A rumble of discontent is being heard across the dietary supplement industry since a draft guidance document was published last month by the US Food and Drug Administration. In response to the FDA Food Safety Modernization Act signed into law in January by President Obama, the FDA was required to produce a documents requiring dietary supplement and foods companies to submit safety information on any new dietary ingredient (NDI) placed into products after 1994.

The guidance document is open for comments from industry but, when issued, a final rule will require dietary supplement products to file a claim of a New Dietary Ingredient (NDI) for any supplement component that was not part of the diet before 1994. What seems to be riling up the industry is that any change in supplement composition after 1994 will require filing of a NDI disclosure. That is, if you as a manufacturer add more DHA to your fish oil supplement, you have to file a NDI notification.

Stepping back, the goal of the FSMA makes perfect sense: it shifts regulators attention from responding to food contamination issues to preventing them. And because the Dietary Supplement Health and Education Act of 1994 (DSHEA) treats herbal and non-botanical dietary supplements as foods and not drugs, the supplement industry has largely been immune to requirements of prospective demonstration of safety and efficacy. Perhaps the greatest change has been that manufacturing standards have improved greatly since FDA issued a final rule in 2007 on Good Manufacturing Practices for dietary supplements.

But to be sure, the FDA draft guidance on New Dietary Ingredients is a bit complicated. The draft guidance indicates that FDA doesn’t have a reference list of dietary ingredients that could be grandfathered in (i.e., sold before 1994). Instead, companies are required to provide that information. And the NDI notification process is complex, leading to at least one consulting company with NDI experience offering its services. While prospective safety testing is not required, the NDI process requires a reasonable calculation of safety based upon known LD50 values for dietary components in non-human species relative to the intended human dose.

The guidance indicates that FDA will even require companies to produce NDI documentation even if their solvent extraction processes have changed for a product intended to contain the same dietary ingredients.

Regular reader Jeff Engel dropped me a note with links to a spectrum of reactions from dietary supplement advocates. Most have the same type of objections from back in the early 1990s when FDA Commissioner David Kessler indicated that soem regulation was going to be placed on the supplement industry, efforts that led to the rather watered-down DSHEA legislation.

For example, Byron Richards spends most of his screed arguing that the FDA is putting in these regulations because of the influence of Big Pharma. There, the straw man is out in force, with much of the article citing challenges in the drug industry as driving FDA to kill the dietary supplement industry.

The FDA Law Blog (not an FDA site) made the interesting observation that FDA measures to regulate the dietary supplement industry have come in two 17-to-18-year cycles.

The Life Extension Foundation goes even further calling the draft guidance, “FDA’s Latest Attempt to Ban Your Dietary Supplements”:

It appears that the FDA is claiming that dietary supplements are unsafe, and in order to “protect consumers” the agency must place a stranglehold on the dietary supplement industry by requesting exorbitant safety testing. These ludicrous safety thresholds are in excess of those required by pharmaceutical drugs despite studies showing supplements are far safer than drugs. [The emphases are theirs - DJK]

I hate to tell the LEF folks this but drug companies have themselves been saddled with terrific troubles in having to demonstrate that long-marketed drugs are actually approved products. The Unapproved Drugs initiative revealed that many formulations of recognizable drugs (codeine, ergotamine, nitroglycerin) were never formally approved as drugs. In the last two years, FDA has fined companies for $20 million to more than $300 million dollars for selling “old” drugs without providing evidence that they were actually approved. One of the best known of these drugs is the expectorant, guaifenesin. The fact that big companies were opened the door for then-small company Reckitt Bensicker to gain over-the-counter approval for the drug and the highly successful launch of Mucinex products. Mucinex has benefitted further by FDA’s subsequent action against companies selling timed-release versions of guaifenesin – again, the Mucinex products are the only ones thus far with FDA approval.

My view is that the FDA is consistently applying rules across the industries and that the dietary supplement industry is still treated far, far less stringently. Remember, dietary supplement companies do not have to demonstrate effectiveness of their products. Yet they are still marketed with thinly-veiled claims for “effectiveness.”

NutraIngredients-USA.com has a good roundup on industry reactions. One of the more reasonable discussions includes an interview with Mark Blumenthal, executive director of the non-profit American Botanical Council (ABC), an organization that actively cultivates input from top academic pharmacognosy experts. Blumenthal makes a very good point on whether a biochemical supplement extracted from a plant vs. made by fermentation is truly different – what about synthetic vitamin C?

“ABC is willing to concede, in principle, that synthetic ingredients might be considered NDIs ipso facto. However, we add one reservation: Chemical synthesis makes a ‘synthetic’ material, per se. However, a process like fermentation creates an ingredient via biosynthesis, and this is the source of numerous dietary ingredients.

“While ABC prefers to focus on natural plant materials, plant extracts, and plant-derived compounds, we are aware that some plant-based dietary ingredients are now produced – for the sake of cost and efficiency – via fermentation.

“L-theanine may be an example, where the resulting ingredient made via fermentation is claimed to be chemically identical and, presumably, biologically similar or identical in action to the L-theanine found in green tea leaves.”

For now, those objecting to the proposed FDA guidelines can submit their objections, as did Bill Sardi who posted his letter at his Knowledge of Health website.

By the end of reading through all of the confusing information necessary to put together this post, I’ve come to at least one conclusion: I doubt very much that these rules will affect what I’ve seen as the greatest threat to public health with dietary supplements: the adulteration of supplement products with prescription drugs.

