At the conclusion of my previous post on Health Concerns, a Traditional Chinese Herbal Medicine company, it seemed clear to me that their claims of being based on modern science and good quality research are heavily exaggerated.  This didn’t sit well with me, as their repeated references to having done double-blind research on the Health Concerns formulas Enhance and Clear Heat for HIV/AIDS patients always omit links to the actual studies.  It took some time, but I found the full text published research which on the surface reports no significant difference than placebo for the Chinese herbs.  The best study showed significant worsening of HIV loads in the herb group and significant gastrointestinal disturbances.

This led me to dig further as it’s a very important issue for me personally and professionally.  The two main herbalists involved in this are influential in the American Acupuncture and Oriental Medicine world.  Andrew Gaeddert is the founder of Health Concerns, and is not an acupuncturist, but nevertheless a well known businessman.  Misha Cohen, OMD, L.Ac. is very prominent in the field, and has received several public honors for her work with AIDS/HIV.

The key ethical issue is whether it’s deceptive to promote and sell these formulas for HIV/AIDS patients if all the research has concluded that they are no better than placebo.  If their “secret good intention” is that confidently promoted placebos help patients “feel” better, even though their actual symptoms and lab results don’t improve at all, it’s time to admit it openly.  Frankly, to sell (for profit) something to other practitioners with the suggestion that research has shown it to have antiviral properties better than placebo, a “secret good intention” so patients “feel” better is still deception, as those practitioners could probably find a different protocol which is supported by better research, is less expensive, or has fewer gastrointestinal side effects.  [When I wrote this paragraph, I hadn't discovered that "no better than placebo" was itself a deceptive spin on negative study results.  Read on for the true story, which is far worse.]

Spoiler Summary for those without time to read the whole post:

Misha Cohen developed two formulas for treating HIV, “Clear Heat” and “Enhance,” both of which are made and sold by Health Concerns, founded by Andrew Gaeddert.  Gaeddert and Cohen regularly refer to their research studies on HIV with these formulas, though they don’t directly quote from them, nor do they link to them.  Both of the studies, co-authored by Cohen, state in the abstracts that the herbs had no significant benefit over placebo.  The abstract of the second, larger study did report increased gastrointestinal disturbance in the herb group, but reported all other findings to be no different than placebo.

The data for the second study show a significant improvement in HIV counts in patients taking the placebo who were also taking pharmaceutical antiretroviral medications.  Patients who were taking the Chinese herbs and on antiretrovirals had significant worsening of their HIV counts.  These results were not calculated or discussed in the study.  Additionally, 2 people in the Chinese herb group died, but death wasn’t considered an adverse or significant event.

The herbs appear to have completely reversed the positive effects of antiretroviral therapy, more than doubling viral counts instead of reducing them to less than 1% of baseline as the antiretrovirals did without the herbs.

Despite the negative research findings, these formulas haven’t been changed and are still being promoted as having specific antiviral properties for patients with HIV.  Additionally, Health Concerns promotes these to take with with western antiretrovirals, claiming they reduce side effects and increase positive outcomes, which is the opposite of what the research indicated.

Introduction:  Where I’m coming from

In my personal journey with Chinese Medicine and science, I’ve recently been influenced to look at research with a critical eye by reading _Trick or Treatment_ and _Snake Oil Science_, both written by former alternative medicine proponents and researchers who grew discouraged as they learned what the best research has actually found.  It didn’t help to discover by reading _Natural Causes: Death, Lies and Politics in America’s Vitamin and Herbal Supplement Industry_ that a couple of my teachers (while I was a student at the Oregon College of Oriental Medicine) had caused kidney failure in a patient, settled out of court, and kept it very quiet (though the details ended up in that journalist’s book).  The Seven Forests formulas she was taking which definitely had the toxic Aristolochic Acid in them (not all by mistake), were never recalled.

This process of disappointing discovery has led me to be a very critical investigative reporter on issues of scientific research, promotional claims, and consumer protection in the western Chinese medicine world.  When I started reading books that were skeptical and critical of Complementary and Alternative Medicine (CAM), I planned to easily dismiss their (hopefully weak) arguments and write well-referenced defenses which would win respect and honors from my acupuncturist colleagues.  Unfortunately, that hasn’t been where this path has led so far.

Contrasting the product claims and presentation in promotional literature with the findings in the actual research articles is the purpose of this post.  I ask you, dear reader, to imagine that you or a loved one has HIV/AIDS, have limited time and money, and are trying to make a decision about what course of treatment to choose.  Also, please consider that you are a licensed acupuncturist trying to provide safe, effective, ethical treatment to patients you deeply care for.

