fantastic level of ignorance and stupidity in order to be true…

    Yeah, maybe she needs some professional help, after all; but of another kind. It’s way beyond cynical to play this way with the feelings of people who care for you. I feel sorry for her parents and friends.

  16. #16 Mack Heywood
    December 8, 2009

    Is there a way to easily translate these quantities to parts per million? I’ve been wanting compare homeopathic ingredients to my annual water quality statement as I think this will be a great illustration of what a load of nonsense it all is.

  17. #17 Armand K.
    December 8, 2009

    Re: Mack Heywood

    Is there a way to easily translate these quantities to parts per million?
    The homeopathic “X” (or “D”) scale is practically a base-10 logarithmic scale scale; an “nX” (or “nD”) dilution is one part of active ingredient in 10 to the power of ‘n’ total solution.
    1X=1:10^1 (=1:10, or 10%); 2X=1:10^2 (=1:100, or 1%); 3X=1:10^3 (=1:1000, or .1%, or 1000ppm); …; 6X=1:10^6 (1ppm); 8X=1:10^8 (0.01 ppm); etc.

    The “C” scale uses the same principle, only it’s a base-100 logarithmic scale, therefore every ‘nC’ “potency” (or how the hell “they” call it) is a dilution of 1 in 100 to the power of ‘n’.

    I suggest Wikipedia for details.

  18. #18 Abel Pharmboy
    December 8, 2009

    I’m on the side of all who feel that this was a serious cry for help from a talented young woman. T. Bruce Neeley (#9) raises the important potential for a family history of depression and suicide attempts with her father’s 1970 experiences.

    To clarify the answers to Dave X’s question (#1) is that the remedy was made by drying down, for example, 30 μL of a 1000-fold dilution of Aconitum and so forth.

    That raises another question I’ve also pondered: how can lyophilized homeopathic remedies still retain the claimed “memory of water.” Isn’t the remedy then lost when dried down into a tablet with excipients?

    Thanks, jre, for pointing out that homeopathic remedies are actually more tightly regulated than herbal dietary supplements.

    And vielen Dank to paraphen and his wife for translating my post into German at her site. Wow!

  19. #19 Abel Pharmboy
    December 9, 2009

    I neglected to mention that there was a valuable Twitter exchange on Monday with Dr Brent Stockwell, Professor of Biology and Chemistry at Columbia University. Dr Stockwell’s contributions were fueled by the input of his brother, Rodd, is a MD who has an integrative medicine practice in Middleton, MA.

    The Doctors Stockwell pointed out with regard to Belladonna, a source of the anticholinergic alkaloids atropine and scopolamine, that 75 mg of “4X” Belladonna (a 10,000-fold dilution of the original) would still give 7.5 μg of compounds with potent competitive antagonist activity at muscarinic cholinergic receptors. Atropine is still used in the emergency setting during resuscitation from cardiac arrest at a IV dose of 0.5-1.0 mg (as the sulfate) because it blocks the negative influence of the vagus nerve on heart rate. Scopolamine is most commonly encountered today in motion sickness transdermal delivery patches (e.g. Transderm Scop™) with a dose of 1 mg that is released over three days. So, on initial calculations, Ms Joel taking eight tablets with 7.5 μg of Belladonna alkaloids could have given her an increase in heart rate and sense of fear or panic that might have driven her to call for help. A very astute and wise observation.

    I thought about this for a moment, especially in the context of jre’s comment that homeopathic remedies are tightly regulated by FDA to ensure that no active compounds are present. I recognized that we must also consider the nature of the starting material used by the homeopathic manufacturer. It was not pure Belladonna alkaloids but rather, as in the homeopathic and herbal traditions, Belladonna plant material, usually leaves. In literature dating back to a 1921 paper in the Journal of Pharmacology and Experimental Therapeutics, the alkaloid composition of Belladonna plant material ranges from 0.4% to 1.2% by weight. One can purchase such Belladonna plant material on the wholesale global market that is largely standardized to 1.0% atropine. So, taking 1.0% as a nice round number, the 7.5 μg cited above now becomes 75 ng of total alkaloids per Traumeel tablet. Even eight tablets would only provide 600 ng (or 0.0006 mg) of total alkaloids, a dose that would be highly unlikely to cause any biological effect.

    Many thanks to everyone for being so active in contributing to this discussion. We’re fortunate that we are not discussing a drug tragedy for a change but this has been an excellent opportunity to address the differences between herbal medicine and homeopathy, as well as to revisit the pharmacology of the Belladonna alkaloids.

    But paramount in these discussions is that a talented young woman in anguish fortunately did not choose to take a dangerous substance. So again, we send our very best wishes to Ms Joel as she moves forward.

  20. #20 Anirban
    December 9, 2009

    That is an exceptional commentary. Thanks for the analysis of the JPET paper!

  21. #21 Joe
    December 10, 2009

    Yes, thanks for the JPET paper. I have a colleague who is an authority on homeopathy, we have co-authored two articles on the topic, one of which appeared in the “journal” Homeopathy. So, there is our cred.

    When I first heard of Traumeel, someone questioned if it was dilute-enough to be homeopathic. It is my opinion that a 1X, succussed solution qualifies; but I contacted my friend to ask what she thinks qualifies. She replied “How long is a piece of string?” So, now I am reduced to measuring bits of string.

    There is yet another problem with calling Traumeel homeopathic. Traditionally, homeopaths don’t use mixtures. As with any form of quackery, proponents are free to make things up as they go along.

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