The article is fortunately published in open access, and so I can reprint it here (full article is below). What I think David and I convincingly demonstrated is that, according to the usual standards of medicine, acupuncture does not work.

Let me explain what I mean by that. Clinical research can never prove that an intervention has an effect size of zero. Rather, clinical research assumes the null hypothesis, that the treatment does not work, and the burden of proof lies with demonstrating adequate evidence to reject the null hypothesis. So, when being technical, researchers will conclude that a negative study “fails to reject the null hypothesis.”

Further, negative studies do not demonstrate an effect size of zero, but rather that any possible effect is likely to be smaller than the power of existing research to detect. The greater the number and power of such studies, however, the closer this remaining possible effect size gets to zero. At some point the remaining possible effect becomes clinically insignificant.

In other words, clinical research may not be able to detect the difference between zero effect and a tiny effect, but at some point it becomes irrelevant.

What David and I have convincingly argued, in my opinion, is that after decades of research and more than 3000 trials, acupuncture researchers have failed to reject the null hypothesis, and any remaining possible specific effect from acupuncture is so tiny as to be clinically insignificant.

In layman’s terms, acupuncture does not work – for anything.

This has profound clinical, ethical, scientific, and practical implications. In my opinion humanity should not waste another penny, another moment, another patient – any further resources on this dead end. We should consider this a lesson learned, cut our losses, and move on.

I suspect, however, human nature being what it is, that this will not happen anytime soon.

________________

Full article reprinted from Anesthesia & Analgesia

Acupuncture Is Theatrical Placebo

• Copyright © 2013 International Anesthesia Research Society

It’s also nice that Steve Novella and I were both interviewed. Now, excuse me while I get back to doing what I really should have had finished a month or two ago: Reading Dr. Offit’s excellent book.

Skin tags

Skin tags (acrochordon) are benign growths, often raised on a pedicle with a tiny stem. 46% of the population has one or more of them.  They are usually ignored, but some people think they are ugly and want to get rid of them, and sometimes the lesions rub on clothing and become irritated. Never fear! Tag Away is here!

I saw it advertised on TV.  They said it is “not available in stores.” But they only meant their special TV offer is not available in stores. You can buy Tag Away on Amazon.com, at Walgreens, at Walmart, and elsewhere. Tag Away is an all-natural product that promises to remove unsightly skin tags painlessly. It comes in a 15 cc bottle and is applied with a cotton swab 3 times daily for 3-8 weeks. One website claims:

One of the secrets of this product’s amazing success rate is Thuka [sic] Occidentalis, which is world-renowned for its ability to eradicate even the largest, most unsightly skin tags.

That’s not true. It doesn’t have an amazing success rate, it’s not world-renowned, and there’s no evidence that it can actually remove skin tags of any size.

Evidence

There isn’t any. It has never been tested in controlled trials.

Testimonials

There are the usual testimonials saying that it works, but there are many more testimonials saying that it does not work.  On the Amazon website, negative customer reviews far outnumber the positive reviews. “The only thing this product was capable of effectively removing was money from my wallet!” “Does nothing but smell funny.”  Some said even if it does work, it takes too long and stinks.

It stinks

Customers report a horrible smell. Some called it nauseating. Some said bystanders had asked them “what the hell is that smell?” One compared it to deer urine. One couple reported “The smell is so bad that there is no way you could apply this and leave the house…gave us terrible headaches.”

What’s in it?

The active ingredient is Thuja occidentalis, an essential oil. Other (presumably inactive) ingredients are cedar leaf oil, Melaleuca alternifolia leaf oil, and Ricinus communis seed oil.

Thuja occidentalis is a small tree, also known as white cedar, yellow cedar, arborvitae, and numerous other names. Despite the names, it’s not part of the cedar family.  It has had a number of traditional uses, including teas for constipation and headache and external application for warts, ringworm, thrush, osteoarthritis joint pain, muscle pain, skin diseases, and as an insect repellent.  The Natural Medicines Comprehensive Database (NMCD) says there is insufficient reliable information to determine its effectiveness. It warns against use during lactation and lists reported adverse reactions from oral use including seizures and death.

Melaleuca alternifolia is tea tree oil. It has been used topically for nail fungus, athlete’s foot and acne and is rated “possibly effective.” Topical application can cause irritation and inflammation in some patients.

Cedar leaf oil = Thuja occidentalis. It’s just another name for the active ingredient, yet it is listed as an inactive additive.

Ricinus communis = castor. It has been used topically as an emollient and to dissolve cysts, growths, warts, for osteoarthritis, and to soften bunions and corns, but there is no scientific evidence that it is effective for these uses.

Tag Away is advertised as “homeopathic.” Lists of the homeopathic uses of Thuja are endless, but they don’t mention skin tags. Interesting. I tried to find out what homeopathic dilution they were using, and it took 3 inquiries to the company to get an answer. They eventually divulged that the active Thuja is a 6X dilution. That’s not one of the extreme dilutions where no molecules are left. 6X means there is one part of Thuja to a million parts of water. It seems unlikely that a one to a million dilution would have any therapeutic effect, especially since there’s no evidence that full-strength Thuja has any effect.  They said the other 3 ingredients were not homeopathic dilutions but they had no information about the amounts. The company does not claim that these other ingredients are “active,” but could there be enough to have some kind of positive or negative effect? A concerned consumer would like to know how much was present. If Thuja is the active ingredient, what does it mean when one of the presumably inactive ingredients is also Thuja? Did they realize the homeopathic dilution was insufficient and decide they needed to add more Thuja? And why did they add the tea tree oil and castor? A plausible rationale does not readily come to mind.

Questionable business practices

There is a money-back guarantee but it doesn’t include the $9.95 shipping and handling charge, and it is only for 30 days. They say it takes up to 8 weeks to work. So if you try it for 8 weeks and still have your skin tag, it’s too late to ask for your money back.  By buying the product, you automatically commit yourself to an arbitration agreement that requires dissatisfied customers to submit to binding arbitration rather than attempting to resolve disputes in a court of law. In other words, you give up your right to sue. Customers are only released from the arbitration agreement if they return the product within 14 days.

There have been many complaints about the company, describing questionable business practices. They sell customer information to telemarketers and customers are bombarded with phone calls. Unauthorized charges are made to credit cards. One customer said he was unable to get the recurrent credit card charges blocked and had to close that card number and get a new one.

What other treatments are available?

Skin tags can easily be removed by a dermatologist using excision, ligation, cauterization, or freezing with liquid nitrogen. If they are pedunculated, they can also be removed at home by tying a string (dental floss?) around the base of the stem to cut off blood supply: the dead tissue falls off after a few days. One dissatisfied Tag Away customer reported, “Dental floss worked in about 2 weeks.” Other home treatments mentioned online are vitamin E oil, Compound W, and duct tape, but there’s no evidence that they work.

Amazon.com also sells other products for skin tag removal containing the same ingredients: Tag Be Gone, Tag No More, Miracle of Aloe Miracle Skin Tag Remover, Naturasil, and Tea Tree Oil.

Bottom line

These lesions are easy to treat at home or in a doctor’s office, with results much more rapid than 3-8 weeks. There’s no evidence that Tag Away works, and there are testimonials galore saying it doesn’t work. In my opinion, this product stinks in more ways than one.

As was the case for the nonexistent cell phone-cancer link, there has now been a steady drip-drip-drip of bad studies touted by anti-GMO activists as “evidence” that GMOs are the work of Satan that will corrupt or kill us all (and make us fat, to boot). Not too long ago, I came across one such study, a truly execrable excuse for science by Gilles-Eric Séralini at the University of Caen purporting to demonstrate that Roundup-resistant genetically modified maize can cause horrific tumors in rats. I looked at the methods and conclusions and what I found was some of the worst science I had ever seen, every bit as bad as the quack “science” used by the antivaccine movement. It wasn’t for nothing that I made the comparison, because the anti-GMO movement is very much like the antivaccine movement and the cranks who claim that cell phone radiation causes cancer. As if to demonstrate that very point, last week I came across an article by the all-purpose crank to rule all cranks, Mike Adams, at NaturalNews.com entitled GMO feed turns pig stomachs to mush! Shocking photos reveal severe damage caused by GM soy and corn:

If you have stomach problems or gastrointestinal problems, a new study led by Dr. Judy Carman may help explain why: pigs fed a diet of genetically engineered soy and corn showed a 267% increase in severe stomach inflammation compared to those fed non-GMO diets. In males, the difference was even more pronounced: a 400% increase. (For the record, most autistic children are males, and nearly all of them have severe intestinal inflammation.)

The study was conducted on 168 young pigs on an authentic farm environment and was carried out over a 23-week period by eight researchers across Australia and the USA. The lead researcher, Dr. Judy Carman, is from the Institute of Health and Environmental Research in Kensington Park, Australia. The study has now been published in the Journal of Organic Systems, a peer-reviewed science journal.

It sounds pretty damning, doesn’t it? It sounds truly horrific, just as the Séralini study did. Adams is useful in that he takes the messages of anti-GMO activists (well, actually, he takes the messages of just about all cranks and quacks) and, as they said in This Is Spinal Tap, turns them up to 11. On the surface, it does, anyway. But what about the actual study. There was really only one thing for me to do, and that’s the same thing I did with the Séralini study: Go and see for myself. So I did.

What hath Judy Carman wrought?

Judy Carman’s study was, fortunately, published in an open access journal, and there was a direct link to the study itself. The first thing I did was to look at the journal. I had never heard of it before. The journal seems to cater to the organic crowd, being sponsored by groups like the Organic Federation of Australia and CSAFE, while the guidelines for authors state that “topics are to be consistent with current principles of organic farming and its associated industries, especially those in Australia, New Zealand, Asia, and the Pacific Islands.” The journal itself appears not to be indexed on PubMed, which tends to indicate either that it’s a new journal or not a very good journal. On the other hand, to be fair, there are plenty of CAM journals indexed in PubMed, and many of them are pure pseudoscience; so I can no longer conclude that lack of indexing in PubMed automatically means a journal is dodgy. It is, however, often an indication that it is. Moreover, if you wander over to Judy Carman’s website, gmojudycarman.org, you’ll see that it’s chock full of anti-GMO activism.

After having seen this study, I think that the editors of this open access journal have made a massive mistake and have, either wittingly or unwittingly, allowed their journal to become a tool of anti-GMO activist groups, a couple of which which gleefully announced the results of the study with press releases (for example here and here) calling the study “groundbreaking,” asserting that it was evidence of “adverse effects” due to GMO feed, and claiming that the results show “…clear evidence that regulators need to safety assess GM crops containing mixtures of GM genes, regardless of whether those genes occur in the one GM plant or in a mixture of GM plants eaten in the same meal, even if regulators have already assessed GM plants containing single GM genes in the mixture.”

Here’s a hint: It’s none of the above.

As I read the study itself, the first thing that became apparent to me is that it’s a massive fishing expedition. What do I mean by that? I mean that there’s no clear hypothesis. Basically, the only seeming hypothesis was “GMOs bad,” and the study was designed to find bad things associated with GMOs. At first glance, the design seems simple enough. The investigators used 168 just-weaned pigs at a commercial piggery in the US. The pigs were fed a standard diet, but half the pigs were fed widely used varieties of GM soy and GM corn, while the control group fed an equivalent non-GM diet. Basically, one protein made the plant resistant to a herbicide and two proteins were insecticides. The specific GM varieties used were as follows:

The corn used in this study contained 90% DK 42-88 RR YG PL (a triple stack of NK603, MON863 and MON810 genes) with the remainder being equal quantities of Pannar 5E-900RR (containing NK603), Pannar 4E-705RR/Bt (a double stack of NK603 and MON810) and Producers 5152 RR (containing NK603). Therefore, the GM corn that was used was genetically modified to produce three new proteins. Two were Bt proteins that protected the plant against insect attack, while the third protein provided the plant with tolerance to the herbicide glyphosate (Testbiotech, 2012; Monsanto, 2012). Because Roundup Ready^TM (RR) soy is predominant in the GM soy market, this was used. This crop contains a gene that provides tolerance to the herbicide glyphosate. GM DNA analysis (Genetic ID, Fairfield, Iowa, US) confirmed that the GM corn contained a combination of NK603, MON863 and MON810 genes (expressing the CP4 EPSPS, Cry 3Bb1 and Cry 1Ab proteins respectively), that the RR soy was 100% RR soy (expressing the CP4 EPSPS protein), that the non-GM feed contained a median of 0.4% GM corn and that the non-GM soy contained a median of 1.6% GM soy. Such GM contamination of apparent non-GM material is common in the US.

So the investigators fed piglets a diet of GMO grain versus non-GMO grain, let the pigs mature according to the normal methodology, and then after slaughter looked at a variety of outcomes. Worse, the authors measured these variables without any sort of control for multiple comparisons. Of course they found differences! Actually, what surprised me is how few differences they found between the groups, not how many. I’m going to hone in on the main finding of the paper first. It’s the finding that seemed the most dramatic and was the most highly publicized, the one mentioned by Mike Adams in his breathless description of he results, as though it was slam-dunk evidence that GMOs are evil. I’m referring, of course, to the claim that more stomach inflammation was observed in the pigs fed a GMO diet, specifically a 267% increase in severe stomach inflammation in the GMO group, with a whopping 400% increase in male pigs. It’s the result that produced pictures like this one in the paper (and, not surprisingly the same picture posted to many an anti-GMO website):

These images certainly look striking, but what do they mean? Well, not much. First of all, as many have pointed out, the photos chosen are deceptive in that not enough of the groups are shown, nor can we be sure that these are representative. Also, as Mark Hoofnagle points out, the assay for inflammation in the gastric mucosa of the piglets was only based on gross pathology. Basically, there was no histological study and pathological examination of the tissue to detect and quantify actual inflammation. Basically, the assay was based just on a gross visual inspection of the the tissue by a veterinarian (not even a veterinary pathologist even, as far as I can tell). Unfortunately, such inspections can be highly misleading, particularly after animals have been slaughtered in an abattoir, as described by Professor Robert Friendship, University of Guelph:

Dr. Robert Friendship, a professor in the Department of Population Medicine at the Ontario Veterinary College, University of Guelph and a swine health management specialist, reviewed the paper [see reference below]. He concluded that ‘it was incorrect for the researchers to conclude that one group had more stomach inflammation than the other group because the researchers did not examine stomach inflammation. They did a visual scoring of the colour of the lining of the stomach of pigs at the abattoir and misinterpreted redness to indicate evidence of inflammation. It does not. They would have had to take a tissue sample and prepare histological slides and examine these samples for evidence of inflammatory response such as white blood cell infiltration and other changes to determine if there was inflammation. There is no relationship between the colour of the stomach in the dead, bled-out pig at a slaughter plant and inflammation. The researchers should have included a veterinary pathologist on their team and this mistake would not have happened. They found no difference between the two experimental groups in pathology that can be determined by gross inspection.’

What I found particularly suspicious was Table 3. Notice how the level of inflammation is divided into no inflammation, mild inflammation, moderate inflammation, severe inflammation, erosions, pin-point ulcers, frank ulcers, and bleeding ulcers. This is not really a standard way of scoring inflammation. I don’t know about pigs, but in humans there are a variety of scoring systems for the endoscopic assessment of inflammation (for example, this one), particularly chronic gastritis (which is what we’re talking about, although such redness as described would, if associated with gastritis, be more associated with acute gastritis). Worse, gross visual assessment of gastric mucosa is subject to high inter-observer variability, and, although the personnel caring for the pigs and doing the autopsies were blinded to the experimental group (which is good), I don’t see any attempt to control for inter-observer variability, and, again, no control for multiple comparisons.

I also note that the difference between pin-point ulcers, frank ulcers, and bleeding ulcers is rather arbitrarily defined and not entirely clear. Also notice how twice as many pigs had no inflammation in the non-GMO group and that there was actually a lower risk of mild and moderate inflammation, as well as erosions and pin-point ulcers. Of course, the p-values are all non-significant, except for one: that for severe inflammation. In fact, on the entire table, the only “statistically significant” result is for “severe inflammation.” In fact, as Mark Lynas points out, many more pigs fed non-GMO feed had stomach inflammation than those with GMO feed.

Lynas also points out that the data are all over the place with respect to reported levels of inflammation, asking the very apt question, “If GMO feed is causing the severe inflammation, why is the non-GMO feed causing far more mild to moderate inflammation?” One also can’t help but notice that for “moderate” inflammation, there was a difference favoring the non-GMO feed, and I echo the question, “Do Carman et al perform a test for statistical significance to see if GMO feed has a protective effect on pigs stomachs? Of course not – that’s not the result they are after.” Exactly. Even worse, they used the wrong statistical analysis to analyze categorical data. When the data are analyzed more appropriately, there appears to be no statistically significant difference between the groups, just as there was no real statistically significant difference in the tumor burden of the rats in the Séralini study. Come to think of it, Carman’s study resembles the Seralini study in that it basically looks at a whole lot of outcomes in a fairly arbitrary fashion and cherry picks the inevitable “positive” result. In fact, if you take all the groups together, there actually appears to be a non-statistically significant trend towards less stomach inflammation in the GMO group. Yes, less. As Karl Haro von Mogel put it, the authors appeared to be “trying to shoe-horn individual categories that aren’t binary data into a statistical test designed for binary data is the wrong approach.” Basically, however you look at it, there’s just no “there” there. Analyzed correctly, there is no statistically significant (or, no doubt, biologically significant) difference in stomach inflammation in this study. As for the reported increase in uterus weights, as Professor David Spiegelhalter, Winton Professor of the Public Understanding of Risk at the University of Cambridge points out, “There are also 19 other reported statistical tests, which means we would expect one significant association just by chance: and so the apparent difference in uterus weight is likely to be a false positive.”

There’s another aspect of this paper that’s very troubling, and it is that these animals were all very sick. Indeed, I have to wonder how they were being cared for. Over half the animals are reported in Table 3 to have pneumonia, defined as “consolidating bronchopneumonia of the cranial ventral lung lobe(s) and/or caudal lobes.” That is just not normal, and it doesn’t sound like a minor pneumonia. True, this pneumonia wasn’t histologically verified either, as far as I can tell, although pneumonia can be viewed grossly if it’s bad enough. It is, after all, basically puss mixed with mucous in the alveolae and bronchial passages. As has been pointed out in multiple discussions of this study, such a high percentage of animals with pneumonia is an indicator of very bad animal husbandry, indeed. The bottom line is that there are many, many problems with this study, the totality of which are more than enough to render its results meaningless. There is no dose-dependent mechanism for the effects reported, no rhyme or reason consistent with a mechanism that would explain why GMOs would affect just the stomach (and then only to cause severe inflammation) and uterus size. The study was a fishing expedition and not hypothesis-driven. It’s not surprising that it found something. I’d be shocked if it hadn’t. In the end, this study abused a fairly large number of innocent pigs to produce no useful data. She might try to defend it against criticism, but she basically fails. In particular, one notes that she can’t seem to defend against the charge of a lack of hypothesis and that she didn’t even try to defend the criticism that she didn’t bother to look at stomach histology to verify that there really was inflammation in the gastric mucosa, despite Carman’s touting that the “authors have over 60 years of combined experience and expertise in medicine, animal husbandry, animal nutrition, animal health, veterinary science, biochemistry, toxicology, medical research, histology, risk assessment, epidemiology and statistics.” Sad that they didn’t use all that experience to produce a paper whose results are believable and useful.

This isn’t Judy Carman’s first time…

In reading this study, I couldn’t help but notice the corresponding author: Judy Carman. I had heard that name before. But where? Oh, yes. I remembered. I had encountered her making some truly ridiculous claims about GMOs, so ridiculous that I think it’s worth bringing up now. She didn’t write the commentary I’m about to describe, but she voiced support for its findings, providing tactical air support to its author, Jack Heineman. I had wanted to write about it at the time I came across it, but, for whatever reason, didn’t manage it. So now’s as good a time as any. In brief, Carman appears to be an anti-GMO activist who, along with another anti-GMO activist, Professor Jack Heinemann at the University of Canterbury’s Centre for Integrated Research in Biosafety, made some truly nonsensical claims about GMOs. I first encountered these nonsensical claims in the blog of a homeopath named Heidi Stevenson, who claimed that genetically modified wheat may damage human genetics permanently.

Stevenson prefaces her article with this scary paragraph:

The Australian government, in the form of its science research arm, is joining Agribusiness profiteering by designing a GM wheat that could kill people who eat it & be inherited by their children.

Scared yet? Does Stevenson have your attention? Who are these nefarious scientists, and why would they want to make genetically modified wheat that would do these things? They wouldn’t, of course, but, like the Frankenstein that anti-GMO activists think scientists are, it’s a matter of messing with nature resulting in unintended consequences. In fact, the hilarity is such that I think it’s worth quoting a decent sized chunk of the first part of Stevenson’s article:

We have not yet seen the worst damage that genetic engineering may do. Australia’s governmental agency, Commonwealth Scientific and Industrial Research Organisation (CSIRO), is developing a wheat species that is engineered to turn off genes permanently.

Professor Jack Heinemann at the University of Canterbury’s Centre for Integrated Research in Biosafety has studied the wheat’s potential. Digital Journal reports that he says¹:

What we found is that the molecules created in this wheat, intended to silence wheat genes, can match human genes, and through ingestion, these molecules can enter human beings and potentially silence our genes. The findings are absolutely assured. There is no doubt that these matches exist.

The implications are clarified by Professor Judy Carman of Flinders University:

If this silences the same gene in us that it silences in the wheat—well, children who are born with this enzyme not working tend to die by the age of about five.

Silencing the equivalent gene in humans that is silenced in this genetically modified wheat holds the potential of killing people. But it gets worse. Silenced genes are permanently silenced and can be passed down the generations.

Yes, that’s the very same Judy Carman who published this awful “stomach inflammation” study that I just discussed.

Basically, Carman’s claim here is that a variety of genetically modified wheat under development by the CSIRO will kill your children. I kid you not. And Judy Carman has not only promoted this idea but amplified it by emphasizing that she thinks children could die. Of course, Stevenson apparently doesn’t see the contradiction between saying that this GM wheat will kill your children but that its gene-silencing effects will also be passed down the generations. Neither does Carman, who continued:

As a result, there is a chain of evidence to show that there is a risk that the dsRNA from this GM wheat may survive digestion, enter the tissues of people that eat it and silence a gene or genes in those people. There is also evidence that any genetic changes so produced may be stable and become established in many cells of an organ. Furthermore, there a possibility that these changes may be passed-on to future generations.

In any case, I could recognize some amazing speculation and fear mongering right off the bat; so it’s time to explain.

Gene “silencing” means what the name implies: Shutting down the activity of a gene so that it stops making its gene product. Of course, gene silencing is not an all-or-nothing phenomenon. Like other forms of gene regulation, silencing happens on a continuum from zero to complete silencing, depending on the level and activity of the silencing agent. In this case, the silencing agent that is being turned into the bogeyman du jour is RNA. Specifically, it’s a type of RNA-mediated gene silencing called RNA interference (or RNAi), also known as post transcriptional gene silencing (PTGS). The idea is that the CSIRO is apparently engineering a strain of wheat that produces a short RNA molecule designed to silence specific genes in the wheat. Most of the time, when we talk about RNA, we talk about messenger RNA (mRNA), the RNA that is the intermediary between DNA and protein. However, back in the late 1990s, it was discovered that there are other RNA molecules that actually regulate gene expression by binding to complementary sequences on mRNAs. These molecules include classes of RNAs called microRNAs, as well as double-stranded RNA molecules known as short interfering RNA (siRNA), that can participate in cellular pathways that contribute to gene silencing, most commonly through binding to complementary sequences and inducing the degradation of different mRNAs in a sequence-specific manner. In fact, siRNAs were first discovered in plant genetics and only later was it discovered that short RNAs serve as a gene regulatory mechanism in mammalian cells as well.

An excellent video explanation of RNAi can be found, courtesy of Nature:

So what’s the problem? Heinemann and Carman are apparently worried that the siRNA that will be used to silence two genes in wheat called SEI and SEII. Heinemann apparently did an analysis based on the sequence of the SEI and SEII genes, comparing them against the human genome and looking for matches. He found them in the gene for the enzyme mentioned by Judy Carman. In humans, the equivalent gene is known as glucan (1,4‐alpha‐), branching enzyme 1, abbreviated GBE. Based on some similarities he found between SEI and GBE, Heinemann sounded an alarm through an anti-GMO activist group known as the Safe Food Foundation & Institute. Humans store carbohydrates as glycogen, and GBE makes branches in glycogen. There is a consequence to not being able to branch one’s glycogen, although not branching it in wheat could be useful for decreasing its glycemic index. There is a disease known as glycogen storage disease IV, which leads to damage to the liver over time. That’s the disease that Judy Carman was referring to.