Part 1:  The Promotional Materials from Health Concerns

The two formulas combined in the published research are Enhance and Clear Heat.  In the 2012 Health Concerns Practitioner Handbook, these are still clearly recommended for HIV.  While the Handbook is intended for practitioners, there are sites directly using its text and pictures.  This is despite Health Concerns’ clearly stated “no internet direct to consumer” and “no pictures of our products on any sites” policy.  I mention this to show that “the cat is already out of the bag” and I’m not revealing anything that isn’t already publicly available as marketing material for these formulas.

Here are some relevent excerpts from the current Handbook for Clear Heat (my highlights in bold):

Therapeutic Actions

Take for viral, bacterial, and fungal infections. Especially designed for persons with HIV infections. May be used also for chronic immune dysfunction syndrome (CIDS), chronic fatigue syndrome (CFS), chronic herpes, viral warts, and other chronic viral infections…

Formula Rationale

Clear Heat was developed by Misha Cohen, OMD, L.Ac., as the primary adjunct to Enhance. It has been used with Enhance in two double blind research projects. It contains 25% concentrated Isatis extract (ban lan gen and da qing ye). Isatis is the chief herb because of its strong antiviral activity against hepatitis, herpes simplex, herpes zoster, and viral warts. Viola (zi hua di ding), prunella (xia ku cao), oldenlandia (bai hua she she cao), lonicera (jin yin hua), and andrographis (chuan xin lian) are all herbs in the clear heat toxin category, and possess specific antiviral, antibacterial, and anti-fungal effects. Laminaria (kun bu) clears phlegm nodules and reduces lymph node swelling. Cordyceps (dong chong xia cao) tonifies kidney essence while strengthening lung yin, and also has anti-cancer and antibacterial activities; it is also used to tonify after debilitating illness, and helps the other herbs in the formula to enter the deepest areas of the body. Licorice (gan cao) has antiviral and antibacterial effects; it harmonizes the formula and induces the remaining herbs to enter their respective channels.

Clinical Notes

1. Viola has the strongest HIV virucidal effect among all the herbs in the study conducted by Chang and Yeung at UC Davis and Hong Kong University. Several of the other HIV virucidal herbs included in that study are also in Clear Heat

2. Cordyceps has numerous actions. It inhibits the growth of staphylococci, streptococci, and Mycobacterium avian. Chinese research has also found this herb possesses significant anti-cancer activity

3. Clear Heat may be used for all chronic viral infections as several of the herbs appear to have strong anti-herpes, anti-Epstein-Barr virus, and anti-cytomegalovirus effects.

Here are excerpts from the Health Concerns Handbook on Enhance:

Therapeutic Actions
This formula is taken for immune enhancement and immune regulation in conjunction with disorders of chronic viral inflammation and infection. Useful in persons with chronic viral syndromes such as HIV-disease, chronic fatigue immune dysfunction syndrome (CFIDS)/chronic fatigue syndrome (CFS), and herpes, may also be used with most other immune dysfunction disorders. Addresses fatigue, weight loss, night sweats, spontaneous sweating, fever, diarrhea, digestive disorders, muscle aches, inability to concentrate, swollen lymph nodes, low sexual energy…

this formula is designed as a balanced formula for immune enhancement and chronic viral syndromes and may be used continuously.
Enhance is designed to be part of the Quan Yin treatment protocol. It should not be substituted for any prescription or experimental drugs. Enhance should be taken under medical supervision. It is available only to licensed health care professionals… [and on Sears.com and many other sites... --KO]

Formula Rationale

Enhance is comprised solely of Chinese herbs and is the base formula used in the Quan Yin Herbal Program for HIV Positive persons. It has been designed by Misha Cohen, OMD, L.Ac. based on her experience and the experience at the Quan Yin Clinic in treating thousands of HIV positive patients. Enhance is based on fu zheng therapy, which means “restoring normality.” The formula differs from other approaches used in that it is designed to be easier to digest (protects the spleen and stomach) and contains a greater percentage of herbs that are believed to have anti-bacterial and antiviral activity according to Chinese and American research. Enhance also has a higher percentage of herbs to tonify and vitalize blood because of the crucial nature of protecting and strengthening the bone marrow in HIV positive persons…

• Clear Heat was designed to be used as the primary adjunct formula to Enhance. Enhance, along with Clear Heat, has been the subject of two double blind studies (see Professional Health Concerns Newsletter, Vol. 5, #3). Clear Heat is specifically used for its antiviral and antibacterial activities and is helpful for swollen lymph nodes. Included is a special ingredient, Cordyceps, which is on the forefront of Chinese cancer research.

