May 22 2009

License for Homeopathic Pill in UK

Published by under Uncategorized
Comments: 40

Regulations for health products are increasingly becoming absurd in the US, UK and other countries. More and more there are double standards – one scientific standard for regular medicine, and then a separate fantasy-land standard for so-called alternative medicines.

Recently the Medicines and Healthcare Products Regulatory Agency (MHRA) has granted an arnica homeopathic product a licence for the relief of sprains or bruising. This means that the product can now state on its label:

“A homeopathic medicinal product used within the homeopathic tradition for symptomatic relief of sprains, muscular aches and bruising or swelling after contusions.”

What does that mean – within the homeopathic tradition? Does this qualifier admit, in a way, that these claims are not legitimate within the scientific tradition? And, by extension, that homeopathy is not scientific? I think it does. But of course the goal is for the consumer to see the specific claims and to feel that they must be legitimate if the MHRA has allowed it.

To anyone who understand anything about science and homeopathy, this is sorry state of affairs. Homeopathy is a pseudoscientific notion that involves remedies that generally are diluted past there point where there is any active ingredient left. The prior-plausibility of homeopathy approaches zero.

In addition, we have copious amounts of clinical evidence to show that homeopathic remedies simply do not work. Edzard Ernst wrote a review of systematic reviews in homeopathy, and concluded:

In particular, there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions. Similarly, there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo. It is concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice.

In short, the science says that homeopathy does not work.  With regard to the specific claim here, homeopathic dilutions of the poison arnica, the evidence is also negative. This review, for example, concluded:

The claim that homeopathic arnica is efficacious beyond a placebo effect is not supported by rigorous clinical trials.

So why would a regulatory body whose job it is to protect the public from false claims for medical products allow a company to claim an effect when the science clearly shows no effect? Here is what an MHRA spokesperson had to say:

The MHRA said that the National Rules scheme was introduced to resolve an inconsistency in European legislation that meant that homeopathic products introduced before 1992 could state indications for their use, whereas remedies approved after that date could not make such claims.

There was another way to resolve the discrepancy – repeal the right to make unscientific and false claims for homeopathic remedies introduced prior to 1992.

We have the same problem in the US in that the homeopathic pharmacopeia was grandfathered in to FDA approval, so that homeopathic remedies did not have to go through testing of safety and efficacy individually to get approval.

There is now an overwhelming body of scientific evidence to show that homeopathic remedies are nothing more than placebos, which is in exact accord with the basic science which says there should be no physiological effect. Why can’t regulatory agencies acknowledge that basic fact which is supported by the vast majority of the scientific community? Until they do, they have no credibility. They are doing a disservice to the public and giving a huge and undeserved boost to quackery.

Now more than ever we need a single, rational, evidence and science-based system of regulation for health products. The public can no longer afford a double standard, where quackery gets a free ride as long as its ideological supporters and profiteers lobby loudly enough.

We are also in the midst of a health care crisis which is resulting in the rationing of care and/or huge debts because of the expense of modern medicine. Addressing this crisis will involve difficult trade-offs. But there is a win-win whenever we can increase the efficiency of health care. There is nothing more inefficient than health care interventions that do not work or are harmful. Therefore it is in everyone’s interest to purge the system of worthless interventions and outdated unscientific notions.

Homeopathy, in its entirety, should be the first to go.

40 responses so far

40 Responses to “License for Homeopathic Pill in UK”

  1. Enzoon 22 May 2009 at 3:44 pm

    “…the homeopathic pharmacopeia was grandfathered in to FDA approval…”

    I really have to do more reading on the approval process. I just don’t understand why FDA approval is not required for so many things. Obviously not every product on the market can be subjected to the rigorous FDA standards drugs have to meet, but I wonder why new formulations/usages of “remedies” or nutritional supplements don’t have to undergo any studies for safety/efficacy.

    Are there simply easier criteria to meet? Or is it the case, like your quote suggests, that if the formulation of a product meets X, Y, Z no further approval is necessary? Do they base it on a list of known active ingredients and their safety?

    Seems odd that anyone can put out some absurd formulation and make efficacy claims as long as they are sufficiently vague and cleverly worded. Some of those huge volume energy drinks are like doing speed, but they don’t have to be evaluated for safety? Hmm…

  2. Steven Novellaon 22 May 2009 at 4:28 pm

    In the US – DSHEA in 1994 removed all herbs and supplements from the FDA approval process and created a new kind of claim, called “structure function” claims, that can be made without any oversight.

    The FTC can still go after companies for fraud, but they can only deal with a tiny percentage of what’s out there.

  3. DanaUllmanon 22 May 2009 at 6:11 pm

    Before discussing research issues, the people reading your blog might be intrigued to discover how much military’s thinking has invaded Western medical thinking. In so doing, we have created a “doctatorship” of the worst kind.

    You will probably be shocked to learn about the serious problems incurred by what you think is “scientific” thinking, which may more accurately be considered militaristic thinking.

    Read this: http://www.odemagazine.com/doc/63/military-medicine/

    I certainly question your assertion that homeopathy is a “pseudoscience,” and I encourage you to become more familiar with the body of evidence that presently exists for it.

    http://www.homeopathic.com/articles/view,132

    As for Arnica research, I certainly acknowledge that Arnica is not effective in treating “everything” (of course). Giving it to long-distance runners does not seem to have an effect…but that doesn’t mean that it isn’t effective when used correctly…

    A randomized double-blind placebo-controlled study on the use of a novel programmed dosage regimen of Arnica, named SinEcch developed by Alpine Pharmaceuticals, a marketing division of Hahnemann Laboratories, Inc. (San Rafael, CA.) was conducted by the head of the Facial Plastic Surgery Department at the Univeristy of California San Francisco (Seeley, Denton, Ahm, Maas, 2006). SinEcch is comprised of Arnica 1M and 12C and was tested in the treatment of people undergoing an extensive deep level facelift. This is the first successful homeopathic Arnica trial to be published in a major surgery journal, let alone one published by the American Medical Association. Arnica 1M was given in three doses (pre-op, post-op, and bedtime on the day of surgery). Arnica 12C was given three times a day for three days, starting on the day after the surgery. Of special importance is the fact that this trial utilized a novel computerized model for objective analysis of skin color changes based on high quality digital photographs of the patients.

    Patients receiving Arnica experienced decreased ecchymosis (bruising) as measured by the computer that calculated the number of square centimenters of ecchymosis for each patient on postoperative days 1, 5, 7, and 10 (all of the days in which this measurement was tested), with statistically significant differences on day 1 (P0.36). The patients receiving Arnica were significantly younger than the treatment group (mean age 32.6 vs. 37.9) (P

  4. DanaUllmanon 22 May 2009 at 6:13 pm

    (It seems that a large part of my post was truncated. Here’s the remaining part, starting at the full last paragraph from above.)