What do you think?

<!--<!--

What do Tylenol, Excedrin Extra Strength, Nyquil Cold & Flu, Vicodin, and Anacin Aspirin Free have in common? They all contain the drug acetaminophen. Taking multiple acetaminophen-containing drugs can be risky: while acetaminophen is safe when used at appropriate doses, at excessive doses, it is highly toxic to the liver. Take enough, and you’ll almost certainly end up hospitalized with liver failure. Acetaminophen poisonings, whether intentional or not, are a considerable public health issue. In the USA, poisonings from this drug alone result in 56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year. [PDF] This makes acetaminophen responsible for more overdoses, and overdose deaths [PDF], than any other pharmaceutical product.

Last week, Johnson & Johnson announced that it’s lowering the maximum recommended daily dose for its flagship analgesic, Extra Strength Tylenol, from 8 tablets per day (4000mg) to 6 tablets per day (3000mg). Why? According to the manufacturer,

The change is designed to help encourage appropriate acetaminophen use and reduce the risk of accidental overdose.

What’s an appropriate acetaminophen dose?

The dosage of any drug is based in part on its therapeutic window — the difference between the dose needed to cause a beneficial effect, and that which causes unwanted effects. In the case of acetaminophen, the limitation is how acetaminophen is eliminated from the body. Once ingested, acetaminophen is quickly absorbed from the gastrointestinal tract into the bloodstream. About 25% of the drug is immediately metabolized by the liver because of the first-pass effect. And the liver acts on the rest as it circulates through the body. Liver metabolism involves converting acetaminophen into substances (metabolites) that are easier to eliminate by the kidneys — and that’s where the risk of toxicity comes from.

Multiple liver enzymes can act on acetaminophen. The main metabolic pathways, sulfation and glucuronidatation, transform acetaminophen into harmless products that can then be excreted in the urine. In overdosage situations, however, these pathways become saturated, and eventually exhausted — so other metabolic pathways kick in. Unfortunately, these other pathways create toxic versions of acetaminophen that attach to, and destroy, liver cells. So at normal doses, acetaminophen causes no toxicity. At high doses, liver injury is almost a certainty. This chart illustrates the science of metabolism and toxicity: blue is good, and red is bad.

(Paracetamol is another name for acetaminophen.)

What leads to poisonings?

While many acetaminophen overdoses are intentional poisonings, a substantial number of cases are unintentional. In adults, the maximum recommended daily dose has traditionally been 4000mg. That’s eight extra-strength (500 mg) Tylenol tablets, or twelve regular-strength (325 mg) tablets.  A single dose of 7,500mg can cause liver injury, and consumption of 10,000 to 15,000 mg can be fatal. It’s important to note that 4000mg is the maximum daily dose from all sources — and that’s where many accidental poisonings come from. Combining cough and cold products, or taking too many painkillers, and bumping your total daily dose slightly over 4000mg in a single 24 hour period is unlikely to cause any harm. But take enough at once, or take regular moderately excessive amounts (say in the case of someone abusing Vicodin, Percocet, or even cough syrup), and unplanned overdoses can result. Chronic consumption of acetaminophen is is not uncommon: I’ve seen patients taking well over a dozen Percocet per day, for weeks or months — pushing acetaminophen consumption into the toxic range. They are surprised when I tell them my primary concern isn’t the narcotic consumption, but rather the huge amount of acetaminophen they’re consuming daily, which is almost certainly damaging their liver.

In 2009, the FDA held a series of hearings to address this issue of acetaminophen toxicity. (Harriet Hall covered it then.) It’s not a problem unique to J&J’s Tylenol. Acetaminophen is in hundreds of prescription and non-prescription products, and is used at all stages in life, starting in infancy: 28 billion doses of acetaminophen were consumed by Americans in 2005. Besides fever, headaches, and other everyday aches and pains, acetaminophen is the usual first drug of choice for treating chronic conditions like osteoarthritis. And hydrocodone-acetaminophen combination drugs (e.g., Vicodin) are among the most frequently prescribed drugs.

The FDA’s hearings resulted in an  expert panel making several recommendations, including advice that the maximum recommended daily dose of acetaminophen should be reduced, to lower the likelihood that patients will exceed a safe daily dose. This recommendation was made despite some advice (PDF) to the contrary. So while there remains some debate about the toxic dose, it was felt this measure would reduce the incidence of poisoning.

Unexpected consequences?

From a public health perspective, we should try to reduce the risk of acetaminophen poisoning. Cutting the maximum daily dose of Tylenol Extra Strength should reduce the risk of poisoning in the event it’s combined with other acetaminophen-containing drugs. There’s even some evidence that suggests that 4000mg per day for prolonged periods may cause elevations in liver enzymes — data which led to the American Liver Foundation recommending (PDF) the maximum chronic dose should be 3000mg per day. So there may be a clinical rationale, too. But changing the maximum dose won’t mean much to consumers that don’t read the label. And from the individual patient perspective, forcing a hard maximum of 3000mg per day for all patients may have unwanted consequences, too. To start, you may need to take 650-1000mg of acetaminophen at a time to achieve analgesic effects beyond placebo. So achieving prolonged pain control, while also not exceeding 3000mg per day, may be difficult. Yet higher doses could be preferable to alternatives, such as anti-inflammatory drugs, or narcotics, especially when used regularly, for chronic conditions. So will the dose change have any measurable effect? Here’s your control group: The maximum dose isn’t changing in Canada.