The Handbook references a Newsletter which was also on the 2012 CD-ROM they sent me.  Here is how the research is presented there:

 

The San Francisco General Hospital Study

 

This study was undertaken in early 1993. The principle investigators were Jeff Burack, M.D., of San
Francisco General Hospital and Misha Cohen, L.Ac., OMD, of Quan Yin Healing Arts Center in San Francisco. The herbs used in the study were donated by Health Concerns, and the placebo was funded by the University of California, San Francisco.
The objectives of the study were to evaluate the safety, efficacy, and toxicity of a preparation of Chinese herbs while attempting to reduce the patients’ symptoms and improve their well-being. Subjects who were chosen had moderately advanced, symptomatic HIV infection….

A randomized, double-blind, placebo-controlled, twelve-week pilot study was conducted. Subjects were HIV-infected adults with CD4 counts of 200-500, without an AIDS diagnosis, and experiencing at least two HIV-related symptoms. Subjects took 28 pills per day of either a standardized preparation of Chinese herbs selected for their anti-viral and immunomodulatory properties, or an identical placebo. Chief outcome variables were changes from baseline in overall well-being, physical and social functioning, and symptoms. Secondary outcome variables included changes in weight, CD4 count, hemoglobin, depression, anxiety, and adherence to regimens.

 

Preliminary results indicate that life satisfaction improved significantly in the Chinese formula group as compared to the placebo group (median test p=. O2). Improvement was also observed in fatigue (p=. 046), gastrointestinal (p=. 02), and neurological symptoms (p=. 046) in the herb group versus the placebo group. Moderate improvement in pain (p=. 136) and sleep (p= .058) were also seen. Other symptoms tested, as well as CD4 counts and laboratory parameters, did not exhibit any statistically significant changes. Interestingly, dermatological symptoms improved in the placebo group, perhaps due to anomaly or to the increase in fiber consumed. One patient who received the placebo developed diarrhea which required discontinuation of the study. Otherwise, none of the remaining subjects in either group experienced toxicity symptoms.

Part 2:  What the 1993 San Francisco Study Actually Reports

Nowhere in any of the Health Concerns literature is the abstract for this study printed or linked to.  For my first post about it, I just used the abstract from PubMed (http://www.ncbi.nlm.nih.gov/pubmed/8673548).  For this post, I found the full text of the study.  Here it is (I’ll be excerpting the most interesting parts, but of course you’re welcome to read the whole thing):

http://journals.lww.com/jaids/Fulltext/1996/08010/Pilot_Randomized_Controlled_Trial_of_Chinese.9.aspx

The paper is called “Pilot Randomized Controlled Trial of Chinese Herbal Treatment for HIV-Associated Symptoms.”  This first part is from the abstract:

Primary outcome measures were changes in life satisfaction, perceived health, and number and severity of symptoms. Other outcomes included adherence, and changes in weight, CD4⁺ count, depression, anxiety, physical and social function, and mental health… No differences between treatment groups reached the p < 0.05 level [this is the level of statistical significance, meaning no significant differences were found]…  There were trends toward greater improvements among herb-treated subjects on all symptom subscales except dermatologic. Believing that one was receiving herbs was strongly associated with reporting that the treatment had helped…, but not with changes in life satisfaction or symptoms.

When critically evaluating double-blind research, the quality of the blinding is paramount.  I believe this is the weakest spot in this study, and it was carefully danced around in the full paper, glossed over in the abstract, and completely misrepresented in the publicly presented articles about the study.    Here are some relevant excerpts from the study:

One group received a standardized oral preparation of Chinese herbs, IGM-1, a combination of the Enhance and Clear Heat preparations developed by one of the investigators (M.R.C.) for treatment of HIV-related symptoms. Of 31 herbal ingredients in the 650-mg tablet, those present in high concentration included Ganoderma lucidum, Isatis tinctoria, Astragalus membranaceus, Andrographis paniculata, Lonicera japonica, Milletia reticulata, Oldenlandia diffusa, and Laminaria japonica. The other group received a 650-mg placebo, composed primarily of microcrystalline cellulose to approximate the fiber content of the herbal preparation. Both tablets, prepared by Health Concerns (Alameda, CA, U.S.A.), were coated with titanium dioxide so that they would be odorless and tasteless. Subjects were instructed to take seven pills four times a day on an empty stomach for a period of 12 weeks.

As an herbalist, I have taken, tasted, smelled, and chewed all of these herbs.  I do not believe that the placebo pills would be odorless and tasteless, especially if 28 were taken per day for 3 months.  Chewing the pills, burping after taking them, and likely even smelling the pills or having water dissolve the coating in the mouth would all lead to the detection of strongly bitter components in the herbs.  The Ganoderma and the Andrographis are extremely bitter.  The data in this study show many people in the herb group guessed they were getting the active medication.  This is important in noting the increased subjective statements of improvement.  The fact that the people taking the herbs who also figured out they were in the active treatment group didn’t have any significant improvement in measurable health indicators gives this study a particularly negative conclusion.  It disproves the “power of the mind” theory as well as these Chinese herbs as having a real effect on lab results for HIV/AIDS.

