#ClinicSpeak: have you been taken for a ride by a prostitute called Turmeric?

We need an evidence base to support the use of Turmeric in MS. #ClinicSpeak #MSBlog

So many of my patients have asked what I  think of Turmeric as a treatment for MS and my stock answer has been that there is no class 1 or 2 evidence (randomised controlled trials) to support the claims that it helps people with MS. Nothing has changed except I can now say that there is now no biological evidence that Turmeric has any medicinal effects

The editorial from last week's Nature on a meta-analysis suggests we have all been duped by the chemical properties of the curcumin, the proposed active ingredient in Turmeric. They show that curcumin is a promiscuous compound and interferes with most drug-screening assays, which have led to false claims about its biological effects. It is a molecular prostitute, i.e. binding promiscuously to many proteins and membranes, and giving false signals or faking it.


I would be interested to know how many of you have tried Turmeric for your MS.



Monya Baker. Deceptive curcumin offers cautionary tale for chemists. Nature 541, 144–145 (09 January 2017) doi:10.1038/541144a

Spice extract dupes assays and leads some drug hunters astray.

Excerpts:

..... Inside the golden-yellow spice turmeric lurks a chemical deceiver: curcumin, a molecule that is widely touted as having medicinal activity, but which also gives false signals in drug screening tests. For years, chemists have urged caution about curcumin and other compounds that can mislead naive drug hunters.

......  the most comprehensive critical review yet of curcumin — concluding that there’s no evidence it has any specific therapeutic benefits, despite thousands of research papers and more than 120 clinical trials. The scientists hope that their report will prevent further wasted research and alert the unwary to the possibility that chemicals may often show up as ‘hits’ in drug screens, but be unlikely to yield a drug......

...... “Curcumin is a cautionary tale,” says Michael Walters, a medicinal chemist at the University of Minnesota in Minneapolis, and lead author of the review (K. M. Nelson et al. J. Med. Chem. http://dx.doi.org/10.1021/acs.jmedchem.6b00975; 2017), published on 11 January......

......  Commonly used drug screens detect whether a chemical latches on to a binding site of a protein implicated in disease — a hint that it may be the starting point for a drug. But some molecules, such as curcumin, seem to show such specific activity when there is none. The molecules may fluoresce naturally, foiling attempts to use fluorescence as a signal of protein binding. They may disrupt cell membranes, duping assays that try to spot drugs targeting specific cell-membrane proteins. And they may surreptitiously degrade into other compounds that have different properties, or contain impurities that have their own biological activity......

...... Chemists call these irritants PAINS (pan-assay interference compounds) — and curcumin is one of the worst.....

...... Misinterpretations feed on themselves, Walters says. Curcumin gets reported as having an effect even if the assay was flawed. “People accept what is in the literature as being correct and then build a hypothesis, even though it doesn’t hold up.” And scientists don’t seem to check the literature to see whether compounds have been flagged as problematic. At least 15 articles on curcumin have been retracted since 2009 and dozens more corrected......

....... But the review shows that getting real answers will be tough, says Bill Zuercher, a chemical biologist at the University of North Carolina at Chapel Hill. “It may very well be the case that curcumin or turmeric extracts do have beneficial effects, but getting to the bottom of that is complex and might be impossible,” he says. Walters isn’t confident that his report will stop poorly conducted research. “The people who should be reading this probably won’t,” he says ......

Nelson et al. The Essential Medicinal Chemistry of Curcumin. J Med Chem. 2017 Jan 11. doi: 10.1021/acs.jmedchem.6b00975.

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. 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. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

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