    Patients receiving Arnica experienced decreased ecchymosis (bruising) as measured by the computer that calculated the number of square centimenters of ecchymosis for each patient on postoperative days 1, 5, 7, and 10 (all of the days in which this measurement was tested), with statistically significant differences on day 1 (P0.36). The patients receiving Arnica were significantly younger than the treatment group (mean age 32.6 vs. 37.9) (P

  5. artfulDon 22 May 2009 at 6:43 pm

    Such an exhibition of “intelligent optimism” places you right up there with the likes of guru Deepak Chopra and Dr. Andrew Weil.

  6. Steven Novellaon 22 May 2009 at 6:51 pm

    Science as militaristic – is that the new anti-scientific meme being pushed.

    What many of us are advocating is simply the proper application of science to medical questions – science-based medicine. The science clearly shows that homeopathy does not work.

    Cherry picking individual studies is not the way to determine what the scientific evidence shows. When the entire homeopathy literature is looked at from an objective and scientific perspective, as I believe Edzard Ernst and others have done, the clear pattern that emerges is consistent with the conclusion that homeopathic remedies are placebos, and nothing more.

    Apologists for pseudoscience always play the conspiracy, suppression, closed minded, and now “militaristic” card. It’s all special pleading for the lack of scientific evidence.

  7. Jim Shaveron 22 May 2009 at 9:47 pm

    Okay, let me get this straight. In the magical, mysterious world of homeopathy, a 12C dilution means a ratio of 10^(-24), and a 1M dilution means that you start with a dilution of 1:100 and repeat that dilution 1000 times, for a final ratio of (incredibly) 10^(-2000)! At a dilution of 10^(-24), typically no more than one molecule of the original Arnica toxin will exist in the “remedy”, and the chances of there being at least one molecule in a “remedy” made from a 10^(-2000) dilution is so ridiculously, infinitesimally small I can’t calculate it in my head.

    OMG, Dana Ullman believes in some really stupid crap.

  8. RickKon 22 May 2009 at 10:41 pm

    DanaUllman,

    OK, let me get this straight:

    – the patients themselves could not tell a difference in bruising between the control group and the SinEcch group – in fact the SinEcch group did slightly worse;

    – the trained nurse and physicians could not tell a difference between the test and control groups;

    – when asked “when were you comfortable to go out in public”, the SinEcch group scored worse;

    – the data from the objective computer model was unexplainably erratic; but

    you’ve concluded the study was dramatic success for SinEcch.

    Did the authors of this study learn their protocols from Andrew Wakefield?

    Given the complete, repeatedly documented, dramatic failure of homeopathy to deliver any effect beyond a well-marketed placebo, don’t you feel even the tiniest responsibility to have these results repeated by a rival (or at least independent) researcher before plastering the results all over the box labels? Doesn’t throwing yourself behind one highly-questionable, atypical study cause even the faintest blip on your ethical radar?

    And given that homeopathy has to date been utterly bereft of anything remotely resembling a mechanism, aren’t you even the least bit curious where the water molecules store their memory?

  9. tmac57on 22 May 2009 at 11:06 pm

    DanaUllman:”You will probably be shocked to learn about the serious problems incurred by what you think is “scientific” thinking, which may more accurately be considered militaristic thinking.”

    Dear Mr. Ullman:
    Your INTERCOURSE on this seems a little bit OFF.
    Best regards,
    TMAC57

  10. Joeon 23 May 2009 at 2:13 pm

    The Dull-Man Law”
    http://www.sciencebasedmedicine.org/?p=448
    “In any discussion involving science or medicine, being Dana Ullman loses you the argument immediately…and gets you laughed out of the room.”

  11. DanaUllmanon 23 May 2009 at 2:25 pm

    Steve…something isn’t working here…I just reformated it (again).

    I certainly question your assertion that homeopathy is a “pseudoscience,” and I encourage
    you to become more familiar with the body of evidence that presently exists for it.

    http://www.homeopathic.com/articles/view,132

    As for Arnica research, I certainly acknowledge that Arnica is not effective in treating “everything” (of course). Giving it to long-distance runners does not seem to have an effect…but that doesn’t mean that it isn’t effective when used correctly…

    A randomized double-blind placebo-controlled study on the use of a novel programmed dosage regimen of Arnica, named SinEcch developed by Alpine Pharmaceuticals, a marketing division of Hahnemann Laboratories, Inc. (San Rafael, CA.) was conducted by the head of the Facial Plastic Surgery Department at the Univeristy of California San Francisco (Seeley, Denton, Ahm, Maas, 2006). SinEcch is comprised of Arnica 1M and 12C and was tested in the treatment of people undergoing an extensive deep level facelift. This is the first successful homeopathic Arnica trial to be published in a major surgery journal, let alone one published by the American Medical Association. Arnica 1M was given in three doses (pre-op, post-op, and bedtime on the day of surgery). Arnica 12C was given three times a day for three days, starting on the day after the surgery. Of special importance is the fact that this trial utilized a novel computerized model for objective analysis of skin color changes based on high quality digital photographs of the patients.

    Patients receiving Arnica experienced decreased ecchymosis (bruising) as measured by the computer that calculated the number of square centimenters of ecchymosis for each patient on postoperative days 1, 5, 7, and 10 (all of the days in which this measurement was tested), with statistically significant differences on day 1 (P0.36). The patients receiving Arnica were significantly younger than the treatment group (mean age 32.6 vs. 37.9) (P

  12. artfulDon 23 May 2009 at 2:46 pm

    Hey, Dana, three times wasn’t enough – the post still came back stupid.

  13. daedalus2uon 23 May 2009 at 3:00 pm

    Dana, when you use “greater than” and “less than” signs they are interpreted as HTML symbols and the formatting of the post is adjusted.

    Homeopathy certainly is pseudoscience. There is not a bit of science behind it. There is no coherent and credible theory of how it might work (that is consistent with the rest of scienc). There are no positive results in experimental animals. There are no well done, large, placebo controlled clinical trials.

  14. Steven Novellaon 23 May 2009 at 4:10 pm

    Dana – If there is part missing at the end then just post the part that is missing (not the whole thing) – maybe you are exceeding some limit.

  15. Enzoon 23 May 2009 at 5:38 pm

    “with statistically significant differences on day 1 (P0.36).”

