Respectful Insolence

Acupuncture for Parkinson’s disease?

Critics who don’t like my insistence on applying the scientific method to the claims of alternative medicine sometimes accuse me of unrelenting hostility towards alternative medicine, as though no amount of evidence would ever convince me of the efficacy of various alternative medicine therapies. Nothing could be further from the truth; I merely insist, as I have from the very beginning, that, at the very least, the claims of alternative medicine should be subject to the same testing by the scientific method that “conventional” or “scientific” medical treatments (a.k.a. evidence-based medicine, or EBM for short) are before being adopted by physicians. In other words, I reject the very term “alternative medicine” as a false dichotomy between “standard” medicine and an “alternative.” To me it should all be just medicine.

Some alternative medical treatments (such as homeopathy, for example) are so obviously implausible scientifically that it doesn’t take much testing to be able to dismiss them as the bunk that they are. However, for others, the evidence is not so clear-cut, even when the scientific rationale may be a bit dubious. To me, acupuncture falls into this latter category. Certainly, the whole thing about qi (energy) and using needles to “unblock the flow of qi” by placing them through the skin along certain “meridians” is nothing but a lot of mystical hokum, and certainly these meridians are not based on any anatomic structures that we know of. Even so, it’s possible that acupuncturists may have stumbled on something, even if their rationale is full of crap, scientifically speaking. The lack of scientific rationale wouldn’t bother me so much if acupuncturists didn’t still insist on invoking qi as the reason for its alleged efficacy and downplaying the possibility of complications (for example, there are 81 articles in PubMed about pneumothorax as a complication of acupuncture and even reports of the occasional fatality). Still, it’s always possible that sticking needles in someone’s skin somehow releases endorphins or does something therapeutic, although it doesn’t seem to matter whether the needles are stuck along the “meridians” or not.

So what, then, am I to make of this study whose abstract follows below the fold?

Kang JM, Park HJ, Choi YG, Choe IH, Park JH, Kim YS, Lim S. Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Brain Res. 2007 Feb 2;1131(1):211-9.

Department of Meridian and Acupoints, College of Korean Medicine, Kyung Hee University, Seoul, South Korea; WHO Collaborating Centre for Traditional Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul, South Korea.

Using a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD), this study investigated on the neuroprotective effects of acupuncture by examining whether acupuncture contributed to inhibiting microglial activation and inflammatory events. C57BL/6 mice were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. Acupuncture was then applied to acupoints Yanglingquan (GB34) and Taichong (LR3) starting 2 h after the first MPTP administration and then at 48 h intervals until the mice were sacrificed for analyses at 1, 3, and 7 days after the last MPTP injection. These experiments demonstrated that acupuncture inhibited the decreased of the tyrosine hydroxylase (TH) immunoreactivity (IR) and generated a neuroprotective effects in the striatum (ST) and the substantia nigra (SN) on days 1, 3, and 7 post-MPTP injections. Acupuncture attenuated the increase of macrophage antigen complex-1 (MAC-1), a marker of microglial activation, at 1 and 3 days and reduced the increases in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression on days 1, 3, and 7. In MPTP group, striatal dopamine (DA) was measured by 46% at 7 days, whereas DA in the acupuncture group was 78%. On the basis of these results, we suggest that acupuncture could be used as a neuroprotective intervention for the purpose of inhibiting microglial activation and inflammatory events in PD.

Basically, this study looked at a mouse model of Parkinson’s disease that results in similar clinical symptoms as sporadic Parkinson’s disease in humans. It is the loss of dopamine-producing neurons in a part of the brain called the substantia nigra that is responsible for the development of Parkinson’s disease, and at present treatment is based on trying to replenish the disappearing dopamine with a drug called L-dopa, which is converted into dopamine by these same neurons. Basically, the injection of a chemical (MPTP) mimics this condition in mice by causing inflammation and destruction of dopamine-producing neurons in the mouse brain.

What the investigators did was to divide the mice up into four groups: (1) control; (2) MPTP alone; (3) MPTP plus acupuncture at the Taichong (LR3) and Yanglingquan (GB34) acupoints (whatever they are); apparently they’re in the leg); (4) MPTP plus sham acupuncture in the hips. Mice were all treated identically, as far as I could tell, even up to having the groups of mice that didn’t get acupuncture restrained for 30 seconds, just as the mice who received acupuncture were. The methodology seems pretty good, at least in the overall experimental design. The results reported an attenuation of increases in substances associated with activation of inflammatory cells and a relative preservation of dopamine levels in the MPTP-treated mice also treated with acupuncture. It also seemed to be specific, because the sham acupuncture groups didn’t show the same apparently protective effect.