With 15 subjects per arm…, the minimum statistically detectable effect size would have been improvement in 45-50% of subjects receiving herbal treatment over and above the percentage improving with placebo. Despite the low probability of demonstrating so large a difference, we chose to proceed with a pilot study, both to test the study methods and to identify any trends of potential clinical significance.

They state that the test group was smaller than needed (30 people) to get a convincing statistical picture, but calculated what would have been required to show a statistically significant result in favor of the herbs.  They fell far short of that, yet still report on the study as if it showed benefit.  The study was done in 1993, and the same formulas are being sold in 2012 as being useful for HIV/AIDS patients.

This next part mentions the role that thinking one is in the treatment group plays.  I removed most of the math for smooth reading:

…no differences between treatment groups reached… statistical significance. Life satisfaction improved in subjects treated with herbs but not in those receiving placebo, and there was a trend toward greater improvement among herb-treated subjects… Subjects treated with herbs reported a reduction in symptoms, whereas there was no change among those receiving placebo… There were no differences between treatment groups in changes in symptom severity, weight, absolute CD4+ count, and reported average health or in the functional subscales, anxiety and depression…

 

Although only 20% of herb-treated subjects and 27% receiving placebo reported that their overall health had improved, 60% of those treated with herbs reported that the treatment had helped them, as compared with 27% receiving placebo… These included 8 of the 10 subjects who correctly guessed that they were receiving herbs as compared with only 1 of 5 who believed they were receiving placebo. Of placebo-treated subjects, none of the 6 who guessed correctly reported that treatment had helped, as compared with 4 of 9 who believed they were receiving herbs; i.e., 12 of 19 subjects (63%) who believed they were receiving herbs, but only 1 of 11 (9%) who believed they were receiving placebo said that the treatment had helped.

The main finding here is that believing one was in the treatment group led to the subjective report of feeling better, but even then there were no objective improvements, including on scales of depression and symptom severity.  This type of finding mainly shows that the patients wanted the study to be successful and believed that the herbs would help them.  The discussion part is where the spin and researcher bias starts to be obvious:

Most subjects in both groups were inclined to believe that they were receiving active herbs, and 47% guessed their assignment incorrectly, suggesting that the placebo formulation was convincing and that blinding was effective.

This conclusion is a statistical manipulation.  A table from the study makes it clear that 10 out of 15 in the herb group guessed they were getting the real thing (67%).  6 out of 14 in the placebo group thought they were getting the inert pills (40%).  The most likely conclusion is that the herbs had a flavor or odor which gave them away.  The placebo effect is stronger when you believe you are getting the active treatment.  People who volunteered for this study on herbs probably did so because they already believed that herbs would help.

The Newsletter excerpt notes improvements in the treatment group which were statistically insignificant.  Here are the insignificant trends in the other direction that didn’t get reported:

We did not observe trends favoring herbal treatment in CD4 count and body weight, which might have bolstered the observed trends in subjective endpoints. Indeed, CD4 decrease was smaller and weight gain was slightly greater among subjects receiving placebo…

CD4 decrease is bad and weight gain is good if you have HIV/AIDS.

Although a subject’s guess as to treatment assignment was not associated with changes in health perception or life satisfaction, most subjects who believed themselves to be receiving herbs and almost none of those who believed that they were receiving placebo reported that the treatment had helped them. Yet only half of those who said the treatment had helped also reported improvement in overall health. Therefore, in these highly motivated volunteers who presumably believed in herbal treatment, asking whether the treatment had helped them may have primarily assayed their beliefs about whether or not they were receiving herbs rather than tracking changes in perceived well-being.

The study paper concludes by throwing doubt on the usefulness of this type of study design and calling for larger studies.  Reluctant to admit that these herbs don’t appear to have any real benefit in HIV/AIDS patients, the authors use what’s called a “special pleading” appeal that Chinese Medicine works better in a standard acupuncture clinic due to factors “including but not limited to the placebo effect and the power of the therapeutic relationship.”  While the greater individualized attention in a standard acupuncture clinic may increase the placebo effects, it’s unlikely to increase the antiviral properties of this herbal protocol.  This is precisely why a well-blinded, placebo-controlled study is done:  to equalize the attention, expectation, and social factors so the actual benefits of the test medication can be measured.