    Dana,

    Is that a p-value? If so, 0.36 is hardly considered as statistically significant value. That’s basically saying there is a 36% probability of the results being explained by chance. Scientists and statisticians would be looking for a p-value no greater than 0.05 (5%). Also, Day 1 values are not terribly convincing. Especially with the criteria of skin color as a readout, I would think the variation would be extremely large. People heal differently, which I bet would show up in stringent statistical analysis. This study would have to be much, much tighter to make the claims it is trying to make. Please disregard. =)

  16. Watcheron 23 May 2009 at 6:32 pm

    Hi Dana,

    My foot is hurting (I stepped on a staple in my office while walking around barefoot). I was told by my homeopath that honey is a good substitute for antibiotics. How much should i use? I’d hate to waste good honey …

    Thanks

    OH! Also, what was the sample size of the Arnica experiment?

  17. DanaUllmanon 23 May 2009 at 7:11 pm

    In a randomized double-blinded, parallel-group study, the efficacy of Arnica D4 (aka 4X) (taken 3 times per day) and diclofenac sodium, 50 mg taken 3 times per day) were investigated for equivalence in 88 patients 4 days after bunion (hallux valgus) surgery (Karow, Abt, Frohling, 2008). Diclofenac is a popular nonsteroidal anti-inflammatory drug that is commonly prescribed after this surgery. Arnica D4 and diclofenac were found to be equivalent for wound irritation and patient mobility. A descriptive analysis showed the superiority of Arnica D4 with respect to patient mobility (p = 0.045). With respect to pain, Arnica D4 was inferior to diclofenac, though there were no significant differences in the use of additional analgesics during the 4 postoperative days. Arnica D4 was significantly better tolerated than diclofenac (p = 0.049). Nine (9) patients 20.45%) of the diclofenac group and 2 (4.5%) of the Arnica D4 group reported intolerance. There was no disturbance in wound healing in any of the patients. Arnica D4 is 60% cheaper than diclofenac.

    Ultimately, the researchers concluded that after bunion foot operations, Arnica D4 can be used instead of diclofenac to reduce wound irritation.

    In one randomized, double-blind, placebo-controlled trial with 60 patients who underwent varicose vein surgery, 43% of those patients given Arnica 12X (also called D12) pre- and postoperatively experienced remission or improvement in pain, while only 27% of those taking a placebo experienced a similar degree of relief (Wolfe, 2003). There were also trends towards a beneficial effect in the size of the hematoma (the pooling of blood under the skin) between groups. The homeopathic group took Arnica the night before the surgery, then once preoperatively and hourly postoperative dosages during the first day and three times a day during days 2-14.

    Randomised double blind, placebo controlled trial at a tertiary referral center was conducted with 190 patients over the age of 18 undergoing tonsillectomy (Robertson A, Suryanarayanan R,
    Banerjee A, 2007). Patients were randomised into intervention and control groups receiving either Arnica 30C or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work.

    The researchers found that 111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p

  18. DanaUllmanon 23 May 2009 at 7:12 pm

    I give up…it is truncating everything I write…I tried.

    Can I email my statement to someone?

  19. artfulDon 23 May 2009 at 8:38 pm

    Yeah, send it here: maria.caride@fda.hhs.gov

  20. DanaUllmanon 23 May 2009 at 9:23 pm

    Good one, kidder, but I’m not falling for that one, even though she would be impressed to read about the research on Arnica that exists. Give me YOUR email or Steve’s or someone who will post it here…

  21. studio34on 23 May 2009 at 11:37 pm

    Dana,

    Your message appears to truncate where you use the “less than” symbol which is being mistaken for html code. Write the word out instead of using the symbol and it should work.

    You need to pay attention to what Steve said in that cherry-picking data is not sufficient. The bulk of scientific research shows that there is no effect beyone what we would expect from placebo. Furthermore, you cannot ignore the fact that there is no plausible explanation for homeopathy. It defies all current knowledge of physics and biochemistry. The notion that water “has memory” is ludicrous. You need to address these issues as well if you want uphold your end of the debate.

    S

  22. CKavaon 24 May 2009 at 4:28 am

    studi34> What have you done! You’ve provided the key to infinite nonsense!

    Also in regards “you need to pay attention to what Steve said in that cherry-picking data is not sufficient… you cannot ignore the fact that there is no plausible explanation for homeopathy… you need to address these issues… if you want to phold your end of the debate”.

    You are in for surprise if you think D-Ullman cannot and will not ignore all the valid points and press on with the citing of poor studies and the ignoring of rebuttals.

  23. DanaUllmanon 24 May 2009 at 11:34 am

    Before discussing research issues, the people reading your blog might be intrigued to discover how much military’s thinking has invaded Western medical thinking. In so doing, we have created a “doctatorship” of the worst kind.

    You will probably be shocked to learn about the serious problems incurred by what you think is “scientific” thinking, which may more accurately be considered militaristic thinking.

    Read this: http://www.odemagazine.com/doc/63/military-medicine/

    I certainly question your assertion that homeopathy is a “pseudoscience,” and I encourage you to become more familiar with the body of evidence that presently exists for it.

    http://www.homeopathic.com/articles/view,132

    As for Arnica research, I certainly acknowledge that Arnica is not effective in treating “everything” (of course). Giving it to long-distance runners does not seem to have an effect…but that doesn’t mean that it isn’t effective when used correctly…

    A randomized double-blind placebo-controlled study on the use of a novel programmed dosage regimen of Arnica, named SinEcch developed by Alpine Pharmaceuticals, a marketing division of Hahnemann Laboratories, Inc. (San Rafael, CA.) was conducted by the head of the Facial Plastic Surgery Department at the Univeristy of California San Francisco (Seeley, Denton, Ahm, Maas, 2006). SinEcch is comprised of Arnica 1M and 12C and was tested in the treatment of people undergoing an extensive deep level facelift. This is the first successful homeopathic Arnica trial to be published in a major surgery journal, let alone one published by the American Medical Association. Arnica 1M was given in three doses (pre-op, post-op, and bedtime on the day of surgery). Arnica 12C was given three times a day for three days, starting on the day after the surgery. Of special importance is the fact that this trial utilized a novel computerized model for objective analysis of skin color changes based on high quality digital photographs of the patients.

    Patients receiving Arnica experienced decreased ecchymosis (bruising) as measured by the computer that calculated the number of square centimenters of ecchymosis for each patient on postoperative days 1, 5, 7, and 10 (all of the days in which this measurement was tested), with statistically significant differences on day 1 (P=0.005) and on day 7 (P=0.001). People who didn’t take Arnica had between 11%-41% more bruising than those who took this homeopathic regimen and took 50% longer to reduce their level of bruising to the level of bruising with SinEcch. On post-op day 7, the placebo patients had 30 square centimeters (4.5 square inches) more bruising on their faces than the Arnica treated group.

