Death by intravenous "turmeric": Naturopaths circle the wagons and the chair of the Naturopathic Medical Committee of California looks for dirt on conventional medicine

Yesterday, I wrote about the case of Jade Erick, a 30-year-old woman whose death was caused by naturopathic quackery. It's not entirely clear if it was intravenous turmeric that killed her. That's what the press consistently reported. It's more likely that it was intravenous curcumin, which is derived from turmeric. Whatever the case, Erick very rapidly went into cardiac arrest as the infusion began. When first I discussed the Erick case, the identity of the naturopath was unknown because, for whatever reason, the press was not reporting it at the time. But yesterday the naturopath was identified as Kim Kelly, ND.

To me, the most significant part of this revelation was not so much the name of the naturopathic quack. Rather, it was the revelation that this particular naturopath is not only a fully licensed naturopath, but a naturopath who had attended what naturopaths consider to be one of their finest schools, Bastyr University. He was in every way what naturopaths want their "profession." (The scare quotes are basically mandatory to me when using the words "profession" and "naturopaths" in the same sentence.) Yet his website indicates that he offered the same cornucopia of quackery that most naturopaths offer. That is, of course, because the quackery is "baked into" naturopathy. It's inherent in naturopathy. It can't be separated from naturopathy. No matter how much naturopaths and groups representing them, such as the American Association of Naturopathic Physicians (AANP), try to argue that naturopathy is evidence- and science-based, they can't hide the simple fact that it isn't.

Not that that stops them from trying.

I wish I had seen this yesterday, because I could have added it to my post yesterday, but there's enough there to rate its own post. Basically, the AANP issued a press release that is the very model of the "no true Scotsman" fallacy, trying to convince people that this death doesn't mean that turmeric- and curcumin-based remedies are unsafe. Besides, it lets me revisit the topic of curcumin, in particular a certain naturopath who features in this press release and who is apparently the greatest popularizer of intravenous curcumin.

Before I get into that, there are two statements on the press release that, even though they're not near the beginning of the statement, demand a heapin' helpin' of not-so-Respectful Insolence before I delve a bit more into the weeds. I'm referring to this:

For the protection of patients, the AANP offers the following advice to anyone interested in turmeric or curcumin medical treatments:

1. Consult with a naturopathic (ND) or conventional doctor (MD) before being treated with turmeric or curcumin. Make sure you know which drug is being recommended and talk to your physician about which one is right for you and how it should be administered in your situation.

2. Make sure your ND is licensed or certified. Not all practitioners who call themselves naturopathic doctors are licensed or certified to practice naturopathic medicine. To be licensed or certified, a doctor must have completed a four-year program at a naturopathic medical school accredited by agencies recognized by the U.S. Department of Education. The AANP maintains a list of states and U.S. territories that license naturopathic physicians.

As I said before, quackery is inherent in naturopathy. It's embedded in the "profession," from its very philosophy, which embraces prescientific vitalism, to the treatments that naturopaths embrace. For example, there is The One Quackery To Rule Them All, homeopathy. You can't have naturopathy without homeopathy because homeopathy is an integral part of naturopathic education. Many hours are spent studying naturopathy in naturopathy school, and homeopathy is an integral part of the NPLEX, the examination that naturopaths must pass in states that license them, like California.

That sure helped Jade Erick, didn't it?

But let's go back to what the AANP said about turmeric and curcumin before its self-serving advice to consult only licensed naturopaths. Now, you might think that a profession, when faced with negative publicity over a story in which one of their own treated a patient with a drug that resulted in her rapid death, might do some soul-searching, that it might question whether its enthusiasm for a treatment with little evidence to support it is justified. Not naturopaths. Their belief is true. Instead, the AANP decided to cynically use Jade Erick's death as a "teachable moment" about the difference between turmeric and curcumin, given that the press reported that it was intravenous turmeric that killed Erick when it was probably intravenous curcumin:

Washington, DC - The American Association of Naturopathic Physicians (AANP) released the following information and advice for patients on the difference between turmeric and curcumin when they are used as medical treatments:

Turmeric is a plant that when harvested, cleaned, dried, and powdered becomes a gold-colored spice. Commonly used in Asian food, turmeric is the main spice in curry. Turmeric has been used for centuries to treat a wide variety of conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders.

Curcumin is the main active ingredient in turmeric. First chemically characterized in 1910, today curcumin is used for its anti-inflammatory and antioxidant properties.