Of course, the problem with Dr. Heinemann’s highly speculative analysis is that he didn’t know the actual siRNA sequences that were going to be used. Without that information his analysis was pretty pointless. At the very best, it was highly speculative. At the worst, it was ideologically and politically motivated.

So how could this possibly matter? After all, it’s RNA. It’s really unstable, isn’t it? Well, not exactly. Single stranded RNA is very unstable. It can’t survive long outside of the cell. However, dsRNA can be quite stable, even outside of a cell. But that still leaves the question of whether dsRNA from a plant that is eaten can have any effect. To do that, the siRNA would have to survive digestion, be absorbed into the bloodstream, enter other cells, and act on gene expression. Heinemann notes that such a phenomenon can be observed in insects and worms.

But can it happen in humans? Well, there is one paper that Heinemann latched on to because he thinks it demonstrates that the same phenomenon can happen in humans. It’s a paper by Zhang et al. published in Cell Research that showed that showed that a plant-derived microRNA (miR-168a) from rice can be found in human serum after ingesting rice and that it can actually bind to the mRNA for low-density lipoprotein receptor adapter protein 1, thus inhibiting the expression of this protein. It’s an interesting observation, but there are a number of questions. For one thing, although the microRNAs are detectable in serum they circulate at a really low concentration, namely the femtomolar range (10^-15 mole/Liter). News stories describing the study at the time were quite credulous, but a better discussion can be found at Sandwalk. In any case, the exceedingly low concentration of microRNA observed in the bloodstream leaves a huge question in that there is no known mechanism by which such a low concentration could have such an effect. When I first read the study, I thought it plausible, but the more I think about it the more I agree with the Sandwalk commenter who says it screams “artifact” to him. Or this commenter:

There is probably 10 fM of everything in the blood. Sheesh, that’s less than 4×10^9 molecules per whole body consisting of about 7×10^12 cells and containing no more than 7×10^10 hepatocytes. That’s less than 0.1 miRNA per liver cell in the best possible scenario. What are these RNAs, totally magic?

Maybe they’re homeopathic, although admittedly fM concentrations are far and away greater than the concentrations of most homeopathic remedies (i.e., zero). In any case, stoichiometry is your friend when figuring these things out. Personally, I’ll wait for some confirmation that this happens from other groups before I buy it. True, another group has reported finding miR-168a, but it also reported a huge variety of microRNAs in the serum from a variety of sources, including bacteria and fungi as well as from other species, such as various insects. Basically, we’re awash in microRNAs from other species that we come into contact with. So far, the only evidence that they have any effect whatsoever is that one study suggesting that miR-168a might regulate one gene, even though it’s hard to figure out by what mechanism it could possibly accomplish this. Add to that the utter lack of evidence that any circulating microRNA can not only silence a gene in human cells but actually induce epigenetic changes, and Professor Heinemann’s speculation becomes ever more…speculative. This is true particularly in light of the fact that we regularly eat plants that make many siRNAs and microRNAs. Why would GM wheat siRNAs be any different or more dangerous, particularly given the very low concentrations involved?

Let’s put it this way. For Heinemann and Carman’s fear mongering to be a real concern, any siRNA or microRNA from genetically modified wheat would not only have to be made in sufficient quantity at least to equal the normal concentration of miR-168a in rice, but also be stable enough to pass through stomach acid and the gut lining undigested, and get into the bloodstream at a high enough level to affect gene expression. That’s leaving aside the question of whether there is even enough sequence match that the siRNA could even target the human GBE mRNA in the first place, which is impossible to say because we don’t know the actual sequence of the siRNA being used. It’s true that Heinemann has updated his “report.” However, that update doesn’t really show anything new or contribute to the plausibility of Heinemann’s concerns. In fact, it trashes the plausibility even more because the homology (in laymen’s terms, match) to the glycogen enzyme that Heinemann was promoting pretty much disappears in this reanalysis. (In fact, if you look at it in depth, it wasn’t even there to begin with, and it’s questionable whether he even used the right wheat sequence in his BLAST analyses.) Even in the reanalysis, the only areas of match appeared in introns, which, as Biofortified put it:

However, all of the matches he highlights are either to introns – which would not matter for the mechanism of action that is the issue here. Or they are in the genome desert areas, thousands of bases away from anything that appears to be a gene.

Result: Take a deep breath. The GMO wheat that forms the basis of this claim will not kill your children or permanently alter your genome.

More interestingly, I decided to check back and see if the human GBE gene is still sticking with this sequence switcheroo. The main fear-based claim was that the GBE gene would be suppressed and children with a disorder of this can die by the age of 5. So let’s see–let’s do an analysis of this new sequence and compare it to GBE. If you perform a BLASTn at NCBI with these two sequences and default settings as Jack says he does, what do we get?

The result? No significant similarity found.

That’s right. The entire foundation of the fear–the match to GBE–is gone. Evaporated. Vanished. Nada. Zip.

No wonder Australian and New Zealand regulators have rejected the concerns.

Add to that the enormous lack of likelihood that, even if the siRNAs and microRNAs in GM wheat could actually make it into the bloodstream in concentrations sufficient to alter gene expression, it’s incredibly unlikely that such RNAs could actually induce “permanent” epigenetic changes to justify the fear mongering.

There might be questions about GMOs, but by and large they are not issues of safety. Rather, they are issues of intellectual property; i.e., how large companies developing GMOs behave. Hysteria of the like generated by the likes of Jack Heinemann and Judy Carman and parroted by useful idiots like Heidi Stevenson generate heat, but no light. Nor does the latest round of attempts to generate hysterical fear mongering based on Carman’s latest study. Both Heinemann’s speculations and Carman’s most recent bit of data mining are of a piece. They are not designed to provide a dispassionate analysis of the true potential risks and benefits of GMOs. They are designed to be propaganda to produce fear, uncertainty, and doubt about GMOs, just like Andrew Wakefield’s studies about the MMR vaccine, just like Mark and David Geier’s studies of thimerosal in vaccines, just like the studies of any variety of antivaccine cranks. It is the equivalent of shouting “fire!” in a crowded theater.

Unfortunately, the pseudoscience is metastasizing. GMO Pundit points out the next frontier of anti-GMO fear mongering.:

Yes, because a new flu vaccine Flublok is made in “insect cells” (specifically, the baculovirus system, a very common system of expressing mammalian proteins for use in genetically engineered products), it is now a “GMO product” and to be feared as much as GMO-derived foods. In actuality, Flublok should end up being safer than the old flu vaccine because it doesn’t include all those extraneous proteins, such as egg protein, just the three hemagglutinin, or HA proteins, of the most common flu strains circulating in any given year.

What’s next? Telling diabetics that they shouldn’t take insulin derived from genetic engineering because the protein is made in—gasp!—bacteria or yeast?

Sometimes, in the course of blogging, I come across a story that I don’t know what to make of. Sometimes, it’s a quack or a crank taking a seemingly science-based position. Sometimes it’s something out of the ordinary. Other times, it’s a story that’s just weird, such that I strongly suspect that something else is going on but can’t prove it. So it was a few months ago when I came across the story of Alex Spourdalakis, a 14-year-old autistic boy who became a cause célèbre of the antivaccine crank blog Age of Autism.

I first noticed the story in early March when perusing AoA and came across a post by Lisa Goes entitled Day 19: Chicago Hospital Locks Down Autistic Patient. In the post was a shocking picture of a large 14-year-old boy in a a hospital bed in four-point restraints. He was naked, except for a sheet covering his genitals. A huge gash was torn in the bedsheet, revealing the black vinyl of the hospital bed beneath. The boy’s name, we were informed, was Alex Spourdalakis. Further down in the post was another, equally shocking, picture of Alex that, according to Goes, showed severe dermatitis on Alex’s back due to the hospital sheets. The photos shocked me for two reasons. First, if the story was as advertised (something always to be doubted about any story posted at AoA), for once I thought that I might be agreeing with Goes and thinking that AoA was actually doing a good thing, as disconcerting as that possibility was to me. Second, however, I was extremely disturbed by the publication of such revealing photos of the boy. Undoubtedly, Alex’s mother must have given permission. What kind of mother posts pictures like that of her son for all the world to see? Then there appeared a Facebook page, Help Support Alex Spourdalakis, which pled for readers to help the Spourdalakis family.

As I said, something just didn’t seem right at the time.

Now I know that something most definitely wasn’t right, but I still can’t yet figure out what was wrong at that time three months ago. What is wrong now is that a little more than a week ago Alex was brutally murdered by his mother and caregiver, stabbed to death, in fact. The murder was carefully premeditated and quite gruesome:

Convinced that Alex Spourdalakis’ severe autism was growing worse, his mother and caregiver allegedly planned for at least a week to kill the River Grove teenager and themselves.

But the alleged murder plot initially went awry last weekend when the stocky 14-year-old didn’t succumb to an overdose of his prescription medications.

After waiting for several hours, Dorothy Spourdalakis, fatally stabbed her 225-pound son four times with a kitchen knife, then cut his wrist so deeply she nearly severed his hand, Cook County prosecutors said Wednesday.

His caregiver, Jolanta Agata Skrodzka, later stabbed the family cat with the same knife, then washed the utensil and put it back in a butcher’s block, prosecutors said.

Their suicide pact never succeeded: Both women took drug overdoses, then locked themselves in the bedroom with the slain teenager.

They were found semi-conscious inside the second-floor apartment on Sunday afternoon when Alex’s father and uncle came to check on the teen, prosecutors said as the women appeared in court to face first-degree murder charges.

More details are described in this Chicago Tribune story about the murder. Dorothy Spourdalakis and Alex’s caregiver Jolanta Agata Skrodzka had apparently discussed the plan to kill Alex using an overdose of prescription sleeping pills and explained why they did it in a letter. Apparently they killed the cat because they didn’t want it to end up in a shelter after they committed suicide. We also learned that police had been to the house several times to assist with transporting Alex to doctors’ appointments because “he was big and strong and unwilling to go to the doctor.”

Over the last three months, as I occasionally read articles and posts about Alex Spourdalakis, going back to March, I increasingly got the distinct impression that there was more going on that met the eye. Now, on the one hand, Lisa Goes might have been right. That has to be conceded. But while I occasionally looked at stories about Alex on AoA, they just didn’t seem to pass the “smell test” to me. Something, it seemed to me, was being left out. Neither did a lot of the claims being made about the care Alex was receiving strike me entirely credible. At the very least, it was very clear that a highly biased, one-sided version of events was being presented. For instance, Goes claimed that Alex was kept in four-point restraints 24 hours a day at two different hospitals, Gottleib Hospital and Loyola University Medical Center (LUMC), for 19 days:

According to her, at 14 years of age, Alex has a diagnosis of severe autism and cognitive impairment. He is non-verbal. In October of 2012, Alex began to suffer neurological events that prevented a healthy sleep cycle. He was awake for many hours at a time. Agitation and aggression ensued as a result of sleep deprivation. During this time, symptoms and behaviors that were indicative of severe gastrointestinal distress developed as well. A cycle of constipation, diarrhea and formed bowel movements surfaced and became a chronic problem. On February 16th at 5:00 am, with the assistance of police and paramedics, Dorothy took her inconsolable and highly-distressed non-verbal child to Gottlieb Hospital in Melrose Park, Illinois.

Because of Alex’s physical aggression, he was placed in locked restraints. At that time, Dorothy did not know the ER would be their home for the next several days, as Alex lay naked, in locked restraints, suffering bouts of violent vomiting, severe constipation and diarrhea. Neither she nor Alex bathed for the next 13 days while hospital staff and administrators attempted to devise a plan to care for Alex. “He was given Colace for his constipation and sometimes it would take security staff and nurses more than 15 minutes to arrive to help unshackle him so he could use the bathroom,” Dorothy explained. “Alex would scream as best he could when he knew he was going to have a vomiting episode, but security took several minutes to respond so Alex would lay in his own vomit, waiting to be released by a representative of security. He would be wiped down and returned to the same restraints.”

Sure, it was possible that the boy was being abused so horribly, first at Gottleib Hospital and then at LUMC, but the story as presented struck me as implausible, although at the time I had no way of refuting or confirming the increasingly lurid stories being posted at AoA about Alex. For one thing, there are very strict laws these days about patient restraint, particularly when it comes to children. The last time I ever had to order four-point restraints was over 14 years ago, back when I moonlighted as a trauma attending in, yes, the Chicago area, the same metropolitan area where Alex lived and died. Before that I sometimes had to deal with the restraint of patients when as a resident I rotated on the trauma services at the hospitals where I trained. Sometimes patients with head injuries or severe intoxication would be violent and require restraint. There was always a strict protocol that we followed, even back then. My understanding is that the protocols have only gotten more strict. Restraining a patient, particularly a minor, is not something that is undertaken lightly, nor should it be. To believe the AoA account, we have to believe that a severely autistic teenaged boy would be kept in the emergency room for several days (also very, very unlikely) and put in restraints in an abusive fashion at not just one but two different hospitals, continuing after Alex was transferred from Gottlieb Hospital to Loyola University Medical Center on February 28. Actually, it was three different hospitals, because later Alex was shown in four-point restraints at Lutheran General Hospital during his last admission in May. More on that later.

Also missing from these stories was a clear and cogent explanation of why Alex was ever admitted to Gottleib Hospital and then transferred to LUMC in the first place. It’s mentioned in some places that Alex was “inconsolable, highly-distressed and suffering bouts of violent vomiting, severe constipation and diarrhea.” I had to look for clues to explain it, and, I must admit, I still remain puzzled. Certainly, these Change.org petitions demanding that LUMC provide what Ms. Spourdalakis considers to be “standard medical treatment,” which to her included gastroenterology. Peppered through various reports were indications that Alex had multiple allergies and GI issues. Having observed a fair amount of autism quackery on the Internet, these terms were huge red flags to me that strongly suggested the possibility that Ms. Spourdalakis was heavily into “autism biomed.” Another hint as to what might have been really going on comes from reports of a care plan conference on March 12. Allegedly (we only have one side of the story given that the hospital and doctors are bound by HIPAA privacy law not to discuss the case), if Ms. Spourdalakis failed to agree completely to the care plan Alex would be placed in the care of the Illinois Division of Family and Children Services (DFCS).

Elsewhere, I found references to demands that LUMC consult with an “Autism Medical Specialist to ensure Alex’s dietary needs were met to ensure his food allergies and intolerance’s were not aggravating any underlying gastrointestinal or other medical conditions that may also cause adverse behaviors”, which sounded suspiciously like an autism biomed quack. In this post, Lisa Goes described a visit to LUMC with Jeanna Reed of Autism Is Medical, whose website if chock full of standard antivaccine and “autism biomed” tropes, such as a section on mitochondrial disorders, banners asking if autism is vaccine injury, and the like. It’s actually a pretty bare-bones website with lots of bugs, but the intent is clear. Besides, it’s obvious (to me, at least) that Lisa Goes is antivaccine, given that she has been a regular at the (Not-So) Thinking Moms’ Revolution. Indeed, in the very same post, Lisa Goes unwittingly portrayed Jeanna Reed as ranting and haranguing Alex’s doctors with pleas to read quack studies and claims that “many of these children present with bowel disease and mitochondrial dysfunction. He could have GERD, duodenitis, esophagitis, ulcers in the small intestines, colitis. How can we know if we don’t test?” This was pure autism biomed rhetoric, leavened with the arrogance of ignorance. When one of the doctors referred to autism as a “mystery,” Goes totally lost it, yelling, “No! No! It’s not. It’s a medical illness that causes bad behavior. All you have to do IS READ*!”

Such is the arrogance of ignorance that leads antivaccinationists to lecture physicians.

Based on what was in retrospect in plain sight on the antivaccine blogs, it’s hard for me not to suspect at least a little bit that Dorothy Spourdalakis was subjecting Alex to “autism biomed” treatments, that she came to know Ms. Reed and thereby spread her story to the wider autism biomed movement at large. If my suspicions are ultimately revealed to be true through police investigation of the murder and in the upcoming trial of Alex’s mother and caregiver, it would certainly explain a lot. Certainly, it would explain why Lisa Goes and AoA rallied to Alex’s cause so enthusiastically. It would also explain why the hero of the autism biomed movement himself, Andrew Wakefield, visited Alex during Autism One and posted to YouTube on the Autism Media Channel a video making an appeal for Alex:

Note that, in this incredibly creepy video (is it just me, or does Wakefield look creepier and creepier each time I see him?), Wakefield stated that Alex was scheduled to go to long term psychiatric care in 72 hours, as if that were the worst fate imaginable for him. He appealed for funds to allow Alex to be transferred to a facility where he would “get the care he needs.” What that facility is, Wakefield does not say. What also isn’t clear is why Alex was back in the hospital again. I say “back in the hospital” because on March 23 his mother published a post on AoA announcing that Alex was being discharged from LUMC. She thanked everyone at AoA, but she also revealed her antivaccine proclivities:

It is during times like this we as a family realize our full potential. We know no one will help us unless we help ourselves. The continued abuse, medical neglect, discrimination and ignorance have to stop. Vaccines have maimed too many already and there are many more to come. The CDC’s latest stats confirm that. We are not going away, nor are we giving up. My son Alex is just one of millions of children and adults who no longer will be silenced.

We as a group have been deceived and lied to long enough. Our children have paid and are continuing to pay the ultimate price because of greed. The health care system has failed terribly. It is our responsibility to continue to bring about change.

Please continue to follow Alex on his journey toward better health. Allow us to be a part of your lives. Our strength will continue to come from everyone and anyone who would like to continue with us. Alex will hopefully get the medical testing he needs but was denied until now. So much needs to happen in order for us ensure his recovery and I still need so much help! Please continue to follow my team of helpers for updates and fundraising efforts. I cannot tell you how much I appreciate and value every single one of you who have gotten us to this place. Thank God for the internet and facebook!

To me, this was the strongest suggestive evidence that Ms. Spourdalakis had likely been subjecting Alex to autism biomed treatments. The language was pure “autism recovery”-speak. The antivaccine sentiment was there. So was the conspiracy-mongering against conventional medicine and big pharma. In another story, I learned that another antivaccinationist and advocate of “autism biomed,” Polly Tommey of the Autism Media Channel, was involved with the Spourdalakis case, and Ms. Spourdalakis claimed that all Alex needed was “something simple, in the country, where he can run around, get the treatment that he needs so he can get better.” For some reason, however, in May Alex was back in the hospital. When the new reports of Alex in the hospital started coming out, even AoA denizens and supporters wondered what had happened, for instance, on the Facebook post announcing Andrew Wakefield’s appeal. The response from Jeanna Reed:

He’s back in the hospital. The sad truth is that this will be what is left, the only path…unless we start to treat the MEDICAL conditions, provide an appropriate treatment plan and support the families while doing it. A VERY TALL ORDER but one that has to become the norm. Alex does NOT belong in a psychiatric facility. Sadly, this is the only option so many face when all of the above is not available. We did our very best to try and help them, and will continue to do what we can but it’s not enough. We know so many who (if given the opportunity) could heal. So complicated…at the minimum PRAY for them and again realize this could be any one of our children.

I don’t know about you, but if I had seen this at the time it was actually published instead of now, knowing the ultimate outcome, I would have still found the language ominous. In any case, not long after Wakefield’s appeal, Alex was released from the hospital. Andrew Wakefield provided a statement to the Daily Mail after Alex’s death explaining what happened and covering his posterior in the process:

On Sunday May 26, members of the Autism Media Channel (AMC) went to the Lutheran General Hospital in Park Ridge, Illinois. There we visited the late Alex Spourdalakis, his mother Dorothy, and his Godmother. Alex was in four-point restraint and apparently refusing to eat or drink.

His mother was beyond exhaustion and despair. The main reason for her despair was the prospect of Alex being sent to a long-stay psychiatric hospital and heavily medicated with behavior-altering drugs drugs [sic] without any treatment of his underlying medical problems.

AMC issued an appeal on Alex’s behalf to protect him from this fate. We did not, at any stage, advocate for his release from the Lutheran General Hospital.

The following day Dorothy informed us that the hospital could find nowhere that would take Alex and that his insurance carrier had refused to pay for any further inpatient care at the Lutheran General Hospital.

It appears that, as a consequence, he was discharged from that hospital despite his precarious position and that of his carers. It is our opinion that Alex’s tragic death reflects the abject failings of a medical system that has no effective answer to the autism crisis.

In the interests of complete openness, I should point out right now that I used to work part time as a trauma attending at Lutheran General Hospital from 1997 to 1999. It was how I made some extra money while I was a surgical oncology fellow at the University of Chicago. (Chicago is an expensive city to live in, and I didn’t make that much as a fellow.) LGH was a fine hospital then, and I have no reason to think that anything’s changed. Be that as it may, do I detect the stench of self-justification from Wakefield? He’s desperately trying to cover his posterior, but his fetid flatus of blame-deflection leaks out anyway. It’s what he does. Even so, if what Wakefield says is true, it does point out another aspect of this tragedy, namely support for parents with children with special needs.

That being said, what’s also utterly despicable is the reaction of the denizens of AoA and other antivaccinationists to the news of the murder of Alex Spourdalakis. For instance, it is not infrequent to see antivaccinationists blame—of course!—vaccines for Alex’s death, the apparent underlying “logic” being that if he hadn’t become autistic because of vaccine injury then none of this would ever have happened. Such “logic” prevails in the comments of AoA posts about Alex’s death, such as this one and this one. For instance:

Though I can’t support the choice these two women made, it isn’t hard to imagine the desperation and hopelessness they were engulfed in. To watch your precious child suffer for so many years and then endure what this past spring brought for them. They fought and fought the beast head on and felt the hatred against them. It isn’t hard to imagine that they were exhausted. All of this happening in America no less.

No, these two women were, as far as I can tell, offered help but refused it because it was standard conventional therapy. From what I can tell from various blog and Internet articles, they appear to have subjected Alex to biomedical quackery and were unhappy that if Alex were transferred to a psychiatric hospital’s long-term care ward he would no longer be able to receive “autism biomed” treatments. Time and investigation by the authorities will tell if that was the case. Whether that is what happened or not, I nonetheless reject the “logic” of such antivaccinationists such as it is, that only makes sense only if you accept the pseudoscience claiming that vaccines cause autism. While one can sympathize with a parent facing the task of caring for a severely autistic child who is very large, very strong, and very difficult to control, as Jo Ashline says, autism is not an excuse to kill your child, ever. As one blogger put it:

So one of the reasons I’m really pissed off is because of the usual [eye rolling] “Oh, he’s in heaven now”. My favorite is the thing that one of the groups that was intended to work towards getting Alex out of the hospital was a letter to Alex in heaven suggesting that he thank his mother for stabbing him in the chest. [Sarcastic eye rolling] “Thank you so much for brutalizing me, it’s my favorite”. Because now, you see, he’s in heaven, which I don’t think exists. And he doesn’t have autism.

Harsh? Yes. But it rings true. The entire narrative of the autism biomed movement is that autism “stole” the parents’ “real child” away from them. Since the idea that vaccines cause autism is basically holy writ for the autism biomed movement, that means vaccines “stole” the real child away by making him autistic. Parents who try to “recover” that “real” child are thus viewed as heroic, rather than abusive, because they’re willing to do whatever it takes to defeat the scourge of autism (and vaccines) in order to rescue the “real” child within. One can’t help but wonder whether what was really happening was that DFCS was going to put Alex into a conventional long term care facility because his mother clearly couldn’t handle him anymore and was treating him with autism biomed. Unfortunately, it appears from what we know right now that Alex’s mother seems to have thought that he would be better-off dead than not being given access to what she viewed as “curative” treatments for autism. Events and evidence from the investigation and trial might prove that initial assessment incorrect, but for now it seems to fit with what we know. Was Alex collateral damage in this never-ending war by antivaccinationists against autism? Although what we know now suggests that this might be the case, we just don’t know yet. We’ll have to keep an eye on the results of the investigation into Alex’s murder to find out.

In the meantime, watching the denizens of the antivaccine crank blog AoA hold candlelight vigils for Alex is very hard to take, as they rant about how the medical system failed Alex. Maybe it did (that remains to be seen), but what Lisa Goes and Andrew Wakefield did themselves certainly didn’t help Alex either.