Conclusion

Acetaminophen is a remarkably safe and effective drug when taken at appropriate doses, yet it is also the cause of hundreds of deaths per year. Manufacturers are now acting, based on the FDA’s advice, with the intent of reducing the chance of accidental poisoning. The pragmatic approach? Read labels and be cautious when combining different over-the-counter drugs. For most adults, keeping daily consumption below 4000mg is the safest approach to minimizing risk.  And in some cases, a maximum of 3000mg may be more appropriate. But these are general approaches, that may not appropriate for everyone. A maximum dose of 3000mg make make sense at the population level, but may be problematic in terms of individual pain control. Regardless of the dose, if you regularly take high doses of acetaminophen, either alone or as a combination of products, a discussion with a health professional to discuss the risks and benefits may be warranted.

<!--<!--

Part of the Complementary and Alternative Medicine (CAM) movement is an attempt to insert spirituality into the philosophy and practice of medicine. Most energy healing modalities, for example, have spiritual underpinnings. At the same time there are many attempts to use science to validate the healing power of faith.  This is also an issue that is very attractive to the media, who love articles and headlines about the power of prayer. In our culture – faith sells.

A recent article in the Detroit Free Press is an excellent example of bad reporting and the sensationalizing of this issue. It does a good job of maximally confusing the issue.

To be clear, SBM is not anti-faith or anti-religion. But the issue of faith in medicine raises two main areas of concern. The first is the misrepresentation of the scientific evidence, both for intercessory prayer and the health effects of faith. The second are the ethical and professional implications of mixing faith with medical practice.

Intercessory Prayer

The Detroit Free Press article makes no attempt to distinguish the various issues with faith and medicine, and confuses them together in a misleading way. Intercessory prayer is, essentially, praying for the health of another person. There have been about a dozen such trials with reasonable design. In most the subjects know they may be prayed for. But of course, none of the trials can control for those who are not part of the study praying for a study subject.

Every time such a study shows a hint of positive results the media have a frenzy of reporting that “science proves faith.” When such studies are negative, the footprint in the media is much smaller. What we find when we look at all the studies of intercessory prayer is the type of scatter of results we would expect from a null intervention – one with no effect at all. A 2009 Cochrane review of intercessory prayer studies concluded:

These findings are equivocal and, although some of the results of individual studies suggest a positive effect of intercessory prayer,the majority do not and the evidence does not support a recommendation either in favour or against the use of intercessory prayer. We are not convinced that further trials of this intervention should be undertaken and would prefer to see any resources available for such a trial used to investigate other questions in health care.

These wishy washy conclusions are essentially saying the evidence is negative. The review was also criticized for its methods and discussion of the results – specifically mixing theological and scientific arguments in the discussion and failing to mention significant flaws of the positive studies. But even with these complaints, the results of the review are what we would expect from a treatment effect of zero.

The results of existing research are not sufficient to rule out a small and inconsistent effect – but medical research is never designed to reach such a conclusion, and not being completely disproved is hardly a sufficient reason to endorse a medical intervention.

Again – to be clear – the point of reviewing the evidence is not to argue that individuals should not pray for their loved-ones who are ill. Rather it is important to accurately report the results of the research that has been done – there is no scientific evidence that intercessory prayer is efficacious. Therefore the scientific evidence cannot be used as a justification for inserting religious faith into the practice of medicine.

The Health Effect of Faith

A completely separate question from intercessory prayer is that of the health benefits of having or practicing faith. This is a much more difficult question to assess scientifically. With intercessory prayer there is a specific intervention that can be isolated as a variable. The variable of faith, however, is very difficult to isolate, and most studies barely attempt to do so at all. Most such studies are retrospective and use surveys or questionnaires to gather data, which are plagued by artifacts.

One such study, highlighted in the recent Detroit Free Press article, looked at 88 patients who had suffered Traumatic Brain Injury in the last 10 years. They found a positive correlation between feeling a personal connection with god and having better rehabilitation outcomes. The authors concluded that personal faith “predicts” a good outcome, and the press release (dutifully reprinted by most news outlets) reported that personal faith improves TBI outcomes.

There are two major problems with this study, however. The first is that the survey process itself is likely to bias reporting. If you ask people about their faith (or that of a family member) and then ask them how they are doing, the answer to the one question is likely to influence the answer to the other.

Second – the study found a correlation only, and was not designed to infer any cause and effect. One possible interpretation is that those who were doing better in terms of their recovery from TBI were more likely, as a result, to feel positive about their connection to god.

Much of the research into the question of faith and health is similarly plagued by such flaws, which makes interpreting the research problematic at best.

However, my reading of the literature on this question leads me to conclude that there is a consistent signal in the noise – having a social network consistently positively correlates with better health outcomes. This can be through reduced stress and better practical and emotional support. Humans are social animals, and we simply do better when we are part of a social network than when we are isolated. Religion can provide a useful social network. Faith and religion itself, however, are not the important variable – it’s the social network.

Further, faith both encourages and may result from a positive and hopeful outlook, which can certainly influence the reporting of health outcomes in addition to reducing stress and encouraging better self-care. These variables are rarely controlled for or isolated, however.