“While turmeric is the parent botanical that curcumin comes from, they are different chemical compounds,” said Dr. Paul Anderson, a naturopathic doctor, pharmacology and biochemistry professor, and leading authority in intravenous (IV) therapy formulation and infusion techniques, including IV administration of curcumin. “An unfortunate circumstance is that many people, including clinicians and researchers, use the terms ‘turmeric’ and ‘curcumin’ interchangeably. This can cause confusion among patients seeking information on the medical treatments available using them and is a disservice to those who might benefit from the therapeutic use of these compounds.”

So let me get this straight. A young woman died because a naturopath injected her with IV curcumin (probably) to treat her eczema, and what the AANP and Paul Anderson are concerned about is that their customers might be confused how the terms "turmeric" and "curcumin" are often used interchangeably. Seriously? This is what the AANP thought to be the most important point to lead with?

Next up, the AANP wants to make sure that its marks patients by only super duper extra pure approved curcumin:

However, according to Dr. Anderson, patients considering IV administrations of curcumin should be aware that while turmeric and curcumin are related, they are not the same thing.

“For curcumin, there are FDA-registered compounding pharmacies manufacturing curcumin designed for IV administration as a compounded drug with FDA-approved products,” said Dr. Anderson. “There is also an intravenous curcumin medication currently in Phase II of the FDA approval process and no adverse events have occurred. And there are numerous scientific trials using intravenous curcumin underway. For turmeric, there are no trials for intravenous use and, to the best of my knowledge, no turmeric is being manufactured for IV administration in the United States.”

Got it? Turmeric bad (at least IV). Curcumin good. I also can't help but note that Anderson doesn't seem to savvy with respect to the FDA approval process. "Phase II" refers to a type of clinical trial, not to a phase of the FDA approval process. Since Anderson didn't actually reference the clinical trial to which he was referring, I did a little digging on ClinicalTrials.gov searching using the term "intravenous curcumin." I found only two trials, one completed and one still under way. The completed trial was a phase 1 trial of liposomal curcumin; so that's obviously not the one to which Anderson was referring. That leaves this trial, "Curcumin" in Combination With Chemotherapy in Advanced Breast Cancer. Basically, the trial tests the effect of adding an intravenous form of curcumin to standard a standard chemotherapy drug (paclitaxel) for breast cancer. I note that this trial is being conducted in Armenia, not the US. Given that it's the only trial that is registered with ClinicalTrials.gov and using intravenous curcumin, I can only conclude that Anderson has some sort of "insider information." I must also wonder if he's telling us the whole story. The study itself is new, having only opened to patient accrual March 20, 2017 and proposing an ambitious timeline of randomizing 75 and collecting data on the primary outcome measure by March 2018 and closing by July 2018. The principal investigator is Tatul Saghatelyan, PhD of the Armenian Association of Telemedicine.

Ex-naturopath Britt Hermes, a woman who made the mistake of becoming a fully trained naturopath who had the courage to do what most of us have a hard time doing; that is, questioning the entire basis for her career, admitting a major error, and radically changing her life course also noted the other day that Anderson appears to have been "privy to insider information" given how he makes statements like the ones above so confidently and, in his previous statement, notes that the compound Erick received (and that killed her) was a "was a sterile intravenous drug (curcumin) from an FDA registered source and FDA compliant pharmacy” that passed quality assurance tests.

Basically, this AANP release is about spin and an attempt to convince people that just because one of its own used a treatment with basically no convincing evidence of efficacy, resulting in the death of a young woman, is not a reason to view its members as quacks. It's also about attacking science-based medicine:

5. Know that no medication or medical treatment is 100% safe, including some that are commonly used by many people every day. For example, there over 1,000 FDA-approved drugs that list the terms “fatal” and “anaphylaxis” (pertaining to Type 1 allergy) in their adverse event section. Even a commonly used medicine such as acetaminophen (Tylenol) presents significant risks, with more than 56,000 emergency room visits, 2,600 hospitalizations, and an estimated 458 deaths due to acute liver failure from the use of acetaminophen.

I've addressed such issues before. The difference here is that there is strong evidence of efficacy for all of the treatments above listed, making a reasonable discussion of risk/benefit ratios possible. When there is no evidence of efficacy, then a treatment is all risk, no benefit. It's a point I frequently make about acupuncture when acupuncturists' defend their complications by saying that conventional medicine has risks and complications, too.