The conceptual framework I use, and that used by others in medicine, does not concern itself with the application of the Supplements, Complementary and Alternative Medicines that occupy the attention of this blog. In acute care medicine SCAMs are of virtually no importance yet the approaches we need to take with patients and medicine are, with slight changes in emphasis, as applicable to SCAMs as real medicine. You need to remember, however, that the topic is not necessarily based in known reality.

Two viewpoints in JAMA caught my attention this month, both more thoughtful and reasoned than I am probably capable of. While focused on the application of reality-based medical practice, they apply to the topics of SBM as well.

The first is Evidence-based persuasion: an ethical imperative.

Evidence-based persuasion.  At some level the raison d’être of this blog and the antithesis of the SCAM world. That it is considered an ethical imperative makes its lack of use in the SCAM world all the more damning.

The article points out in the introduction that:

There are at least 3 different types of persuasion. The first is the removal of bias. The second is recommending a particular course of action and providing evidence and reasons in favor of it; and the third is the potential creation of new bias, which could cross the line into unethical manipulation.

They go on to give examples applied to the practice of medicine. How about science-based medicine?

The first kind of persuasion, the removal bias, is the primary theme of this blog. Readers and writers of this blog are aware of all the types of bias that can warp judgment. I have long said that the three most dangerous words in medicine are “in my experience” because experience is unreliable in helping decide what works.  Experience in medicine is the worst bias.

Ignoring experience is an unnatural way for humans to behave. Everything we do is a result of experience. The best restaurant in town*? The fastest way to work? Best headphones? In every aspect of life we rely on our experience and that of our social network to decide what to do. And then we get to medicine, the attempt to heal illness and relieve suffering, and we are asked to lay aside a lifetime’s approach to the world and rely on clinical trials? Not likely.

I had a patient just a few weeks ago ask me if she could take colloidal silver for her infection and I told her it does nothing. She countered that I was wrong, that she had used it many times in the past and it had always cured what ailed her. I knew I had not a chance in hell if convincing her otherwise for as Groucho said, who are you going be believe, me or your lying eyes?

Perhaps people are able to alter their biases when presented with the evidence, but I am not sure everyone is capable. When someone suggests that the reason I recommend vaccines, or any other reality-based therapy, is because I am a paid shill of big Pharma, I know that we inhabit two radically different realities that do not overlap. Such sentiments are not uncommon:

…one in seven Americans think the pharmaceutical industry is colluding to “invent” new diseases in order to profit off them…

Weird. Sure Big Pharma, like all companies, can behave with all the ethics of a psychotic shark, but the conspiratorial nature of some biases is just nuts.

In medicine when we discuss diagnostic and therapeutic interventions we sometimes have to dissuade people of erroneous ideas that could prevent them from accepting care. It is rare in my world. Most people, when acutely infected, accept the interventions I have to offer since the alternatives are rather unpleasant. The only common interaction is the occasional new AIDS patient who refuses HAART because they are convinced the medications are toxic and kill people. After explaining the history of HIV treatment I usually convince them to give it a try. As a result I have many patients who would have died in months in the bad old days who are now alive a decade later. Very satisfying.

But what if your whole practice is based on bias, on unreality, and you cannot realize it? The only bias you can alter is to convince your patients that real medicine is fantasy and that fantasy is reality. Welcome to Natural News, the bizarro world of medicine.

How about the second? “Recommending a particular course of action and providing evidence and reasons in favor of it.”  Hard for a SCAM provider.

In my practice, hospital-based acute infectious diseases, it is reasonably simple. I know most of the pertinent literature for the common infections and if I have some weird bug in an odd place I research the problem and tell the patient the whys and wherefores of the proposed treatment. I know the science, I know literature (not always the same thing) and I know the best options.

What about a homeopath or acupuncturist or reiki practitioner? Can an Integrative Medicine Department ethically offer using these therapies after comparing them to the known world?

It is an interesting psychology: based on nonsense that is a polar opposite to the understanding of reality, the only favorable evidence that can be offered is “in my experience.’ It is a curiosity that real medicine uses what can be the least convincing arguments, those from the literature, while the homeopath has to rely of the least valid but most powerful argument, experience.

My patients often want to know what kind of experience I have. Has this worked before, how many of similar cases have I managed, and what would I suggest if it were my mother? I am always slightly unnerved with the question because I know how faulty my memory is, especially after almost 30 years of medicine. That’s maybe 25,000 cases. Like I can remember? But that is all the average SCAM provider has to offer.

The last form of persuasion, that of creating new biases, is the most interesting. It is an interesting balance. Patient autonomy is paramount in US medicine. They are the captain of their ship and it is my job to give them my best opinion as to their diagnosis and treatment. On the other hand, the process of explanation will persuade them and we all know the context of how information is given can create bias.

However all SCAM is about creating new biases that are divorced from reality.

It would interesting to get an ethics consult and ask the question of a hospital’s integrative medicine department if they can live up to the recommendations of ethical persuasion:

1) Remove bias and access the patient’s autonomous wishes
2) Provide honest, impartial, evidence-based information about prospective harms and benefits
3) Provide a rational interpretation of this information including facts about the belief set and views regarding the best decision
4) Use reason rather than emotion while sometimes appealing to the patient’s emotions to counterbalance their existing emotional responses
5) Avoid creating new biases
6) Be sensitive to the patient’s changing preferences because persuasion is likely to change the patient’s outlook and perspectives.

The heart of all SCAM is in violation of the first 5. Given they are not based on known reality, they cannot follow those recommendations and it should be unethical to offered in a real medical environments.

However, SCAMs make money, and where money is concerned, rationalizations will follow.

The other viewpoint that caught my eye in JAMA was Synthesizing evidence: shifting the focus from individual studies to the body of evidence.

The first sentence is intriguing:

The research enterprise behaves as if a single study could provide the ultimate answer to a clinical question.

The rest of the essay is an argument that more emphasis should be placed on the results of meta-analyses and not rely on single studies.

I do and do not agree with the authors, but there are always caveats.

One of the issues that has always annoyed me with meta-analyses is that often as new studies are done they are incorporated into the prior analysis but the older, often more poorly done studies are not thrown out, so the bad studies tend to pull down the good ones.

The Cochran Collaboration has a nice overview of the systamatic review process but they are done under the implicit assumption that what they are reviewing are studies that evaluate reality. The Cochrane Reviews usually fail when they apply their methods to topics such as homeopathy or acupuncture, where positive results are always due to bias.

Even though they assess the quality of the studies, they do not take into consideration the prior plausibility that renders most SCAM studies suspect.

There is an arc in the literature concerning most SCAMs. Better and better quality studies demonstrate less and less efficacy until well designed studies demonstrate no effect.

The potential for that arc, as best as I can tell, is not part of the systematic review, but would give a hint as to the validity of studies where the intervention is divorced from reality. A plot of study quality vrs efficacy over time.

Part of my job is that of data synthesizer. What is the best way to treat, say, MRSA pneumonia? It can depend on many factors, some of which are not clear cut or have no data at all. Is the flu vaccine of benefit? The answer depends on what is considered a benefit and in what population; a single meta-analysis that looks at PCR-proven influenza will not include the effects on pregnancy, heart attack and stroke or the lack of spread to populations not vaccinated.

Whether or not a single study is superior or inferior to the collected wisdom of a systematic review depends on the question being asked and the plausibility of the intervention being studied.

I am not so certain that systematic reviews on fiction are a reliable way to understand the therapeutic efficacy of that fiction, but outside that caveat I agree with the authors conclusions: “It is time to focus on the entire body of evidence.”

And the body of evidence concerning most SCAM, as this blog demonstrates repeatedly, is there is no there there.

*Castagna.

In addition to a complete makeover and a slight reorganization of content we’re also changing the way you log in to post to the site. I wanted to spell out what the changes are and why we’re making them.

As you may have heard, Science-Based Medicine has had some web-server troubles of late. There was a fairly nasty security breach and recovering from that on a rebuilt server meant a few glitches and some connectivity problems. After a few software upgrades and a lot of tweaking we now have the server running quickly, efficiently, and with greatly increased security. That allows me to finally move forward on the redesign which if not active right now will be very soon.

Redesign
ScienceBasedMedicine.org is sporting a cutting-edge new layout that’s reminiscent of the previous one but leaner, cleaner and responsive.

If you resize your browser window you’ll note the new design automatically fits to all resolutions and devices. Visitors will no longer see a wildly different “mobile version” on their smartphones vs. desktop browsers vs. tablet devices.

I’ve also taken this time to reduce the visual clutter on the site, pushing a clean, content-focused layout. A lot of the old sidebar information has been moved to links in the menu while important navigation and fundraising sections (support Science-Based Medicine!) remain in the simplified sidebar for posts, while static information pages have enhanced navigation on the left side.

When you’re done reading the content and the sidebar doesn’t have what you need the new footer area has several choices for additional information, from the latest Tweets to Recent Posts and Comments.

Commenting
For security reasons and to reduce strain on the server we’re changing the way you log in to comment here on sciencebasedmedicine.org. We will no longer require a sciencebasedmedicine.org user account, but instead allow logging in with either a WordPress.com, Twitter, or Facebook account. Shortly after changing to this system we’ll be removing the 46,000+ “Subscription” level accounts from the server. Yes, you read that right. Yes, that’s too many for us to administrate, sorry.

Reorganization
I’m also changing the “Permalink” structure of the site to a friendlier version, as well as moving a few pages around within that structure. Old incoming links should auto-redirect to the current address so nothing should become completely broken. If it does, or you see any other errors toss an email to sbmredesign@holycow.com with as much information as you can give me, including relevant URIs, browser, etc.

One more blatant plug, ok? Hi Vancouver Skeptics!

Enjoy the new site!

Some Quick Trim consumers who are not as enthused about the products as the Kardashians filed two class action lawsuits last year alleging violation of consumer protection and other state and federal laws. One is pending in New York and the other in California. The judge in the California suit issued a preliminary approval of a settlement in March, a subject we’ll get to in a minute.

Keeping up with the Kardashians

For those of you lucky enough to live in a corner of the planet where news of every Kardashian family spat, marriage, divorce, pregnancy, baby and assorted other details of their extensively chronicled lives are not forced upon you via every popular media delivery device available, a bit of background is in order. Kim, Khloe and Kourtney Kardashian are sisters and stars of their own popular American TV reality show, Keeping Up With the Kardashians. The sole premise of the show appears to be that there are a lot of people extremely interested in keeping up with the Kardashians and that premise appears to be correct.

The show, which also features their mother, Kris Jenner, wife of Olympic gold medalist Bruce Jenner (who is not the sisters’ father) and various Kardashian husbands, ex-husbands, boyfriends . . . well, you get the idea. The show generated several reality show spinoffs, Kourtney and Khloe Take Miami, Kourtney and Kim Take New York, and Khloe & Lamar, Lamar being Khloe’s husband, NBA player Lamar Odom. These shows, as well as product endorsements and other commercial activities, have made the sisters multi-millionaires. Apparently these folks employ an army of publicists who ensure that the media, and you, are kept well informed of pretty much everything they want you to know about themselves, which is an awful lot. In short, the Kardashians are famous for being famous.

The New York Lawsuit

Several people who purchased QuickTrim in a number of different states brought suit in New York federal district court seeking compensatory and punitive damages in an amount greater than $5,0000,000 (but not otherwise specified), as well as injunctive relief, on behalf of themselves and a class of other QuickTrim product purchasers. Cowan et al. v. Windmill Health Products, LLC et al., Case No. 1:12-cv-01541-VM-AJP (S.D.N.Y.) has not yet been certified as a class action by the court. The Kardashian sisters, as well as companies involved in the manufacture and sale of QuickTrim products, including GNC, the retail and on-line dietary supplement seller, are named as defendants.

The suit alleges statements made by the Kardashians in advertising and the products’ labels are false and misleading, in violation of various state and federal consumer protection laws. In addition, the suit alleges that QuickTrim’s individual product weight loss and appetite suppression claims and the whole QuickTrim system, which is touted as working “synergistically” to promote weight loss and weight control, are actually drug claims within the meaning of the Food, Drug and Cosmetic Act. Because the products do not have FDA approval, plaintiffs claim their distribution also violates the Act.

The “Quick Trim Weight Loss System” includes:

• QuickTrim Extreme Burn
• QuickTrim Fast Cleanse
• QuickTrim Burn & Cleanse
• QuickTrim Hot Stix (“an antioxidant rich, delicious berry drink mix”)
• QuickTrim Sugar & Carb Cheater
• QuickTrim Fast Shake
• QuickTrim Satisfy (a “chocolate fudge soft chew” to “help satisfy between meal cravings”)
• QuickTrim Celluslim (a “body sculpting gel” to fight cellulite, smooth tone and firm, and spot-treat problem areas)

QuickTrim’s claims of easy weight loss and “detoxification” sound depressingly familiar. With apologies for the lengthy quote, the complaint alleges the following product misrepresentations, lifting language directly from product labels and ads:

QuickTrim’s labeling and advertising represents that QuickTrim products (a) are effective for “weight loss,” (b) use “research proven ingredients,” (c) “safely work to help burn calories [and] curb cravings,” (d) that the “sustained release formula allows for greater absorption and controlled release of nutrients providing optimum calorie burning,” (e) are “synergistically designed to work together” with other QuickTrim formulas,(f) “Help Cleanse and Detoxify,” (g) “Help Jump-Start Weight Loss,” (h) “Help Reduce Belly Bloating,” (i) “Help Jump Start Your Weight Loss,” (j) “Help Burn More Calories by Day,” (k) will “Flush Out [your] System Overnight,” (l) “stimulate metabolism to burn more calories and fat through the day,” (m) “help to release and burn stored fat,” (n) “help to remove toxins and impurities out of your system,” (o) “help remove excess water from under the skin,” (p) “Help Block Excess Sugar & Carbs,” (q) “Help Curb Carbohydrate Cravings,” (r) “increase the body’s ability to burn stored fats and decrease the appearance of cellulite while helping increase firmness and elasticity,” (s) “Increase lipolytic effect by 630%,” (t) “Release stored lipids at adipocytes 1064%,” (u) “Reduce indentation by 9.5%,” (v) “Reduce roughness by 32.4%,” (w) “Decrease fat deposits by 33%,” (x) “Help increase circulation to problem areas,” (y) “Help tone, smooth and firm skin,” (z) “attack cellulite by breaking down excess fat stored in the cells,” (aa) “[are] scientifically designed and clinically shown to work with your body naturally to help increase your ability to burn calories,” and also to “reduce carbohydrate cravings,” (bb) “ha[ve] been clinically tested and shown to increase metabolism by burning 278 calories (on average) per day”.

(I’ve removed some of the attorney’s editing, which is necessary for quotations in a document filed with the court but which also makes the quote harder to read.)

I searched the FDA website and could not find that the agency has issued a warning letter to any of the defendants or taken any other regulatory action regarding the QuickTrim products.

Interestingly, according to the complaint, the Kardashian sisters represented that they personally formulated and tested QuickTrim products “to make sure that this was something that really works.” I guess they are scientists in addition to being reality TV stars.

These products are not cheap. You can buy them online for between $12 to $30 a package, depending on the product and the amount supplied, but there is a hefty shipping and handling charge for most sellers, up to $14 per product. A package will last you, again depending on the product, up to 30 days.

The defendants deny any wrongdoing in their answers to the complaint. Specifically, the Kardashian sisters state in their answer

. . .that they have used QuickTrim products, and that they base their statements about QuickTrim products (including on Twitter and Facebook) on their honest opinions, experiences and beliefs about the products.

In a U.S. News & World Report article about QuickTrim and the New York lawsuit, registered dietitian Keri Gans and Adriane Fugh-Berman, a physician and associate professor in the complementary and alternative medicine master’s degree program at Georgetown University Medical Center (sigh), criticized several QuickTrim products and their unproven ingredients. (The reporters said QuickTrim did not respond to repeated requests for comment.)

According to the article, the “Burn and Cleanse 14 Day Diet System” contains products for both morning and evening which provide a total of 400 milligrams of caffeine per day, the equivalent of about 4 cups of coffee, as well as piperine (black pepper) and white willow bark extract, both of which can increase the potency of caffeine.

‘It irritates me that they’re not saying how much caffeine is in these pills,’ Fugh-Berman says. ‘Too much caffeine can make you jittery and increase your blood pressure and pulse. If you pop a couple of these pills with your Starbucks coffee, that’s not good; you could get caffeine poisoning, which can cause heart arrhythmias.’

“IsoCleanse and Flush Herbal Complex,” the evening product, is a combination of “natural” stimulants and bulk laxatives, designed to increase the movement of food and liquid through the body. This is fine, said Fugh-Berman, if you are constipated. If you’re not, “you’ll get diarrhea.” In addition, “stimulant laxatives, of which IsoCleanse is chock-full, can cause your intestines to become dependent on them for stimulation, causing constipation if you stop.”

“Fast Cleanse,” a “48-hour Super Diet Detox,” is a drink rich in fiber ingested four times a day between meals of clear soups, gelatin, fruits and vegetables. This may cause you to drop of few pounds, but Fugh-Berman says you’ll be “putting them right back on.” “Sugar & Carb Cheater” is designed for dieters concerned “that their sugar and carbohydrate intake is keeping them heavy.” I suppose a sensible solution would be to reduce one’s sugar and carb intake, but that’s just me. For those seeking a less taxing solution, the “Cheater” contains chromium, fenugreek seed, bilberry fruit, and vanadyl sulfate and is touted to keep carbs from turning into fat by blocking the enzyme that causes the conversion. To Gans, the registered dietician, “scientifically, it doesn’t make sense . . . It’s offering people false hope.”

Fugh-Berman doesn’t think anyone should take these products. Healther Mangieri, a spokeswoman for the American Dietetic Association added, “The good news is that these products are absolutely not necessary for weight loss. My suggestion is to leave them on the shelf.” Good advice all around.

In March, the judge stayed the New York suit pending the outcome of a proposed settlement in the California case. If the settlement gets final approval, the plaintiffs in the New York suit would be included in the class of QuickTrim product purchasers in the California suit, because its scope is nationwide, unless they opt out of the class, which they say they will do. However, unless their suit covers a different time period than the California action (product purchases made between August 14, 2009 and March 1, 2013), the New York plaintiffs will be able to pursue their claims only as individuals, not as representatives of a class of purchasers, barring some highly unlikely circumstances.

The California Lawsuit

So let us move from the East Coast to the West and to Anaya v. Quick Trim, LLC, et al., Case No. CIV VS 1201177, pending before the Superior Court of the State of California, County of San Bernardino. The same defendants are named, plus Kris Jenner, Jenner Communications, Inc., and additional sellers of QuickTrim products, the CVS pharmacy chain, Walmart, Amazon.com, and Drugstore.com. Also named is Vitaquest International, a New Jersey company that formulates, develops and manufactures dietary supplements for its clients. (I can just imagine the Kardashian sisters in their crisp white lab coats formulating and testing QuickTrim products in the Vitaquest laboratories.) Finally, three corporations with the cutie-pie names Kimsaprincess, Inc., Khlomoney, Inc. and 2Die4Kourt, Inc., are named as defendants.

(And here I will switch, for reasons of economy, from the actual documents filed in the New York action, which can be viewed as they appear in the court’s files for a reasonable charge, to the information available on a website set up by the California settlement administrator, which can be viewed for free.  Viewing the actual documents from the California court’s files costs up to $50 per document.)

Like its New York counterpart, this suit seeks certification as a class action on behalf of purchasers of the same eight QuickTrim products. The California state court has issued a preliminary approval of a class action settlement, the details of which can be found on the website, although not nearly as much information as is available in the New York case.

The plaintiff alleges that improper statements were contained on the product labels and in advertisements, and that these statements violate state consumer protection laws and various other state and federal laws. She seeks, among other remedies, damages and injunctive relief. As is usual in such settlements, the defendants deny any wrongdoing.

If the settlement is approved, plaintiff’s counsel will get $250,000 in fees and costs and the named plaintiff, Teresa Anaya, will get $2,500. QuickTrim will have to “redesign its labeling and packaging to restate the nature of its products and its benefits.” Members of the class who file a claim (other than those who opt out of the settlement) receive different amounts depending on where they bought the product and whether they have proof of purchase. Basically, they can get either a refund or a coupon good towards purchase of another QuickTrim product. In other words, the defendants have managed to turn the settlement into a product promotion event.

We’ll have to wait until August, when the settlement proposal will have a final hearing, to find out what happens.

Conclusion

This is yet another tale of outlandish dietary supplement claims, testimonial “evidence” of effectiveness and the failure of the DSHEA to adequately protect consumers by preventing this sort of thing from happening in the first place. As I have said before, lawsuits are not the ideal way of bringing supplement companies and their enablers to justice. But until the federal law is amended, these suits remain the best way to apply some brakes to the runaway dietary supplement industry.

We also allow people to operate vehicles weighing thousands of pounds at speeds that are potentially deadly if a mishap occurs. In 2011 there were 32,367 motor vehicle deaths in the US (10.4 per 100,000 population). Interestingly, this is down quite a bit from previous years. As a percentage of population the highest motor vehicle death year was 1935, with 34,494 deaths, or 27.1 per 100,000. The highest absolute number of motor vehicle deaths was in 1970, at 52,627.

The number of deaths has been mostly trending down since 1996, which is interesting because over this same period of time cell phone use has risen tremendously. There are various reasons for the decreased in fatalities – helmet laws, seatbelt laws, cracking down on drunk driving, increased car safety, and intermediate drivers licenses for new drivers to name a few. These trends have probably obscured any increase in car accidents from using portable communication devices while driving.

Recent laws have addressed this risk by requiring device users to use only hands-free devices. However, the evidence clearly shows that hands-free device use (talking or texting) is just as dangerous as using a hand-held device.

The problem is not that your hands are occupied, but that your mind is occupied. While talking on a cell phone you are distracted from scanning the road and will have slower reactions to unexpected obstacles. Information processing is the limiting factor.

A recent University of Utah study examined drivers with various levels of distraction. They found:

– Tasks such as listening to the radio ranked as a category “1” level of distraction or a minimal risk.

– Talking on a cell-phone, both handheld and hands-free, resulted in a “2” or a moderate risk.

– Listening and responding to in-vehicle, voice-activated email features increased mental workload and distraction levels of the drivers to a “3” rating or one of extensive risk.

Contributing to this problem is the illusion of multitasking – people believe they can do more than one mental task at the same time, but we can’t. We simply switch back and forth between tasks, further using mental resources to manage this switching. This results in what psychologists call interference -a decrease in performance in any task when distracted by extraneous information or performance of a simultaneous task.

Younger drivers are particularly cavalier about multitasking while driving – something that can be addressed with driver education.  This is important because younger drivers are also less experienced and are already a higher accident risk.

The implications of existing research are clear – to minimize accident risk, do not use mobile devices while driving. Do not be lulled into a false sense of safety by hands-free devices. Minimize distractions while driving – it really does take your full attention, even if it doesn’t feel like it.

Hopefully, technology will get us out of this problem it has gotten us into. Computer-assisted driving technology is advancing rapidly. Google’s driverless car (a bit of a misnomer, as there is always a driver behind the wheel) is now able to drive on city roads, and can go miles between driver interventions. Computers have one extreme advantage over humans – they are not distracted, they do not get tired or lose their attention.

Computer-assisted driving seems like the perfect solution. It will be years before such technology becomes standard, however, so in the meantime – don’t text and drive.

Since knee osteoarthritis is such a ubiquitous annoyance, home remedies and CAM offerings abound.  Previously we have covered a number of CAM options on this blog, including glucosamine, acupuncture, and several others. The American Academy of Orthopaedic Surgeons (AAOS) has just issued a 1200 page report evaluating the evidence for various treatments for knee osteoarthritis short of total knee replacement surgery. A 13 page summary is available online. They have done the heavy lifting for us, reviewing all the available scientific studies for evidence of effectiveness. Here’s what the science says: (I’ve highlighted the ones where the evidence is strong.) 