Conclusion

The existing research does not support the conclusion that there is any efficacy to intercessory prayer. The research also does not allow for the conclusion that there are health benefits to faith or religion as specific variables. This latter question is open to further research, however.

The scientific evidence can therefore not be used to support the intermingling of faith with the practice of medicine. In any case – doing so raises serious ethical and professional concerns. For example, such practices raise the potential of faith-based discrimination against both physicians and patients. Mixing of faith with medicine can also compromise the professional doctor-patient relationship.

Even if one accepts that there is a health benefit to faith – such a benefit can be entirely realized through private means, without involving the medical profession.

<!--<!--

Note: The study discussed here has also been covered by Mark Crislip. I wrote this before his article was published, so please forgive any repetition. I approached it from a different angle; and anyway, if something is worth saying once it’s probably worth saying twice.

Is Echinacea effective for preventing and treating the common cold or is it just a placebo? My interpretation of the evidence is that Echinacea does little or nothing for the common cold. Initial reports were favorable, but were followed by four highly credible negative trials in major medical journals. A Cochrane systematic review was typically wishy-washy  The Natural Medicines Comprehensive Database rates it as only “possibly effective” commenting that

Clinical studies and meta-analyses show that taking some Echinacea preparations can modestly reduce cold symptom severity and duration, possibly by about 10% to 30%; however, this level of symptom reduction might not be clinically meaningful for some patients. Several other clinical studies found no benefit from Echinacea preparations for reducing cold symptoms in adults or children…

A review on the common cold in American Family Physician stated that Echinacea is not recommended as a treatment.

I have a friend who believes in Echinacea. She says for the last several years she has taken Echinacea at the first hint of a cold, and she hasn’t developed a single cold in all that time. I told her that if that was valid evidence that it worked, I had just as valid evidence that it didn’t. For the last several years I have been careful not to take Echinacea at the first hint of a cold, and I haven’t had a single cold in all that time either. So I could claim that not taking Echinacea is an effective cold preventive! I thought my “evidence” cancelled out hers; she said we would just have to agree to disagree.

A recent study looked at the effect of belief on response to Echinacea and dummy pills. “Placebo Effects and the Common Cold: A Randomized Controlled Trial” was published by Barrett et al. in the Annals of Family Medicine. 

A news report about the study said “the placebo effect reduced the duration of common colds.” And that the study “reflected the power of mind over body.” But that is not what the study showed.

Methods

719 subjects with colds were randomized into 4 groups:

1. No pills
2. Placebo, blinded (didn’t know whether they were getting placebo or Echinacea)
3. Echinacea, blinded (didn’t know whether they were getting placebo or Echinacea)
4. Echinacea open label (knew they were getting Echinacea)

How do we know the subjects had colds? We don’t, really.

• They answered yes to either “Do you think you have a cold?” or “Do you think you are coming down with a cold?”
• They scored at least two points on the Jackson scale (8 self-reported symptoms rated from 0 to 3 for severity).

How was improvement measured? Were they really improved? We don’t know.

• Twice a day they answered “Do you think you still have a cold?”
• They answered a questionnaire rating 19 cold symptoms and functional impairment.
• Biomarkers of immune response and inflammation were measured from nasal wash on day 1 and day 3: interleukin 8 and neutrophil counts. Are these biomarkers a reliable way to measure objective improvement in colds? I don’t know. It doesn’t matter anyway, since they didn’t change significantly.

Belief in Echinacea was assessed by asking if they had ever taken Echinacea before and how effective they thought it was on a 100 point scale.

Blinding was adequate: on an exit interview, patients in groups 2 and 3 couldn’t tell which group they were in.

Results

Compared to those receiving no pill, those receiving any pill reported modest improvement regardless of the content of the pill. They reported that their illness was 0.16 to 0.69 days shorter and 8% to 17% less severe. But these results were not statistically significant! Rather than showing that placebos reduced the duration of common colds, it showed that they didn’t have any statistically significant effect.

Contrary to expectations, open label was not superior to blinded Echinacea. (“I know I’m getting it” was no better than “I might be getting it.”) I found that intriguing.

Changes in biomarkers were not statistically significant.

Interestingly, four of the 6 assessed side effects were reported most frequently in the no-pill group. Headache was reported by 62% of those without pills compared with less than 50% in the other 3 groups. Statistical analysis showed that this was not due to chance. Does this mean that not taking pills causes headaches? Or that Echinacea and dummy pills are effective headache remedies? 62% seems like an unusually high incidence of headaches; does that mean that people who enroll in studies are unusually susceptible to headaches? Even if it was “greater than chance,” I suspect that it just represents noise in the data.

The most interesting finding was that those who believed in Echinacea did better regardless of which pill group they were in.  Among the 120 participants who had rated Echinacea’s effectiveness as greater than 50 on a 100-pointscale, illness duration was 2.58 days shorter in those given Echinacea or placebo than in those who got no pill, and mean global severity score was 26% lower but not significantly different.

A Further Question

In his book Snake Oil Science, R. Barker Bausell analyzed research showing that those who believed they got real acupuncture reported more relief than those who believed they got sham acupuncture, regardless of which they actually got. I wondered if this would be true for the Echinacea study as well, if those who believed they got Echinacea reported more improvement than those who believed they didn’t, regardless of whether they actually did or didn’t. I wrote the lead author to ask that question, and he replied

that data hasn’t [sic] been properly analyzed or presented.  Given small subsample sizes, confidant [sic] conclusions would likely be impossible.