So, does this study mean that acupuncture would be useful in the treatment of Parkinson’s disease. Well, not so fast. Maybe it does; maybe it doesn’t. (More likely it doesn’t.) For one thing, some of the effects reported are rather small; and for at least one of them sham acupuncture appeared to have a similar, albeit weaker, protective effect. For another thing, the people looking at the immunohistochemical staining of the tissue slides of mouse brain were not blinded to which experimental group they were in. This is not nearly as much of a concern for the Western blots for protein measurements, mainly because they are not nearly as prone to observer effects, but blinding of the examiner to the experimental group is essential in the reading of any sort of tissue section staining because subtle, unintentional bias can creep in. For example, the tissue sections stained for an enzyme that is an important indicator of the presence and viability of these neurons, tyrosine hydroxylase (TH). Let’s say you’re counting the percentage of the neurons that stain positive for TH; if you know which tissue section belongs to which experimental group, it is very easy in the case of cells that stained weakly to let yourself read such cells as positive on tissue section swhere you expect to see more positive staining (the control and the MPTP plus acupuncture site) and as negative in tissue sections where you don’t (the MPTP alone and MPTP plus sham acupuncture groups). This is not dishonesty, nor is it usually intentional (although occasionally it can be). It is merely a subtle form of confirmation bias, and to guard against it is the very reason blinding to experimental groups is so important, not just in experiments like this but even more so in clinical trials. In any case, the staining didn’t show much, if any, difference in the substantia nigra. At least the tissue sections that the investigators decided to display didn’t show that impressive a difference, and we scientists know that investigators always pick their very best pictures to use in any paper. (Certainly, I always pick my best tissue sections and best blots to display in any paper.) There did appear to be a difference on Western blots of protein, but I’m always a little suspicious of quantifying Western blots because they can be notoriously nonlinear. However, this is no worse than many other papers that do similar sorts of measurements of protein levels; so I have to assume that the evidence does show a treatment effect due to acupuncture on the levels of the proteins examined.

Finally, and perhaps most importantly, I’d really like to see some clinically relevant observations in this animal model, the shortcomings of mouse models of disease notwithstanding. Unfortunately, the investigators never reported whether acupuncture alleviated the symptoms of this experimental model of Parkinson’s disease in their mice, something other researchers have tried to do in a rat model of Parkinson’s disease. Also, some of what was written in the paper also gives me pause. For example, the authors cite a really dubious case series claiming that acupuncture “possesses definite therapeutic effectiveness for Parkinson’s disease” in support of a contention that acupuncture can relieve symptoms of Parkinson’s disease and delay its progression in patients, while failing to cite a more recent double-blinded randomized pilot study that found no statistically significant improvement in their scores on the motor subscale of the Unified Parkinson’s Disease Rating Scale (UPDRS), the Parkinson’s Disease Questionnaire (PDQ-39), and the Geriatric Depression Scale.

Still, I realize that last complaint about the papers the authors chose to cite or not to cite is bordering on nit-picking. It doesn’t change the fact that we’re left with the results of this study, which may indicate a physiologic effect of acupuncture that appears independent of any sort of placebo, given that it’s in a mouse. (That’s all assuming that this result can be replicated by other laboratories, as replication of results like these is critical.) Even so, if you look at the totality of the evidence out there, it is mostly negative as far as demonstrating any likely therapeutic effect of acupuncture in Parkinson’s disease. This study doesn’t change that, and there are always outliers. Whether the results of the study discussed translate into benefits in human patients with Parkinson’s disease or not, there’s one thing we can say: If acupuncture has any therapeutic value at all in Parkinson’s disease (or any other disease or condition), it will be due to an objective, measurable mechanism that is decipherable by science. It will not be due to “altering the flow” of an undefined, unmeasurable “life energy” (qi).

Comments

  1. #1 Joe
    January 29, 2007

    Who the hell “refereed” this article??! If the “researchers” did not “blind” the people doing the evaluations, this should have been rejected as sub-standard for a grade-school science fair! To be fair to the journal- junk occasionally slips into the best publications (I don’t know the reputation of this particular publication).

  2. #2 Nat
    January 29, 2007

    Brain Res is a pretty good journal (Impact factor 2.3). It’s not the New England Journal but it’s not bad.

    As for the lack of blinding- it’s actually very common. Almost everytime I’m in a cross discipline seminar series with a bunch of basic scientists (especially graduate students) they fail to blind for observer bias. Every time I see it I’m intensely annoyed. But it just keeps happening.