1. Exercise – strong evidence for effectiveness
2. Weight loss – moderate evidence for
3. Acupuncture – strong evidence against
4. Physical agents (TENS, ultrasound, etc.) – inconclusive
5. Manual therapy (chiropractic, massage) – inconclusive
6. Valgus-directing force brace – inconclusive
7. Lateral wedge insoles – moderate evidence against
8. Glucosamine and chondroitin – strong evidence against
9. NSAIDs – strong evidence for
10. Acetaminophen, opioids, pain patches – inconclusive (this is particularly interesting since acetaminophen is the standard first-choice drug)
11. Intraarticular corticosteroid injections – inconclusive
12. Hyaluronic acid injections – strong evidence against (and if injections are ineffective, those oral diet supplements certainly don’t have a chance)
13. Growth factor injections and/or platelet-rich plasma – inconclusive
14. Needle lavage – moderate evidence against
15. Arthroscopy with lavage and debridement – strong evidence against
16. Partial meniscectomy in osteoarthritis patients with torn meniscus – inconclusive
17. Valgus-producing proximal tibial osteotomy – limited evidence
18. Free-floating interpositional device – no evidence; consensus against

They apparently didn’t think it was worthwhile even mentioning such things as copper bracelets, magnets, prayer, or supplements like boswellia. Or homeopathy!

Naturopaths and other critics of mainstream medicine claim that MDs don’t recommend lifestyle measures like exercise and weight loss, but here is a mainstream medical organization that clearly does, and even puts them first on its list. Critics who claim doctors are just out to make money, take note: if they were the evil money-grubbers some make them out to be, wouldn’t these surgeons want to promote income-generating arthroscopic lavage and debridement? Wouldn’t they want to suppress information about conservative treatments and keep patients in pain until they were desperate enough to consent to expensive joint replacement surgery? Gee, do you suppose maybe they really are just trying to do what’s best for their patients?

I was glad to see that the AAOS reached the same conclusions we did on SBM regarding acupuncture and glucosamine, but I wasn’t surprised. After all, we are looking at the same published evidence. Unbiased scientific minds think alike. Recommendations on other websites like WebMD and the Mayo Clinic still favor acupuncture and glucosamine. It will be interesting to see if they modify their websites in response to the AAOS report. I’m not holding my breath.

I was curious: if AAOS is an American Academy, why do they spell Orthopaedic the British way?  I looked it up: Orthopaedic is the correct medical spelling! So thanks to the AAOS, I learned something about spelling as well as about knees.

So now that the report was finally aired, how was it? You can either watch it on iPlayer (if you’re in the UK) or on YouTube (if you’re not, assuming it’s still there):

Patients versus false balance, with regulatory issues missing

Although it’s better than the vast majority of reports on Burzynski that I’ve seen, I’m afraid it still ended up being a mixed bag. I’ll start with my general impression and then discuss some specifics that particularly stood out to me. Fortunately, there were parts of the report that hit home, and hit home hard. Unfortunately, every time I thought that Panorama was going in for the kill, the reporter (Richard Bilton) all too often seemed to back off. Perhaps it was the editing. From my interactions with a producer and reports I got from other skeptics who had similarly been contacted by the BBC, the team working on the report seemed to “get it,” which is why I can’t help but wonder if something got watered down in the final edit. Or perhaps it was the story structure imposed on this report, which was simultaneously a “he said, she said” portrait of a patient who believes in Burzynski and thinks he saved her, two Burzynski patients who died but whose families still express little or no regret over having decided to make the trip to Houston, and one patient who thinks Burzynski ripped him off. Interspersed with these stories was an overarching “where’s Waldo?” meta-story of Bilton trying to score an interview with the elusive subject of his report (whom he, predictably, gets to interview near the end of the report), all peppered with brief interviews with experts whose comments are generally critical but often softened with caveats that turn some of the criticisms into mush.

From my perspective, what is simultaneously the greatest strength and greatest weakness of this report is its relentless focus on patients. Specifically, the stories of four patients are covered: Hannah Bradley, Luna Petagine, Amelia Saunders, and Wayne Merritt. The first three patients were U.K. patients who travelled to Houston to be treated by Burzynski; Merritt lives in Georgia. This focus is a strength, because it provides an emotional hook upon which viewers can hang their attention, and, of course, the reason Stanislaw Burzynski’s activities are so harmful. However, this relentless focus is simultaneously a near-fatal weakness in that the obsessive focus on the patients seems to prevent the report from delving into a lot of issues that are also very important in any discussion of Stanislaw Burzynski. For instance, there was little or no mention of the recent FDA investigation of the Burzynski Clinic and the partial clinical hold placed on antineoplaston usage, zero mention of how Burzynski recently managed to beat an effort by the Texas Medical Board to strip him of his medical license by throwing his employed doctors under the bus, and only the most superficial treatment of how in general it is considered unethical to demand payment from patients to participate in clinical trials. Nor is there any mention of how the Burzynski Clinic waged a campaign of harassment against bloggers who criticized Burzynski back in 2011. Indeed, one of the victims of that harassment, Rhys Morgan, was interviewed by the Panorama crew, but he was informed that his interview was cut from the final version because it didn’t fit the narrative. There is even at least one howler in which Bilton intones that “nobody knows exactly what’s in his treatment,” when in fact it is fairly well known what antineoplastons are and has been for at least 25 years. All you have to do is to read Saul Green’s reports on Quackwatch and in The Cancer Letter from the 1990s.

Unfortunately, the story repeatedly falls prey to that weakness of first following this patient or patient’s family, then following that patient or patient’s family. Admittedly, the overall impression of Burzynski left behind is not favorable, but we don’t get a good overview of what he is doing and why it is so wrong, just what he did with respect to these four patients plus a little background. Of the patients, Luna Petagine’s and Amelia Saunders’ stories are the most heart-wrenching. Indeed, Luna’s story was featured last year on a BBC documentary about the Great Ormond Street Hospital, and some excerpts from this documentary are shown to introduce Luna and her story. One of them reminded me very much of the conversation with her NHS oncologist that Laura Hymas recorded and allowed Eric Merola to include in his propaganda piece, except that in video it is so much more intense. In this scene, the oncologist tries to point out to Ms. Petagine that he doesn’t know what Burzynski is doing or how to take care of her daughter when she returns. I really felt for this oncologist, too. However, this segment on Luna also highlights another irritating aspect of this report, which hit me over the head in the very next scene, when Ms. Petagine in essence lambastes the NHS oncologists because they couldn’t save her daughter’s life, saying, “The NHS told me Luna’s going to die. This man is telling me that he thinks he can cure her.”

The report includes interviews with experts like Professor Richard Grundy of Nottingham Children’s Hospital. Grundy points out that Burzynski has not published the complete results of any of his phase II clinical trials. Right after him is Professor Peter Johnson of Cancer Research U.K. discussing the importance of reproduction of results. Actually, this is one of the stronger segments in that it points out the importance of publishing scientific results in the medical literature and how that is the key to convincing other scientists of the validity of your work. That was very clear and concise. It’s also, unfortunately, simultaneously one of the weaker segments in that it ends up sounding as though there’s just no evidence and we don’t know about antineoplastons. In other words, it sounds as though they very well could work, if only the clinical trials were done. It’s a theme that is repeated throughout the report but that ignores the astounding level of sheer deception that goes on at the Burzynski Clinic, the allegations of overfilling, and how Burzynski has abused the clinical trial process to keep treating patients with antineoplastons without actually having to do the science that any other doctor would be required to do to validate a new treatment. True, not all the doctors who question Burzynski’s treatment are that wishy-washy. Dr. Elloise Garside, a research scientist, echoes a lot of the questions I have, such as why Burzynski never explains which genes are targeted by antineoplastons, what the preclinical evidence supporting their efficacy are, or what the scientific rationale is to expect that they might have antitumor activity. (Yes, we’re talking prior plausibility, baby!) This explanation was provided right after Bilton and she sat through a screening of the first Burzynski movie, which was a fairly nice touch.

None of this is to say that there weren’t aspects of the report that were very powerful and spot on. I just wish there were more of them or that more time had been allotted for them. For instance, there was the discussion of how Burzynski attracts new patients, which led to a trip to a screening of Eric Merola’s first foray into medical propaganda; i.e., his first movie in 2010 extolling the glory that to him is Stanislaw Burzynski. There’s even a sarcastic little rejoinder about how Burzynski takes his message to the movies rather than publishing in the peer-reviewed scientific literature. Particularly amusing is how Panorama includes a scene from the first Burzynski movie in which Burzynski lambastes the panel evaluating him, saying how he will get his antineoplastons approved all over the world and bring them to justice, while promising the hundreds of patients who died because of them will come back to haunt them until their deaths.

Yeah, Stan’s as warm and fuzzy as ever.

Panorama also confirms what skeptics have suspected for a long time now, namely that the Burzynski movie has been very, very effective in attracting patients to the Burzynski Clinic. During an interview with Hannah Bradley, whom we’ve met before. There’s no real evidence that Burzynski’s treatment is responsible for Bradley’s good fortune in having lived more than two years with her cancer thus far, but she attributes her survival to him. Unfortunately, she is also incorrect when she says that there’s no evidence that antineoplastons work or that they don’t work. The preponderance of evidence supports the contention that they don’t work, but there is uncertainty, which Burzynski exploits to the max. In any case, as lovely a young woman as I think Ms. Bradley is, the whole segment is painful to watch, as she asks ignorant questions like, “What says radiotherapy works?” When the reporter points out that the peer-reviewed literature says it works, Ms. Bradley says, “But not for everyone,” which is technically true but ignores that there isn’t any evidence comparable to that for radiotherapy that antineoplastons work for anyone. As much as I like Hannah Bradley and her boyfriend Pete Cohen and hope Hannah continues to do well, I can’t let such statements go unchallenged.

Ironically, I can’t help but note that Pete Cohen also showed up on the radio to be interviewed by Victoria Derbyshire on BBC Radio 5 Live (at around the 1:44 mark). I can’t help but mention it here, because Mr. Cohen gives away several interesting tidbits. For instance, it’s very obvious that the Burzynski Clinic is in communication with him, because Mr. Cohen claims that Burzynski is preparing manuscripts for publication and that he has even submitted several to “top journals.” He even claims that Burzynski has asked that they be independently reviewed. In doing so, Cohen echoes the claims in some of the Q&A’s after screenings of Eric Merola’s most recent movie that Burzynski’s papers have been rejected without being sent out for peer review. It’s also not exactly clear what Cohen means by that. Studies submitted to journals won’t be published without going out for peer-review. Maybe he’s referring to some of the papers we’ve heard about from Mr. Cohen and others that were editorially rejected and not even sent out for peer review because the editor either didn’t think them appropriate or didn’t want to waste the reviewers’ time. Mr. Cohen also repeatedly says how he has approached experts in brain cancer and begged them to come out to the Burzynski Clinic to “see for themselves.” Seemingly, he can’t understand that it is not necessary for a scientist or doctor to meet Dr. Burzynski or visit his clinic. It means nothing. Nada. Zero. Zip. In science, all that matters is what you publish, and Burzynski hasn’t published anything other than case reports, tiny case series, and unconvincing studies, mostly (at least over the last decade or so) in crappy journals not even indexed on PubMed.

Without a doubt, the most effective part of the story is the segment in which Dr. Jeanine Graf of the Texas Children’s Hospital is introduced. Dr. Graf is the director of the pediatric intensive care unit there and has taken care of lots of Burzynski patients, as her hospital is “just down the road” from the Burzynski Clinic and these unfortunate children are brought to her hospital when they decompensate. Indeed, coupled with this segment is an interlude where Luna Petagine’s mother complains that the staff there know and recognize Burzynski patients (and, she notes, hate the Burzynski Clinic). Particularly damning is how Ms. Petagine said that the Texas Children’s Hospital Staff “were always cleaning up Burzynski’s messes.” Luna was brought to the Texas Children’s Hospital during her time in Houston, and the staff there recognized right away that she was a Burzynski patient because they had seen so many similar patients suffering the same complications before. It was also clear how much contempt the staff there had for the Burzynski Clinic. If there’s one thing Panorama did right in this report, it’s showing how seeing so many already-dying children show up in their ICU because of hypernatremia due to antineoplaston therapy will do that. Perhaps the most devastating part of this segment was seeing Dr. Graf stating, point blank, that she’s never seen a Burzynski patient survive. True, she does point out that patients don’t come to her until they are in extremis, but the fact remains that she’s never seen any of them live.

It’s a sad and devastating segment.

Unfortunately, during the most critical part of the story of all, in which Bilton finally “finds Waldo” and is granted an audience with Stanislaw Burzynski, Bilton came across (to me, at least) as unprepared. Fortunately for Bilton, Burzynski was, as is so often the case, his own worst enemy, smirking and behaving in his usual arrogant, dismissive manner to any sort of challenge. (You can see a sample of it here, towards the end of the promo.) If Burzynski were a bit less full of himself and the greatness that he thinks he possesses, he could have wiped the floor with Bilton. As it is, the interview was pretty much a draw. Burzynski claims that antineoplastons can cure cancer, but not for everyone. Burzynski smirks when asked how many patients he’s treated and how many have survived, dodging the question by saying that the FDA won’t let him until he’s published his results. Bilton tells him that’s not true; the FDA has told him that Burzynski can tell him as long as he doesn’t promote antineoplastons. Burzynski asks Bilton why he doesn’t have a letter from the FDA. Burzynski dismisses Bilton with retorts like:

You look like a bright man but you’re asking me the same question again and again. Are you catching Alzheimer’s disease or what?

As I said, Burzynski’s arrogance, dismissiveness, and condescension make him his own worst enemy. Bilton was very, very lucky.

Burzynski also pulls out the old trope that, the FDA wouldn’t have let him use antineoplastons for 20 years in clinical trials if they weren’t safe and potentially effective, that the FDA wouldn’t let him “sell hope without evidence.” (Those of us following Burzynski for a while know, unfortunately, that that isn’t necessarily true.) Burzynski then promises that antineoplastons will be approved “soon” (they almost certainly won’t), after which he goes on to repeat the same refrain he’s been repeating for the last decade or so about how he’s on the verge of publishing all the results that will convince everyone. “Just you wait,” Burzynski is saying, in effect, “I’ll show them. I’ll show them all!”

One notes that we’re still waiting.

Ultimately, the Burzynski Clinic did release some results, stating that 776 patients with brain tumors were treated in trials and that 15.5% have survived five years. Of course, this is an utterly meaningless factoid (if factual it even is), because we don’t know what kinds of tumors, what grades, how they were treated beforehand, or any other confounding factors. Burzynski needs to publish, but I highly doubt that he will, at least not in a form that is informative to real oncologists.

Overall, the producers of Panorama did a decent, but flawed job of taking on Burzynski. Part of the problem might have been that a half hour is just too short. It’s really difficult to explain 36 years of history and the ins and outs of Burzynski’s battles with the law and patients in just a half hour; so apparently Panorama didn’t even try. That left it asking the question at the beginning of how Burzynski has gotten away with this for so long but not really even trying to give an answer at the end. It also might be that expectations were too high in the skeptic community, myself included. While I can understand the decision to concentrate on patients as the center of the story, the problem with that decision is that it’s a well-trod path that crowds out too many other important issues that ended up getting short (or, far more commonly, no) shrift in this Panorama episode. In the end, Panorama played it safe, and its report ended up being fairly unoriginal and guaranteed not to be the definitive look at Burzynski. It’s a very good thing that Panorama decided to shine a light into the recesses of the Burzynski Clinic, but at best it’s a first, flawed step. As good as much of this episode is, some of it is not, and I fear that an opportunity has been lost.

Stanislaw Burzynski against his own SEC filings

A lot of things happened last week with respect to Stanislaw Burzynski. In addition to Eric Merola releasing his documentary and Panorama finally airing its report, it was pointed out to me by a number of readers that there was new information to be had in Burzynski’s most recent SEC filings for the Burzynski Research Institute. The reason this is important is that it provides us with information against which we can compare Burzynski’s claims in both Merola’s movie and the Panorama report. Part of what inspired me to look into this was Josephine Jones openly asking whether Burzynski lied to the BBC. Regular followers of the Burzynski saga will remember that in January the FDA showed up at Burzynski’s operations to investigate. As Merola likes to harp on, FDA investigators stayed until March. Currently we are awaiting the FDA’s decision, which is usually posted to the FDA website in the form of a formal letter. In any case, the reason this is relevant is because the FDA put a clinical hold on antineoplastons and barred the enrollment of any new patients in any of Burzynski’s protocols. Moreover, in response to a warning letter from the FDA last fall about promoting an unapproved drug, in January the Burzynski Clinic removed all references to antineoplaston therapy on its website, which is rather like Major League Baseball removing all references to, well, baseball on its website.

To recap, we know that last year a child suffered a severe adverse reaction to antineoplaston therapy, which led to the FDA putting a clinical hold on antineoplastons for children. Then, in January apparently, the clinical hold was placed on antineoplastons for adults as well, although apparently patients already receiving them could continue to do so. Actually, I wondered about that when I saw a rather fascinating part of the Panorama report, namely a tour of Burzynski’s manufacturing facility, which, we are told, can crank out 300 L of antineoplaston solution per day.

Which brings us to the Burzynski Research Institute SEC report, something that Josephine Jones touches on as well. Throughout Eric Merola’s infomercial for Burzynski and the BBC Panorama report, we are told by Burzynski, his acolytes, and his shills that antineoplastons will be approved by the FDA “soon,” that he’s been doing the trials to gain FDA approval over the last 15 or 20 years, and, oh, by the way, not to worry. We have been promised repeatedly that all those phase II clinical trials that Burzynski registered will similarly be published “soon.” Even Pete Cohen, Hannah Bradley’s partner, showed up on BBC Radio 5 promising that Burzynski is furiously submitting manuscripts for publication. But what’s really happening?

Josephine Jones points us to this recent SEC report for the Burzynski Research Institute for the fiscal year ending February 28, suggesting that we read the section entitled Partial Clinical Hold on Phase II and Phase III Clinical Trials. So I did. Now I’m not a businessman, and I don’t understand anything but the very basics of business. A lot of these SEC reports might as well be Greek to me, but I do know cancer science. I also know what Burzynski and his acolytes have been saying, one of which is that the phase III trial will probably never be done because it’s “too expensive.” Yet in the report, we read:

On February 23, 2010, the Company entered into an agreement with Cycle Solutions, Inc., dba ResearchPoint (“Research Point”) to initiate and manage a pivotal Phase III clinical trial of combination Antineoplastons A10 and AS2-1 plus radiation therapy (RT) in patients with newly-diagnosed, diffuse, intrinsic brainstem glioma. Research Point has secured interest and commitments from a number of sites selected. Upon completion of this assessment, a randomized, international Phase III study will commence. The study’s objective is to compare overall survival of children with newly-diagnosed, diffuse, intrinsic brainstem glioma (DBSG) who receive combination Antineoplastons A10 and AS2-1 plus RT versus RT alone.

Three years should be plenty of time to line up clinical sites for a phase III trial. Of course, given that after three years the clinical trial hasn’t been opened, more than likely no reputable institution wants to partner with the Burzynski Research Institute, and ResearchPoint collected its checks. Then came the partial clinical hold, which affected this phase III trial as well as all the phase II trials, and, fortunately for patients, Burzynski’s antineoplaston operation is shut down. Revealed in the SEC report, of all places, is why.

It’s a long excerpt, but I think it’s important. There’s a lot of legalese and FDA bureau-speak, but the meaning should be fairly clear to a layperson:

In a letter dated June 25, 2012, the Company informed the FDA of a serious adverse event which may have been related to the administration of Antineoplastons. On July 30, 2012, the FDA placed a partial clinical hold for enrollment of new pediatric patients under single patient protocols or in any of the active Phase II or Phase III studies under IND 43,742. The FDA imposed this partial clinical hold because, according to the FDA, insufficient information had been submitted by the Company to allow the FDA to determine whether the potential patient benefit justifies the potential risks of treatment use, and that the potential risks are not unreasonable in the context of the disease or condition to be treated. The FDA cited 21 C.F.R. § 312.42(b)(2)(i), 21 C.F.R. § 312.42(b)(1(iv), and 21 C.F.R. § 312.42(b)(3)(i), as grounds for imposition of a clinical hold; and 21 C.F.R. § 312.305(a)(2), a criteria for expanded access use. The FDA advised the Company that until it resolved the matter to FDA’s satisfaction, the Company could not enroll new pediatric patients in any protocol under such IND. The Company later notified the FDA in a September 24, 2012 letter that it was closing pediatric protocol BT-10 (under IND 43,742) for enrollment effective September 25, 2012, and that it would also terminate the protocol once all active patients had completed the study.

In other words, no more antineoplastons for children, not now, and, hopefully, not ever. Burzynski can continue to treat children on his protocols who had already started treatment, but that’s it. This is very good news. After all, the Burzynski Research Institute is shutting down the pediatric protocol.

This ultimately led to the partial clinical hold being extended to adults:

In a teleconference on January 9, 2013 between the FDA and the Company, followed by a letter of the same date, the FDA notified the Company that the agency was placing IND [investigational new drug application] 43,742 on partial clinical hold, due to a lack of a complete response to the issues raised by the FDA and what the FDA deemed a misleading, erroneous, and incomplete investigator brochure. The FDA cited 21 C.F.R. § 312.42(b)(2)(i) and 21 C.F.R. § 312.42(b)(1)(iii), as grounds for imposition of a clinical hold. The FDA further advised the Company that until it resolved the matter to the FDA’s satisfaction, that the Company could not enroll new adult or pediatric patients in any protocol under such IND. The FDA also placed protocols B-52 and B-54 on clinical hold due to what the FDA deemed to be an unreasonable and significant risk of illness or injury to human subjects. The FDA cited 21 C.F.R. § 312.42(b)(2)(i) and 21 C.F.R.§ 312.42(B)(1)(i), as grounds for imposition of a clinical hold. The FDA advised the Company that until it resolved the matter to FDA’s satisfaction, the Company could not legally conduct the identified clinical studies under such IND.

In a letter dated April 9, 2013, the Company responded to the issues raised by the FDA in its January 9, 2013 letter to the Company. In a letter dated May 9, 2013 from the FDA, the FDA advised the Company that the Company’s April 9, 2013 letter was not a complete response to all the issues listed in the FDA’s letter dated January 9, 2013, and the FDA also identified the issues that were not fully addressed by the Company’s response. The FDA further advised the Company that until it satisfactorily addressed all the issues in the FDA’s letter dated January 9, 2013, that the FDA could not complete its review, and the clinical hold could not be removed.

So basically, the FDA extended its clinical hold; the Burzynski Research Institute answered the FDA’s charges; and the FDA was not satisfied. Until the Burzynski Research Institute can adequately address those concerns, there will be no new patients enrolled. If I were a betting man, I’d bet that no new patients ever will be enrolled because maybe, just maybe, the FDA is finally cracking down on Burzynski for real. At least, that’s what I hope. I’m all too aware that it looked just as bad for Burzynski in the 1990s, which was the last time the FDA made a serious run at the Burzynski Research Institute, and Burzynski managed to slither away to come back bigger and stronger than ever. Even so, Burzynski’s own SEC filings suggest that all the bold talk of imminent approval of antineoplastons by the FDA and publication of the papers that will prove to the world that antineoplastons work are pipe dreams, stories to keep the marks on board and hoping. Indeed, even the report seems to concede that antineoplastons will likely never be approved, even going so far as to point out that “the Company cannot predict if and/or when it will submit an NDA [New Drug Application] to the FDA, nor can the Company estimate the number or type of additional trials the FDA may require.” Burzynski also warns:

Notwithstanding the response results of the trials that have reached a Milestone, management believes it is likely that the FDA may require additional clinical trials based upon such protocols to be conducted by an institution not affiliated with the Company or Dr. Burzynski before advising that an NDA filing is warranted. In addition, the FDA has indicated it will not accept the efficacy data, but will accept toxicity data generated by the Phase II study according to Protocol CAN-1 because the trial was partially retrospective. At this time, the Company cannot predict if and/or when it will submit an NDA to the FDA, nor can the Company estimate the number or type of additional trials the FDA may require. Further, there can be no assurance that an NDA for antineoplastons, as a treatment for cancer, will ever be approved by the FDA.

No assurance can be given that any new IND for clinical tests on humans will be approved by the FDA for human clinical trials on cancer or other diseases, that the results of such human clinical trials will prove that antineoplastons are safe or effective in the treatment of cancer or other diseases, or that the FDA would approve the sale of antineoplastons in the United States.

That hardly sounds as though antineoplastons will be approved “soon.” After all, the Burzynski Research Institute’s own SEC filing states that an NDA hasn’t even been submitted and that it can’t be predicted when an NDA will be filed. Presumably if Burzynski were truly on the verge of getting antineoplastons approved by the FDA he would have said so in his SEC filing. That’s why his SEC filings are so revealing. Burzynski can distort and exaggerate when speaking to the public, but lying on an SEC filing could carry potentially serious consequences.