Attacking conventional medicine is a theme taken up by David Field, as I discovered perusing Twitter:

California Naturopathic chair David Field wants dirt on MDs after woman's death from IV curcumin https://t.co/KnoJIAUYT5 @gorskon @DCAnews

— Naturowhat (@naturowhat) April 12, 2017

David Field, in case you don't know who he is, is the Chair of the Naturopathic Medicine Committee for the State of California Department of Consumer Affairs. You'd think that, as the chair of the committee that will be tasked with investigating Kim Kelly's conduct and treatment in Jade Erick's death, he would be interested in finding out what happened. However, if you read the entry from the NatChat discussion group in the link above, you'll find this:

I am in great need of statistics, with references/citations if possible, regarding iatrogenic harm from MDs/DOs, DCs, LAcs, etc. As SOON as POSSIBLE please! ANY and ALL types!

David Field, ND, LAc
Chair, Naturopathic Medical Committee (i.e. Board) of California
Santa Rosa, CA

Colleen Huber (whom we've met before on NatChat) is happy to provide Fields with the information he wants. She lists the usual litany of studies beloved of quacks everywhere that provide huge (and often highly implausible) estimates for iatrogenic harm, but that's not enough. She finishes with this:

And Mercola.com addresses these questions frequently, but doesn't bother to cite original sources:
Death by Medicine by Gary Null, Carolyn Dean, et al. is a 2003 article looking at iatrogenic mortality statistics:

http://articles.mercola.com/sites/articles/archive/2003/11/26/death-by-…

You'd think that anyone citing Joe Mercola or Gary Null, two mega-quacks who've built online and media health empires peddling quackery would be laughed out of the conversation. You'd be wrong:

thank you, Colleen. Exactly what I needed. I knew the approximate numbers but needed a reference.

One wonders if Field is going to cite Mercola and Null in the proceedings against Kelly.

The above exchange strongly indicates that Field will have his finger on the scale of justice in Kelly's favor when his case inevitably comes before his board. It's of a piece with the AANP defense of intravenous curcumin in which conventional medicine is lambasted and portrayed as dangerous, and it's clear that the Kelly's defense will involve claiming that curcumin is safe, that Erick's reaction was a fluke, and that naturopathy is safer than conventional medicine. Just don't pay attention to those efficacy data. When you look objectively at curcumin as a treatment for, well, anything, it's clear that it's been huge disappointment. Curcumin was once the Great Yellow Hope for everything from cancer to inflammatory diseases to just about any condition you can imagine, but the actual results of clinical trials based on initially promising in vitro and animal study results have been underwhelming, to put it mildly.

Indeed, a recent review in the Journal of Medicinal Chemistry was particularly damning:

Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate.The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double- blinded, placebo controlled clinical trial of curcumin has been successful.

But what are PAINS and IMPS candidates? The authors explain:

PAINS, or pan-assay interference compounds, are compounds that have been observed to show activity in multiple types of assays by interfering with the assay readout rather than through specific compound/target interactions. Many compound classes have been codified and identified as PAINS or potential PAINS.40 Compound 1 exhibits all known PAINS-type behaviors: covalent labeling of proteins,⁴¹⁻⁴³ metal chelation,⁴⁴ redox reactivity,⁴⁵ aggregation,⁴⁶ membrane disruption,47 fluorescence interference,⁴⁸ and structural decomposition.^45,49 This suggests that any report of its activity in an assay that does not either exclude or account for these potential modes of assay interference should be treated with caution. This is a very important consideration for reviewers, for example, of U.S. federal proposals that rely on published data regarding the bioactivity of curcumin. The most recent guidelines for the review of U.S. NIH proposals require four new considerations to establish reproducibility: premise, design, variables, and authentication. Consequently, any proposal based on apparent curcumin bioactivity should ensure that the “scientific premise forming the basis of the proposed research” is sound (that is, published activity is not simply a result of assay interference) and that the “chemical resources” are “authenticated”; i.e., analytical and target engagement methods are employed to provide convincing evidence that curcumin is the causative agent of activity.

In other words, PAINS compounds are substances or chemicals that appear to show a lot of specific activity in various assays measuring activity against various proteins, but that "activity" is in reality pseudo-activity that is due to nonspecific activity in the assay.