    Another study using SinEcch was conducting on 29 patients who underwent liposuction surgery (Kullick, 2002). The patients were all women aged 18-45. The surgeon also took photographs of the patients from the front, rear, left side, and right side on Postop weeks 1, 2, 3, and 4. Independent plastic surgeons with experience in liposuction were then asked to rank the 29 patients’ photo sets from most to least bruising/swelling for week 1 and similarly for Postop weeks 2, 3, and 4 separately. There was no statistically significant difference in the volume of fat removed. (P =0.36). The patients receiving Arnica were significantly younger than the treatment group (mean age 32.6 vs. 37.9) (P = .02). However this difference in age was accounted for in the statistical analysis that included a linear mixed-effects model to include treatment group, post-treatment week, and the interaction of the treatment group, time, and patient age.

    The results were highly statistically significant. The P values for three independent plastic surgeons were P=0.006, P

  24. DanaUllmanon 24 May 2009 at 11:35 am

    Before discussing research issues, the people reading your blog might be intrigued to discover
    how much military’s thinking has invaded Western medical thinking. In so doing, we have created a “doctatorship” of the worst kind.

    You will probably be shocked to learn about the serious problems incurred by what you think is
    “scientific” thinking, which may more accurately be considered militaristic thinking.

    Read this: http://www.odemagazine.com/doc/63/military-medicine/

    I certainly question your assertion that homeopathy is a “pseudoscience,” and I encourage
    you to become more familiar with the body of evidence that presently exists for it.

    http://www.homeopathic.com/articles/view,132

    As for Arnica research, I certainly acknowledge that Arnica is not effective in treating “everything” (of course). Giving it to long-distance runners does not seem to have an effect…but that doesn’t mean that it isn’t effective when used correctly…

    A randomized double-blind placebo-controlled study on the use of a novel programmed dosage
    regimen of Arnica, named SinEcch developed by Alpine Pharmaceuticals, a marketing division of
    Hahnemann Laboratories, Inc. (San Rafael, CA.) was conducted by the head of the Facial Plastic
    Surgery Department at the Univeristy of California San Francisco (Seeley, Denton, Ahm, Maas, 2006). SinEcch is comprised of Arnica 1M and 12C and was tested in the treatment of people
    undergoing an extensive deep level facelift. This is the first successful homeopathic Arnica trial to be published in a major surgery journal, let alone one published by the American Medical Association. Arnica 1M was given in three doses (pre-op, post-op, and bedtime on the day of surgery). Arnica 12C was given three times a day for three days, starting on the day after the surgery. Of special importance is the fact that this trial utilized a novel computerized model for objective analysis of skin color changes based on high quality digital photographs of the patients.

    Patients receiving Arnica experienced decreased ecchymosis (bruising) as measured by the computer that calculated the number of square centimenters of ecchymosis for each patient on postoperative days 1, 5, 7, and 10 (all of the days in which this measurement was tested), with statistically significant differences on day 1 (P=0.005) and on day 7 (P=0.001). People who didn’t take Arnica had between 11%-41% more bruising than those who took this homeopathic regimen and took 50% longer to reduce their level of bruising to the level of bruising with SinEcch. On post-op day 7, the placebo patients had 30 square centimeters (4.5 square inches) more bruising on their faces than the Arnica treated group.

    Another study using SinEcch was conducting on 29 patients who underwent liposuction surgery (Kullick, 2002). The patients were all women aged 18-45. The surgeon also took photographs of the patients from the front, rear, left side, and right side on Postop weeks 1, 2, 3, and 4. Independent plastic surgeons with experience in liposuction were then asked to rank the 29 patients’ photo sets from most to least bruising/swelling for week 1 and similarly for Postop weeks 2, 3, and 4 separately. There was no statistically significant difference in the volume of fat removed. (P =0.36). The patients receiving Arnica were significantly younger than the treatment group (mean age 32.6 vs. 37.9) (P = .02). However this difference in age was accounted for in the statistical analysis that included a linear mixed-effects model to include treatment group, post-treatment week, and the interaction of the treatment group, time, and patient age.

    The results were highly statistically significant. The P values for three independent plastic surgeons were P=0.006, P =0.003, and P=0 .0001 in favor of SinEcch reducing bruising and swelling.

    In a randomized double-blinded, parallel-group study, the efficacy of Arnica D4 (aka 4X) (taken 3 times per day) and diclofenac sodium, 50 mg taken 3 times per day) were investigated for equivalence in 88 patients 4 days after bunion (hallux valgus) surgery (Karow, Abt, Frohling, 2008). Diclofenac is a popular nonsteroidal anti-inflammatory drug that is commonly prescribed after this surgery. Arnica D4 and diclofenac were found to be equivalent for wound irritation and patient mobility. A descriptive analysis showed the superiority of Arnica D4 with respect to patient mobility (p = 0.045). With respect to pain, Arnica D4 was inferior to diclofenac, though there were no significant differences in the use of additional analgesics during the 4 postoperative days. Arnica D4 was significantly better tolerated than diclofenac (p = 0.049). Nine (9) patients 20.45%) of the diclofenac group and 2 (4.5%) of the Arnica D4 group reported intolerance. There was no disturbance in wound healing in any of the patients. Arnica D4 is 60% cheaper than diclofenac.

    Ultimately, the researchers concluded that after bunion foot operations, Arnica D4 can be used instead of diclofenac to reduce wound irritation.

    In one randomized, double-blind, placebo-controlled trial with 60 patients who underwent varicose vein surgery, 43% of those patients given Arnica 12X (also called D12) pre- and postoperatively experienced remission or improvement in pain, while only 27% of those taking a placebo experienced a similar degree of relief (Wolfe, 2003). There were also trends towards a beneficial effect in the size of the hematoma (the pooling of blood under the skin) between groups. The homeopathic group took Arnica the night before the surgery, then once preoperatively and hourly postoperative dosages during the first day and three times a day during days 2-14.

    Randomised double blind, placebo controlled trial at a tertiary referral center was conducted with 190 patients over the age of 18 undergoing tonsillectomy (Robertson A, Suryanarayanan R, Banerjee A, 2007). Patients were randomised into intervention and control groups receiving either Arnica 30C or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work.

    The researchers found that 111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p=0.05. The two groups did not differ significantly on analgesic consumption or any of the other secondary outcome measures (number of post-operative visits to GP, use of antibiotics and secondary haemorrhage readmissions). The results of this trial suggest that Arnica given after tonsillectomy provides a small, but statistically significant, decrease in pain scores compared to placebo.

