Monday, 16 January 2017

#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.

42 comments:

  1. Simple rule of thumb...if there are no side effects then there are no effects.

    If you have something that is claimed to be immunomodulatory/immunosuppressive then if it works to stop your MS then it also works to stop your immune system dealing with infection.

    With such hammers you can not have one without the other.

    Yes we see some of these things having impact in animal models..but look at the doses being used they are so high that eating toothpaste will do the same thing.
    THe animals are kept in clean environments and we dont look for infections.

    I know we all want to believe in these things...but it is blind faith
    A pot of tumeric doesn't cost the Earth, but some of the complementary medicines do. We see time and time again...people being duped.

    I delete claims of curing HIV and HERPES from appearing on the blog every week circulating the web, sometimes every day. In a nutshell, It is all b**ll**ks.

    We are all guilty...there are a load of vitamin D trials aimed at stoppping MS as an immunosuppressive...no side effects. We will see....but you have a prediction.

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    1. P.S. We want people to be Vitamin D replete for health and bone health.

      It is probable that the vitamin D influence is important in disease development such as in utero when your immune system is forming, prevention is where vitamin D trials should be focusing..not as DMT where I predict if there is an effect it will be beneficial but marginal

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    2. I've taken an aspirin many times when I had headache. It did have effects and my headaches stopped. I didn't have any side effects though, even if others have reported them.
      Is the rule of thumb valid then?

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    3. Take too many and you are dead but where is your counter point?

      The point I am making is that if you suppress the immune respose to get rid of MS, it is going to be suppressed to get rid of infection.

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    4. I also believe that the role of Vitamin D is more preventive, perhaps actually during certain stages of life: in gestation, in the passage from childhood to adolescence where hormone peaks exist, etc. Only that in case of doubts I take 10.400 IU every day. "Better safe than sorry"...

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    5. MouseDoctor: and the point I made below was that you like others are assuming that vitamin d IS an immune suppressant. There is no evidence that it is, in the terms used for MS drugs (where is the evidence it kills immune cells). Your aspirin analogy does not hold because the levels of vitamin d 25(OH)D in the blood are still within the levels naturally seen, it is not in overdose. Also aspirin is not normally found in the blood but vitamin d is.

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    6. However it is is been tested as if it is an immune suppressant in clinical trials hence my assumption. NCT01490502.

      Will it have a dramatic effect...I doubt it. Will it have some effect possible. You ask for predictions that is my prediction.

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    7. Have a cut on aspirin, you wont clot as well.

      Will any Neutricutical have a big impact...again I doubt it, it will be incremental.

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    8. I was just recalling my multiple horrendous experiences with cinnamon, which gives me severe interstitial cystytis - to the point of becoming severely bladder incontinent. I now avoid this spice like the plague. I recognise now that the "relaxing", soporific effect it had on me in the beginning was actually a first symptom of poisoning.

      So don't underestimate the power of nutriceuticals - for good and ill! Not wishing to be argumentative - I would say that an argument that something which works must have negative side effects is flawed. There is no real logic to that. It would, for example, not necessarily be the case with a therapy for MS which doesn't hammer the whole immune system, but intelligently targets the one vital link in the chain which sets all the damage in motion... EBV?

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  2. Why do people believe vitamin d is an immunosuppressive? The evidence is that it is used by part of the innate immune system, and having sufficient allows that part of the immune system to work correctly. If the innate immune system handles the infection and the active immune system is not triggered is that a suppression of the immune system?

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    1. Many people beleive that the innate immune system is a driver of nerve damage...will this be made optiumal?

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    2. Sorry - I'm not clear on what your answer to Anon means. Since I personally have PPMS and reason to believe that my innate immune system is highly efficient, very active, and does all the work in fighting off infections (e.g. I get next to NO respiratory symptoms with colds, not since early teens, i.e. for around 25 years), I'd like to know:

      Does vitamin D (a) potentially increase the amount of damage an "insane" innate immune system is capable of doing, or (b) does it potentially cause the innate immune system to "behave more normally", cause less damage? Or (c) is there just no evidence for any effect on the innate immune system of vitamin D at all?

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    3. I don,t know I would have to do some research

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    4. To translate my answer Anon says they believe if makes innate system work better, then it can work better to create damage if the innate system is made to be optimal.