Also, I do so love the term "invalid metabolic panacea" (IMP). It's a lovely term that tells you exactly what it is through its name. Basically, it's a compound that shows apparent activity influencing a wide variety of physiologic and metabolic processes (hence the word "panacea") but in reality are poor drug lead compounds:

From a collective point of view, IMPS are invalid metabolic panaceas located inside the center of the black hole of natural products⁴ that tend to exhaust research resources. As singular elements, IMPS are prototypes of improbable metabolic panaceas that exhibit feeble performance as drug leads. The reported bioactive properties of IMPS are highly complicated by several factors that may be in addition to PAINS characteristics but often are separate from them.⁴ After evaluating bioactivity profiles of curcumin reported in the global literature, two broad observations raise red flags: (1) the high rate at which this compound, or mixture, is reported as being bioactive and especially (2) the relatively high ratio of positive activities seen in proportion to the total number of distinct bioactivities reported: just over 300 as assessed using the NAPRALERT database.4 NAPRALERT (www.napralert. org) is a relational database on the chemistry, biological activity, and folkloric use of natural products housed since 1975 at the Program for Collaborative Research in the Pharmaceutical Sciences at the College of Pharmacy, University of Illinois at Chicago.

In other words, the main red flags that curcumin is a PAINS/IMP-type compound are just how promiscuously it interacts and reacts and the sheer number of positive findings in assays studying it. All of this leads the authors of the review to conclude:

With respect to curcumin/curcuminoids and in vivo studies and clinical trials, we believe there is rather “much ado about nothing”. Certainly, the low systemic exposure levels reported in clinical trials do not support its further investigation as a therapeutic. Circumventing the requirement for systemic circulation, curcumin might provide benefit by acting on gut microbiota. Thus far, there is limited evidence to support this hypothesis, which will also limit the utility of this delivery method. Delivery systems such as lipid vesicles, nanoparticles, and nanofibers might be able to boost the bioavailability of 1, but this could also conceivably narrow its therapeutic window and lead to off-target toxicity by aforementioned processes. Available evidence demonstrates curcumin will ultimately degrade upon release into physiologic media, no matter the delivery mechanism. Analogues of 1 might address some of the delivery challenges but would be new chemical entities and would have to proceed through expensive preclinical work to be approved for clinical trials. In our opinion, analogues of curcumin are based on a fairly weak foundation.

There are numerous examples of research dollars and time being wasted chasing the activity of PAINS compounds.

Derek Lowe agrees. Blogging at Science, he warns his fellow medicinal chemists that Curcumin Will Waste Your Time and explains why, noting that PAINS is a term that's been used in natural products research for natural products that "seem to have all sorts of weakish activity all over the place." It's a problem well known in pharmacognosy research (researching natural products for use as potential drugs). Naturopaths, not surprisingly, are blissfully oblivious to such real-world scientific problems with which real pharmacologists have wrestled for literally decades. They latch on to each weak new association as though it were The Truth handed down by Nature indicating the usefulness of a certain plant or its extracts, and then run straight off a cliff with it, extrapolating to claims that the plant must be useful against every disease in which the physiological processes that it appears to influence in in vitro assays, bioavailability, solubility, and tendency to aggregate be damned.

Here's a general rule of thumb, particularly with a compound like curcumin. When clinical studies are this unimpressive and everyone's scrambling to handwave "alternative explanations" for efficacy, it's not a good sign. Indeed, the enthusiasm for curcumin among cancer researchers has always puzzled me, given how weak the existing evidence base is for its efficacy and the serious drawbacks it has in terms of solubility, instability, and bioavailability. Naturopaths, as is their wont when looking for legitimacy, take that enthusiasm and turn it up to 11, because the success and adoption of curcumin by conventional medicine would validate their world view about the usefulness of natural products. It is this world view that leads to tragedies like the death of Jade Erick.

Unfortunately, the AANP statement and David Field's backchannel request for dirt on conventional medicine show that naturopaths will learn nothing from this tragedy. Instead, they will attack conventional medicine and portray Erick's unnecessary death as a tragic but unavoidable adverse event from their "evidence-based" therapy. The problem is that IV curcumin for eczema is anything but evidence-based, making it all risk and no reward.

I noted yesterday that the law providing for naturopathic licensure in California is scheduled to sunset at the end of this year. There is, however, a new bill (SB 796), introduced by Jerry Hill (D-San Mateo) that would extend naturopathic licensure to 2022. The case of Jade Erick and the way that David Field appears to be preparing to whitewash what Kim Kelly did when he and the Naturopathic Medical Committee of California take up the case are yet more strong arguments why SB 796 should be defeated.