    A randomized double-blind, placebo-controlled of 60 patients (33 women and 27 men, with an average age of 39) who were suffering from dental neuralgia after tooth extraction were either prescribed a placebo or Arnica 7C and Hypericum 15C (alternatively at four hour intervals)(Albertini, Goldberg, Sanguy, et al, 1985). Patients who were using anti-inflammatory drugs were excluded from the study. The patients were treated for three days and asked to assess their pain on a decimal scale. The patients were also asked whether reasonable pain control had been achieved. This study found that patients given the two homeopathic medicines experienced a statistically significant (p

  25. DanaUllmanon 24 May 2009 at 11:38 am

    Finally…I have gotten rid of ALL of the “

  26. DanaUllmanon 24 May 2009 at 11:40 am

    Before discussing research issues, the people reading your blog might be intrigued to discover
    how much military’s thinking has invaded Western medical thinking. In so doing, we have created a “doctatorship” of the worst kind.

    You will probably be shocked to learn about the serious problems incurred by what you think is
    “scientific” thinking, which may more accurately be considered militaristic thinking.

    Read this: http://www.odemagazine.com/doc/63/military-medicine/

    I certainly question your assertion that homeopathy is a “pseudoscience,” and I encourage
    you to become more familiar with the body of evidence that presently exists for it.

    http://www.homeopathic.com/articles/view,132

    As for Arnica research, I certainly acknowledge that Arnica is not effective in treating “everything” (of course). Giving it to long-distance runners does not seem to have an effect…but that doesn’t mean that it isn’t effective when used correctly…

    A randomized double-blind placebo-controlled study on the use of a novel programmed dosage
    regimen of Arnica, named SinEcch developed by Alpine Pharmaceuticals, a marketing division of
    Hahnemann Laboratories, Inc. (San Rafael, CA.) was conducted by the head of the Facial Plastic
    Surgery Department at the Univeristy of California San Francisco (Seeley, Denton, Ahm, Maas, 2006). SinEcch is comprised of Arnica 1M and 12C and was tested in the treatment of people
    undergoing an extensive deep level facelift. This is the first successful homeopathic Arnica trial to be published in a major surgery journal, let alone one published by the American Medical Association. Arnica 1M was given in three doses (pre-op, post-op, and bedtime on the day of surgery). Arnica 12C was given three times a day for three days, starting on the day after the surgery. Of special importance is the fact that this trial utilized a novel computerized model for objective analysis of skin color changes based on high quality digital photographs of the patients.

    Patients receiving Arnica experienced decreased ecchymosis (bruising) as measured by the computer that calculated the number of square centimenters of ecchymosis for each patient on postoperative days 1, 5, 7, and 10 (all of the days in which this measurement was tested), with statistically significant differences on day 1 (P=0.005) and on day 7 (P=0.001). People who didn’t take Arnica had between 11%-41% more bruising than those who took this homeopathic regimen and took 50% longer to reduce their level of bruising to the level of bruising with SinEcch. On post-op day 7, the placebo patients had 30 square centimeters (4.5 square inches) more bruising on their faces than the Arnica treated group.

    Another study using SinEcch was conducting on 29 patients who underwent liposuction surgery (Kullick, 2002). The patients were all women aged 18-45. The surgeon also took photographs of the patients from the front, rear, left side, and right side on Postop weeks 1, 2, 3, and 4. Independent plastic surgeons with experience in liposuction were then asked to rank the 29 patients’ photo sets from most to least bruising/swelling for week 1 and similarly for Postop weeks 2, 3, and 4 separately. There was no statistically significant difference in the volume of fat removed. (P =0.36). The patients receiving Arnica were significantly younger than the treatment group (mean age 32.6 vs. 37.9) (P = .02). However this difference in age was accounted for in the statistical analysis that included a linear mixed-effects model to include treatment group, post-treatment week, and the interaction of the treatment group, time, and patient age.

    The results were highly statistically significant. The P values for three independent plastic surgeons were P=0.006, P =0.003, and P=0 .0001 in favor of SinEcch reducing bruising and swelling.

    In a randomized double-blinded, parallel-group study, the efficacy of Arnica D4 (aka 4X) (taken 3 times per day) and diclofenac sodium, 50 mg taken 3 times per day) were investigated for equivalence in 88 patients 4 days after bunion (hallux valgus) surgery (Karow, Abt, Frohling, 2008). Diclofenac is a popular nonsteroidal anti-inflammatory drug that is commonly prescribed after this surgery. Arnica D4 and diclofenac were found to be equivalent for wound irritation and patient mobility. A descriptive analysis showed the superiority of Arnica D4 with respect to patient mobility (p = 0.045). With respect to pain, Arnica D4 was inferior to diclofenac, though there were no significant differences in the use of additional analgesics during the 4 postoperative days. Arnica D4 was significantly better tolerated than diclofenac (p = 0.049). Nine (9) patients 20.45%) of the diclofenac group and 2 (4.5%) of the Arnica D4 group reported intolerance. There was no disturbance in wound healing in any of the patients. Arnica D4 is 60% cheaper than diclofenac.

    Ultimately, the researchers concluded that after bunion foot operations, Arnica D4 can be used instead of diclofenac to reduce wound irritation.

    In one randomized, double-blind, placebo-controlled trial with 60 patients who underwent varicose vein surgery, 43% of those patients given Arnica 12X (also called D12) pre- and postoperatively experienced remission or improvement in pain, while only 27% of those taking a placebo experienced a similar degree of relief (Wolfe, 2003). There were also trends towards a beneficial effect in the size of the hematoma (the pooling of blood under the skin) between groups. The homeopathic group took Arnica the night before the surgery, then once preoperatively and hourly postoperative dosages during the first day and three times a day during days 2-14.

    Randomised double blind, placebo controlled trial at a tertiary referral center was conducted with 190 patients over the age of 18 undergoing tonsillectomy (Robertson A, Suryanarayanan R, Banerjee A, 2007). Patients were randomised into intervention and control groups receiving either Arnica 30C or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work.

    The researchers found that 111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p=0.05. The two groups did not differ significantly on analgesic consumption or any of the other secondary outcome measures (number of post-operative visits to GP, use of antibiotics and secondary haemorrhage readmissions). The results of this trial suggest that Arnica given after tonsillectomy provides a small, but statistically significant, decrease in pain scores compared to placebo.

    A randomized double-blind, placebo-controlled of 60 patients (33 women and 27 men, with an average age of 39) who were suffering from dental neuralgia after tooth extraction were either prescribed a placebo or Arnica 7C and Hypericum 15C (alternatively at four hour intervals)(Albertini, Goldberg, Sanguy, et al, 1985). Patients who were using anti-inflammatory drugs were excluded from the study. The patients were treated for three days and asked to assess their pain on a decimal scale. The patients were also asked whether reasonable pain control had been achieved. This study found that patients given the two homeopathic medicines experienced a statistically significant (p=0.01) reduction in pain on days 2 and 3 (not on day 1). A statistically significant percentage of patients given the homeopathic medicines deems that the treatment achieve reasonable pain control as compared to those given the placebo (p=0.01).