Another interesting tidbit in the SEC filing is Burzynski’s report of the results of several of his clinical trials. They aren’t really “results’ per se, in that the information presented really isn’t provided in a form that really allows other investigators to evaluate it and potentially replicate it. Basically it’s a big table listing Burzynski Research Institute clinical trials and response rates reported. One thing that I noticed right away is that in most trials, the number of evaluable patients is smaller, sometimes much smaller, than the number of patients accrued. This is a huge red flag. For instance, in trial BT-20, there were 40 patients accrued by only 22 were evaluable. This sort of dropout rate is a huge red flag. We don’t know the reasons for this dropout rate. It could certainly skew the results, but even that’s impossible to tell from just a table of response rates and no further information. Of course, I realize that this is an SEC filing, not a scientific paper in the peer-reviewed literature, but if Burzynski has all this data to produce this table it boggles the mind that, given at least a decade and a half since these trials began, he hasn’t been able to publish any meaningful data thus far. That he hasn’t been able to do so is also a big red flag.

One can’t help but wonder why BBC Panorama didn’t look at this information. It could easily have fit into the narrative. Imagine a more prepared reporter, faced with the confident and sarcastic bloviation from Burzynski that antineoplastons will be approved “soon,” pulling out Burzynski’s own SEC filings and telling him that that’s not what he said in those filings. I can only imagine two reasons Bilton didn’t do that: The report wasn’t out when the interview occurred (which is possible, given the mentions of a date in early May) or lack of preparation. If it were the former situation, a more prepared reporter could have hammered Burzynski on how he could possibly say so confidently that antineoplastons were going to be approved “soon” with partial clinical holds by the FDA on children since the fall of 2012 and on adults since January 2013. These are hardly the sorts of issues that suggest imminent approval, contrary to Burzynski’s statements, which now must be viewed, in my opinion, as outright lies. Indeed, even if the SEC filing wasn’t published yet at the time this interview took place, imagine a voiceover tacked on after Burzynski’s statement pointing out that his own SEC filings contradicted his assertions. Moreover, bringing up these issues would arguably have fit into the narrative perfectly to point out that Burzynski is still promoting antineoplastons through surrogates by saying that FDA approval is imminent when, according to his SEC filing, he apparently hasn’t even filed an NDA yet. As much as the BBC got right in its coverage of Burzynski, aspects of its Panorama episode on Burzynski were pure frustration to those of us who have been following Burzynski for a while.

I wonder if Brian Deer would be interested in looking into the Burzynski Clinic and the Burzynski Research Institute.

Jann Bellamy has recently authored an excellent piece on the limitations of the FDA and how the DSHEA actually protects the profits of supplement manufacturers rather than the health and well-being of consumers. Bellamy used the very poignant and currently “controversial” example of DMAA (methylhexanamine or 1,3-dimethylamylamine) to illustrate her point regarding the loopholes and lack of enforcement power of the FDA. The authors of this piece had been considering writing about DMAA and felt this would be an excellent time to further expound on Bellamy’s work. The goal of this article will be twofold: 1) to discuss the known history and pharmacology of DMAA, especially in regards to the basic methodology for evaluating novel substances or novel uses of substances in the context of lacking RCT level evidence (i.e. the concept of science vs. evidence based medicine) and 2) how the DMAA story clearly and unequivocally demonstrates how the DSHEA allows for unscrupulous profiteers to game the system with little, if any, consequence and nothing but profit until the cost in lives forces the issue.

History

DMAA was originally developed by Eli-Lilly in 1948 and then later trademarked as Forthane to be used as a nasal decongestant (there are varying accounts but it seems that Eli Lilly patented the molecule in the early 1940’s and then trademarked and marketed it as Forthane in 1971 for allergic rhinitis and then voluntarily withdrew it in 1983). The mechanism of action was vasoconstriction – the blood vessels in the nose would constrict so that less blood flow would lead to less nasal discharge. This is a mechanism used by common OTC nasal sprays like oxymetazoline (Afrin) and is indeed quite effective. However, Forthane was later withdrawn from the market because of significant side effects including headaches, tremors, and increased blood pressure. These effects likely occur because DMAA is structurally similar to amphetamine and as a result, the compound is not only a vasoconstricting agent but is also a central nervous system (CNS) stimulant. 

Pharmacology

A 2011 study looked at the physiological effects of DMAA and claimed that “[t]o our knowledge, no data are available concerning the effects of oral geranamine intake on heart rate (HR) and blood pressure in individuals.”  Literature searches for any of a number of variations of DMAA including various equivalent chemical names, trade names, and geranium derivatives also revealed no studies on the physiological effects of DMAA (except for one article in JAMA from 1950 which has no text available entitled “NEW and nonofficial remedies: methylhexamine; forthane.”) prior to the 2011 study. Since then, there have only been a few studies, many of them done this year. The only data available on the compound is from chemical safety manuals like the Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals from 1989 listing toxicological data of the compound in animals. The toxicology report is rather telling:

• TYPE OF TEST: LDLo — Lowest published lethal dose
• ROUTE OF EXPOSURE: Unreported
• SPECIES OBSERVED: Rodent — mouse
• DOSE/DURATION: 20 mg/kg
• TOXIC EFFECTS:
  • Behavioral — convulsions or effect on seizure threshold
  • Behavioral — ataxia
  • Lungs, Thorax, or Respiration — other changes

Based on this limited report, it is difficult to determine clinical safety and efficacy effects of the compound. As with all vague things in the biomedical world, unsubstantiated declarations can be fabricated as long as they don’t make specific disease claims. 

But do were really have no idea what this compound could or would do? Is there truly an absence of evidence? From the strictest interpretation of the hierarchy of evidence in EBM there is so little evidence as to be akin to no evidence. This is where science-based medicine steps in. Here at SBM we often talk about prior probability in the context of most CAM modalities having none, thus a p-value can indeed be spurious and safely disregarded in the proper context, regardless of “how significant” it is. But prior probability also works the other way and is indeed the basis physicians use for off-label prescription of medications, amongst other things. So in the case of DMAA we can look at the chemical structure, the side effects that led to the withdrawal of Forthane decades ago, the known vasoconstrictive effects that Eli Lilly exploited as the mechanism for their drug, the Merck toxicology data, and especially the fact that DMAA interferes with immunoassays for amphetamines to draw a conclusion that in the absence of better evidence it is quite reasonable to conclude that the primary and side effects, as well as dangers of DMAA would be very close to those of amphetamine – a compound we have studied extensively. A little bit of intellectual honesty would then lead someone to realize quite rapidly that unless we felt comfortable putting amphetamines out on the open market for anyone of any age to buy and consume, we shouldn’t do the same for DMAA. This is regardless of the source since coming from a plant won’t magically make the compound any safer or have different effects. Unless of course you believe in magic.
 
In a recent Google search, many websites devoted to bodybuilding and health supplementation have made the claim that DMAA is safe or at least is safe in “appropriate” doses while recognizing that taking too much can have adverse effects. Yet what can this possibly be based on? We have no idea what the elimination route actually is, what the half life is, if it builds up in tissues over time, if it causes damage to particular organs (like the liver or kidneys), or what the long term effects would be at any dosage. Many of these sites use anecdotal data – individuals using it didn’t die or have horrible effects and felt great whilst taking it. Yet this cannot possibly take into account the previously mentioned considerations. Some sites even list recommended dosages and frequencies of administration. Once again, based on what? Nobody has any idea if the compound accumulates in the body or what the half-life is to make such a claim. But, such claims are perfectly legal and reasonable in the world of the DSHEA.

How to game the system using the DSHEA

So now that we have established that DMAA is a synthetically derived amphetamine-like molecule, how did we go from a drug that was discarded from medical use decades ago to a “natural” and “safe” dietary “supplement?”

It seems to have started in 1996 with an article out of China called “A study on the chemical constituents of geranium oil” (Ping et al. Journal of Guizhou Institute of Technology, 1996.) Despite our best search efforts, we could not find that actual article, merely hundreds of references to it. We attempted to go directly to the journal website, but none exists. Despite this, it is the most commonly cited reference for the “natural” origins of DMAA as it claimed that this study found evidence of DMAA in geranium extracts.
 
That’s it. Really. That is all that was needed, despite all of the long synthetic history of the compound, to make it legal to market under the DSHEA. The Human Performance Resource Center has a pretty comprehensive list of all the companies and products that sell DMAA-containing compounds (PDF) under the protection of the DSHEA. There are 79 different products with almost as many companies. And that is just the list of products still currently marketed. There is a much longer list of products that are no more or no longer use DMAA. Sure makes that FDA warning to 10 companies seem even more pitiful, doesn’t it?
 
Since the unfindable Ping et al. study there have been a few more that have used extremely sensitive techniques and not been able to find any DMAA in geranium extracts. USPLabs rebuts by claiming that these studies didn’t look at the correct (and incredibly specific) geranium plant and states that “critics are uninformed”. Interestingly enough, in that same article “[a USPLabs spokesperson] did not clarify whether the DMAA contained in Jack3d and OxyElite Pro was actually sourced from geranium…” Thankfully, we have science to help us answer that question.
 
A recent study did actually find some DMAA in geranium extracts. However this was in the 0.6 to 1.4 ng/g range. That’s nanograms – as in one billionth of a gram, or 1/10^-9 grams of active substance per gram of geranium. The amount of DMAA in Jack3d by USPLabs appears to be a secret. Reading that thread from the USPLabs official blog is quite telling in and of itself, with comments from USPLabs claiming it has been studied and determined safe, citing their own in-house studies and press releases as evidence of this (as well as one actual peer reviewed study). However, in perusing the various sources and recommendations on the web anything ranging from 20 mg-75 mg is the recommended dosage with 50 mg being most commonly mentioned. That means USPLabs would have to be processing 50,000 kg of geranium to produce one dose of their product. What was that about prior plausibility again? If that weren’t enough yet another study demonstrated that:

the enantiomeric and diastereomeric ratios of two different known synthetic DMAA compounds, as well as the total concentrations of DMAA and its stereoisomeric ratios in 13 different supplements, were determined by gas chromatography. The stereoisomeric ratios of DMAA in the synthetic standards and in all the commercial supplements were indistinguishable.

In organic chemistry, molecules that have the exact same number and type of atoms can have different configurations in three dimensions. Even if they have the same exact number and type of bonds this can occur. This is biologically very important since most of our enzymes have evolved to process one particular configuration of compounds that have multiple configurations. In synthetic chemistry, making a compound that has exactly the three dimensional shape that you want is often rather tricky and is called “controlling” the stereogenic or chiral centers. So when you do a synthetic reaction, you often get a mixture of these various configurations and the ratios are determined by the initial conditions and the reaction conditions. What this paper is telling us is that an actual sample of products that contain DMAA has ratios that are identical to what you would get from the standard laboratory synthesis of the compound. Of course, it is possible that this could be entirely coincidental and the geranium plant just happens to have the exact same ratios as well. However, for reasons that would go well beyond the scope of this article, that is almost as likely as homeopathy working. For a more in-depth discussion of how incredibly implausible the claims are, there is an excellent article dissecting every claim and every molecule as well.
 
Since there is a potential profit, USPLabs has created an entire website devoted to trying to prove many of these studies to be false accusations. They only address a handful of the criticisms above and none of them actually demonstrate the safety of DMAA. So why even bother? Because if DMAA is not a “natural” compound used for “hundreds” of years and generally recognized as safe (GRAS) then DMAA would be considered a novel drug and USPLabs would actually have to demonstrate safety and efficacy data in order to stay on the market. By asserting it is a “natural geranium extract” it can be shielded by the DSHEA and make all the burden of proof lay with the FDA while selling their product. Some consumers clearly know it is an amphetamine and use it as such for performance enhancement. At least they are (marginally) informed consumers. But many do not realize this and believe the marketing hype that this is a safe and an all-natural product, and have paid with their health and their lives.

Conclusion

Despite USPLabs protestations, there is no reasonable way that DMAA can be considered a natural or safe product for sale as a supplement under the DSHEA. And even if it did meet DSHEA requirements, this is an excellent example of the dangers of the law in the first place that allows so-called natural compounds to be marketed without prior safety and efficacy testing. The authors recognize that in the vast majority of cases such compounds have no effect at all, whether positive or negative, and the primary harm is in wasting people’s money with claims that are tantamount to fraud. However, there are clearly cases where that is not the case and harm is established about as clearly as one could expect without people dropping like flies. And that doesn’t take into account the less severe or acute harms experienced by vast numbers of people taking untested supplements.

But even more alarming to us is the fact that this DMAA saga exposes quite clearly how unscrupulous companies driven by nothing more than profit can game the system using the DSHEA as a shield with such incredibly paltry evidence as a single article that can’t even be found as anything but a reference to support their claim for exemption under the DSHEA. While it is not established to any legal certainty, it seems quite clear to these authors that there is a preponderance of evidence demonstrating USPLabs and potentially other DMAA product manufacturers are knowingly selling a synthetically-derived drug and using the popular notion of the Naturalistic Fallacy to market it for significant profits.

Authors

Igor I. Bussel graduated from the University of California, Irvine in 2006 with a BS in Biological Sciences and distinction for excellence in research, and matriculated at the Chicago Medical School at RFUMS as a dual-degree student and has earned an MS in Healthcare Administration and Management. Igor recently completed the Doris Duke Clinical Research Fellowship at the University of Pittsburgh ophthalmic imaging research laboratory and will be pursuing residency training in ophthalmology and aspires to become a clinician-scientist.


Andrey Pavlov Jr. graduated from the University of California, Irvine in 2005 with BS in Biological Sciences and a BA in Anthropology. After graduation he worked in the ER at a Level 1 Trauma facility for 3 years and then entered the University of Queensland-Ochsner medical program. During this time he lead development of the US Medical Licensing Examination adjunct curriculum for the School of Medicine and was an executive founding member of the Ochsner Medical Student Association of which he is currently President. Andrey will be pursuing Internal Medicine residency training followed by a Critical Care and Pulmonology fellowship, with specific interest in sepsis, space medicine, and comparative effectiveness research.

If you grew up in the seventies, you may remember the same food fads as I do. There was the oat bran buzz that was replaced by the wheat germ movement, the family fondue set and the homemade yogurt maker. And for a while I remember my father making what I called “aquarium water” – a foul-looking jug sitting on the kitchen counter with a gelatinous white mass floating on top. Despite the assurances it was good for me, I declined the taste tests. They didn’t push it and I never volunteered to drink this “cure all”. I thought kombucha had gone the way of gelatin-based salads and entrees, until a friend told me she was drinking it. Not only is it still a home-brew darling, kombucha isn’t just for hippies: There’s probably some for sale at your local organic grocery. Yet after a bit of digging, kombucha culture still seems mired in the 1970′s. It’s still touted as a panacea, and it’s still one of the more questionable folk remedies out there.

I understand the intrinsic appeal of the folk remedy. In an era where we can buy everything we possibly need, there’s something meaningful and satisfying about making your own food from scratch. I prefer bread, particularly sourdough – but I’m not making any health claims. Like food recipes, some home remedies are handed down from generation to generation, or passed on by word-of mouth. The attractiveness is both an appeal to antiquity combined with pattern-seeking and anecdotes. We remember the “hits” of those home remedies but not the misses. And we never test causality. Is it possible that kombucha could have medicinal effects? Sure. Beer and wine didn’t come out of a medicinal chemistry laboratory either – and look how helpful those fermented products are. As a fan of beer, cheese, sauerkraut, and yogurt, I’m strongly pro-fermentation. So while we can’t make Tylenol in our bathtub, or grow our own antibiotics, how about an odd-flavoured tea-based beverage filled with the magical healing properties of yeast and bacteria? I’m told it’s all about the microbiome, so perhaps they were on to something in the 1970s. Authentic and artisanal is where it’s at today, and what could be more artisanal than home fermentation of a remedy?

As with most folk remedies there are multiple claims for kombucha’s ancestry, from the Ukraine to Asia, from “millennia ago” to a few hundred years ago. However or whenever it occurred, the recipe is similar. Kombucha is sweetened black tea fermented by a mixture of yeasts and bacteria that form what looks like a “mat” on the surface. Sometimes called a symbiotic colony of bacteria and yeast (SCOBY), the “mushroom” or simply the “mother”, this “zoogleal mat” ferments the sugar, producing alcohol, vinegar, and other by-products. To get started, you need to obtain a starter mat – you can order them online, or ask someone that already grows their own. The result of fermenting on your counter is exactly what I remember growing in our kitchen, though it actually looks more brackish than I remember.  After fermentation it’s lightly carbonated. Taste reports of kombucha vary from “refreshing apple cider” to “vomit”.

Like other folk remedies, kombucha’s efficacy is apparently legion. HIV, aging, hair growth, gout, diabetes, hemorrhoids, memory loss, PMS, cancer, hypertension, and the perennial “boosting” the immune system are no match for the healing and restorative power of kombucha.

What is that growing on and in my drink?

Several researchers have examined the bacteria and yeast in the kombucha mat. Content can vary considerably, based on the geography, climate, and local bacteria and yeasts. Bacteria include Bacterium xylinum, Bacterium gluconium, Acetobacter hetogenum, Pichia fermentons. Sometime antibiotic-producing bacteria like Penicillium species can be detected. And then there’s the toxic bacteria that has been detected, such as Bacillus anthracis - anthrax. Yeasts include Schizosaccharomyces pombe, Torulaspora delbrueckii and Zygosaccharomyces bailii.  Contamination with Aspergillus fungus has also been reported, as well as Candida. Yes, that fungus that’s poisoning us all (according to alternative medicine proponents). Various Candida species including C. albicans, C. kefyr, and C. krusei are also found in kombucha.

The final ingredients vary with the bacteria and yeast in the mat, as well as the extent to which fermentation has taken place. Analyses have identified small amounts of alcohol (usually under 0.5%), substantial acetic acid (vinegar), ethyl acetate, glucoronic acid, and lactic acid. There’s some residual sugar, depending on how long it’s been fermenting. Caffeine is still present and may be responsible for some of the energy claims. It’s claimed to contain B vitamins, though I could locate no reliable source to confirms this.

The kombucha “mother”

The evidence

Despite the hundreds of thousands of posts on kombucha praising its medicinal and health effects, I was unable to identify a single clinical trial for any specific use. There’s a systematic review by Edzard Ernst dating to 2003 that also failed to find any clinical trials or even case series that suggest kombucha has medically beneficial uses. So there is no evidence to demonstrate or even hint at efficacy. Based on what’s known about the active ingredients, there’s no reason to expect it would offer any medicinal effects other than the consequence of low levels of alcohol or caffeine.

The toxicity

Given this is usually a home-brew concoction, there is the significant risk of contamination. In contrast to the lack of benefit, there is good documentation of the potential for harms associated with kombucha:

• an alcoholic developed jaundice after two weeks, which resolved after discontinuation
• dizziness, nausea and vomiting that resolved with discontinuation and restarted with rechallenge
• toxic hepatitis that resolved with discontinuation
• metabolic acidosis and disseminated intravascular coagulopathy, resulting in subsequent cardiac arrest and death
• metabolic acidosis, cardiac arrest (with recovery)
• anthrax infections of the skin through topical application of kombucha
• lactic acidosis and acute renal failure
• lead poisoning secondary to making it in a ceramic pot

Given the potential for kombucha to grow potentially dangerous pathogens, it’s particularly important for those with compromised immune systems to avoid the product. Given the risks, pregnant or lactating women should avoid kombucha as well.

Kombucha sells out

Kombucha isn’t limited to the home brewer anymore, there are several commercial suppliers such as Synergy (touted by Dr. Oz, of course) and the requisite story of the breast cancer survivor who credits kombucha for her health (but not the chemo and radiation she also accepted). The claims come fast and furious: the fermented liquid heals all and cures all – digestion, immune system “boosting”, amino acids that “detoxify”. You can now find it combined with different juices and flavors, for those that don’t like the taste of the original.  The recipes are the same, and the final products are not pasteurized, a situation that caused products to be pulled in the United States until producers found ways to stop the alcohol from exceeding 0.5%.

The bottom line

The best that can be said about kombucha is that it probably won’t kill you. There are no documented health benefits, so unless you really like the taste, there’s no clear reason to consume it. As I have written before, health decisions should be based on an evaluation of the risks and benefits. In the case of kombucha, the benefits, other than the subjective, are unsubstantiated. The risks are real, but also rare. So if that bet still looks attractive, kombucha may be for you. To each his own fermentation. As for me, I’ll stick with my own favourite fermentations: IPA and wheat beer, and pass on the moonshine panacea.
Photo from flickr user parkerthompson and flickr user Jasonunbound used under a CC licence.

The basic story is often the same, with a few variations. First, however, let me describe what should happen when someone comes up with an idea for a new medical treatment.

Background research – The first step, whether the innovator is within or without the medical community, is to familiarize oneself with existing research. Is the idea plausible, has it been investigated before, are there any similar treatments that can act as a guide to predicting how this new treatment will work?

Test basic principles – If the idea still makes sense after existing research is taken into account, then new research into the potential treatment is justified. This should start with some basic proofs of concept. Is the treatment safe, does it actually do something, what are the possible mechanisms at work. This level of research may involve in vitro studies (test tubes and petri dishes), and eventually animal research. If the treatment is something that does not have a pre-clinical model (say, for instance, a new therapy technique) then early safety and tolerability studies should be done. If there is any component of the new treatment that involves new or untested scientific principles, they should be studied before they are applied to a treatment (the human energy field and therapeutic touch come to mind).

Preliminary human trials – If the treatment still seems plausible and seems to be safe and supported by basic principles, then some preliminary early human studies are justified. These may be formal FDA phase I trials, or generic pilot studies. These usually involve few subjects, may not be blinded, and are simply intended to get some idea of the effects and safety of the treatment.

Confirmatory trials – Everything so far is simply preliminary and used to determine if large, double-blind, expensive and elaborate studies are justified. These trials are designed to answer, as definitively as possible, if the treatment has specific positive effects and what the risks and negative effects are. These trials may also compare the new treatment to existing standard treatment.

It is only after these confirmatory trials that any health claims can be reasonably justified, that patients should be charged for treatments, that the treatment should be incorporated into medical practice, and insurance companies pay for the treatments. You can make an argument for compassionate use of treatments based on preliminary evidence if there are no other options, but every effort should be made to do this as part of further research.

Press interest in the treatment should also follow this pattern. Only the technical and professional literature and news really should deal with new treatments in the introductory phase. The general lay press should not be trumpeting new treatments that are not even in the preliminary human trial phase. Reporting preliminary human trials should also be done carefully, and put into the proper context. The sensational headlines about a new treatment should be reserved for those that are well established by confirmatory research.

Everything I just described above often does happen when new treatment ideas emerge within the culture of scientific medicine and is handled properly by professionals. Every day medical scientists are sorting out what works from what doesn’t work using some version of this process, and the public usually only hears about new treatments that make it over the finish line.

Alongside this traditional, tested, science-based process there is a growing infrastructure of medical pseudoscience that follows a completely different paradigm. Their process goes something like this:

An innovator comes up with an idea for a new medical treatment (device, supplement, procedure, etc.). They immediately start using the new treatment (if they are a practitioner) or at least trying it out anecdotally on themselves or a few others. Based upon either this limited or no experience, and no actual research, they then market the new treatment directly to the public.

If a pseudoprofessional gets their hands on the treatment, then it is instantly institutionalized. The device is marketed, clinics are established, articles and books are written, and people are treated.

The lay press then give free advertising to the new treatment by writing gullible articles following a predictable narrative – a maverick innovator has come up with a “miracle cure” with dramatic anecdotes. If they developed the treatment in order to treat themselves or, better yet, a loved-one, then that, of course, is the angle. There is token mention of the nasty skeptics, but how could they deny the stunning testimonials?

These two versions of events are simply two ends of a spectrum – science vs. pseudoscience, or legitimate medicine vs. dangerous quackery. I do think that there is a bimodal distribution of new treatments based upon culture. People either function within a culture of science or a culture of pseudo and anti-science, but there is a scattering of treatment across this continuum.

Let’s see where this new treatment, the gyrostim, falls.

GyroStim
The GyroStim was developed by Kevin Maher, who is an engineer, not a medical scientist. He developed the device in order to help his daughter, who suffers from cerebral palsy. He and his wife were told that stimulating the vestibular system, by spinning around or doing somersaults, could help with balance and motor development. Motivated to aggressively treat his daughter to give her the best chance of improvement, they put her through “nearly 1,000 of these spinning motions per day.”