      Does it do that...probably not

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    5. Okay; thanks for replying.

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    6. Anon here. I would say that having enough vitamin d makes the immune system work correctly, not having enough vitamin d makes it work incorrectly, as it requires vitamin d to work. Once replete in 25(OH)D (what ever that is) I would expect no change in how the immune system works until toxicity sets in, and then who knows.

      It is worth reminding people that two independent journal papers have shown that the IOM miscalculated the RDA for vitamin d. The IOM looked at the data from a number of studies and then worked out the mean and standard deviation of those studies. unfortunately they did it from the means of all the other studies not the actual distributions. They are out by a factor of 8 to 10, so 5000IU a day is within the new recalculated RDA. The IOM have neither agreed with or refuted these papers they have ignored them.

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  3. Haha! My daughter (a plant biologist) got my husband wrapping a turmeric poultice around his knee for a running injury a few years ago, he's religiously continued ever since and keeps dying everything yellow... same daughter is always talking about the importance of going back to the original research evidence ;-)
    So, have just completed survey (shocked to find my EDSS now coming out at 6.0, it was 4.0 this time last year). On a lighter note turmeric is fantastic in a curry!

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    1. I think that's the best use of turmeric, in curry. If it has a beneficial effect, great, otherwise - curry, what's not to like? ;-D

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  4. Could turmeric be the reason why fewer people from Asia have MS compared to Europeans? So far I have read that observation might be because of exposure to sunlight, but perhaps it is due to consumption of turmeric?

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  5. Re, Vit D,I tend to look at it as something that can help my immune system fight infections, which will hopefully cut back on relapses. Pre diagnosis, I had approx 3 or 4 chest infections per year. However, I haven't had any since I upped my vit D and I'm also on Gilenya. Maybe it's the vit D or maybe it's my overactive immune system attacking everything. I'm too scared to lower the vit D though just incase...

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    1. A study published in 2009 looked at respiratory infections and vitamin D levels in adults. These researchers took information from a very large study that was done previously. Over 18,000 adults were looked at for this study. They found that:
      People with the lowest vitamin D levels had a 55% higher chance of getting a respiratory infection, compared to people with the highest vitamin D levels.
      People with vitamin D levels of 30 ng/mL
      had the most protection against getting respiratory infections.

      Ginde AA, Mansbach JM & Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 2009;169(4):384-390.

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    2. Thank you. That gives some validity to my experience.

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  6. Thank you doctors for clearing this up for me, really, now the earth is flat again. Of course natural remedies are just bogus, and the real deal are the drugs which only you can prescribe and only Pharma can produce and only pharmacies can sell and the Journal, oh dear, oh dear.

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    1. We need hard evidence before something is recommended. No-one is saying all natural remedies are bogus, cannabis for example is now accepted as having a positive effect on spasticity in pwMS in a report just released by the American Academy of Sciences but it has taken 17 years of hard evidence (of which we were the first) for this to be achieved.
      As the old saying goes, anecdotal data is no data.

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    2. We didn't do the review/editorial, nor the research, we only reported it. Why are you are trying to shoot the messenger(s)?

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    3. during those 17 years (and beyond) people with cancer, ms, etc have been smoking or inhaling pot.

      ps. evidence rocks. but sometimes inaction for lack of class 1 evidence can hurt too (not us healthy ones, though). for us, the question is always does the benefit (imagined or otherwise) outweigh the risk.

      just googled tumeric - i had no idea that it was a miracle herb. apparently, pot is for losers, could have cured the world ills with tumeric.

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    4. Turmeric is as Prof G so eloquently states is a prostitute; she is very accommodating but any reaction is likely to be faked, or in scientific terms a false positive.

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    5. A false orgasm or a placebo response.