    Another study found that people on long-term IV usage benefited from homeopathic doses of Arnica (Amodeo, 1997). A randomized, double-blind, placebo-controlled study of 130 consecutive patients undergoing saphenous stripping were prescribed a single dose of Arnica 5C or a placebo (Ramelet, Buchheim Lorenz, 2000). Clinical evaluation of hematomas was conducted 6 days postoperatively, but there was no statistically significance (p=0.342). A serious problem with this study, however, was that the researchers only allowed a single dose of Arnica 5C before the operation and one dose just afterwards. This is clearly an inadequate dosing of this remedy, especially in the lower potency of 5C. One might also wonder if these results might have been different if researchers evaluated the patients earlier than six days because most people would not have any hematomas at this time whether there was an effective treatment or no treatment.

    Despite some trials testing Arnica that have had a negative outcome, some basic science research has confirmed the anti-inflammatory activity of Arnica 6C (Macedo, Ferreira, Perazzo, 2004). The anti-inflammatory effect of Arnica montana 6CH (also called Arnica 6C) was evaluated using acute and chronic inflammation models. In the acute, model, carrageenin-induced rat paw oedema,* the group treated with Arnica montana 6CH showed 30% inhibition compared to control (P = 0.05). Treatment with Arnica 6CH, 30 min prior to carrageenin, did not produce any inhibition of the inflammatory process. In the chronic model, Nystatin-induced edema, the group treated 3 days previously with Arnica montana 6CH had reduced inflammation 6 hours after the inflammatory agent was applied (P = 0.05). When treatment was given
    6 hours after Nystatin treatment, there was no significant inhibitory effect. In a model based on histamine-induced increase of vascular permeability, pretreatment with Arnica montana 6CH blocked the action of histamine in increasing vascular permeability.

    In addition to the above clinical studies, a study on rats who underwent a titanium micro-implant is worthy of reference (Sakakura, Neto, Bellucci, et al, 2008). Eight rats were divided into two groups of 24 animals each: a control group (C) and a test group (SO). Each animal received one titanium micro-implant placed in the tibia. The animals in Group SO were subjected to 10 drops of comfrey 6CH per day mixed into their drinking water until the day of sacrifice. Eight animals of each group were sacrificed at 7, 14 and 28 days post-surgery, respectively.

    Standardized digital radiographs were obtained on the day of implant installation (baseline images) and on the day of sacrifice (final images). Digital subtraction of the two corresponding images was performed to evaluate changes in bone density and the area related to change around the implant between baseline and final images. Subtraction images demonstrated that a significant difference existed in mean shade of gray at 14 days post-surgery between Group SO (mean 175.3±14.4) and Group C (mean 146.2±5.2). Regarding the area in pixels corresponding to the bone gain in Group SO, the differences observed between the sacrifice periods and groups were only significant at 7 days sacrifice between Group SO (mean 171.2±21.9) and Group C (mean 64.5±60.4).

    The fact that this study showed improved healing more rapidly (within 7 days) suggests a therapeutic benefit from this homeopathic medicine.

    REFERENCES:

    Albertini, H, Goldberg, W, Sanguy, BB, Toulza, C, Homeopathic Treatment of Dental Neuralgia Using Arnica and Hypericum: A Summary of 60 Observations,” Journal of the American Institute
    of Homeopathy, 78,3: September, 1985: 126-128.

    Amodeo, C, et al., “The Role of Arnica in the Prevention of Venous Pathology from Long-term Intravenous Therapy,” Ninth National Conference for the Italian Society for Vascular Pathology, Capanello, June 6-9, 1987.

    Hart, O, Mullee, MA, Lewith, G, et al., Double-blind, Placebo-controlled, Randomized Clinical Trial of Homoeopathic Arnica C30 for Pain and Infection After Total Abdominal Hysterectomy, Journal of the Royal Society of Medicine, February 1997;90(4):239-40.

    Karow, Jens-Hagen, Abt, Hans-Peter, Froling, Markus, Ackermann, Hanns. Efficacy of Arnica montana D4 for Healing of Wounds After Hallux Valgus Surgery Compared to Diclofenac. The Journal of Alternative and Complementary Medicine. January, 2008, 14(1): 17-25. doi:10.1089/acm.2007.0560.

    Kulick, M, Clinical Research Study of SinEcch (Alpine Pharmaceuticals brand and dosage regimen of Homeopathic Arnica Montana) in the Reduction of Ecchymosis and Edema in Liposuction. Reported at the Research and Innovative Technology Scientific Session of the American Society of Aesthetic Plastic Surgery meeting, Las Vegas, April 29, 2002

    Macedo, SB, Feerreira, LR, Perazzo, FF, and Tavares Carvalho, JC, Anti-inflammatory Activity of Arnica Montana 6CH: Preclinical Study in Animals, Homeopathy (2004)93:84-87.

    Paris A, Gonnet N, Chaussard C, Belon P, Rocourt F, Saragaglia D, Cracowski JL. Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study. Br J Clin Pharmacol. 2008 Feb;65(2):180-7.

    Ramelet, AA, Buchheim, G, Lorenz, A, et al., Homeopathic Arnica in Postoperative Hematomas: A Double-blind Study, Dermatology, 2000;201(4):347-8.

    Robertson A, Suryanarayanan R, Banerjee A. Homeopathic Arnica montana for post-tonsillectomy analgesia: a randomised placebo control trial. Homeopathy. 2007 Jan;96(1):17-21.

    Sakakura CE, Neto RS, Bellucci M, Wenzel A, Scaf G, Marcantonio E Jr. Influence of homeopathic treatment with comfrey on bone density around titanium implants. A digital subtraction radiography study in rats. Clin. Oral Impl. Res. 2008,19,6:624-628. doi: 10.1111/j.1600-0501.2007.01514.x

    Seeley BM, Denton AB, Ahn MS, Maas CS, Effect of homeopathic Arnica montana on bruising in face-lifts: results of a randomized, double-blind, placebo-controlled clinical trial. Arch Facial Plast Surg. 2006 Jan-Feb;8(1):54-9.

    Wolf, M, Tamachke, C, Mayer, W, Heger, M [Efficacy of Arnica in Varicose Vein Surgery: Results of a Randomized, Double-blind, Placebo-controlled Pilot Trial][Article in German] Forsch Komplementarmed Klass Naturheilkd. 2003, Oct;19(5):242-7.

  27. artfulDon 24 May 2009 at 1:45 pm

    Can you send that again? The credibility factors seem to have been omitted.

  28. Doctor Evidenceon 24 May 2009 at 2:09 pm

    from wikipedia. the last sentence is pretty funny.