I asked if it would be possible for someone to go back and look at the data and he answered:

It would take many dozens of hours to adequately address the question, and I’m afraid that the sample size is too small.  And resources too limited. I am advising several post-docs and leading several papers and this one just doesn’t merit the attention.  If you want to come to Madison for a month and can write up the background and methods section for the paper beforehand, I could probably get someone to do the data analysis and join you as a co-author.

I’m still curious, but I don’t want to know that badly!

Conclusion

The significant new finding of this study was that belief in Echinacea was more important than the content of the pill, regardless of whether subjects received Echinacea or placebo. To be more precise, it showed that subjects who thought they had a cold and who thought Echinacea was effective and who got either Echinacea or a placebo and who either knew they were getting Echinacea or thought they might be getting Echinacea were more likely to think their cold was gone sooner than if they got no pills.

Otherwise, the study only confirms some things we already knew. Patients report more subjective improvement with any pill than with no pill, and with any intervention compared to no intervention. Administering a placebo elicits self-reports of improvement. Echinacea is no more effective than placebo. The placebo phenomenon in colds is subjective and of such small magnitude that it can be considered not clinically important.

The authors said

Overall, this trial could be interpreted either as an appropriately powered trial that failed to conclusively show placebo effects, or as a trial suggesting small but perhaps meaningful effects related to expectation and pill-allocation.

Then they misrepresented their findings in the abstract when they said

Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills.

Yes, they “tended” to have (more correctly, to “report”) longer and more severe illnesses, but the tendency was not statistically significant. Why didn’t they follow the usual convention for scientific articles and say there was no significant difference between the groups?

No matter how you look at it, the news report was wrong:  the study is interesting, but it didn’t show that the placebo effect reduced the duration of common colds and it didn’t show the power of mind over body. It did show the power of mind to put a spin on study findings.

<!--<!--

In the three and a half years that the Science-Based Medicine blog has existed, we contributors have come in for our share of criticism. Sometimes, the criticism is relatively mild; often it’s based on a misunderstanding of what SBM is; but sometimes it’s quite nasty. I can’t speak for the rest of the SBM crew on this, but I’ve gotten used to it. It comes with the territory, and there’s little to do about it other than to skim each criticism as it comes in to see if the author makes any valid points and, if he doesn’t, to ignore it and move on. Indeed, there’s enough criticism being flung our way that I rarely respond directly anymore. Exceptions tend to be egregious examples, incidents that spark real problems, such as when Age of Autism blogger and anti-vaccine activist Jake Crosby tried to paint me as being hopelessly in the thrall of big pharma, which resulted in the anti-vaccine horde who read that blog to try to get me fired by sending complaints to the Board of Governors at my university and the dean of my medical school. Other examples tend to be what I call “teachable moments,” in which the mistakes made in the criticism provide fodder for making a point about SBM versus alternative medicine, “complementary and alternative medicine” (CAM), or “integrative medicine” (IM)—or whatever the nom du jour is.

File this next one under the “teachable moment” variety of criticism directed at SBM.

A pain researcher takes Steve and me to task

In order to stoke my massive ego (if you don’t believe I have a massive ego, just ask my critics), I have a Google Alerts set to my name. One thing I learn from these alerts is that there are a lot of people out there named David Gorski, few of them doing medicine and not all of them particularly reputable. The other thing I learn is that I’m actually mentioned on the web and in the blogosphere more times than I ever would have imagined possible a few years ago. More importantly, I’m quickly aware of criticisms directed my way. So it was that I found out about an article by someone named Stewart B. Leavitt, MA, PhD entitled A Burgeoning Klatch of Science Skeptics, which managed to attack both Steve Novella and myself in a manner that’s so off-base that it presents said “teachable moment,” much as an earlier criticism by Steve Simon provided such a moment.

You know right off the bat that Dr. Leavitt is going to go far off base when his opening paragraph contains the passage:

As it turns out, skepticism regarding modern science, including the field of pain medicine, is somewhat of an international movement. Its mantra might be “Stop the B.S.” (with the irreverent logo at right); yet, there is an apparent danger of skepticism becoming close-minded cynicism falling into the trap of contempt prior to investigation that might preclude truly objective analyses of research.

The community of skeptics, worldwide, serves an important function in modern society, as they always have. It was probably skeptics who asked, “What makes you think the Earth is flat — where’s your proof?” When it comes to healthcare, skeptics at their best evaluate medical treatments and products in a scientific light, promoting the highest standards and traditions of scientific inquiry; however, at their worst, skeptics may merely be naysayers, stirring up the pot of already-established evidence to draw attention to themselves.