Maher decided to make this process easier by building a robotic chair in which a person can be strapped, and the chair would then spin in every axis. The chair seems to do what it is designed to do – spin a person around in every direction. If your goal is to do this a thousand times a day, this certainly seems like an advantage over doing somersaults. To that extent, the device works.

The deeper question is, however, what are the net risks and benefits of this kind of spinning therapy? But before I get into that, let me finish the story.

A GyroStim machine has apparently been sold to the Mayo Clinic for research, and another to the Air Force Academy for aerospace medical research. So far, so good.

But then Maher apparently was sucked into the rank pseudoscience of chiropractic neurology. His device was purchased by a Richard Turmel, DC, a self-described functional neurologist in Quebec. He says of the machine:

This might be the most amazing machine I’ve ever seen in medicine, and we’re only just at the beginning. I am seeing, quite frankly, new miracles almost every day with this. There are still skeptics out there in the medical community about this, but I’m sure when electricity was first invented, some people said it might be bad.

Hype, anecdotes, and dismissal of legitimate skepticism – the quack trifecta.

Another chiropractic neurologist, Ted Carrick, is also enamored of the GyroStim. I have discussed Carrick before (as has Harriet Hall), he makes many dubious claims and offers only testimonials and poorly-conceived studies as evidence.

The GyroStim is, unfortunately, now associated with the dark underbelly of medicine, the world of pseudoscience. Treatments with the GyroStim cost $2,500 – $6,000 per week, and the claims made for the treatment are expanding – concussion, cerebral palsy, and even autism (of course).

Hopefully the device will at least also go through the standard scientific evaluation. There is some plausibility for this type of treatment for vertigo. In fact, vestibular therapy is already an established and evidence-based treatment for chronic vertigo. Physical therapists develop an exercise program for patients that involve maneuvers to stimulate the vestibular system, which does tend to reduce the vertigo. This probably works through normal brain plasticity.

Vertigo can have many causes, but the common end result is that the brain is not properly integrating various sensory inputs (visual, proprioception, and vestibular) which is necessary for proper cerebellar function (balance and coordination). Forcing the brain to integrate vestibular stimulation may accelerate the process of essentially learning how to establish more normal sensory integration.

One cause of vertigo and poor balance is concussion – the brain is traumatized, which can cause diffuse damage interrupting the amount of connections that the brain makes with itself. This can interrupt sensory integration, causing vertigo. Vestibular therapy is therefore a legitimate treatment for the vertigo that results from head injuries.

The GyroStim is, essentially, automated vestibular therapy. In this regard it is nothing new. The open questions are – is it as or more effective than standard vestibular therapy, and is it cost effective? It’s very expensive, and so the cost-effectiveness question is not trivial. If it is as effective, perhaps there is a niche for it to administer vestibular therapy to patients who cannot physically comply with standard therapy.

Claims that the GyroStim can help with symptoms other than vertigo and balance, however, are not plausible. Existing evidence suggests that the benefits of these types of interventions do not extend beyond the tasks themselves. There is no global brain-training. Training in a task, for example, improves performance on the task, but not general performance.

Likewise – vestibular stimulation can plausibly help with the integration of vestibular sensory information with other sensory information and improve vestibular function, but there is no reason to suspect that it will improve any other aspect of neurological function.

Conclusion
The GyroStim is nothing more than automated vestibular therapy. Before it is mass produced and incorporated into medical treatment, it needs to be tested to see if it is safe, effective, and cost effective for conditions that are already treated by standard vestibular therapy.

If it is effective for vestibular therapy, then it can be studied to see if there are benefits for other conditions. I am skeptical of such benefits, however, because they lack plausibility. Only high quality confirmatory clinical research will be adequate to establish the GyroStim as a legitimate treatment for any such condition. Until then, promoting or using the GryroStim for anything other than vestibular therapy is pure quackery.

The “science” of acupuncture trudges ever onward without really getting anywhere. New developments include a report of turtlepuncture  and a study about treating low back pain with a new kind of “motion style” acupuncture using passive or active movement while the needles are in place. I found the first amusing and the second unconvincing.

Turtlepuncture 

A group of Ridley sea turtles were rescued after being stranded during a cold spell that left them hypothermic and unable to function. In addition to the usual rescue and rehabilitation efforts, two of the turtles, Dexter and Fletcher Moon, were treated with acupuncture. It was intended to  “decrease inflammation and swelling on their front flippers, restore a full range of motion on those limbs and help the animals regain their appetites.” It allegedly worked: their appetite and the use of their limbs improved. But without any controlled observations, this is only an anecdotal report and means very little. They might have recovered just as well without the treatment, for all we know.

I searched for studies on turtle acupuncture. I found studies on the miraculous turtle eight meridians method, the eight methods of intelligent turtle, turtle probing needling, green turtle searching and boring acupuncture, the extraordinary turtle flying method, and turtle probing the cave needle manipulation, and one case report of treating an American red-footed tortoise. Nothing on treating turtles.

How did they know where to put the needles? They worked with a veterinarian to find analogies between the anatomy of turtles and other animals. And acupuncture points in animals are based on analogies with humans, sometimes with amusing results: diagrams for horse acupuncture show a gall bladder meridian but horses don’t have gall bladders!

I’m glad the turtles got better, but I don’t give acupuncture the credit.

Motion Style Acupuncture

A Korean study was published in the journal Pain.  It was a multicenter, randomized, controlled, comparative effectiveness trial with a total of 58 patients with acute low back pain. It compared one session of motion style acupuncture to one injection of diclofenac. Patients in the acupuncture group improved more than those in the diclofenac group.

What Is It? The authors tell us that motion style acupuncture treatment (MSAT) is a relatively novel method that has been recently used increasingly often in South Korea, but the only reference they offer refers to two case reports. In their MSAT protocol, two assistants stood on both sides of the patient with their arms around his waist. Acupuncture needles were inserted at points selected according to Traditional Chinese Medicine and previous clinical experience. The deqi sensation was not sought, but practitioners “occasionally” manually stimulated the needle at the GV16 point. With the needles in place, the patients were asked to walk with assistance. As walking improved, less support was provided. When the patient was walking without support, the needles were removed and he was asked to continue walking for 1-2 minutes. The patients were given verbal encouragement.

Why Diclofenac? The comparison treatment was a 75 mg intramuscular injection of diclofenac sodium,  a nonsteroidal anti-inflammatory drug or NSAID. The rationale for choosing it as a comparison was unclear. NSAIDs have been proven effective for acute low back pain, but they are usually given orally. A recent view of acute low back pain treatment does not mention the IM option.  Neither does the Mayo Clinic website.   I couldn’t find any sources that recommended IM administration over the oral route. I’m guessing they chose it for this study because it was a convenient way to give one strong, rapidly acting dose for comparison with one acupuncture treatment.

Results. Pain was assessed on a scale according to subjective patient self-reports, and disability was assessed by a questionnaire at 30 min, 2 weeks, 4 weeks and 24 weeks after treatment. The outcomes were significantly better for MSAT for the earlier times but not at 24 weeks.

Does This Really Support Acupuncture?  They called this a comparative effectiveness trial. Comparative effectiveness trials are typically used to compare established interventions to see which of two effective treatments is more effective. They are not intended to explore a new, untested treatment like MSAT. There are problems with this study. The subjects were Koreans who may have been culturally predisposed to expect results from acupuncture. Endpoints were subjective. Blinding was not possible. Instead of a single treatment and an atypical control, it would have been better to compare typical MSAT treatment to standard conventional treatment of low back pain.

What bothers me the most is that the MSAT group essentially got two treatments: acupuncture and assisted mobilization. I’d like to know what would happen if they got the second without the first. Maybe the needles were superfluous.

Patients with acute back pain avoid walking because it hurts. If they avoid using the muscles due to fear of pain, they can become conditioned to expect pain. Often they have severe pain when they first start walking, but if they can keep walking the pain tends to diminish. Patients who remain active recover faster; that’s why bed rest is no longer recommended. And a recent study showed statistically and clinically significant benefit from cognitive functional therapy. This involves re-framing and confidence-building as described here.

So what if all back pain patients were encouraged to walk and were assisted with the support and cheerleading? This acupuncture study would have been a far better study if it had included a motion-style treatment control group without the acupuncture component: MST instead of MSAT.

Conclusion

Color me skeptical. I question the use of acupuncture on turtles and on non-chelonian patients with acute back pain. The evidence doesn’t support it. I’m optimistic that assisted walking with physical support and encouragement might prove to be an effective treatment for patients with acute low back pain. I hope further studies will investigate that.

After having heard of Eric Merola’s plan to make a sequel to his 2010 propaganda “documentary” about Stanislaw Burzynski, Burzynski The Movie: Cancer Is Serious Business, which I labeled a bad movie, bad medicine, and bad PR, I’ve finally actually seen the finished product, such as it is. Of course, during the months between when Eric Merola first offered me an “opportunity” to appear in the sequel based on my intense criticism of Burzynski’s science, abuse of the clinical trials process, and human subjects research ethics during the last 18 months or so, there has been intense speculation about what this movie would contain, particularly given how Merola’s publicity campaign involved demonizing skeptics, now rechristened by Merola as “The Skeptics,” a shadowy cabal of people apparently dedicated (according to Merola) to protecting big pharma and making sure that patients with deadly cancers don’t have access to Burzynski’s magic peptides, presumably cackling all the way to the bank to cash those big pharma checks.

The movie, Burzynski: Cancer Is A Serious Business, Part 2, was released to online sources on Saturday and will be released on DVD on July 1. As much as I detest Eric Merola and don’t want him to profit from his deceptions, I also wanted to see what the finished product actually looked like. So I swallowed hard, paid, and watched. It was probably the worst $15 I ever spent, but at least it’s tax-deductible for my not-so-secret other blog, from which I do earn a small amount of money for my writing. Of course, from my perspective, actually seeing the movie is almost anticlimactic given that we’ve had detailed reports from screenings of the movie by skeptics (excuse me, Skeptics) who attended, replete with conspiracy mongering, repeating claims to the movie to an echo chamber, and even Fabio Lanzoni. However, there are things one can’t adequately evaluate using second hand reports. Moreover, it just so happens that tonight the BBC will be airing an episode of its long-running news series Panorama about Burzynski. The episode is entitled Cancer: Hope for Sale? Although I fear the producers falling into the trap of false balance, I’ve heard enough from my connections to suspect that Burzynski won’t be happy at all about the story. After all, his minions have been pre-emptively attacking Panorama since Burzynski patients have let it be known that they had been interviewed for the report. Now, if we “Skeptics” were the all-powerful, overarching, nefarious force that Burzynski’s acolytes paint us as, one might think that we had planned it this way, to have the BBC Panorama episode come out the Monday after the release of Eric Merola’s movie. I’ll let Eric Merola puzzle over that one. No doubt he’ll build another one of his—shall we say?—imaginative conspiracy theories over this.

So what about the movie itself? First, let me point out that, after having seen the movie (which I will henceforth call “Burzynski II”, to distinguish it from the first Burzynski movie, which I will call “Burzynski I”), there’s nothing I would change in my original discussion of it. Burzynski II really is just like Burzynski I, only more so. I refer you to the link for my discussion of many of the problems with the movie. Here I will concentrate mainly on issues that I haven’t discussed before, because actually seeing Burzynski II was a revelation. (Heh, I put that sentence there on purpose Eric Merola; quote mine it if you dare!) First, as a movie, Burzynski II is at least as bad as Burzynski I. Eric Merola is a crappy, crappy filmmaker. The narration is done by the same creepy-sounding narrator such that it sounds like a low bit rate MP3 (say, 32 kbps); certain medical terms are mispronounced; there are lots of errors; and Merola demonstrates the same tendency to switch back and forth between camera angles in which the subjects of his interviews are looking at the camera to angles where they are not. The effect, I’m guessing, was intended to be edgy. What it ended up being (to me, at least) was irritating as hell. The music and cheesy graphics are also much the same as they were in Burzynski I.

The other thing that I wasn’t prepared for was just how unrelenting Burzynski II was in its propaganda. Burzynski I was one-sided to the point of ridiculousness, but Burzynski II takes that ridiculousness to the next level, much as each sequel to the original Transformers or The Fast and the Furious movies tends to be bigger, louder, and dumber than its predecessor. This is not a good thing. In Burzynski II, I mentioned that the messages are:

1. Stanislaw Burzynski is a genius who invented “personalized gene targeted cancer therapy,” and is now being emulated by centers like M.D. Anderson, which are furiously trying to catch up.
2. Burzynski is a Brave Maverick Doctor who is curing patients that conventional science can’t cure, and it’s not his fault when he can’t.
3. Burzynski is a real scientist with tons of data supporting antineoplaston therapy who is being unjustly hounded by the FDA, the NCI, and big pharma to prevent him from bringing his cancer cure to market.
4. The Japanese are on the verge of publishing definitive clinical trial evidence that antineoplastons work!
5. Skeptics are evil meanies who cackle evilly as they terrorize cancer patients online and delight in crushing their hope.

Unfortunately, in Burzynski II the messages are even less subtle (if that were possible) than in Burzynski I. Whereas Burzynski I hit you over the head with its messages repeatedly if they were a series of 2x4s, in Burzynski II the 2x4s have bricks attached to their ends.

Burzynski II does have a slightly different structure than Burzynski I, however, although overall it’s very similar in many ways. Burzynski I spent the first 30 minutes or so discussing patient anecdotes to “prove antineoplastons work,” and then spent most of its last hour or so lambasting the FDA, the Texas Medical Board, and big pharma. Burzynski II, on the other hand, although it begins similarly with some text declaring just how awesome Burzynski is and how evil the FDA, the Texas Medical Board, and big pharma are, followed by a montage of news and TV segments extolling Burzynski and/or attacking his critics, is a bit more free-form, interspersing patient anecdotes with attacks on big pharma, plus a truly bizarre segment attacking “The Skeptics” near the end. I’ve already dealt with at least four of these anecdotes before, those of Laura Hymas (whose anecdote is the main one), Hannah Bradley (who gets surprisingly little screen time), Tori Moreno, and Amelia Saunders (whose anecdote is perhaps the most heart-wrenching if you know what happened—more on that later); so I won’t dwell on these anecdotes again here except for aspects that I haven’t discussed before that seeing the actual finished movie bears light on.

An ethical conundrum dealt with correctly

One of the things I wondered about last time was a segment in the movie in which Laura and her fiancé Ben Hymas, having decided to go to the Burzynski Clinic, met with Ms. Hymas’ NHS oncologist to try to find out if the NHS would continue to cover her MRI scans, blood tests, and other medical “necessities” once she returned home to the U.K. Ms. Hymas, as you might recall, is a young woman who developed a brain tumor, underwent conventional therapy that only had limited success in slowing the tumor, and ultimately ended up deciding to go to the Burzynski Clinic. It is revealed in the movie that Ben Hymas had decided to record the conversation with the oncologist, and Eric Merola decided to include the recording in his movie. The results are not exactly what Merola intended. Merola clearly intended it to be damning of the NHS; in reality what I saw was a clinician desperately trying to do the right thing and dissuade Laura from a course of action that he considered to have almost no likelihood of helping. For instance, when Ms. Hymas says that the oncologist (who is not named) would not treat her if she went to Burzynski, here’s what he said:

Oh, no, no, no, no, no. Let’s make it very clear. Dr. Burzynski is a person who provides “private care,” in a non-conventional way—that we do not quite understand, or would condone.

Later, he says:

It’s not just his antineoplaston approach, which is controversial to say the least. I’ve had patients there who got cocktails of medications that could have a rationale to work in brain tumor patients but have never been tried and tested in this excessive combination.

The oncologist tries to point out that Burzynski’s clinical trials are not supported by the NHS or his hospital and explains that Ms. Hymas can’t expect the NHS to pick up the tab for tests required by Burzynski for a clinical trial not sanctioned by the NHS. He goes on to explain how the trial is not ethically approved at any NHS hospital and that because he’s not convinced that this is a useful therapy he can’t treat her according to Burzynski’s protocol and that he can’t provide care to her as long as she is under Burzynski’s care.

And here’s where the FDA’s failure has put doctors like this one in a bad position. Ms. Hymas’ mother keeps harping on how if the FDA approved these trials they must be legitimate and can’t be unethical. You know and I know that that’s not necessarily true (and, in fact, I’ve recently learned a lot about how and why these trials were originally approved by the FDA despite the lack of adequate preclinical evidence, but that’s a topic for another post). Another doctor at the NHS also apparently did agree to such an arrangement, which also put this poor oncologist on the spot in talking with the Hymas. Still, in the end, this oncologist said point blank that he does not feel it would be right of him to take instructions or even advice from Burzynski for what is and is not required, although he did appear to indicate a receptiveness to ordering Laura’s scans.

I keep thinking of what I would do if I were in that oncologist’s shoes. I don’t know. I do find it despicable that Merola would use an apparently secret recording of a private conversation and put it in a public movie. This should serve as a warning to all cancer doctors: If you have a Burzynski patient, expect to be taped and conduct yourself as though your words could show up in the next Merola infomercial.

The patients again and an ethical conundrum dealt with incorrectly

To the old familiar anecdotes are added new ones. I’m going to start with the one that is both new to me and most horrifying to me as a cancer surgeon, even more so than the cases I’ve discussed before such as Amelia Saunders or Hannah Bradley. I’m referring to Chris Onuekwusi, a man who was diagnosed with stage I colon cancer. Yes, you read that right. I’m referring to a patient with a stage I colon cancer. You should know that stage I colorectal cancer is very, very treatable. Resecting the involved segment of the colon or rectum containing the cancer has a high probability of curing it. Assuming it really is stage I, chemotherapy might not even be needed. (We don’t know for sure that Onuekwusi’s cancer really was stage I, because often surgeons don’t know the full stage of colorectal cancer until after surgery.) Instead of undergoing straightforward surgery that we know to have a high probability of success (which, I’ll also point out, can be done these days through minimally invasive laparoscopic techniques), Onuekwusi balked, as described in more detail than in the movie in this article on the Burzynski Patient Group website. He had even gone for a second opinion at one of the leading cancer centers in the world, the University of Texas M.D. Anderson Cancer Center, where the surgeon told him the same thing. He needed surgery first.

So what did Burzynski recommend instead of surgery? He recommended a cocktail of three drugs given off-label: Zolinza, Xeloda, and Avastin. Zolinza is vorinostat, a histone deacetylase inhibitor; Xeloda is capecitabine, which is a prodrug for 5-fluorouracil (5-FU), a pyrimidine analog that inhibits the enzyme thymidylate synthetase and thereby inhibits DNA synthesis to toxic effect in rapidly dividing cells; and Avastin is bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor-A (VEGF-A). As I described in a previous post about Burzynski’s “personalized, gene-targeted cancer therapy,” apparently Burzynski sent Onuekwusi’s tumor to Caris for testing. Caris generated a report, as it always does, and Burzynski came up with a witches’ brew of new expensive targeted agents, all said to be “off-label.” Well, not exactly. One of these drugs is just an old chemotherapy drug in a new form. Xeloda is, in essence, 5-FU, a chemotherapeutic drug that has been used to treat colorectal cancer, both as adjuvant chemotherapy and first-line therapy for metastatic disease, for over 40 years. There’s nothing really “targeted” about the drug except that it inhibits an enzyme, the way that many drugs do and have been known to do for decades. The advantage of Xeloda is that it can be administered orally, which is a good thing. Similarly, Avastin, although relatively new, is also commonly used for colorectal cancer, albeit usually for metastatic disease and not as adjuvant chemotherapy. That leaves Zolinza, which is an HDAC inhibitor used to treat cutaneous T cell lymphoma. One wonders if Burzynski included a second HDAC inhibitor, his second favorite drug after antineoplastons, sodium phenylbutyrate.

So why was I so horrified by this anecdote compared to others? The reason is simple. Onuekwusi appears to have had a relatively easily curable cancer with standard surgery, and that surgery is usually not particularly morbid, given that the scans shown in the movie indicated that it was a right colon lesion, as opposed to a sigmoid or rectal lesion. It is, in my opinion, medical malpractice to treat such a patient first with chemotherapy (and yes, what Onuekwusi received was chemotherapy, as Xeloda is basically an oral form of one of the workhorses of chemotherapeutic drugs, 5-FU). We know that chemotherapy usually doesn’t do a lot of good as primary therapy of solid tumors like colorectal cancers, although as adjuvant therapy it is quite effective at decreasing the risk of recurrence after surgery. In contrast, we know that surgery is highly effective for stage I colorectal cancer. We even know that if this really were stage I colorectal cancer, Onuekwusi wouldn’t even have even needed chemotherapy! Surgery alone is the treatment of choice. So, by Merola’s own description, what Burzynski did was to administer a toxic form of treatment that was probably not needed (chemotherapy) using drugs that were not approved for that indication, and apparently didn’t insist that the patient needed surgery. Now, it’s possible that the combination of drugs did eliminate the tumor. It’s also possible that the tumor was very small and completely removed with colonoscopic biopsy, leaving an inflammatory reaction behind to be imaged on the PET-CT images shown in the movie, a reaction that subsided over three months. Either way, Onuekwusi (and Burzynski) might have gotten lucky. But they both took an enormous gamble that could well have cost Onuekwusi his life. In my opinion, Burzynski deserves to have his medical license taken away on the basis of how he treated Chris Onuekwusi alone, not even considering all the other dubious things he’s done.

The rest of the “new” cases (i.e., cases I hadn’t been familiar with) followed a similar pattern to cases I’ve discussed before, wherein it’s impossible to tell whether the patient’s good fortune is due to Burzynski’s treatment or not. That includes the patients with brainstem gliomas. We are told repeatedly by the narrator that spontaneous remission of a brainstem glioma has never been documented in the medical literature, despite an exhaustive search. All I can say is that Merola and Burzynski must not have searched very hard, because I quickly found a few, for instance, of pontine glioma (and two more) and a brainstem cavernoma. Remember Tori Moreno? She is a teenager who was diagnosed with a brainstem glioma as a neonate who features prominently in this film as a Burzynski success story. Despite what Tori’s father and Eric Merola claim, it’s quite possible that she underwent a spontaneous remission. True, such remissions are rare, but it’s not correct to say that they never happen. Truly, Merola’s “exhaustive” research skills need some upgrading. It took me two minutes to find those articles. No, I’m not saying that that’s definitely what happened; I’m merely pointing out that it could have happened, which is why clinical trials are so important.

Among the “new” patients is also a woman named Patricia Clarkson with multiple myeloma, who is filmed with her husband in front of large windows with the sun shining in. Yes, they are mostly backlit; one would think that Merola could have found a better, less distracting room to interview them in. Be that as it may, the segment is introduced with in essence a rant about the FDA requiring that patient fail standard therapy before they can have antineoplastons. That is, of course, a standard requirement for new cancer drugs because on an ethical basis doctors can’t administer experimental therapy whose efficacy is unknown if there are treatments whose efficacy is known. Another common design for a clinical trial is to compare standard of care treatment against standard of care treatment plus the experimental therapy.

This segment is introduced by a black screen of white text that says:

Even if the FDA’s prerequisite if fulfilled, the FDA holds full dictatorial rights to refuse patients’ access to antineoplastons if they choose.

Merola says that as if it were a bad thing. It’s a rule designed to protect patients. Merola makes it sound as though this is an arbitrary rule designed solely to keep patients from getting antineoplastons. Mr. Clarkson, of course, rails against the FDA for making it so difficult for his wife to be treated with antineoplastons. What is not shown is that Burzynski did treat her with sodium phenylbutyrate, the orphan drug that is a prodrug for one antineoplaston. As is the case with nearly every Burzynski testimonial, it’s impossible to tell whether Burzynski’s treatment has done any good due to confounding factors. In Clarkson’s case, multiple myeloma tends to be a disease that has a highly variable clinical course and can take years before it can kill, sometimes several years. In other words, its survival curve tends to have a long tail. Mrs. Clarkson was only diagnosed in 2011 It’s also a drug that almost always seems to be included with Burzynski’s “personalized gene-targeted cancer therapy regimens,” almost no matter what.

Seeing is believing?