Part 3:  The Switzerland Study on Enhance and Clear Heat for HIV/AIDS Patients

The same formulas were tested in a larger, more carefully controlled study in Switzerland, apparently costing $500,000 and funded by the Swiss government.  This research was published in 1999.  The abstract is available on PubMed (http://www.ncbi.nlm.nih.gov/pubmed/10534147), but there is no direct link to the full text (nor is the abstract or full text directly offered in any of Health Concerns’ practitioner resources).  However, the full text is freely available here:

http://journals.lww.com/jaids/Fulltext/1999/09010/Randomized,_Placebo_Controlled_Trial_of_Chinese.7.aspx

With a larger study group and six years to improve the research protocol, the results should be more revealing.  The unfortunate trend in CAM research is that the better the study is, the less of an effect it shows.  This is usually attributed to better blinding and less chance for bias to creep in.

The study group here was 68 people who took 4 doses of 7 pills every day for 6 months (more than twice as many people for twice as long as the first study).  Here’s the conclusion from the abstract:

Conclusions: This standardized formulation of Chinese herbs for HIV-infected individuals did not improve quality of life, clinical manifestations, plasma virus loads, or CD4 cell counts. The data suggest that this formulation of Chinese herbs is not effective when administered in a Western medicine setting.

Already here we can see the spin starting with the suggestion that it may be more effective if given in an Eastern medicine setting.  The study designers had time to improve the protocol and patient selection if they thought it would lead to a more favorable outcome.  The claim in the marketing materials is clearly that these formulas were designed for HIV and have specific HIV antiviral properties.  That is what this study was designed to test, though it also tested subjective reports of symptom improvement.  Here are the core results from the abstract:

Patients taking Chinese herbs reported significantly more gastrointestinal disturbances (79% versus 38%;p=.003) than those receiving placebo. No therapy-related toxicities were observed. At completion of the study, no significant differences between the intervention and placebo groups were found regarding plasma viral loads, CD4 cell counts, symptoms, and psychometric parameters.

Very clearly, the only reported difference between the herb group and placebo group was gastrointestinal disturbance (we will soon see that this is incorrect, in that the placebo groups had far better viral loads).  Looking at the ingredients of these formulas, I suspect it is due to the Rehmannia root (Shu Di Huang) and the Polygonum multiflorum root (He Shou Wu).  Both of these are known to cause intestinal disturbance.

The study describes the intervention and ingredients, mentioning that Misha Ruth Cohen (M.R.C) developed this formula.  I’ve bolded the two ingredients I suspect caused the most GI upset.

Intervention

Participants were randomly allocated to either a standardized preparation of 35 Chinese herbs or to placebo. Previous treatments remained unchanged. All study subjects were prescribed seven pills four times daily for 6 months. Both placebo and herb tablets weighed 700 mg and could not be distinguished by consistency or taste, but differed slightly in color.

The herb preparation was developed by one of the investigators (M.R.C.) and prepared by Health Concerns (Oakland, CA, U.S.A.). It contained:

Ganoderma lucidum, Isatis tinctoria, Milletia reticulata, Astragalus membranaceus, Tremella fuciformis, Andrographis paniculata, Lonicera japonica, Aquilaria agallocha, Epimedium macranthum, Oldenladia diffusa, Cistanche salsa, Lycium chinense fructus, Laminaria japonica, Angelica sinensis, Polygonum cuspidatum, Panax quinquefolium, Schizandra chinensis, Ligustrum lucidum, Atractylodes macrocephala, Rehmannia glutinosa, Salvia miltiorrhiza, Curcuma longa, Viola yedonensis, Citrus reticulata, Paeonia lactiflora, Polygonum multiflorum, Eucommia ulmoides, Amomum villosum, Glycyrrhiza uralensis, Prunella vulgaris, Cordyceps sinensis, Pogostemum cablin, Crataegus cuneata, Massa medica fermentata, Hordeum vulgare, Oryza sativa, plus magnesium stearate, silicon dioxide, and gum acacia as tableting agents. Placebo pills contained microcrystalline cellulose, magnesium stearate, silicon dioxide, and gum acacia.

Bias against natural medicines can be largely ruled out not just because Misha Cohen is a co-author, but because the clinical assessment was done by a Naturopathic MD:

Follow-Up and Clinical Assessment

All clinical consultations were performed by M. Loy, a licensed medical doctor and also a doctor of naturopathy.

In proper form for a double-blind, the assessors didn’t know which patient was in the active group:

All investigators remained blinded throughout the data analysis.