This is the classic confusing of skepticism with nihilism or cynicism. In my experience, sometimes skepticism and cynicism are conflated intentionally by opponents of SBM in order to dismiss skepticism as nothing more than a cynical “Dr. No” approach in which claims are reflexively rejected without consideration, but sometimes (and perhaps more frequently) the two are conflated through ignorance because the difference between the two is not understood. I rather suspect that Dr. Leavitt does not understand the difference. (At least, I will give him the benefit of the doubt.) And this criticism can be true to a point: As skeptics we have to be very careful to avoid falling into the trap of cynicism, of rejecting claims without giving them a fair hearing. Indeed, most of us have said as much ourselves on this very blog on multiple occasions, particularly how we ourselves have to try to avoid falling into the trap of motivated reasoning, which is wielded to great effect by proponents of pseudoscience to protect themselves from having to change their minds about cherished views. On the other hand, how many times do clinical trials of pseudoscience like, for example, homeopathy have to fail and how often do we have to point out that the principles by which homeopaths claim homeopathy works violate well-established laws of physics and chemistry before we’re allowed the shorthand of provisionally rejecting homeopathy until its proponents produce data compelling enough to make us question the laws of physics as currently understood?

I won’t take on Leavitt’s criticism of Steve Novella (much). After all, Steve is more than capable of taking care of himself, having been in the skeptic biz at a higher level several years longer than I have. I do note, however, that, although Leavitt links to both Steve’s blog and SBM, he does not directly link to the posts that he cites, making it difficult to see what is being said in context. For example, Leavitt cites Novella as saying:

I have become thoroughly convinced of the axiom that there is no claim so absurd that it cannot attract flocks of true believers. The default mode of human psychology is to think with our emotions, then deftly rationalize our decisions. As a result there do not appear to be any practical limits to human gullibility.

An excellent quote, succinctly summing up the situation. It comes from a post in which Steve deconstructed an example of pure health supplement quackery. In the context of Steve’s post, it makes perfect sense. Yet Leavitt dismisses this as an “emotive” appeal. Similarly, he is very unhappy when I say things that he views as similarly emotive, in particular, when I refer to the “integration” of alternative medicine modalities into medicine as “quackademic medicine” and refer to “integrative medicine” as “integrating quackery with medicine.” I’ll be the first to admit that I came up with these sorts of pithy phrases (aside from “quackademic medicine,” whose origin I cannot claim, as much as I would like to) to make a point in a memorable way that can be easily repeated. This is how one communicates complex topics in a sound bite world, and it worked at TAM in that my point about “integrating quackery with medicine” was Tweeted and re-Tweeted rather extensively.

Of course, it is rather amusing to note that Leavitt dismisses our appeals as “emotive,” while he himself denigrates skeptics using language at least as emotive as ours, describing us, in essence, as cynics who “posture” and preach to the choir in the proverbial echo chamber, such as meetings like TAM, which Leavitt describes as:

The most recent TAM brought together skeptics from around the world and a long list of guest speakers and panelists. Workshops included: Defending Evolution, Skeptical Activism , Advancing Skepticism Online, Investigating Monster Mysteries, Raising Skeptics, and others. And, among the sessions discrediting UFOs and paranormal phenomena were the usual attacks against “alternative therapies” in healthcare and pain management.

Note the dismissive tone about sessions including the “usual attacks” against “alternative therapies.”

More telling is Leavitt’s attempt to contrast the type of skepticism that he claims he promotes, which he characterizes as “healthy skepticism” and “educated skepticism,” with our skepticism. He begins with a nonsequitur:

Along with that, however, we have acknowledged that it is far easier to criticize science — asking tough questions, pointing out flaws or weaknesses — than it is to do good science. Therefore, we were somewhat dismayed by the writings and posturing of the self-proclaimed community of professional skeptics.

So what if it’s easier to criticize science and to point out flaws or weaknesses than it is to do good science? Even if true, this observation on Leavitt’s part serves no other purpose besides denigrating critics of CAM. As someone who does what I like to think is good science myself and has been funded by the NIH, the Department of Defense, and the Conquer Cancer Foundation of ASCO, I find Leavitt’s comment profoundly insulting. His argument boils down to, in essence, a claim that if you don’t do pain research science you aren’t qualified to criticize bad CAM research about pain treatments. From my perspective, though, good science is good science, and bad science is bad science. It doesn’t matter who is doing the criticism; what matters is whether the criticisms are valid. In fact, Leavitt’s use of language is as clever as that of the CAM proponents we routinely discuss. His skepticism is “healthy” and “educated.” Left unspoken is what our skepticism must be—presumably by contrast “unhealthy” and “uneducated”—while Leavitt also characterizes us as “posturing.”

Logical fallacies and false dichotomies on parade

After the warmup, Leavitt gets to the meat of his objections, or so it would appear:

For example, their diatribes against CAM and integrative therapies — which actually can be vital modalities for effective pain management — seem guided more by emotional arguments than a systematic study of all available evidence. Hence, when Novella writes (as noted above), “The default mode of human psychology is to think with our emotions, then deftly rationalize our decisions. As a result there do not appear to be any practical limits to human gullibility,” we wonder if he also is describing how a credulous community of skeptics approach their subjects of scorn.

And, when Gorski asserts that “integrative medicine is all too often in reality nothing more than ‘integrating’ pseudoscience with science, quackery with medicine,” we might assume he has solid evidence to justify such claims; but, if so, he is keeping it secret. And, his far-reaching denigration of NCCAM, the Bravewell Collaborative, and unnamed medical schools adds emotive impact to arguments that might have no basis in fact.

Leavitt amuses me in this passage. His first criticism of Steve is a deftly executed tu quoque argument, in which he seems to concede that the default mode of human psychology is to think with our emotions (which it is, by the way) but turns it around to accuse skeptics of the same thing. Here’s the difference, though. Skeptics know that the default mode of human thought is to think with our emotions, to leap to conclusions first and then to try to find evidence to justify our opinions. Skepticism, science, and critical thinking are all methods designed to try to minimize that very human tendency and to minimize the effects of the cognitive quirks we all share that mislead us, including confusing confirmation bias, confusing correlation with causation, regression to the mean, and placebo responses.