I can’t do a review of this movie without revisiting stories we’ve seen before. Even though I’ve extensively covered the cases of Laura Hymas and Amelia Saunders before, to me seeing is knowing just how intellectually dishonest Eric Merola is. For instance, seeing the Saunders family, rather than just hearing about them from second-hand reports, was truly heart wrenching. They are such a caring family who were so desperate to do anything for their daughter. Worse, however, is the way that Merola makes it sound as though the reason that Amelia Saunders ultimately did not survive her tumor is because her parents decided to take her off the antineoplaston therapy. I’ve discussed this issue before. Briefly, in November 2012 it was noted that Amelia’s tumor had started to develop cystic regions. Burzynski told the Saunders that this was evidence that the tumor was dying. As I pointed out at the time, this was almost certainly nothing more than the tumor outgrowing its blood supply and developing necrosis in the center, not evidence of an antitumor effect. Sadly, two weeks later, pediatric oncologists at the Great Ormond Street Hospital told the Saunders the same thing and that they thought Amelia was in the end stage of her disease. It was at that point that the Saunders made the completely reasonable decision to take Amelia off the antineoplastons.

This is how Merola describes it:

Two months after this interview, Amelia’s brain tumor began to swell and fill with fluid. There was confusion and disagreement between their local radiologists and the radiologists in Houston about why this was happening—so her parents decided to discontinue antineoplaston therapy. Amelia passed away with her parents at her side on January 6, 2013.

Merola then opines:

Brainstem glioma is as rare as it is deadly. Approximately 500 children a year in the United States and 40 a year in England are diagnosed with it. An exhaustive search spanning 27 years of all available medical literature worldwide reveals the absence of any patient ever being cured or living five years after diagnosis.

As I said before, Merola’s research skills leave much to be desired. True, five year survival is very uncommon, but not so uncommon that it can’t be studied. Similarly, as I pointed out before, it’s not true that spontaneous remission of brainstem tumors in children “never happens.” It’s rare, but it does happen.

Seeing The Skeptics

I’ve already extensively discussed Merola’s attacks on skeptics before, in particular his misinformation and paranoid conspiracy mongering. He goes out of his way to portray us as either incredibly misguided (“they mean good but do evil!”), hopelessly in the pay of big pharma, or so evil that we, as I put it before, cackle with glee as we condemn cancer patients to certain death by taking their antineoplastons away. It’s so heavy handed that even Leni Reifenstahl would turn away in embarrassment if she were alive today and subjected to a viewing. (Some of that would also be due to her recognition of Eric Merola as a talentless hack when it comes to being a filmmaker.)

Particularly seemingly damning are a series of Tweets flashed on the screen saying things like the Hope for Laura fund (the fund set up by Laura Hymas to pay for her treatment at the Burzynski Clinic) “appears to be just a money laundry for a lying quack fraud” and “when Laura dies #Burzynski will just move on to his next mark if she doesn’t run out of money first.” I think I know whose Tweets these were, and all I can say to that person is this: Zip it. In fact, if I’m correct about whose Tweets these are I think I have already done so on Twitter when I’ve seen this person getting too close to attacking cancer patients. Still, as utterly insensitive and “dickish” as those Tweets were, they do not represent the majority of skeptics, but rather a few jerks. However, we as skeptics need to remember that a few jerks perceived (or painted) as attacking cancer patients can do immeasurable damage to the cause of science-based medicine. So if you’re one of those skeptics making comments like that, knock it off. If I see you doing it, I will call you out publicly.

In contrast, I find it very hard to believe that any but the most deluded hard-core Burzynski believers will find the segment in which Bob Blaskiewicz, creator of The Other Burzynski Patient Group and the force behind the idea of promoting donations to a real cancer charity and challenging Burzynski to match it, anything but completely risible. His voice is electronically altered to make it sound ominous and evil; his face is blurred out, and the Virtual Skeptics podcast in which he discussed Burzynski is represented as a “Skeptics’ teleconference,” in which it is implied that Merola somehow obtained a secret discussion. It’s all very silly. I’d say it’s almost Monty Pythonesque, except that Monty Python were brilliant and produced such effects on purpose. Merola is a hack and is only funny by accident because he has no filters that tell him when he’s going way over the top.

So is Merola’s treatment of yours truly. There’s a hilarious picture of my SBM page with my picture partially blurred out, onto which Burzynski places marks for emphasis that I’ve been funded by the DoD (past tense, Eric, not the present tense that you used), the NIH, ASCO, and other organizations (as if getting peer-reviewed research funding were a bad thing). Then there’s the bit about my former funding, a small grant that’s been expired nearly a year now from Bayer Healthcare. Then, of course, there’s my not-so-super-secret other blog, which—gasp!—accepts advertisements from pharmaceutical companies. I knew about all of that before, but actually seeing it onscreen was rather bizarre. I can only wonder what it would have been like to be sitting at a screening of this movie and seeing it.

Then, there was the kicker.

Eric Merola and Laura Hymas’ fiancé Ben Hymas called me a liar. Regarding this particular blog post, they claim that I intentionally linked to an older blog post describing Ms. Hymas’ MRI results and ignored a more recent MRI. Their claim is patently untrue. Note the date of the post in question: November 30, 2011 at 1 AM. (Yes, the post was written on November 29 and set to go live at 1 AM the next day.) Now note when Ms. Hymas underwent that other MRI scan: November 29, 2011. Finally, note when Ms. Hymas posted the results of that scan? November 30, 2011, after the blog post in question went live. I suppose the accusation is that I am not psychic and able to have anticipated that there would be an MRI scan. Moreover, I agree with a commenter who showed up on January 8 and pointed out:

He never claimed they were the November results. He was analyzing the October vs. September results. In fact, the October vs. September results are more significant (in terms of size) than the November vs. October results. Laura is misrepresenting the report.

Here is a breakdown of the sizes of the tumor (in cm or cm2:

Sept = 2.0×2.5 = 5.00

Oct = 1.8×2.1 = 3.78

Nov = 1.7×1.9 = 3.23

Now, the percent reduction in size:

Sept->Oct = (5.00-3.78)/5.00 = 24.4%

Oct->Nov = (3.78-3.23)/3.78 = 14.6%

Sept->Nov = (5.00-3.23)/5.00 = 35.4%

In other words, the 36% reduction was over 12 weeks, not 6 as claimed, and about 2/3rds of that reduction occurred between the two scans ORAC analyzed. Interesting that Laura never posted the MRI from the November scan for comparison, nor any of the earlier scans from when she was undergoing conventional treatment. Also interesting that she claims she was told that her radiotherapy couldn’t have any effect because she only completed 7 of 44 doses of chemotherapy.

My post from November 30, 2011 was correct as written at the time it was written. Ben Hymas is quite mistaken in saying about me, “He’s lying to them.” Moreover, if I had screwed up, I would have admitted it. Indeed, part of the reason I looked into this so closely was because I wondered if somehow Merola had actually found a mistake I had made. You know the saying about the proverbial blind squirrel occasionally managing to find a nut? It’s possible, albeit unlikely, and in fact there was no mistake. Well, that’s not entirely true. I did misspell Ms. Hymas’ name; it’s a mistake I went back and corrected when I discovered it. (You’ll have to forgive me, as it was the first time I had read about the Hymas case.) In any case, the only reason I didn’t post an update was because the commenters had done such a good job addressing the criticisms that showed up a couple of days later. Whether you think that I should have posted an update or not, one can’t help but note that nowhere does Eric Merola mention that I wrote a much more recent analysis of Ms. Hymas’ clinical situation in February 2013 that incorporates all updates. It also pains me that Mr. Hymas would take Merola’s explanation at face value. I feel nothing but sympathy for relatives and friends of cancer patients, and I want Ms. Hymas to do well, but it hurts to hear Ben Hymas repeat Eric Merola’s demonstrably false accusation against me.

In case either Hymas sees this post, let me briefly repeat my most recent assessment of Ms. Hymas’ history as described online, my basic conclusion about Ms. Hymas’ case in February was this:

Laura Hymas is different in that she provides somewhat more suggestive evidence for a possible antitumor effect from antineoplastons, given the longer period of time since she finished her radiation therapy and since her still being in complete remission five and a half months after her first scan showing no residual tumor. However, her case is by no means the slam-dunk evidence that Burzynski supporters claim it to be (or, for that matter, that Merola touts it as in his upcoming movie), given that it has been less than six months since confirmation of a complete response. Moreover, given that HDAC inhibitors do seem to have some efficacy against glioblastoma, it is not unreasonable to expect that antineoplastons might actually have had activity in Laura’s case. Making claims, as Burzynski does, however, that his antineoplaston therapy is more efficacious than conventional therapy is unwarranted based on a single patient. Conventional therapy can produce durable remissions and complete responses, too, and, although they are still rare, they are becoming more common. That’s why legitimate randomized clinical trials are needed to determine if PB/antineoplastons have antitumor effects in humans; which tumors are sensitive; if there are any biomarkers of sensitivity; and to separate the signal from the noise. Anecdotes like those of Hannah Bradley and Laura Hymas can be suggestive, but in and of themselves prove nothing.

There is nothing in Merola’s deceptive movie to change my assessment of what happened in the case of Laura Hymas’ brain tumor or my opinion of Eric Merola. If anything, having seen Burzynski II, my opinion of Merola has plummeted even further, something I hadn’t thought possible.

Evidence, evidence, wherefore art thou, evidence?

Another section of the movie that I was highly interested in, having discussed it before twice, was Dr. Hideaki Tsuda’s antineoplaston research in Japan, which Keir Liddle characterized as underwhelming, and rightly so. This segment came near the end of the movie, right after the segment on The Skeptics and obviously meant as a retort to Burzynski critics.

What I learned about the trial was this. The trial was of a design like what I mentioned above, chemotherapy alone versus chemotherapy plus antineoplastons. Specifically, the trial tested 5-FU infused directly into the hepatic artery for liver metastases versus 5-FU plus antineoplaston A10 and AS2.1. A10 was administered intravenously for one week, and AS2.1 was given in the form of capsules for at least one year. Dr. Tsuda takes pains to insist that he got no advice or assistance from Burzynski, but that protocol is very specific. Why antineoplastons A10 and A2.1? Why A10 for only one week? Why A2.1 for a year? I also note that this is a rather old technique. Back in the 1990s, intra-arterial chemotherapy for liver metastases was all the rage, but these days, because of more aggressive resection of liver metastases and newer, more effective chemotherapy regimens for metastatic colorectal cancer, intra-arterial chemotherapy is seldom used anymore, much less intra-arterial 5-FU. That’s not even considering the technical complexity of placing the intra-arterial infusion pump and the potential complications from having a catheter in the hepatic artery. Dr. Tsuda is behind the times. Indeed, one notes that the CT scans shown from Dr. Tsuda’s group purporting to demonstrate responses to his combined regimen all date back to 1999, which makes me wonder just when this trial was done and, if it was done so long ago, why it hasn’t been published already.

As for the trial, were 65 patients, 33 in the control group and 32 in the antineoplaston group. Dr. Tsuda reported in the movie that the median survival for the control group was 36 months (which is actually rather long for liver metastases treated with intra-arterial 5-FU alone) and that the median survival for the 5-FU plus antineoplaston group was 70 months. Again, all I can do is to emphasize the usual things. This study is not published in peer-reviewed literature, and it was, in my estimation, highly irresponsible of Dr. Tsuda to promote it in a propaganda film before he actually published the results. We have no way of knowing whether the two groups were well-matched or if there were other methodological problems with the study. Let’s just put it this way. It’s way premature of Dr. Tsuda to proclaim that it’s “obviously not anecdotal any more.” Publish first, and let the scientific community be the judge of that.

There was also another part that makes me wonder whether this study will ever be published. Right after Dr. Tsuda proclaims antineoplastons not to be anecdotal any more, we’re treated to this quote from him:

We can’t go any further with these clinical trials allowing antineoplastons to gain market approval exclusively for the Japanese people—due to the Unites States FDA and the power they have over the world market.

The FDA would retaliate against any Japanese pharmaceutical company who would try to get antineoplastons approved in Japan by no longer approving their other drugs for the market in the USA.

It’s the perfect conspiracy theory. Dr. Tsuda claims to have data from a randomized clinical trial that’s good enough to use to gain approval for antineoplastons from Japan’s equivalent of the FDA, but he says he can’t because the FDA would retaliate against Japanese pharmaceutical companies. As I said, one wonders whether Dr. Tsuda will ever publish the results of his trial.

That leaves us with John James, who is listed as a research scientist with Targacept Pharmaceuticals, ranting about how cancer is profitable, how pharmaceutical companies have no incentive to find cures for cancers, instead preferring chronically administered drugs, and telling the sheeple (OK, he doesn’t actually use that word, but the meaning is clear) to “wake up.” What’s not pointed out is that Dr. James no longer works for Targacept and instead has started working for Healing Seekers, a group that does expeditions to remote areas of the world looking for “natural” cures. In fact, he appears to have left Targacept in October 2012, which makes me wonder whether if his participation in this movie had anything to do with it, as the timing fits. Or perhaps he was just a victim of the wave of layoffs that hit in October in the wake of the failure of Targacept’s two ADHD drugs in recent clinical trials. After a similar round of layoffs earlier in 2012, perhaps James saw the writing on the wall.

No, none of it is particularly convincing if you know anything about cancer research. I could change my mind if Dr. Tsuda actually published his results and it turns out that his trial was very well designed, but from seeing him describe them in a propaganda movie like this? Not so much.

In the end, if Burzynski had the evidence, he would have very likely published it by now. Through other skeptics who attended a screening of Burzynski II in the San Francisco area, I’ve learned that Ric Schiff, whom we’ve met before both here and elsewhere and who is now, according to reports I’ve been getting, really peeved that I questioned his claim that he is an “expert” in detecting medical fraud when as a cop he views himself as a “fraud expert,” is claiming that all the phase II studies recently wrapped up and are being prepared for publication. I have my doubts about that, but let’s assume it’s true for the moment. If that’s the case, then I submit that Merola should have waited until after some of those complete phase II have been published in the peer-reviewed literature to release his movie. Then his trumpeting of Burzynski’s “triumph” over the FDA, the Texas Medical Board, big pharma, and The Skeptics might have been somewhat more convincing. Data talks. BS walks. And there’s no doubt that Burzynski II is pure BS.

Now, all I have to do for now is to wait until I have access to the episode of Panorama airing tonight in the U.K.

I like animals and hate to see them suffer unnecessarily. Like sticking them with needles. Frontal lobes are nice to have. They can let you know that pain is coming and provide preparation and compensation. Once I had a steel bar smack me on the head, opening up a six-inch cut to the bone. No, my brain was not affected, thank you very much. Everything predates the head trauma. When the ER doc numbed the scalp for sutures, he missed the last half-inch and I felt the needle. Knowing what was going on I steeled myself and let him do the last two sutures with no lidocaine, since the needle hurt only a little worse than the lidocaine injection. I have had many other unpleasant medical procedures in my 56 years but knowing what was coming and understanding why makes it easier to tolerate a needle popping into the knee joint or an abdominal drain being pulled.

Animals, and young humans, lack the ability to comprehend the what and why of pain inflicted as part of medicine. Adults can make a conscious decision to be endure pain and fool themselves into thinking it is of benefit. No pain, no gain. Animals can make no such choice.

For example consider sea turtles, who, apparently, are subjected to all sorts of nonsense at the New England Aquarium including acupuncture and laser therapy. As is obvious, I am no veterinarian, the only animal of which I have any understanding of anatomy and physiology is a human, but even with that background it is remarkable what is reported from New England. I used to say the ‘B’ students went into journalism; given the credulous reporting perhaps the standards have been lowered. They certainly have for marine biologists and veterinarians, who are evidently shortchanged in their education.

Several hundred sea turtles were washed ashore in New England after a severe storm. Hypothermic, injured, infected and malnourished, they were transferred to the New England Aquarium for care. It sounds like the animals were quite ill.

Some animals were not getting better rapidly enough with conventional medicine. Conventional medicine: based on known reality. The application of physiology, biochemistry, anatomy, epidemiology, etc to disease that has led to astounding increases in life expectancy and relief from innumerable diseases that plagued humankind.

So they decided to inflict a pair of fantasy based, I mean alternative, therapies on some of the turtles. Alternative: not based on physiology, biochemistry, anatomy, epidemiology, and has never had an impact on any important disease, ever.

At first I read the headline (with the obligatory pun) ”Slow pokes: Acupuncture helps hypothermic turtles” as the acupuncture was being used to help hypothermia, which made me laugh. Turtle thermoregulation is complex but just moving them from the cold sea to a warm lab should raise their temperature. But then I realized I misinterpreted the headline. Acupuncture was being used as ineffective therapy for conditions other than hypothermia.

To summarize acupuncture, a topic discussed at length in this blog, its basic principles, those of meridians and chi, are fictional. I tried to find a meridian map of turtles and failed. I found a pig, a cat, a dog, a cow and a horse diagram, but no turtle. Not that it matters, since the meridians are fantasy. The horse, which has no gallbladder, does have a gallbladder meridian, although it conveniently has nothing to do with the gallbladder:

Although the horse does not have a gall bladder organ as such, the meridian is the same as in the human, and it has a lot to do with the integrity of ligaments especially in the hips and pelvis.

Like I said. Fantasy anatomy and physiology.

I note again that on every human and animal acupuncture map there are no meridians or puncture points in the genitalia. Ironically no important life energy runs through the reproductive organs, perhaps explaining why there is no acupuncture-based (or alternative therapy of any kind for that matter) birth control, although a few needles in the genitalia could certainly have a negative effect on reproduction.

Acupuncture does not have any effect on physiological processes outside of those that determine perception. It doesn’t matter where you put the needles, or even if you use needles. Twirled toothpicks have the same effect. Acupuncture only has effects on subjective outcomes and only then if the receiver is a believer and thinks they are receiving acupuncture. I am always amused by those who note sticking a needle into flesh yields a pain response:

The mechanisms underlying pain relief from insertion of needles are unknown, but it has been suggested that it may involve recruitment of the body’s own pain reduction system, possibly attended by an increased release of endorphins, serotonin, norepinephrine, or gamma-aminobutyric acid.

Gee, acupuncture does cause the physiologic effects one would expect from the noxious stimuli of being poked with a needle. Or hitting one’s toe with a hammer.

Acupuncture does not, as the report says,

…reduce stress, increase blood flow and boost the immune system.

Can an animal have a response to a therapy whose entire result is dependent on higher-level cognitive functions that convince the receiver they are improved? The same effect as your mother kissing your injury to make it better? I am, well, skeptical.

In the photographs the turtle looks nonplussed, although they appear to be holding the poor animal so it cannot escape. But then, every turtle in every picture looks nonplussed. Expressive faces are not in the reptilian repertoire. Usually. Not like some dogs who, to my anthropomorphizing eye, do not look happy being stuck with needles.

I am a very ill turtle. Infected, injured, starving. I have been hauled out of my usual environment, taken out of the water, held down on a table by enormous creatures who are sticking me with needles. I would think that the turtle would, in its tiny ‘I don’t want to get eaten’ brain’, be having the turtle equivalent of NONONONONONONONONO I DON’T WANT TO DIE.

But that’s probably just me who thinks perhaps the whole process of worthless needling would only be stressful for the turtle.

The turtle gets combined reality and fantasy based therapies and gets better, the fantasy based therapy gets some of the credit:

Dexter and Fletcher Moon have already had three acupuncture sessions, scheduled once a week, said Merigo, who broke into a broad smile as she described their improvements over the past three weeks.

“These two turtles really had very limited limb use and they weren’t eating. We are seeing improved limb use and improved appetite,” Merigo said. “They are eating on their own, which is fantastic.”

McManus, the acupuncturist, was restrained when describing her reaction to the results.

“It makes me feel very happy,” McManus said. “Acupuncture is not alternative to conventional medicine – they are also receiving Western treatments as well, but the fact that it can work in conjunction with the other treatments they are getting makes me very happy.”

Although the stress of being punctured may have slowed their recovery, it is the usual mistake of crediting effects where there is none.

It was nice that, unlike most acupuncturists, animal and human, the practitioner is using gloves, although everyone appears to wear gloves when handling the turtles.

I am extrapolating from humans and am probably in error when applying what I know to turtles. When humans have severe pneumonia or other severe infectious diseases or trauma, like these turtles, the inflammatory response may be followed by an anti-inflammatory response. A week or two into their hospitalization, a patient may have an increased risk of infection, not only from all the interventions but also because they are at an immune nadir. The greater the initial insult, the greater the subsequent immune dysfunction and risk of infection. Stress is bad.

Take the stress of the initial insult, the infections and malnutrition, being held down and poked with needles and then, with new holes in your hide, being tossed in bacteria-laden salt water. Can’t be good.

Years ago I was sitting in the wards of a hospital in LA when a patient started yelling in pain. The surgeon had ordered sugar for an open wound and the cafeteria had sent up salt by mistake, making the aphorism all too real. I doubt the needles were causing enough damage to the hide to sting when placed back in the salt water, nor to allow the bacteria in the water a chance to find a toe hold (pili hold?) but who can say? Yertle ain’t talking and, like all turtles all the time, looks unfazed.

The preponderance of data suggests that acupuncture effects are almost entirely in the mind of the beholder. The well-designed studies demonstrate that the effects are due almost entirely to bias and are clinically trivial. A placebo effect, the archetype of which was in Penn and Teller’s episode on magnetism. A gutter downspout was bent into the shape of a giant magnet and guess what? The patient had an effect from the fake therapy. That is the basic mechanism of all alternative medicine, including acupuncture.

I went searching the Pubmeds for animal clinical trials of acupuncture and found little, although human trials are animal trials.

Acupuncture being the needling equivalent of faux magnets makes experiments and therapies on animals a little discomforting. There are many animal models for acupuncture and I would wonder if they cross the ethical Rubicon. Is it OK to do studies on animals when the prior plausibility of efficacy is as close to zero as one could want and well-done clinical trials show effects are limited to higher cognitive abilities the animals lack? Is it OK to poke a turtle to induce a marginal placebo effect when it lacks the higher functions to generate such an effect? At some level are not all animal acupuncture studies animal abuse? I wonder.

Animal acupuncture raises other questions: are the rat, dog or turtle meridians the same as humans? If so, why? Genetics? Is the chi same? If so, why? Does a species as evolutionarily removed from humans as a sea turtle have the same response to acupuncture? Does the shell not have any acupuncture sites? If not, why not? It appears from the pictures on the web they only target the soft structures. If human meridians map onto reptiles, are they not missing important sites hidden under the shell, leading to misaligning the energy flow, like only balancing two tires on a car? Of course, asking reality-based questions about acupuncture is like asking about the genetic differences between Orcs, Elves, and Hobbits. It is all fiction.

At some level I can understand trying acupuncture as it has a certain cachet in popular culture, albeit an undeserved one. Most people are not going to wander to the pages of SBM looking for a critical appraisal of acupuncture. But lasers? Really? Laser therapy is nuts, unless you like to get your therapeutic interventions from advertising copy:

When all the results were in it turned out this turtle has a systemic infection. We started treating for the infection but the swelling did not seem to diminish. As we continued the antibiotics we also started using a laser for the edema (swelling) of the joint area.

How does the laser therapy work?
I found this at the Companion Therapy Laser website:

The Companion therapy laser system sends photons, or packets of light energy, deep into tissue without damaging it. These photons are absorbed within the mitochondria of the cells and induce a chemical change called “photo-bio-modulation”. This light energy then inspires production of ATP in the cell. ATP is the fuel, or energy, cells need for repair and rejuvenation. Impaired or injured cells do not make this fuel at an optimal rate. Increased ATP production leads to healthier cells, healthier tissue, and healthier animals.

Show of hands. Does this modified photosynthesis make sense to anyone? I guess the biochemistry of turtles resembles plants more than I suspected. And why did it make sense to the veterinarians at the New England Aquarium?

The closest explanation I could find of this bizarro statement was:

ATP production, according to Kremer’s research, is not based on chemical energy release, as taught in universities today, but rests on the absorption of photons of light from the zero-point quantum medium.

