Jade Erick, 30, had eczema, which is a benign condition but can have a significant effect on quality of life. She sought treatment from a licensed health professional, someone who can legally call themselves a “doctor,” who is part of a state approved regulated profession.

Unfortunately for her, that “doctor” was a naturopath, Kim Kelly. Kelly had started offering intravenous (IV) curcumin, a component of the spice turmeric, for a variety of indications. On his website (on a page he has since removed, but which is archived) he writes:

I also am excited to announce that I now offer Intravenous Curcumin for people experiencing pain (arthritis, inflammation, etc) and which is also proving to be highly beneficial for those experiencing Alzheimer’s/Dementia.

The result of his exciting treatment, according to the medical examiner, is that Jade Erick died.

The evidence for curcumin/turmeric

The history of curcumin nicely encapsulates much of what we discuss here on science-based medicine. There have been thousands of pre-clinical studies of curcumin over the last half century, looking at its effects against certain proteins or cell lines, showing anti-inflammatory and anti-cancer potential. Many researchers are excited about its potential, and the list of possible diseases it can treat are huge.

But that history contains a cautionary clue – if it has been a promising potential drug candidate for 50 years, why hasn’t it already been adopted as a treatment? Where are all the curcumin-based drugs?

Over that same period of time there have been around 120 clinical trials of curcumin. Collectively they have failed to show that curcumin works for any single indication. How can such a promising agent fail so miserably in clinical trials? There are several reasons for this.

One reason is that it has poor bioavailability and pharmacokinetics. It doesn’t matter what a molecule does when you drip it directly on cells in a petri dish. The compound has to have a suite of pharmacological properties in order to be a useful drug. It needs to be sufficiently absorbed, it has to be biologically stable with a decent half-life, it has to reach the target tissue in sufficient concentrations, and it needs to have a therapeutic range where the beneficial clinical effects are significant but the toxic side effects are tolerable (including all of its metabolites).

Curcumin is simply an unstable compound that has terrible pharmacokinetic properties. Its bioavailability is around 1% and its half-life is measured in mere minutes. Sometimes drug company chemists can tweak and alter the structure of potential compounds to give it the properties it needs to be a good drug. This has just not worked out for curcumin.

There is, however, an even bigger reason why curcumin has not cured dozens of diseases. There are compounds which researchers call pan-assay interference compounds, or PAINS. These are compounds that seem to have a lot of activity against specific proteins, but it turns out they are false positives. The assays used to test for such protein activity show artifacts of non-specific activity which mimics specific protein activity.

Curcumin is apparently one of the worst offenders. In a commentary for Science Translational Medicine, Derek Lowe details why curcumin is so bad:

The paper cites a long list of references demonstrating that curcumin participates in pretty much every undesirable behavior possible in an assay: it reacts with proteins, it’s a redox cycler, it coordinates metal ions, it aggregates, it disrupts membranes nonspecifically, it interferes with fluorescent readouts, and it decomposes. Other than that, it’s a perfectly good hit.

Other reviewers call curcumin an “invalid metabolic panacea,” which is a term used to describe compounds, mostly natural compounds like curcumin, which seem to have all sorts of biological activity but nothing that amounts to a useful clinical effect.

A Nature article explains why PAINS are becoming more of a pain:

Until the past decade or so, screening work was mainly performed at pharmaceutical companies, and supported by experienced chemists. It is now increasingly common in academic environments, in which the same support may not exist.

So we are seeing a lot of research by academics who are not as familiar with drug discovery and don’t have the experience to weed out the false positives from the genuine candidates. This effect is hugely exaggerated in the natural medicines culture. As a result we have a compound, curcumin, with thousands of studies, a great deal of hype, and all sorts of claims but the whole thing is a sham. It is a chemical illusion of a particularly terrible compound whose major feature is that it generates false positive results on biological assays.

Pre-clinical vs clinical research

All of this is precisely why SBM advocates are sticklers for clinical research. Actually, we like all research. We want basic science research to establish plausibility and elucidate mechanisms of action, and high-quality clinical research to determine safety and efficacy. You really need both. In the case of curcumin the basic science is a bust, nothing but apparent false positives and 50 years of wasted resources. The clinical research is comprised of preliminary studies, which are all but worthless, and more rigorous studies which are negative.

To date curcumin in any form has not been proven efficacious for any indication. This is not surprising if you understand the basic science.

All of this is why clinical practice should not be based on pre-clinical data alone. Having interesting activity in the petri dish is only a possible indication of future research, and even that has to be viewed with caution. Most promising therapeutic targets will not work out. Most treatments which appear to work in preliminary studies do not, in fact, work.

Those agents which make it through rigorous double-blind placebo controlled trials represent the tiny tip of a huge pyramid of failed treatments. That is why SBM advocates for sticking with the upper part of that pyramid. The alternative medicine movement, however, is largely about relaxing standards and using treatments from farther down the pyramid of evidence, even dipping below the pyramid itself into a prescientific world of magic.

Naturopaths and evidence

This brings us back to naturopaths and the death of Jade Erick. This case nicely demonstrates why the naturopathic profession, on the whole, is pseudoscientific. They practice down in the lower levels of the evidence pyramid. This is the standard (as much as there can be said to be one) within the naturopathic profession.

Kelly was impressed with the pre-clinical evidence for curcumin, and thought that it could treat an impressively long list of diseases. He was apparently not bothered by the lack of clinical data. Anecdotes and some flashy assays were enough. He felt confident enough to treat a patient with a benign condition with intravenous curcumin.

SBM guest blogger Britt Hermes who was trained as a naturopath but eventually noticed how unscientific her chosen profession was (and has told her personal history of using naturopathy to treat a skin condition) has been following this story. She notes that Kelly quickly scrubbed his website of any mention of curcumin after his patient died. The response of the naturopathic community was similar – duck and cover. She reports:

In the wake of Erick’s death and my investigation, naturopathic doctor Jason Phan, who owns LIVV Natural Health in San Diego, scrubbed his practice website, like Kim Kelly did, of any mention of curcumin, which included this description of how intravenous curcumin works:

I don’t want to overwhelm you with lots of science and big word [sic] such as cytochrome P450. But summarizing how IV curcumin and its effects on cancer is curcumin increases: glutathione synthesis (major antioxidant), induces cell cycle arrest and apoptosis (directly killing cancer cells), and inhibition of tumor invasion and angiogenesis (decrease blood supply to cancer cells). Hopefully this gives you enough information to believe in curcumin and its effects on cancer.

When interviewed other naturopaths refused to condemn the practice, and in fact defended the use of curcumin as a treatment. They simply protected themselves by saying they don’t offer it IV (only orally) but that IV treatment is valid.

This is clearly not just an outlier, the failure of an individual, or an unavoidable fluke. This is a failure of the naturopathic profession. This episode exposes what is clear from any review of naturopathic practice – they base their treatments on a pathetically low standard of evidence. They do not make meaningful risk vs benefit analyses. They do not police their own profession to maintain a standard of care.

Naturopaths are what you get when you abandon science-based medicine, an eclectic hodge-podge of nonsense, worthless, and sometimes harmful treatments.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the president and co-founder of the New England Skeptical Society, the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also contributes every Sunday to The Rogues Gallery, the official blog of the SGU.