I’m further amused that Leavitt would think that I don’t provide solid evidence to justify my claims. Once again, he doesn’t directly link to the post from which that quote comes, which is entitled The ultimate in “integrative medicine,” continued, which described a cooperative agreement between Georgetown University School of Medicine and the Bastyr University, the latter of which is a school of naturopathy. Clearly, Leavitt doesn’t support the notion that much of naturopathy is quackery and pseudoscience. Even if that’s the case and he disagrees, Leavitt reveals pure laziness in his statement, given that I’ve written copiously, logorrheically even, about this issue, providing numerous examples. For example, here are a few:

1. The ultimate in “integrative medicine”: Integrating the unscientific into the medical school curriculum
2. The ultimate in “integrative medicine,” continued
3. A University of Michigan Medical School alumnus confronts anthroposophic medicine at his alma mater
4. An open letter to NIH Director Francis Collins regarding his appearance at the Society for Integrative Oncology
5. “Integrative” oncology: Trojan horse, quackademic medicine, or both?
6. The National Center for Complementary and Alternative Medicine (NCCAM): Your tax dollars hard at work
7. Cancer Treatment Centers of America and “naturopathic oncology”
8. NCCAM Director Dr. Josephine Briggs and the American Association of Naturopathic Physicians
9. Surprise, surprise! Dr. Andrew Weil doesn’t like evidence-based medicine

As I particularly glaring example selected from the posts above, I submit that the “integration” of anthroposophic medicine with real medicine at my alma mater is the integration of quackery and pseudoscience with medicine.

I’ve also provided multiple lines of evidence on my other blog, and my fellow SBM bloggers have written about this issue, in particular Kimball Atwood. Gratifyingly, we’re even starting to have some success, as the Cochrane Reviews editors have been showing signs of starting to “get” SBM.

Then, after stating that neither Steve nor I have taken the time to study the issues of “integrative medicine” in depth, Leavitt concedes:

Admittedly, the comments above from Gorski and Novella are mere snippets of their voluminous writings, described out of context. Readers can themselves visit the blogs of these skeptics (linked above) to decide the merits of their arguments. For example, we find using words like “pseudoscience” and “quackery,” as they do, to be rather slanderous and empty invectives.

In other words, Leavitt admits to quoting us out of context and then just links to our blogs in general, all the while not providing a single concrete example of our committing the offenses of which he accuses us. These tactics are disingenuous at best and intellectually dishonest at worst, particularly given that Leavitt never bothered to link directly to the posts from which he extracted our comments out of context. Basically, this gambit allows Leavitt to give the appearance of being fair while misrepresenting our arguments and trying to paint us as emotion-driven, biased, and “uneducated” about CAM. Think of it this way. It’s asking a lot—and I do mean a lot—for anyone to visit two blogs that have been in existence for several years, each with thousands of posts, and to try to evaluate the core of the voluminous arguments there. What will happen is that without guidance regarding where to start even the small minority who click on links in a blog post will be quickly overwhelmed by the volume of verbiage and tend simply to accept Leavitt’s characterization without too much investigation.

Leavitt concludes with a false dichotomy:

The lesson in all this is that our understanding of “healthy skepticism,” as advocated in these Pain-Topics UPDATES, may have an objective of “stopping the B.S.,” but it is not necessarily bent on “spoiling anyone’s fun.” And, it is not a close-minded approach that encourages contempt prior to adequate investigation.

Skepticism in pain research should drive a search for truth that recognizes and acknowledges the boundaries of uncertainty. Unfortunately, a great deal of research in the pain field seems driven by political agendas and hidden self-interests, so educated skeptics have much work ahead. We hope our readers are up to the task.

There are two problems here. (Actually, there are more than that, but I’ll concentrate on two.) First, as I said, it’s a false dichotomy. Either you accept Leavitt’s dismissive definition of skepticism, or you’re necessarily “spoiling someone’s fun.” And make no mistake, Leavitt is a pretty credulous fellow. For instance, he has made a holiday “wish list” for “holistic care” that includes a number of pseudoscientific alternative medicine modalities—is that an oxymoron?—including acupuncture, ayurveda, energy medicine (healing touch and reiki), and traditional Chinese medicine, among others. About homeopathy, Leavitt says, “Homeopathy is a therapeutic modality practiced worldwide, it is very popular among some patients, and it has withstood the test of time,” while expressing disappointment in a study of homeopathy for rheumatoid arthritis showed no therapeutic effect and trying to attribute the negative result of the study to its being underpowered. In yet another example, Leavitt critiques Edzard Ernst’s recent review of acupuncture systematic reviews, and while much of what he writes in this particular post is not unreasonable, he can’t help but drop bombs of credulity on the science, saying, for example, that “comparing acupuncture to a molecular entity, such as a drug for pain, may reflect a Western bias regarding how medical treatments are expected to work” and citing an acupuncture proponent who concludes that “it is probably no coincidence that many positive trials of [acupuncture and related techniques] have come from China where the techniques have been practiced for centuries; whereas, studies conducted in other countries often use divergent forms of acupuncture that also may be hindered by poor or improper technique, such as using only a limited number of sites or incorrect acupoints.”