    Unlike ORAC a lot of basic ‘scientists’ don’t know a great deal about general scientific design of experiments. They are not trained to distrust their subjective judgements.

  3. #3 Nat
    January 29, 2007

    Brain Res is a pretty good journal (Impact factor 2.3). It’s not the New England Journal but it’s not bad.

    As for the lack of blinding- it’s actually very common. Almost everytime I’m in a cross discipline seminar series with a bunch of basic scientists (especially graduate students) they fail to blind for observer bias. Every time I see it I’m intensely annoyed. But it just keeps happening. Immunology labs in particular (but this is just my own limited sample). Others may feel free to disagree?

    Unlike ORAC a lot of basic ‘scientists’ don’t know a great deal about general scientific design of experiments. They are not trained to distrust their subjective judgements and are not trained to recognise bias in research. Hence the lack of blinding or randomisation or control common in these fields.

  4. #4 CatherinaB
    January 29, 2007

    “pretty good” means that you want to blind your observers. I have reviewed papers for Brain Res and would have rejected the paper without it.

    What I find interesting is that there is an effect in the ‘real’ acupuncture and the ‘sham’ acupuncture group. This has also been found in the large German acupuncture trials – so I wonder whether there is something to the treatment after all.

    However, the observers will have been aware of these results, too. You really cannot tell until someone has looked the slides without bias.

  5. #5 Orac
    January 29, 2007

    True enough; however, the investigators also extracted protein from the tissues and did Western blots, which are less prone to observer bias, which is the only thing that kept me from just trashing this paper completely. Of course, I’m always a bit leery of using densitometry to quantify Western blots, because, depending on the exact methodologies used, they can be notoriously nonlinear, so that little differences can be magnified into big differences.

    Still, I sort of believe the Western blots in this paper.

  6. #6 James
    January 29, 2007

    Even given the experimental flaws this an interesting result. Now somone just needs to do a larger test with a better design. I would also like to see a 5th groups where the mice are given acupuncture to arbitrary but consistent points.

  7. #7 Nathan J. Yoder
    January 30, 2007

    Downplaying potential complications with acupuncture? According the paper you cited, they’re very rare and fatalities are super-extraordinarily rare (not “occasional”). The only reason to even bring up fatalities is as a clear emotional ploy, the same kind employed by alties.

    Stating the facts isn’t playing it down and this makes me think that you’re deliberately trying to exaggerate, in a flagrantly pseudoscientific manner, to make acupuncture look bad.

    This is from that paper you cited:
    “the risk of a serious adverse event with acupuncture is estimated to be 0.05 per 10 000 treatments, and 0.55 per 10 00 individual patients.”

    What’s that they’re downplaying again?

    I also enjoy the “and still, it’s always possible,” even though it’s already been shown through many studies to do something therapeutic. Stop it with the selective downplaying and selective criticism. This article isn’t skeptical, it’s very much an altie mindset article with the particular category of treatment reversed.

    P.S. “To me it should all just be medicine, but I still call it ‘alternative medicine’ and use ‘alternative medicine’ as a category and in no way diverge from the usage of ‘alternative medicine’” doesn’t sound right, somehow.

  8. #8 Orac
    January 30, 2007

    I use the term “alternative medicine” because it’s so entrenched; in reality what it should be called is “non-evidence-based medicine” as opposed to “evidence-based medicine.” When enough studies indicate efficacy, then specific modalities could then fall into the “evidence-based” category.

    As for acupuncture in Parkinson’s disease, the evidence really is almost all negative; for acupuncture in other diseases, the evidence is conflicting and mostly negative, which tells me that the therapeutic effect, if any, is small.

    Regarding complications, my point was that, like so many other “alternative” medicines, acupuncture is sold as being almost perfectly safe. While it is pretty safe, serious complications do occasionally occur, including pneumothorax, nerve injury, infection, and even the occasional death.

  9. #9 Amy Alkon
    January 30, 2007

    “Non-evidence-based” medicine is a terrific term — one I’ll try to use when I link to pieces from your blog. It works as a term for those who believe in The Imaginary Friend as well. Then again, “primitive, ridiculous, nonthink-based belief” works pretty well, too.

  10. #10 Stephen
    January 30, 2007

    Does the paper make it explicit that all the mice were killed at the 1, 3 and 7 day points? Or is it possible that some were killed each day, with days 1, 3 and 7 just happening to produce effects in the desired direction?