Many of the subjects were also using other CAM therapies, such as homeopathy, energy balancing, and even other herbs.  It’s worth noting that the CD4 levels worsened in both the placebo and active group, so this is not a situation where there was improvement in both groups.  In the first study it was noted, even in the abstract, that one of the placebo patients experienced diarrhea.  That tidbit showed up in the Health Concerns newsletter.  Check out what was left out of all mentions of this study:

Adverse Events

The incidence of side effects was higher in the treatment group than the placebo group (p= .003), entirely as a result of gastrointestinal symptoms (Table 2). Hematologic or serum chemistry laboratory values showed no evidence of toxicity from the study drugs. However, 2 patients died during the study period. Both were severely immunodeficient and had a preenrollment history of multiple severe opportunistic complications. Although both were in the treatment group, their causes of death were not related to the study medication.

I’m not concluding that the herbs killed these patients, though they certainly didn’t save them.  However, out of the 34 people in the active group, 5.88% of them died, vs. 0% in the placebo group.  Out of 15 patients who didn’t complete the study, 13.3% did so because they were dead (100% of those were in the active treatment group), which makes this statement seem out of touch:  ”Participants who withdrew did not differ from those who completed the study in terms of symptoms, HIV disease stage, CD4 cell counts, plasma viral load and psychosocial scores.”

There was a significant worsening of CD4 levels in the herb group and a significant improvment in the placebo group (likely attributed to their standard medications):

At completion of the study, no significant differences between the intervention and placebo groups were found in terms of plasma viral loads… On-treatment analyses showed statistically significant CD4 lymphocyte declines in the treatment group… the placebo group experienced statistically significant, but not clinically significant, CD4 increases…

While Table 4 omits looking directly at just the patients who were on antiretroviral therapy during the study, it clearly shows that the placebo group had improvements in their viral load levels.  From what I can tell, an unspoken finding of the study was that the Chinese herbs interfered with the efficacy of antiretroviral therapy.  Here’s the table, let me know if you see something different in this data:

The next table has a category for “significant AIDS defining events” such as progression from HIV stage A to stage B.  Apparently death is not considered a significant AIDS defining event in this study, as the 2 deaths in the herb group aren’t in the reported statistics.  Without those, the presented results show less difference between placebo and active group:

Progression of HIV infection (i.e., the occurrence of new opportunistic infections or malignancies during the study), body mass indices, and reported physical and mental symptoms were not significantly different between the treatment and placebo groups at baseline, during the study, or at study end (Table 5).

As we’ll see in my table and statistical analysis below, there was a significant worsening in the HIV loads of the herb group, especially when looking at the patients taking antiretrovirals at the same time.

The discussion portion of the study paper begins:

The results of this placebo-controlled clinical trial do not support claims that the standardized Chinese herbal formula is helpful for HIV-infected individuals. Participants in the treatment arm did not differ from those in the control arm regarding clinical, psychosocial, quality-of-life, and virologic data. In both arms, declining CD4 cell counts indicated HIV progression. In addition, tongue diagnosis-determined health ratings did not change during the study period. The only discernible effect of the herbal mixture was an increase in mild gastrointestinal complaints.

The Health Concerns Chinese herbs reversed positive effects of Antiretroviral therapy

Is it an accurate statement that the only discernible effect was GI upset and that both groups had similar HIV progression?  An uncrunched statistic is sticking out like a sore thumb in the table I included as a graphic above.  This is the HIV-1 RNA figures (the viral load) at baseline and study end.  The stats for all participants (both using and not using standard antiretrovirals) shows that the Chinese Herb group had an increase in viral load of 49.86% (53,371/35,612) whereas the placebo group had a decrease of 36% (52,027-33,254).  Truthfully, I’m still a little confused about calculating P values, but this 85.86% gap in HIV levels in such clearly different directions is significant any way you look at it.  If this statistic had been in favor of the herb group, it would have been the star of the show.  However, it wasn’t even calculated in the study’s discussion, so it didn’t count it as a “discernible effect of the herb mixture.”

Table 4 has a ‘without antiretroviral’ column and a ‘with or without antiretroviral’ column, but it doesn’t have a ‘with antiretroviral’ column, even though that’s become the most interesting and important statistic from this study.  Looking at the data provided, it’s clear that the subjects taking the antiretroviral medications and the placebo had a good improvement in HIV counts, but the subjects taking antiretrovirals and the Chinese herbs had a worsening.  This suggests the herb interfered with the antiretrovirals.  To know how much, I teased out the data for the patients who were taking antiretrovirals.  I had some difficulty at first, and encourage anyone who crunches these numbers in a different way to share your results.  Here is what I found:

The 4 patients in the Chinese herb group who were taking antiretrovirals had their HIV counts increase 208.69%, from 51,906 to 108,322  I figured this by the difference in percentages, here’s my formula:  =(134.19*24-20*119.29)/4.  The 7 patients in the placebo group who were on antiretrovirals had their HIV counts drop to 0.7% of what they were, from 41337 to 291!  Here’s my formula to uncover the missing statistic:  =(91.47*29-22*120.35)/7.  The antiretrovirals were stunningly successful, unless they were combined with the Chinese herbs, which apparently made them work in reverse, doubling viral counts instead of reducing them to less than 1% of what they were.  Here is my table of these results:

Unless I am incredibly mistaken (and if I am please correct me), this Chinese herb regimen is horrible to combine with the antiretroviral therapy.  The antiretroviral therapy is clearly highly effective on its own, when unimpeded by this particular herbal protocol.

Andrew Gaeddert, in his Health Concerns newsletter on HIV, encourages acupuncturists to combine these HIV formulas with standard western pharmaceuticals for HIV:

Most American practitioners are now combining TCM and Western modalities in treating HIV infection. In fact, Chinese herbs can actually help HIV patients better tolerate some pharmaceuticals by reducing or even eliminating their side effects. For example, Marrow Plus which contains Blood tonifying and Blood vitalizing herbs (traditionally aimed at strengthening the bone marrow) was developed specifically to counter anemia and other side effects of AZT and chemotherapy. Currently, we are testing a formula that addresses chronic watery stools in HIV infected patients diagnosed with cryptosporidium.

This recommendation is the opposite of what the studies found.  The herbs only increased side effects, and completely reversed the efficacy of the antiretrovirals.  The practitioner materials for Enhance also still say “Similarly, it appears to be helpful to people with HIV for the side effects of drug therapy such as AZT anemia.”

More about Misha Cohen’s career and research

As presented in my first post on Health Concerns, who trademarked the motto “Combining Modern Science & Ancient Wisdom,” these studies are repeatedly mentioned (without reference to the actual results or abstracts) in support of the entire Health Concerns brand.  Misha Cohen developed these formulas which are sold by Health Concerns and co-authored the research.  It seems reasonable to assume that she has a financial interest in them, though I haven’t seen any disclosure from her one way or another.  Certainly she’s interested in promoting her clinic and professional standing as a teacher, author, and practitioner of Traditional Chinese Medicine.

Misha is on the faculty of the University of California San Franscisco School of Nursing.  Her bio page reports several honors and awards:

2005	AIDS Hero Award–Lifetime Achievement, AIDS/HIV and Chinese Medicine, AIDS Candlelight Vigil, San Francisco
2004	Who’s Who in Executives and Professionals, National Register
2002	Certificate of Appreciation in honor of efforts in the fight against HIV/AIDS, received from Willie Brown, Mayor of San Francisco
2001	Researcher of the Year Award, Chinese Medicine Research, Acupuncture and Oriental Medicine Alliance Annual Conference
2001	Misha Cohen Day–November 8, 2001, City and County of San Francisco, Quan Yin Healing Arts Center

Under the Selected Publications section, this HIV research is conspicuously absent.

On her own site, www.docmisha.com, we learn that she is the Executive Director of the Misha Ruth Cohen Educational Foundation.  She is an “internationally recognized expert” at combining Chinese medicine and Western medicine for HIV and other conditions, and was once selected as one of the top 50 AIDS researchers.  She also wrote a book on combining eastern and western treatments for HIV.

For more than twenty years, she has developed treatment protocols for people with HIV/AIDS. She was a member of the Ad Hoc Subpanel on Alternative and Complementary Therapy Research of the NIH Office of AIDS Research and in 1996 was selected by POZ Magazine as one of 50 top AIDS researchers.

…

Research

In Dr. Cohen’s years with Quan Yin, she has conducted herbal and acupuncture research. Her collaboration with Western physicians at San Francisco General Hospital in a double-blind placebo pilot clinical trial using Chinese herbal medicine for HIV+ persons led to the first peer-reviewed published study of Chinese herbal medicine for HIV (JAIDS, 1996). Misha was a co-investigator in five additional completed university studies: a peer-reviewed published study of herbal medicine for HIV-related symptoms at the Zürich University Hospital, Zürich, Switzerland (JAIDS, 1999)…

Dr. Cohen has created Chinese traditional medicine treatment protocols for PMS, infertility, hepatitis, HIV, endometriosis, HPV-related diseases and menopausal syndromes that are used at Quan Yin Healing Arts Center and Chicken Soup Chinese Medicine. She has also developed herbal formulas for HIV, Hepatitis C, chronic viral illness, cancer support, fibromyalgia, and the common cold.