    Some modern homeopaths have considered more esoteric substances, known as “imponderables” because they do not originate from a material but from electromagnetic energy presumed to have been “captured” by alcohol or lactose. Examples include X-rays[69] and sunlight.[70] Recent ventures by homeopaths into even more esoteric substances include thunderstorms (prepared from collected rainwater).[71] Today there are about 3,000 different remedies commonly used in homeopathy.[72] Some homeopaths also use techniques that are regarded by other practitioners as controversial. These include paper remedies, where the substance and dilution are written on a piece of paper and either pinned to the patient’s clothing, put in their pocket, or placed under a glass of water that is then given to the patient, as well as the use of radionics to prepare remedies. Such practices have been strongly criticised by classical homeopaths as unfounded, speculative and verging upon magic and superstition.

  29. Joeon 24 May 2009 at 2:44 pm

    Dana,

    You have provided the obligatory, obfuscatory data-dump; you expect us to go through your database and tell you if anything there is legitimate. Choose the study that you think is best, you can add a recent review (or a more recent study that provides leading references).

    Early, you cited the study that is the penultimate reference (Seeley et al 2006) in your data-dump, immediately above.

    Somebody asked how many subjects- 29, little more than an anecdote. Also, the claimed benefits only showed up on one measure, and only on two of four days. Also note that when research uses multiple measures (computer analysis, visual assessments by doctors, and by patients, …), p=.05 is too lax a threshold for significance. http://archfaci.ama-assn.org/cgi/content/full/8/1/54

    One should also note that the authors tested a new method of evaluation on an unproven treatment. They must have missed those years in school when controlled studies were discussed.

  30. Joeon 24 May 2009 at 2:54 pm

    My post, above, may be confusing- the URL connects to Seeley et al 2006, not an explanation of p-values appropriate to studies with multiple measures.

  31. katoon 24 May 2009 at 3:43 pm

    There are no positive animal experiments? There must be! After all there is this: http://www.petpainspray.com. That’s right, a homeopathic remedy for your dog. No placebo there…

  32. tmac57on 24 May 2009 at 5:15 pm

    Doctor Evidence-“Some homeopaths also use techniques that are regarded by other practitioners as controversial. These include paper remedies, where the substance and dilution are written on a piece of paper and either pinned to the patient’s clothing, put in their pocket,”
    My doctor uses this technique too. She calls it a …hmmmmm what’s the word… per… no pro….er….. prescription… yeah ,that’s the one ,prescription. It works for me ! So what’s wrong with that?

  33. Steven Novellaon 24 May 2009 at 7:23 pm

    kato – the notion that there cannot be a placebo effect for animals is naive. Remember – “the” placebo effect is actually a number of different effects – it is anything other than a physiological response to an active intervention.

    For animals this includes human attention associated with getting a remedy, but also a biased human has to decide if the animal is responding to the treatment and this opens the door to confirmation bias.

  34. katoon 24 May 2009 at 8:55 pm

    I guess I wasn’t thinking about the human half of the treatment program. I suppose that’s exactly what I was naive to. For some reason I expect everyone to be as objective as (most) of us here.

  35. criticaliston 25 May 2009 at 2:37 am

    So its a day off, and I’m bored, so I thought I might take a detailed look at some of Dana’s references. Or at least the clinically relevant ones I can easily access.

    First up is the post op abdominal hysterectomy trial. I assume Dana put this in because it was published in the Journal of the Royal Society of Medicine, and therefore sounds good, but he can’t of read it because its a negative study. To quote the discussion “In terms of pain, analgesia, infection and operative severity this study revealed no significant differences between arnica and placebo”.

    Fairly straightforward then. Onto the the post op bunion surgery study from journal of alternative and complementary medicine. By an odd coincidence this issue also contains a report of a debate about homeopathy featuring some character called “Novella”.

    This study rather brilliantly shows that the patients getting Arnica had significantly more pain on Day 1 post op than the patients getting diclofenac, an actual analgesic. The rest of the ludicrously complicated statistical analysis purports to show no difference between Arnica and diclofenac for measures of swelling and inflammation, but is completely invalidated by the observation that the Arnica group were also given diclofenac and other analgesics as part of their post op treatment. Dana says ” there were no significant differences in the use of additional analgesics during the 4 postoperative days”. Naughty Dana! -thats a porky!! Page 22 in the results section ” When each day was analysed Tramal was used in the Arnica group significantly more on the first post op day.

    More pain, and more analgesia use does not really add up to equivalence.

    Finally, the tonsillectomy study, or “how to massacre the data to give us the result we want”.

    We have 14 days worth of self reported visual analogue pain scores starting from day 1 post op. Days 1 to 9 show no difference between arnica and placebo. Differences are seen on days 10, 11 and 14. The researchers decide to analyse this data by comparing the mean fall in VAS scores, an interesting and unjustifiable approach as it allows them to completely ignore the fact that there was no observed difference for the first 9 days! One wonders if they decided on this unusual analytic technique before or after seeing their data? The other point of note is that there was no difference in standard analgesic use between the two groups; rather hard to explain that if you are postulating arnica has an analgesic effect.

    I cant go on any longer; Dana is this really the best you can do? Can you honestly not see the problem with these hopeless studies?

  36. daedalus2uon 25 May 2009 at 6:17 am

    Dana is simply applying homeopathic principles to his study of the literature. Start with nothing, shake it vigorously, dilute with even more nothing and more shaking and you end up with homeopathy.

  37. daedalus2uon 25 May 2009 at 9:45 am

    Critacalist, rather than waste time on homeopathy, there is quite an important paper in sepsis.

    http://www.ncbi.nlm.nih.gov/pubmed/12133657

    I don’t think the authors appreciate how important their result is. Not their conclusion, but their data. What they found was that the ATP level in skeletal muscle during sepsis was higher (in those that survived) than in matched controls, and lower in those that did not survive.

    My conclusion is that the ATP level is so high because of the high NO level from iNOS. NO regulates ATP level via their combined effect on sGC. That high NO level does preclude mitochondria from operating because the NO blocks the consumption of O2 by cytochrome c oxidase, but the high ATP level means the mitochondria don’t need to produce ATP. That high ATP level has to be coming from glycolysis.

    I think that is why blood glucose goes up during sepsis, it is the body desperately trying to supply enough glucose to cells for them to generate ATP via glycolysis. It takes 19x more glucose to supply ATP via glycolysis than via oxidative phosphorylation. To supply that amount of glucose the muscles get turned into amino acids which get turned into glucose. The glucose level that is important is not the level in the bulk blood, only a few percent of cells get glucose directly from the blood. Virtually all cells get glucose from plasma flowing in the extravascular space. The most important glucose level is adjacent to the cell that is taking it up. Glucose transport into cells is active and saturatable. This saturation is a feature, so that the first cells the extravascular fluid encounters don’t take up all the glucose and leave nothing for the cells farther away. This is where insulin come is, insulin increases the number of GLUT transporters in the cell and increases its glucose uptake. Insulin transport into cells is saturatable too, and that saturation is also a feature that allows insulin to get to cells that are farther away. Insulin resistance is what allows cells farther from a capillary to still get some insulin.