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    6. @"shooting the messenger" and "we need hard evidence" (sorry my French): the wording of Nature editoral was "deceptive", yours is "prostitution", the latter maybe even a bit stronger. Why this personification into devilment of what is just a godly spice with the potential to prevent people from getting sick when used properly? It reminds me of Dawkins flawed opinion, using the active voice in a manipulative way “80% of natural remedies have never subjected themselves to controlled scientific trials” as if those natural remedies were cognitive beings with a scientific PhD that just opt out of clinical trials in order to deceive people? How ridiculous! I tell you what: A placebo-controlled randomized and so on phase-III trial is like the death star of science, only the dark empire would build one. Why? Do you know how much a P-3 costs? These are insane costs which nobody would spend on a godly spice USD20/kilo even with shot-gun like chemical properties (call it lack of a business model). You guys make it look like the other way round, like as if there was a fair race between natural godly remedies and patentable man-made drugs and the better one (drugs of course) did work as assessed by an independent (neither godly, nor manly, so what?) scientific method. Decide you must, on which side of the force settle you will…

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    7. Unfortunately, 2 x Phase 3 double-blind placebo controlled trials = scientific or should I say relgulatory religion. The regulators were not created by scientists, but politicians, who were put in place by democracy. You can have it all. What do you want? Two sets of standards? One for for drugs and another for nutriceuticals? Ask your politicians to sort out the mess. We are just trying to practice evidence-based medicine. The latter demands high standards.

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    8. What I want, I can have it all? I want you to get some sleep and then restart your strategy. EBM is good to get drugs on the market, complexity good to use as an excuse, but who if not you should focus on finding the one clue that makes this MStery disappear?

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  7. You say "I am the science doctor, I tell you what works". And I tell you: "You doctors are clearly biased towards the drug commerce". Steroids have been prescribed for decades with only marginal evidence for certain indications, not to speak of the CRAB drugs. And suddenly, with curcumin, you try to checkmate it by claiming "there is no evidence" and all this in a manipulative language ("prostitute"). I am not impressed...

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    1. No I don't tell you what works I tell you this is the evidence. I am not a fan of CRAB drugs either, but there is evidence they do something.

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  8. I thought Dr Michael Mosely said in that BBC programme that it was only cooked turmeric which did anything. Which pleased me, as I never wanted to take curcumin as a supplement, but love turmeric in my lentil dahl... Whatever it does, or doesn't, it tastes great.

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    1. Yes that's right.

      Could turmeric really boost your health? BBC Magazine 20th Sept 2016.

      Results from turmeric experiment:
      "We didn't find any changes in the group taking the placebo," he told me. That was not surprising.

      "The supplement group also didn't also show any difference," he went on.

      That was surprising and somewhat disappointing.

      "But the group who mixed turmeric powder into their food," he continued, "there we saw quite substantial changes. It was really exciting, to be honest. We found one particular gene which showed the biggest difference. And what's interesting is that we know this particular gene is involved in three specific diseases: depression, asthma and eczema, and cancer. This is a really striking finding."

      It certainly is. But why did we see changes only in those eating turmeric, not in those taking the same amount as a supplement?

      Dr Kirsten Brandt, who is a senior lecturer at Newcastle University and who helped run the experiment, thinks it may have something to do with the way the turmeric was consumed.

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    2. Hope it wasn't some of the BBC pseudo science garbage that they do so well:-)

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    3. It might have been - I'm not sure - although Dr Mosley is very convincing! I found a bit about what I mean on the Internet:

      "Because the placebo group changed as much as the two turmeric groups we cannot attribute any change to the turmeric.

      The white blood cell count also showed that in all three groups, the number of their immune cells had decreased, equally across the groups.

      However, the DNA methylation test we did showed VERY exciting results.

      There was no difference in the methylation of the DNA of our volunteers who took the placebo pills, or those who took the supplement pills, but there was a very significant change in the methylation patterns in the group who were _cooking_ with turmeric powder."

      http://www.bbc.co.uk/programmes/articles/PSTGKKt3HR08tmK69w7J1b/does-turmeric-really-help-protect-us-from-cancer

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    4. Yep sounds like the usual BBC guff let's do an experiment

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  9. Re.. No double-blinded, placebo controlled clinical trial of curcumin has been successful.
    If it was a trial using curcumin as a supplement then that's not surprising it's been unsuccessful. They need to do a trial of it cooked in food.

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  10. http://mobile.nutraingredients-usa.com/Research/Experts-hit-back-at-inaccurate-headlines-after-review-questions-curcumin

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    1. needs a conflicts of interest statements, they need to go back to the journal

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