At the Misha Ruth Cohen Educational Foundation (a non-profit), we see that the mission statement focuses on combining eastern and western medicine for HIV and other serious problems:

The foundation focuses on integrating western and eastern medicine, specifically Chinese traditional medicine, in the treatment of complex health issues including:

• HIV/AIDS
• Hepatitis B & C
• Cancer Support
• Gynecological problems
• Chronic viral diseases

OK, let me make sure I get this right…

Misha Cohen developed two formulas for treating HIV, “Clear Heat” and “Enhance,” both of which are made and sold by Health Concerns, founded by Andrew Gaeddert.  Gaeddert and Cohen refer regularly to their research studies on HIV with these formulas, though they don’t directly quote from them, nor do they link to them.  Both of the studies, co-authored by Cohen, state in the abstracts that the herbs had no significant benefit over placebo.  The second, larger study did report increased gastrointestinal disturbance in the herb group, but reported all other findings to be no better than placebo.

The data for the second study show a clear and significant improvement in HIV counts in patients taking the placebo who were also taking pharmaceutical antiretroviral medications.  Patients who were taking the Chinese herbs and on antiretrovirals had significant worsening of their HIV counts.  These results were neither calculated nor discussed in the study.  Additionally, 2 people in the Chinese herb group died, but that wasn’t considered an adverse or significant event (even though someone who got diarrhea while on the placebo in the first study got mentioned in the abstract).

At best, the research shows Clear Heat and Enhance cause upset guts and provide no benefit over placebo.  At worst, they completely reverse the positive effects of antiretroviral therapy, more than doubling viral counts instead of reducing them to less than 1% of baseline.  In either case, the research clearly shows no one with HIV has anything to gain from taking these formulas, though at $2.80-$4 per day (at 4 doses of 7 tablets in a 420 tab bottle for $42-$60), there is plenty of time and money to be lost.

Despite the negative research, these formulas haven’t been changed and are still being promoted as having specific antiviral properties for patients with HIV.  Additionally, they are promoted for combining with western antiretrovirals to reduce side effects and increase positive results.

This is clearly a deceptive and harmful misrepresentation for personal and monetary gain, in my opinion.  The deceptive spin started in the study discussion by ignoring the significant different directions the HIV-1 RNA counts in all patients.  There was an 85.86% difference in HIV-1 RNA levels favoring the placebo group (counting both those who were and weren’t using antiretrovirals).  The deception is cemented in the study’s abstract:

At completion of the study, no significant differences between the intervention and placebo groups were found regarding plasma viral loads, CD4 cell counts, symptoms, and psychometric parameters. HIV-1 RNA level was unchanged at study end.

I find this to be a false, deceptive, misleading statement.  I have no doubt that if the figures were in the opposite direction with such a big difference, it would have been proclaimed as a huge success for the Chinese herbs.  This would be the star statistic in all of the promotional literature.  Instead the true findings were not just ignored, but completely misrepresented.

It is inconceivable to me the parties involved are ignorant of the real findings.  Being ignorant is the only way that promoting this isn’t having malicious “intent to mislead and defraud” vulnerable patients (in my opinion).  This intent is what turns a misdemeanor labeling violation into a serious count of felony health fraud.

“Clear Heat” and “Enhance” are the only two “Health Concerns” formulas which I found any peer-reviewed research for, yet many others are promoted with strong claims about having anti-viral, anti-bacterial, anti-cancer, anti-fungal and other strong effects on serious diseases.  In the light of the deceptively presented research, it seems reasonable to suspect that those claims are false and misleading as well.

The findings about negative interactions between these Chinese herbs and antiretroviral medications have implications beyond Health Concerns.  Subhuti Dharmananda’s Immune Enhancement Project, for example, has several similar formulas in the Seven Forests line which have been given to HIV/AIDS patients for years, yet I have found no published research on them.  The prudent course would be to assume the Ganoderma, Isatis, etc. have adverse interactions with antiretrovirals (and no positive in vivo effects in any HIV/AIDS patients, even if Chinese research has suggested in vitro effects) until conclusive evidence is produced to the contrary.

On a personal note, I’ve been upset about what I’ve uncovered here for days.  The facts have just gotten worse the deeper I’ve dug into the research.  It is a sad day for me as a TCM-trained herbalist.  Only if I align myself to protecting patients, educating consumers, and learning the truth is this in any way a success for me.  I appreciate the supportive comments I’ve received from other acupuncturists.  As I mentioned in the post, I welcome corrections, suggestions, criticisms, or clarifications.

Disclosure:  I still practice acupuncture and sell Chinese herbs via my clinic and website, ancientway.com.  I mostly sell Plum Flower Brand, including some of the species mentioned in this post.  Writing about this is not expected to help my sales or professional popularity.