  11. #11 Nathan J. Yoder
    January 30, 2007

    >I use the term “alternative medicine” because it’s so entrenched; in reality what it should be called is “non-evidence-based medicine” as opposed to “evidence-based medicine.”

    Except the problem is a large part of the “NEBM” either has been studied or is in the process of doing so. “Alternative” refers to two things: a) how it originated (outside traditional medicine circles) and b) the general acceptance from the medical community as a whole.

    >When enough studies indicate efficacy, then specific modalities could then fall into the “evidence-based” category.

    Conventional medicine always starts this way–it’s no as if large studies pop up overnight. However, I would still call it conventional medicine if it originated from “conventional sources” (e.g. pharmaceutical company research). Additionally, I certainly wouldn’t call pharmaceutical drug candidates “NEBM,” especially considering the intent to study them.

    So say candidate, Ro-123456, has shown some positive results in some internal, early animal studies. Would you call it non-evidence based? After all, it hasn’t demonstrated efficacy in humans yet, nor has it been studied on a large scale even on animals.

    >As for acupuncture in Parkinson’s disease, the evidence really is almost all negative

    Don’t move the goal posts.

    Your first two paragraphs and especially the parts I were referring to, were about acupuncture in general, not just for parkinson’s treatment.

    >the evidence is conflicting and mostly negative, which tells me that the therapeutic effect, if any, is small.

    Look, I don’t really appreciate so-called skeptics who hold double standards like these.

    There are clear positive evidence for some conditions. There’s no “if any” about it. It’s “there is a therapeutic effect.” Specialists in the field, and by that I mean MDs and PhDs (not whatever title TCM practioners have) the consensus is now that it does have therapeutic effects. What you’re doing is dismissing it on the basis that it’s not a cure-all. Who cares?

    The same applies to every traditional treatment in existence, but you’re not downplaying those as having a “small therapeutic effect.”

    Obviously, if you analyze acupuncture as treatment for every treatment in existence, it won’t do well. No treatment would. Again, on this basis, it would be ridiculous to call it a “small therapeutic effect,” then all treatments in existence would qualify for the same.

    I anticipate a response like “but some people claim that it is a cure all,” so I’ll preempt that by saying that’s entirely irrelevant, as we’re talking about how you’re portraying it, not them.

    You haven’t done enough research to keep up with it? Fine. Nothing is wrong with that, no one can humanly follow all research, but what you don’t do is use your authority to act is if it were anything other than casual knowledge.

    >Regarding complications, my point was that, like so many other “alternative” medicines, acupuncture is sold as being almost perfectly safe. While it is pretty safe

    And it IS almost perfectly safe. You even follow it up by saying “it is pretty safe.” Pretty? Perfectly? At best, you’re splitting hairs, at worst, you’re being dishonest.

    >serious complications do occasionally occur, including pneumothorax, nerve injury, infection, and even the occasional death.

    Don’t you mean rarely, as per your own cited data? Deaths are EXTREMELY rare. How does EXTREMELY RARE qualify as “occasional”? Peanuts cause “occasional deaths” too, do you consider those to be just “pretty safe”? If you want to delve into the “extremely rare” realm, almost every substance can cause “occasional deaths.”

    You might have had a valid defense to adding that in if you just stuck with the more common complications, but adding in death only exists for emotive effects.

    This post here doesn’t read like a skeptical post, it reads like an anti-alternative medicine post. You have other good posts, but that doesn’t excuse what’s said here. You even admit at the end that you added a nit picked complaint. Can’t you just admit that held a double standard here?

  12. #12 Orac
    January 30, 2007

    There are clear positive evidence for some conditions. There’s no “if any” about it. It’s “there is a therapeutic effect.” Specialists in the field, and by that I mean MDs and PhDs (not whatever title TCM practioners have) the consensus is now that it does have therapeutic effects. What you’re doing is dismissing it on the basis that it’s not a cure-all. Who cares?

    One can’t help but notice that you keep repeating your contention acupuncture has definite “therapeutic effects” without actually listing any conditions or scientific evidence supporting its efficacy for those conditions. You’re mighty long on rants and short on data, which is ironic, given that, when you boil all your verbiage down to its essence, you seem to be accusing me of the same thing.

  13. #13 MartinM
    January 31, 2007

    Pretty? Perfectly? At best, you’re splitting hairs, at worst, you’re being dishonest.

    Don’t you mean rarely, as per your own cited data? Deaths are EXTREMELY rare. How does EXTREMELY RARE qualify as “occasional”?