Or for those who prefer their gibberish more science-y:

Biochemistry and medical science have failed to this day to explain the function of the adenine groups of ATP as no biochemical reaction with this adenine ring molecule is shown. However, an understanding can be gained, within the framework of the cell symbiosis concept, from the biophysical attributes of light absorption of the adenine group. All essential components of mitochondrial cell respiration are light absorbing molecules with characteristic “frequency windows” of absorption maxima from nearly UV spectrum to the longer wave yellow/orange spectral range of visible light up to ca. 600nm. Yet the source of the electromagnetic energy is not sunlight. In fact a low frequency pulsating electromagnetic field is induced by the constant flow of uncoupled, paramagnetic aligned electrons in the respiratory organelles. The electromotive power generated by this process is catalytically enormously strengthened by the enzyme complexes of the respiratory chain (acceleration factor10¹⁷). This effects an interaction between the electrons and the protons likewise aligned parallel to the induced magnetic field dependent on the strength of the magnetic field between the antiparallel aligned electrons and protons. This process produces a quantum dynamic transfer of information via photon exchange energy. The source of photons is ultimately fluctuations of resonance frequencies of the physical vacuum (zero-point energy field). The transferred information is stored in the spin of the protons that proceed to the ATP synthesis complex via proton gradients. There the resonance information is transferred by a unique rotation system to the adenine group of ATP whose electrons can move freely in the alternating double bonds of the ring molecules. The ATP serves as an “antennae molecule” for the reception and relaying of resonance information from the “morphogenetic background field.” Human symbiosis is consequently not a heat power machine but a light frequency modulated information transforming medium. All the time this cell symbiosis is resonance coupled with the lowest not yet materialized energy status (physical vacuum as inexhaustible “global information pool”).

I suspect the laser they used is not producing a zero-point quantum medium. As to why they further stressed the turtle with useless laser therapy, I cannot say. The internet said it would help, I suppose. In the photos the turtle has the same stoic expression that marks the species, but I can’t imagine that from the turtle perspective the process is any less terrifying than a shark coming at them. Three large animals holding it down, preventing flight or fight and flashing them with a worthless laser.

I just hope the laser unit was donated, as they cost $18,900 to $27,900 depending on the model. My fish would be fried if I was a member of the aquarium and saw that they wasted money on a laser therapy.

I am grateful they saved the turtles but I hope I do not come back as a turtle in the next life. Cold, starving, injured and infected, thrown from the sea, held down to prevent escape then poked with needles and flashed with lasers. Beats dying on the beach, but I hope my caregivers have a little more sense and education.

*I know, a stretch, but I so wanted the acronym PETA.

This is impossible. You cannot “reposition” tissues and organs of the human body by external manipulation.

Why does this tell us everything we need to know about these naturopathic doctors and why they shouldn’t be licensed in Pennsylvania? For one thing, this is no mistake a bill draftsman made in understanding what naturopathic practice includes. House Bill 612 was obviously drafted by naturopaths. That means naturopathic doctors actually believe they can “reposition” your body’s tissues and organs. And that speaks to their poor education and training. They don’t even understand basic anatomy.

For another, it tells us naturopathic doctors reject evidence-based medicine as a standard of practice. There is no evidence that this “repositioning” of organs and tissues is beneficial for any condition or disease, even if they could do it in the first place, which they can’t.

And for yet another, this certainly calls into question their understanding of the disease process and their diagnostic skills. One has to wonder exactly what health problems they think these purportedly out-of-place organs are causing. And how do they go about determining which organs are out of place and where they should go? Or when they have been successfully returned to their proper position? Again, this should raise alarming questions in the legislators’ minds about their education and training.

Yet, if this bill passes, naturopathic doctors will become state-licensed providers of primary care. Yes, primary care providers. It says so right there in the definition of “naturopathic medicine.” (Mark Crislip thoroughly debunked the notion of naturopaths as primary care doctors in a post deconstructing a naturopathic white paper on the subject.) This will allow naturopaths to “reposition” the organs and tissues of unsuspecting Pennsylvania citizens, possibly claiming a right to insurance reimbursement for the privilege, another problem with this bill we’ll get to later.

Of course, this fantasy treatment could be excised from the bill. But that would do nothing to resolve the substantial questions about their education, training, and abilities to perform the most basic tasks of primary care, or any other form of evidence-based healthcare, or even reality-based health care for that matter. And there are plenty more naturopathic fantasy treatments allowed by House Bill 612 even if you get rid of this one. We’ll get to a few more in a minute.

This affinity for fantasy treatments among naturopathic doctors is explained in the first part of the bill, Section 103, which defines “naturopathic medicine” as:

a system of primary health care practiced by doctors of naturopathic medicine for the prevention, diagnosis and treatment of human health conditions, injuries and diseases and that uses education, natural medicines and therapies to support and stimulate the individual’s intrinsic self-healing processes.

This is the central fallacy of naturopathic practice, one that sounds appealing but is at its core meaningless. “Intrinsic self-healing processes” is simply another way of referring to vitalism, a long-discredited, pre-scientific notion that bodily function is controlled by some incorporeal force unknown to science or medicine. As Steve Novella pointed out, vitalism was a placeholder, used to explain bodily functioning until biology, chemistry, physiology and anatomy developed science-based explanations for these functions. Except for naturopaths, who’ve remained stuck in vitalism.

Naturopaths have tried to backfill a scientific explanation into the pre-conceived notion of an “intrinsic self-healing process.” When they can convince a group of respectable physiologists (say, those holding faculty appointments at major research universities or medical schools) that their explanation is credible, I’ll believe it too. Until then, I won’t and no one else should either.

Of course, when you start from the premise that the body is governed by this non-existent life force pretty much anything that you can fit into that paradigm will fly, and naturopaths have used this to their full advantage in devising diagnoses and treatments no responsible medical doctor would agree with. Hence organ repositioning.

More nonsense

Other implausible and unproven treatments either mentioned specifically in the bill or permitted under its broadly defined categories, such as “naturopathic physical medicine,” include all those mentioned in David Gorski’s summary of naturopathic practice:

If I’ve pointed it out once, I’ve pointed it out a thousand times. Naturopathy is a cornucopia of almost every quackery you can think of. Be it homeopathy, traditional Chinese medicine, Ayurvedic medicine, applied kinesiology, anthroposophical medicine, reflexology, craniosacral therapy, Bowen Technique, and pretty much any other form of unscientific or prescientific medicine that you can imagine, it’s hard to think of a single form of pseudoscientific medicine and quackery that naturopathy doesn’t embrace or at least tolerate.

This bill will also allow naturopathic doctors to pump patients full of unnecessary vitamins and minerals intravenously, and use other favorite and potentially dangerous treatments such as peat baths, colonic irrigation (which the Journal of Family Practice warned against in this 2011 article), fasting and severely restricted diets, and recommendation of dietary supplements of unknown safety and effectiveness, to name a few. Naturopaths will be able to diagnose diseases they’ve invented, such as chronic yeast overgrowth, ubiquitous toxins (that no one else seems to be able to find), and food “sensitivities” (again, that no one else seems to be able to detect).

In addition to what we might politely refer to as their “unique” diagnoses and therapies, N.D.s will also be able to use some conventional diagnostic means such as mammography, X-rays, and lab tests. They will be able to perform physical exams, including well baby checkups and vaginal and proctologic exams. But permitting naturopaths to do these things and their knowing what they are doing are two entirely different things.

Naturopathic education, such as it is

I trust no one could get to this point in reading and think that naturopathic doctors have sufficient education and training to diagnose and treat patients. Unfortunately, all naturopathic licensing bills make the mistake of assuming their education and training is somehow the equivalent of, or at least close to, that of a medical doctor.

House Bill 612 makes this same unfounded assumption. An applicant to practice as a naturopathic doctor must have “completed a doctorate-level naturopathic medical program” accredited by an accreditation agency recognized by the U.S. Department of Education and must pass an examination administered by the North American Board of Naturopathic Examiners (The “NPLEX”). Let’s see what this education, accreditation and examination are really like. This is ground we have covered before at SBM, but it bears repeating because I have never seen a shred of evidence that the sponsors of this bill, or any state naturopathic licensing bill, have ever set foot on the campus of a naturopathic school and critically evaluated its programs, or looked at one of these licensing exams or researched the requirements for becoming an accrediting agency. All the bills I’ve read simply parrot language obviously supplied by naturopaths.

So here’s what’s actually going on: These naturopathic “medical” schools have simply appropriated the word “medical” and pasted into the school’s name. There are five of these schools in the U.S. and two in Canada. Unlike medical schools, where students must score well on the grueling MCAT to be accepted, there is no entrance exam. All are private and none are part of a mainstream public or private university or college. Unlike real medical schools and science departments at other colleges and universities, their faculty members have published little and do virtually no research.

The Council on Naturopathic Medical Education has been approved by the U.S. Department of Education to accredit naturopathy schools. While naturopaths pushing licensing seem to want to use this as a sort of federal government seal of approval, it is nothing of the sort. The goal of the Department is to ensure that accredited schools meet certain financial, disclosure and similar requirements in order to protect prospective and current students from such problems as financially unsound institutions or schools that are dishonest about post-graduation job opportunities. It is also designed to determine which schools can take advantage of student loan programs. The accreditation program is not designed to protect the public health by ensuring these schools instruct their students in the use of safe and evidence based healthcare. It does not mean that graduates are capable of practicing primary care, nor of providing health care at all. The Department does not vet course content. That is simply not the function of the accreditation programs.

Nor does passing the NPLEX exam guarantee the delivery of quality healthcare by naturopaths. This somewhat mysterious document seems to be carefully protected by naturopaths. No one outside of naturopathy appears to have seen a copy or reviewed its contents. In fact, even when Kimball Atwood asked for a copy as part of a state-appointed commission reviewing naturopathy licensure for Massachusetts in 2002 he couldn’t get one. (Naturopaths are still not licensed in Massachusetts, even after trying numerous times. I think they are up to a dozen attempts, maybe more.) No person voting on House Bill 612 should miss reading Dr. Atwood’s series on naturopathy, which you can find referenced here.  It would be unconscionable to vote without this information.

Let’s also look at a huge gap in their training, which we’ll discuss in the context of their claims to being “primary care” providers.

Primary Care Practice?

As mentioned, this bill will allow naturopaths to practice primary care. N.D.s would have the same scope of practice as an M.D. or D.O. primary care physician but be limited in some of the therapies they could offer. (For example, they could not prescribe controlled substances.)  They will be able to see, and treat, any patient of any age with any disease or condition, no matter how serious.

Full scope of practice as a primary care physician, including all prescription drugs, is actually the goal of the American Association of Naturopaths. Naturopaths are willing to accept a more narrow scope, as is apparently the case in Pennsylvania, and then return for increased scope once entrenched. They have achieved this in Washington state, including mandatory insurance coverage, with interesting results. Two reviews of insurance claims for naturopathic care revealed that less than 2% of the insured adult and pediatric population made such claims, indicating an extremely low use of licensed naturopathic doctors for health care even where they are fully licensed and covered by insurance.

In defining what a primary care physician does, I turn again to an American Association of Family Physicians definition:

Primary care is that care provided by physicians specifically trained for and skilled in comprehensive first contact and continuing care for persons with any undiagnosed sign, symptom, or health concern (the “undifferentiated” patient) not limited by problem origin (biological, behavioral, or social), organ system, or diagnosis.

Primary care includes health promotion, disease prevention, health maintenance, counseling, patient education, diagnosis and treatment of acute and chronic illnesses in a variety of health care settings (e.g., office, inpatient, critical care, long-term care, home care, day care, etc.). Primary care is performed and managed by a personal physician often collaborating with other health professionals, and utilizing consultation or referral as appropriate.

Note specifically that this bill would allow the N.D. to see and treat the “undifferentiated patient” straight out of N.D. school, with 1200 hours of clinical training.  This training is usually done in naturopathy school clinics where the students typically see patients who have a variety of mild, self-limiting conditions, such as colds and musculoskeletal pain. Compare this to the clinical training medical students must have before they can become board certified in family practice, general internal medicine or pediatrics (the three primary care specialties in medicine). During med school, in the third and fourth year, students see patients in a variety of settings (hospital, office, emergency room) in clinical rotations among a variety of specialists (pediatrics, surgery, oncology, obstetrics etc.). After graduation they also spend an additional three years, at about 80 hours per week, in clinical training. For an idea of what they do during that residency, you can find a broad outline of the curriculum for a three-year family practice residency at Penn Medicine on its website.  Again, naturopathic doctors do not have this training.

Naturopathic treatment of pediatric patients is especially troubling because of naturopathic opposition to vaccination. Studies have found:

• A negative influence of naturopaths on mothers’ decision to vaccinate children.
• Consultation with a naturopath significantly decreased the likelihood of receiving a flu shot among women in contact with young children.
• Children in Washington state were significantly less likely to receive recommended vaccinations if they saw a naturopathic doctor, and significantly more likely to be diagnosed with a vaccine-preventable disease if they received naturopathic care.

Forced insurance reimbursement? And other problems.

To add insult to injury, the Affordable Care Act’s non-discrimination provision may require reimbursement of naturopathic health care if naturopathic doctors are licensed. That is certainly what they are aiming for.  And they aren’t shy about making a huge fuss when they aren’t included in physician practice groups because they don’t practice evidence-based medicine.

House bill 612 will require naturopathic doctors to refer a patient to a physician “when the patient is presenting a contraindication to the practice of naturopathic medicine.” I am not even sure what that means. (Based on what we know about naturopathic practice one might argue that pretty much all patients present with a “contraindication to the practice of naturopathic medicine.”) In any case, note that it will be the N.D. who makes the call here. That presents two problems. First, N.D.s already think they are capable of practicing as primary care physicians. Given this overblown view of their abilities, abilities I feel fairly sure I’ve just demonstrated they do not possess, might one not be concerned that they will fail to realize their shortcomings when a patient needs a referral? Second, given their lack of training in diagnosing patients, who could be confident that they will be able to recognize a disease or condition requiring referral in the first place?

Nor should Pennsylvania legislators take comfort in the fact that naturopaths would be regulated by the state medical board. The board can only regulate within the confines of the scope of naturopathic practice granted by this bill. It will have no authority to prevent naturopaths from doing anything the legislature says they can do. In fact, regulation by the medical board will create quite a quandary. How will the board determine, for example, whether a naturopath’s repositioning of an organ fell below the standard of care? How about an injection of vitamins and minerals for “flu prevention”? Or a prescription for homeopathy?

If I were Rep. Mark Mustio, the bill’s main sponsor, or any of the other legislators who signed on as sponsors, I would be furious with the naturopaths for putting me in this position, subject to ridicule for sponsoring such bill. Rep. Mustio can redeem himself, and save his colleagues a lot of embarrassment, by quietly withdrawing House Bill 612 from consideration before it even comes up for a vote before the House Professional Licensure Committee on June 5th.

While this is an effective marketing term, and a useful principle as far as it goes, as a guide to medical practice it is a bit simplistic. It needs to be viewed in the context of the overall medical infrastructure and the net effect specific practices have on the cost and effectiveness of medical care.

A 2012 NEJM editorial by Charles Bardes nicely summarizes the issues. He notes that patient-centered care represents the next step in a general trend (a good trend) in the medical profession over the last half-century:

The British psychoanalyst Enid Balint appears to have coined the term in 1969. She described a form of mini-psychotherapy that general practitioners could provide for persons who had illnesses that were partially or wholly psychosomatic. Her concept contrasted with “illness-oriented care” and meshed well with other critiques of modern medicine’s emphasis on pathophysiology to the exclusion of other means of knowing and treating the patient. Landmarks in this paradigm shift have included Engel’s proposal for a biopsychosocial model that would “take into account the patient, the social context in which he lives, and the complementary system devised by society to deal with the disruptive effects of illness”; Cassell’s transcriptions of clinical encounters, which provided an empirical basis for understanding the doctor–patient relationship; and Kleinman’s definitions of “disease” and “illness” as contrasting the doctor’s understanding of disordered biomechanics with the patient’s subjective experience of feeling sick.

He concludes, and I agree, that the patient and the physician are both the central actors in the doctor-patient interaction, but that there are interested third parties, like insurance companies, that also affect decision-making.

The optimal balance between the doctor, the patient, and third parties has been a longstanding debate within medicine. Thoughtful engagement on this issue, it seems, has resulted in real progress. The old paternalistic model, in which the patient simply did as they were told without meaningful consultation, has largely been replaced with a more cooperative model and one that properly grants to the patient informed consent.

Unfortunately, complexity intrudes on this comfortable relationship. We have to recognize that we are somewhat at cross-purposes. Optimal medical practice would maximize several outcomes simultaneously — the patient experience, doctor and patient autonomy, medical outcomes, and cost effectiveness, to name the most important. The problem is, you can’t always get all of these things to an optimal degree at the same time.

Medical outcomes, for example, are optimized when quality control measures are put into place, but these measures often reduce patient and doctor autonomy. Cost constraints also may come at the expense of patient experience and doctor-patient autonomy (we hope not medical outcome, but realistically, this also).

Whenever we push or pull on this entangled system, we have to consider the net effects on all the other aspects.
A recent study, for example, looked at the effects of patient participation in decision-making. This was a survey of 22,000 patients admitted to a hospital system, asking them about their desire to be informed about decision-making, and also to participate in medical decision-making. Nearly all of those surveyed responded that they wanted to be informed, but more than 70% also wanted to leave the medical decision-making to their doctors. The rest wanted to participate in the medical decision-making. The researchers then linked the survey results to length of stay and cost of care outcomes and found that:

“Preference to participate in medical decision making increased with educational level and with private health insurance,” the authors note. “…patients who preferred to participate in decision making concerning their care had a 0.26-day longer length of stay and $865 higher total hospitalization costs.”

A recent review of research into health outcomes with patient participation was inconclusive — the existing studies are scant and of poor quality. So this question remains an unknown.

There appears to be a lot of support for shared decision-making as an idea, and most of the published studies focus on how to improve shared decision-making. We need more research, however, on what the actual effects of this shift in practice will have.

I find it interesting that over the same course of time, the last few decades, there has been a shift away from physician experience as the ultimate arbiter of decision-making, to evidence-based medicine, practice standards, and quality control. The evidence is pretty clear that evidence-based guidelines produce better outcomes than physicians relying on their own experience and judgment.

The rising costs of health care make all of these issues much more acute. Can we afford a philosophical shift to greater patient involvement in decision-making when it is associated with higher costs and we don’t really know the net effect on medical outcomes but there is good reason to suspect that it may be negative (when compared to evidence-based standards)? It seems to me we should more thoroughly explore these outcomes before we institute major infrastructural changes.

Meanwhile, what is the best synthesis of the evidence that we do have? The good news is that what most patients want, and how most physicians practice today, are also non-controversial in terms of cost and medical outcome. Patients want to be well-informed, and informed consent is the current standard of care. There does not appear to be any downside to informed consent.

Where it gets tricky is the proper balance of actual decision-making between the doctor, the patient, the insurance company, and other mechanisms of quality control (such as official practice guidelines). The evidence supports heavy reliance on rigorous evidence-based guidelines as much as possible. The health care system and patients would benefit from exploring ways to enhance compliance with such guidelines.

Insurance companies, in my opinion, are a double-edged sword. They can actually reduce health care costs by avoiding unnecessary tests and treatments (when they follow evidence-based guidelines) but can also hamper the practice of medicine with short-sighted rules and requirements and onerous procedural hurdles.

Patient participation in decision-making remains a complex question. Clearly there is no one model for all patients — patients have different desires in this regard, and varying healthcare literacy. Keep in mind, an adult competent patient is 100% in control of their own health care decision-making. The ultimate decision is always theirs. What we are talking about is how the patient and physician should interact.

For example, should a physician present a recommendation to their patient, or a list of options, or both — this is what I recommend, but here are some other options and their strengths and weaknesses. This hybrid approach is what I do and what I find most of my colleagues do, individualized to the patient. There is an art to this that cannot be captured in any algorithm.

One huge advantage to patient participation in the decision-making process is that they are more likely to be compliant with the treatment plan. The best recommendation is wasted if the patient does not follow it. Patients are often reluctant to contradict their physician if a strong recommendation is made without consultation, but then they will not follow the recommendation and will seek a second opinion (at extra cost to the system).

To the extent that patients ask for or the physician offers options, it is necessary to give accurate information about risks and benefits. Patients often need counseling if fear, anxiety, or hidden misconceptions are causing them to make decisions that depart significantly from what the evidence suggests is the best course. This, of course, all depends on what the patient’s goals are, and this is always a good place to begin (rather than assuming what their goals are).

All of this complexity is probably why existing evidence is inconclusive — it is very difficult to capture all of this nuance in a clinical trial. But still, we must try. The stakes are simply too high to make major changes to the practice of medicine based upon feel-good philosophy without the backing of rigorous evidence.

Times have changed. Today we are more lenient about cholesterol in the diet, less concerned about total fat and saturated fat, and more concerned about trans fats. While many major health organizations still discourage its use, coconut oil has not only been rehabilitated in the public mind, but all kinds of health benefits are being claimed for it.

The fats in coconut oil
Coconut oil is high in saturated fats; it contains more saturated fatty acids than any other non-hydrogenated oil. It is stable and has a long shelf life. It is used in movie theaters to pop popcorn and in South Asian cuisine for dishes like curries. A hydrogenated version of coconut oil is an ingredient in non-dairy creamers. Much of the research done on coconut oil studied hydrogenated or partially hydrogenated forms. According to an article in the New York Times:

Partial hydrogenation creates dreaded trans fats. It also destroys many of the good essential fatty acids, antioxidants and other positive components present in virgin coconut oil. And while it’s true that most of the fats in virgin coconut oil are saturated, opinions are changing on whether saturated fats are the arterial villains they were made out to be. “I think we in the nutrition field are beginning to say that saturated fats are not so bad, and the evidence that said they were is not so strong,” Dr. Brenna said.

Coconut oil contains lauric acid, which raises both HDL and LDL cholesterol levels. This may improve the cholesterol profile, although there are concerns that it may promote atherosclerosis by other means. Virgin coconut oil contains medium-chain triglycerides, which are not as risky as some other saturated fats.

Health Claims
Any number of health claims have been made for lauric acid. According to proponents, it’s a wonder substance with possible antibacterial, antimicrobial, antiviral properties that could also, in theory, combat HIV, clear up acne and speed up your metabolism. Researchers are skeptical:

“There are a lot of claims that coconut oil may have health benefits, but there is no concrete scientific data yet to support this,” said Dr. Daniel Hwang, a research molecular biologist specializing in lauric acid at the Western Human Nutrition Research Center at the University of California, Davis.

The hype comes from unreliable sources. Joe Mercola says it is the smartest choice for cooking, is good for your heart, contains the kind of fat found in mothers’ milk, enhances immunity, and helps with weight loss by stimulating metabolism. And of course he sells it. Dr. Oz says it is a heart healthy food that helps resist viruses, bacteria, yeast, fungi, and candida; boosts thyroid function; improves blood sugar control and reduces the need for insulin; increases energy and endurance; increases digestion and improves absorption of vitamins; lowers cholesterol; helps control weight; has anti-aging effects; is good for skin and hair; and is quite safe to take in reasonable amounts. The Wellness Mama website lists 101 uses for coconut oil, including treating sunburns, athlete’s foot, Alzheimer’s disease, nasal allergies, arthritis, insomnia, autism, heartburn, hemorrhoids, depression, acne, cellulite, mosquito bites, and lice.

Alzheimer’s Disease
The Wellness Mama website provides a link to a reference for Alzheimer’s disease but it is only a case study showing that the writer’s husband improved and was able to draw a more accurate picture of a clock after adding coconut oil to his diet. Natural News says coconut oil can prevent and reverse Alzheimer’s. Naturopath Bruce Fife has several books touting the benefits of coconut oil and coconut water. One title claims you can “Stop Alzheimer’s Now!”

A clinical query search for “Alzheimer’s coconut oil” on PubMed yielded no results. Snopes has evaluated the claims for coconut oil and agrees that “there are no peer-reviewed articles addressing research on coconut oil as a treatment for Alzheimer’s disease.” Even the Alzheimer’s Association says: “A few people have reported that coconut oil helped the person with Alzheimer’s, but there’s never been any clinical testing of coconut oil for Alzheimer’s, and there’s no scientific evidence that it helps.”

Coconut water
The liquid inside a coconut is being promoted as a sports drink and as a miracle food. They claim it is so compatible with the human body that it can be infused directly into the bloodstream (indeed, it is likely sterile and there are reports of its use as an intravenous fluid substitute in emergencies when medical saline was unavailable). As with coconut oil, there are a few suggestive studies in animals and test tubes, but no credible evidence for clinical benefits in humans.

Conclusion
Coconut oil is probably not as bad as once thought, but it’s no “miracle” food either. It is probably safe to use it in reasonable amounts to replace other oils in the diet, and doing so may have a favorable effect on lipid profiles; but it’s not clear whether that will actually reduce the risk of cardiovascular events. There is no justification for adding it to the diet on top of the usual consumption of other fats. There is no credible evidence to support any of the many health benefits claimed for using it as a supplement.