    The Cori cycle in the liver requires liver mitochondria to consume the reducing equivalents, but if those mitochondria are blocked from using O2, lactate disposal options are limited. Lactate can’t be excreted, but every cell can turn it into lipid. I think that is why sepsis induces cachexia where lean muscle goes down and body lipid goes up. The site of the lipid formation is indicative of the degree of metabolic difficulty. Depot fat is ok, visceral fat is less good, fatty liver is bad, ectopic fat in skeletal muscle is worse, when fat starts to accumulate in heart muscle then you are at death’s door. The body is using mitochondria where ever they are to consume the reducing equivalents produced when lactate is metabolized.

    I think the most important physiological parameter in sepsis is not blood glucose, but rather cellular ATP levels. Glucose in the blood isn’t doing much, the glucose needs to get into cells. Insulin can greatly improve that, but the capacity to put glucose into the blood is not unlimited.

    My interpretation of the NICE results is somewhat different than the authors. The reason that the physiological response of hyperglycemia during sepsis evolved was to deliver more glucose to cells with increased need for glucose, due to the shut-down of mitochondria and because much of the immune system is run by glycolysis because it must operate in hypoxic tissue compartments.

    Acute hyperglycemia during sepsis is a sign that thing are going south, not because of the hyperglycemia per se, but because hyperglycemia (in the blood where it can be measured) is the response to hypoglycemia in the extravascular space (where it can’t be measured but is more important). If there isn’t enough glucose in the extravascular fluid remote from a capillary, the only control parameter that physiology can change to try and fix it is by raising blood glucose.

    The production of sufficient ATP in cells by glycolysis requires multiple steps including production of substrates for glucogenesis, production of glucose from those substrates, delivery of glucose to the blood, delivery of blood to the tissue compartment, extravascular flow of plasma to the space between capillaries, take up of glucose by those cells (this can be increased by insulin), expression of glycolytic enzymes, production of ATP via glycolysis, export of lactate, transport of lactate into the blood, and removal of excess lactate from the blood.

    Impediments to any step in this ATP production chain will cause insufficient ATP.

    The default assumption of homeostasis that is the basis for trying to keep blood sugar in a certain range is wrong. Physiology doesn’t want to keep glucose constant; it wants to deliver the right amount of glucose to the right tissues at the right time, just as they need it. Circulation of blood takes a few minutes, circulation of lymph takes longer, half an hour perhaps (but is more variable). Physiology puts glucose in the blood, so that when the fluid gets to the tissue compartment that needs it in 15 to 30 minutes, there will be “enough”.

    I have a write-up on mitochondrial failure during sepsis. My hypothesis of how that happens is that when there is insufficient glucose to support ATP production by glycolysis, the ATP level falls, and the mitochondria turn on. I have more details (and references) there.

    http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html

    When mitochondria turn on, electrons start to flow through the respiration chain and the respiration chain becomes reduced. This causes reduction of O2 and the formation of superoxide (which is vectorally generated to the inside of the inner matrix). This is a “feature”, which pulls down the NO level (NO and superoxide react at near diffusion limited kinetics). The 2 membranes of mitochondria are transparent to NO, they block diffusion of superoxide. Superoxide is generated until the NO level gets sufficiently low that cytochrome c oxidase is no longer inhibited. Then O2 can bind and the electrons in the respiration chain are used to reduce O2 to water not superoxide. Mitochondria have unlimited capacity to make superoxide, how ever much they need to make to pull the local NO level down, they can make. When NO and superoxide react, they make peroxynitrite which can nitrate proteins. In the mitochondria matrix there is mitochondrial SOD, this is a Mn-based SOD, which is highly homologous with bacterial SODs (Mn and Fe) and presumably was derived from the bacterial ancestor of mitochondria. The DNA for MnSOD is in the nucleus, so MnSOD can only be made and ported into mitochondria during mitochondria biogenesis.

    Mitochondrial MnSOD is inhibited by the nitration of a single tyrosine. Bacterial FeSOD (which is highly homologous) is not inhibited when 8 out of 9 tyrosines are nitrated. Presumably if bacterial FeSOD could evolve resistance to inhibition by nitration, so could mitochondrial MnSOD, that inhibition by nitration is not necessary for SOD activity. My hypothesis is that inhibition of MnSOD by nitration of a single tyrosine is a “feature”, the equivalent of a circuit interrupter. Because mitochondria have unlimited capacity to generate superoxide, there needs to be a fail-safe off switch to turn them off if they ever get out of whack. When MnSOD is inhibited, there is positive feedback with higher superoxide levels and higher peroxynitrite leading to irreversible inhibition of the respiration chain.

    Mitochondria have a finite lifetime, in the rat, the longest lived are in the CNS where they have a lifetime of about a month. A few percent have to be replaced daily. Turning off a few percent likely has no ill effects and happens every day anyway. Turning off 50%, or even 80% might be tolerable in tissue compartments that can increase their metabolic capacity by 10x, for example heart muscle.

    My hypothesis is that in the paper I cited earlier, the decline in ATP levels that preceded death in sepsis is I think due to an inability to keep up with ATP demand by glycolysis. My thought of how to treat sepsis is to give glucose to maintain modest hyperglycemia, give insulin to get that glucose into cells, and then dialyze with urea containing fluids to get rid of the lactate. I think the endpoint that should be attempted is the prevention of cachexia. If there is sufficient glucose in the blood that cachexia doesn’t happen, then there is “enough”.

  38. eiskrystalon 26 May 2009 at 3:40 am

    – guess I wasn’t thinking about the human half of the treatment program. I suppose that’s exactly what I was naive to-

    and anyone can make a nice website, write a few fancy sounding words and quote references that people like Dana will believe.

    I am irritated beyond belief that a “medicine” should be saleable, not on it’s efficacy but on it’…what…age of discovery? Quite simply the english system needs investigating for fraud and corruption.

  39. HHCon 27 May 2009 at 6:10 pm

    Arnica is a plant of the daisy family. I can’t see how chewing daisies in swallowable form will inhibit bruising. Maybe its useful for distracting yourself from focusing on the bruise. I have strong allergic reactions to Italian dandelion recipes, I don’t think I would feel better after consuming daisies 😉

  40. Mojoon 03 Jun 2009 at 7:02 am

    I particularly like the way Dana, in his “military thinking” article, invokes WMDs in Iraq, for which there was no good evidence, in an attempt to shore up a system of medicine for which there is no good evidence.

Trackback URI | Comments RSS

Leave a Reply

You must be logged in to post a comment.