A Medical Case for Curcumin? Apparently Not
One medical researcher, who reads this blog, sent me a recent article about the vast amount of research that has been carried out on curcumin, which is widely used as a supplement.
Many apparently interesting natural substances suffer from low bioavailability and the arguments put forward in the paper do apply to many other supplements. On the other hand, there are natural substances that do have useful medical properties in humans; it is just very hard to identify which ones, without making your own research.
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. Now, in an attempt to stem a continuing flow of muddled research, scientists have published 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.
The full paper is here:-
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 (panassay 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 doubleblinded, 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.
At first, curcumin appeared to offer great potential for the development of a therapeutic from a NP (turmeric) that is classified as a GRAS material. Unfortunately, no form of curcumin, or its closely related analogues, appears to possess the properties required for a good drug candidate (chemical stability, high water solubility, potent and selective target activity, high bioavailability, broad tissue distribution, stable metabolism, and low toxicity). The in vitro interference properties of curcumin do, however, offer many traps that can trick unprepared researchers into misinterpreting the results of their investigations.
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.
Conclusion
It would be wrong to conclude that natural substances and supplements are of no medicinal value. One reader of this blog with type 1 diabetes has used some of the tips in the blog to improve insulin sensitivity so far that the requirement for insulin to be injected has been reduced by 50%. As medical readers will realise that is quite remarkable. It was all done with antioxidants of one kind or another (alpha lipoic acid, broccoli powder and cocoa flavanols) and without side effects.
Numerous natural substances reduce cholesterol or lower blood pressure and it is very easy to measure the results and see if they really work for you; cinnamon, beetroot juice, tangeretin, the list goes on.
One problem is that even individual compounds often have multiple medical effects and natural substances can contain 20-30 or more different compounds, so it is impossible to say with certainty why broccoli improves insulin sensitivity.
Naturally occurring compounds cannot be patented and so nobody has a financial interest to do rigorous and costly clinical trials to conclusively show beneficial effect. Why would pharmaceutical companies want to reduce the demand for their insulin by 50%? They are apparently not so keen on repurposing cheap existing drugs to treat autism, and neither are some researchers.
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