    Speaking of irony…

  14. #14 Nathan J. Yoder
    February 1, 2007

    >One can’t help but notice that you keep repeating your contention acupuncture has definite “therapeutic effects” without actually listing any conditions or scientific evidence supporting its efficacy for those conditions.

    One can’t help but notice you keep repeating yourself without backing your claim that deaths and these other complications are occasional. In fact, you already cited something proving them wrong.

    >You’re mighty long on rants and short on data, which is ironic, given that, when you boil all your verbiage down to its essence, you seem to be accusing me of the same thing.

    This, coming from the guy who repeatedly evades what I’ve said, repeats himself and then accuses me of repeating MYSELF?

    Ok. I’ve a) proven your claims of being “occasional” wrong with your own citation and b) proven your use of language to be contradictiary, at best (you never addressed B because even that’s ridiculous).

    Add this to the fact that you started off this entire, bold emotive post with some claims you have yet to substantiate. Then your logic flips in: “Hey Nathan, the burden’s on you to prove everything I’ve said wrong, even though you’ve already done that on two points and I NEVER have to back up the point I made. EVER.”

    >Speaking of irony…

    I don’t see the irony there. Who equates “extremely rare” with “occasional”?

  15. #15 Orac
    February 1, 2007

    Nice rant.

    You did it again: No examples of diseases for which acupuncture has definite therapeutic effects.

  16. #16 Nathan J. Yoder
    February 1, 2007

    I never said it has “definite” therapeutic effects, that’s you being dishonest YET AGAIN. Actually, since the implication is that “you said definite or something equivalent,” that makes it a lie, not just dishonest. You refuse to address two main points YET AGAIN.

    If you’re going to be a good sophist, it helps not to engage in blatant dishonesty. At the very least, you have some “weasel room” with extreme hyperbole as you did in point (A) (regarding so-called “occasional” usage).

    And as I explained, you haven’t addressed points (A) and (B) of yours being proven completely wrong. “Hey Nathan, my name is Orac, and I’ll put words into your mouth and make all the bogus claims I want then require you to prove them wrong.”

    Orac, have you ever admitted that you were wrong when you were “bested” on one of your bold claims on your blogs? Better yet, have you admitted when you were wrong when you cited evidence that you were wrong? Your ego is so huge and you can’t even taken any kind of constructive criticism if it goes against your faith-based beliefs–namely the one in this case that all alternative medicines are ineffective (which makes your title of skeptic bogus).

    Let’s be honest here: you’re behaving like a textbook altie, engaging in lies, dishonesty and general evasion, except the argument extremes have been switched. In this post and the other, I also see you moving goal posts and suddenly being polite in backpedaling when you stick your foot in your mouth. OF course, you’re less likely to admit you’re wrong when it’s one of your own main points, proven wrong by your own evidence, by someone who is ‘bolder’ and smarter than you. ;)

  17. #17 Nathan J. Yoder
    February 1, 2007

    P.S. You’re still repeating yourself and refusing to substantiate this claim you made: “…acupuncture in other diseases, the evidence is conflicting and mostly negative, which tells me that the therapeutic effect, if any, is small.”

    Keep on with the double standard though. “Hey, I make blog posts making all kinds of claims, if you DARE to criticise me and prove me wrong on other points, I’ll then require that the BURDEN OF PROOF lie exclusively on you for proving my other bold claims correct.”

    Orac, are you attempting an appeal to expert testimony? I doubt that you’re than expert in this area, which would make it an appeal to [false] authority instead. I see no evidence here, unless you want to count this one anecdotal case.

    !I can appeal to expert testimony! NCCAM’s own expert panel on the subject. I could provide a citation, but given that you’re clearly appealing to your own expertise, you MUST be aware of this already and thus a citation is not necessary. So: you–no evidence, proven wrong on other points, me–proven right on multiple points, provided evidence even without a burden of proof.

    P.P.S. I don’t like this behavior and hope this doesn’t happen, but just in case, please don’t delete comments just because they make you look bad. I’ve had people of various strong faiths do this and it’s a pet peeve.

  18. #18 Orac
    February 2, 2007

    As always, I’m happy to let my readers judge who’s the one that “looks bad” here; I doubt many of them will conclude it’s me.

  19. #19 mc2
    February 6, 2007

    Nathan, the reason Orac has shown you a little “repsectful insolence (TM)” is that you claim to have the proof of your claims and then are shoving the burden on to him to disprove it.

    You are making the claim of benifits so the burden is on you.

    If you have proof, or at least a reference to point us at then, lets see it.

The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.