Leavitt then concludes about acupuncture:

Considering the multitude of patients worldwide who have benefitted from acupuncture in one way or another, it still appears premature to broadly dismiss it as being of little or no value for pain relief.

This is yet another appeal to popularity devoid of science.

Finally, I can’t help but cite one last example in which Leavitt discusses “biofield therapies” (reiki, healing touch, etc.):

Although many traditionally-trained practitioners may remain skeptical, significant numbers of patients apparently seek biofield therapies, often without telling their healthcare providers, and the techniques have been used over millennia in various cultures to allegedly heal physical and mental disorders. In general, complementary and alternative therapies are used by 38% of adults and 12% of children in America, and it is a $34 billion per year business; so, these approaches cannot be easily ignored. The customary caveat — more research is necessary to arrive at definitive conclusions — would seem very appropriate regarding biofield-based therapies for pain. However, as the 16th Century Swiss physician Philipus Aureolus Paracelsus advised, “The art of healing comes from nature, not from the physician. Therefore the physician must start from nature, with an open mind.”

I submit that this more than approaches being so open-minded that one’s brains fall out. It embraces such unskeptical open-mindedness and gives it a big, sloppy kiss on the lips. Basically, what we have here is an appeal to popularity plus an argument from ignorance; i.e., that something is likely to be true simply because it hasn’t been proved false or, equivalently, that something is likely to be false because it hasn’t been proved true. Of course, for modalities like energy healing and homeopathy, it’s a fallacy to say that we don’t know. Basic science, such as physics, can tell us with a high degree of probability that homeopathy can’t work, for instance.

Dr. Leavitt’s straw man caricature of skepticism versus positive skepticism

Near the end of his post, Leavitt defines skepticism as “encouraging contempt prior to adequate investigation.” At the risk of sounding “contemptuous,” I am going to say that this is a fetid load of dingo’s kidneys. It’s a favorite straw man characterization of skepticism by the credulous, be they believers in the paranormal, alternative medicine aficionados, evolution denialists, or other promoters of pseudoscience. Personally, in response to such arguments, I like to cite the writings of Michael Shermer regarding positive skepticism:

This brings me to the larger issue of two forms of skepticism, negative and positive. Stephen Jay Gould began his foreword to my 1997 book, Why People Believe Weird Things, by noting: “Skepticism or debunking often receives the bad rap reserved for activities — like garbage disposal — that absolutely must be done for a safe and sane life, but seem either unglamorous or unworthy of overt celebration.”…

Positive skepticism, however, involves much more than the negative disposal of false claims. In fact, the word “skeptic” comes from the Greek skeptikos, for “thoughtful.” According to the Oxford English Dictionary, “skeptical” has also been used to mean “inquiring,” “reflective,” and, with variations in the ancient Greek, “watchman” or “mark to aim at.” What a positive meaning for what we do! We are thoughtful, inquiring, and reflective, and we are the watchmen who guard against bad ideas in order to discover good ideas, consumer advocates of critical thinking who, through the guidelines of science, establish a mark at which to aim. “Proper debunking is done in the interest of an alternate model of explanation, not as a nihilistic exercise,” Gould concludes. “The alternate model is rationality itself, tied to moral decency —the most powerful joint instrument for good that our planet has ever known.”

In other words, not only is “negative skepticism” not cynicism, but it’s actually a good thing. Indeed, skepticism is far more than just the debunking of claims. It’s the application of the best of human reason, including science, logic, and critical thinking to claims. When properly done, skepticism represents the highest intellectual aspirations of humankind. As Shermer points out, skepticism keeps the borders of science from moving too far into the realm of pseudoscience and non-science, and for every Copernicus, Newton, and Einstein, there are hundreds, if not thousands, of cranks and quacks whose ideas never pass scientific muster because they are nonsense. It might be some day that a CAM modality such as homeopathy or energy healing will pass scientific muster. Unlikely, but possible, and if and when that day comes I will examine the evidence and, if appropriate, change my mind to embrace what I formerly considered pseudoscience. That’s what skepticism really is. Moreover, science-based medicine is not an attempt to turn medicine into a pure science; rather it is the philosophy that science should inform and guide medicine.

To conclude, I realize that I perhaps cite this too often and that some might be offended by its language, which some might consider NSFW, but Tim Minchin put it best in his beat poem Storm:

Science adjusts its beliefs based on what’s observed
Faith is the denial of observation so that Belief can be preserved.
If you show me that, say, homeopathy works,
Then I will change my mind
I’ll spin on a…dime
I’ll be embarrassed as hell,
But I will run through the streets yelling
It’s a miracle! Take physics and bin it!
Water has memory!
And while its memory of a long lost drop of onion juice is Infinite
It somehow forgets all the poo it’s had in it!

You show me that it works and how it works
And when I’ve recovered from the shock
I will take a compass and carve “Fancy that!” on the side of my cock.

And I will, too. Well, except perhaps for the part about the compass and carving. We wouldn’t want to go too far, now, would we? On the other hand, one wonders how rapidly Dr. Leavitt will abandon beliefs that he possesses that are not supported by science. Apparently not very quickly. After all, he remains “open-minded” to energy healing, acupuncture, and other unscientific forms of medicine and shows no sign of changing.

<!--<!--