Jan 12 2017

Curcumin Hype vs Reality

CurcuminCapsA recent systematic review of the alleged health benefits of curcumin show that, yet again, hype based on “traditional use” is not a reliable guide.

Curcumin is a spice that makes up about 5% of turmeric, a yellow spice used in many curries. It is also a traditional herbal treatment. The health claims made for curcumin are numerous – WebMD has this entry:

Other preliminary lab studies suggest that curcumin or turmeric might protect against types of skin diseases, Alzheimer’s disease, colitis, stomach ulcers, and high cholesterol. Based on lab studies, turmeric and curcumin might also help treat upset stomach, scabies, diabetes, HIV, uveitis, and viral infections.

The systematic review had two main findings:

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.

Let’s take the second point first, bioavailability. In order for a drug to be useful when taken orally it has to have adequate bioavailability. This means it needs to be relatively stable, it has to be absorbed in adequate amounts through the GI tract, and then it has to survive a first pass through the liver and be distributed in the body in such a way that it gets to its target tissue is sufficient concentration to have a clinical effect.

Any one of the steps could be a fatal flaw for a potential drug or compound. Most substances do not have all the properties necessary to be an effective treatment. Pharmaceutical companies spend a lot of time and resources studying the pharmacokinetics and pharmacodynamics of drug candidates, and often tweaking them in an attempt to give them the properties they would need to be an effective treatment.

Most herbs do not have these properties. They therefore fail as a therapeutic agent out of the gate. The authors of this review found that studies of curcumin show it does not have the overall bioavailability to be an effective treatment for anything.

Why, then, are there literally thousands of studies with curcumin or turmeric? It is because there is apparently a different set of rules for studying substances that have a traditional use and that are already being hyped to the public as having health benefits.

The usual science-based approach is to study a substance, as I described above, to see if it has the potential to be a therapeutic agent. It then goes through preclinical, animal, and then escalating human trials to determine its safety profile, and its net clinical effect. Most substances do not make it all the way through this chain of research to become approved drugs or proven therapeutics.

Substances deemed “natural” or with a traditional use or just marketed as having a traditional use do not follow this path. They are often marketed without any scientific evidence at all. When studied often there are preclinical trials to see what the substance does to cells in a petri dish. When you apply a chemical directly to cells, this bypasses all the concerns about bioavailability. Invariably stuff happens when you apply a chemical to cells. It is then tempting to speculate wildly from the changes in biochemical markers seen in the petri dish to possible clinical effects.

I need to note that it is notoriously difficult to predict clinical effects from pre-clinical markers. Even putting bioavailability aside, the body is just too complex to anticipate all outcomes. What such studies do, however, is give the illusion of being science-based to the traditional claims made for herbs and other treatments.

Often there are also preliminary human trials – small or unblinded trials, sometimes looking at subjective outcomes. Such studies have a proven massive false-positive bias. These preliminary studies often feed further hype about the alleged natural treatment, which is spread breathlessly and gullibly by the media.

Eventually such “natural” treatments may get to actual double blind clinical trials which are capable of determining if it actually works for any specific indication. Most of the time when studies progress to this level, the rigorous studies show that the substance does not work after all.

Curcumin is just the latest herb to fall into this pattern. It should be no surprise – the preclinical and preliminary studies are a horrible guide to actual clinical effects. So is traditional use, which is essentially just anecdotal evidence, subject to confirmation bias and placebo effects.

The story of curcumin also shows how easy it is to waste scientific resources chasing a lost cause. Chemical analysis of curcumin clearly indicated it was a poor therapeutic candidate due to fatally low bioavailability. This essentially means that all the clinical studies were a waste of time.

Some argue that it is still worthwhile to do the clinical studies in order to inform the public so that people can make better decisions about a product already in use. That is not what happens historically, however. First – most of the research, which is misleading, serves to feed the hype. The research is cherry-picked and presented without proper scientific context. Only when the research matures to a significant degree do we get some reliable conclusions.

Historically, when big and rigorous blinded clinical trials show that a product already in use does not work, this does have a negative impact on sales. However, this negative impact is temporary, and the next overhyped herb or natural treatment must moves up the line. The public never seems to learn the meta-lesson, that they should not believe any of the hype, that “natural” does not mean anything, and that herbs are poorly regulated and the industry cannot be trusted.

17 responses so far

17 Responses to “Curcumin Hype vs Reality”

  1. DevoutCatalyston 12 Jan 2017 at 11:29 am

    I’m so glad I’m not a physician. Last week I visited an orthopedist that trotted out turmeric / curcumin as an anti-inflammatory possibility in case I didn’t want to go the drug route. I never suggested such a thing. I suspect that in this physician’s mind is the desire not to appear a close-minded rube. I used to believe the insinuation that medical doctors are actually ignoramuses, an idea put forth by CAM, I used to think this was intended strictly for the patient but now I wonder if it isn’t also designed to tweak the physician in such a way as to loosen up their standards towards the new standard of care, one of not caring if the junk actually works, if an idea has merit, just shut up and promote it.

    If I were a physician I would be cringing each and every day and I couldn’t bear that. The profession has been compromised by purveyors of smarmy nonsense. Enough already.

  2. Lane Simonianon 12 Jan 2017 at 12:03 pm

    The declarations regarding the demise of curcumin may be premature. There are a number of scientists trying to find a work around the problem of poor bioavailability, including the use of nanoparticles and nebulizers. Perhaps, the people of India have already found a partial work around using black pepper in conjunction with curcumin.

    At present curcumin may work best (if it works at all) in various intestinal inflammatory conditions where problems of entering the bloodstream pose less of a problem.

    http://www.todaysdietitian.com/newarchives/090114p56.shtml

    And one does not have to rely on curcumin as a primary or sole antioxidant and anti-inflammatory. Other methoxyphenols such as ferulic acid, syringic acid, sinapic acid, eugenol, and vanillin may be somewhat more bioavailable and thus potentially more effective.

  3. chikoppion 12 Jan 2017 at 12:23 pm

    To be fair, the article critiques claims made by “traditional use.” If someone is claiming that curcumin is an effective drug as ingested or as a topical agent, there is not sufficient evidence to support that claim.

    This wouldn’t rule-out trials of a synthesized form that improves bioavailability. However, those forms would also have to be demonstrated to be effective in appropriate trials.

  4. bendon 12 Jan 2017 at 1:21 pm

    Lane, well, that’s a different proposition, then, isn’t it? Effective delivery strategies for fragile compounds will not make “golden milk” therapeutically beneficial and whole foods isn’t going to be selling nanopolymer-complexed turmeric. Natural products pharmacology is a genuinely scientific beneficial endeavor and has given us everything from aspirin to docetaxel and artimisinin. But even these compounds needed purification and modification in conjunction with appropriate dosing and delivery mechanisms. Turmeric supplements are likely good for nothing and turmeric itself, for nothing but flavor (but oh, what a flavor).

  5. SteveAon 12 Jan 2017 at 1:29 pm

    Lane Simonian: ‘There are a number of scientists trying to find a work around the problem of poor bioavailability.’

    For what reason?

    If its poor bioavailability means it has no effect, then all the ‘evidence’ that it did anything in the first place has gone up in smoke.

  6. RickKon 12 Jan 2017 at 8:39 pm

    Isn’t interest in curcumin driven somewhat by he low rate of Alzheimer’s in India? I assume that drives Lane’s interest.

  7. Willyon 12 Jan 2017 at 9:06 pm

    Wait! Curcumin isn’t the only “super-product”. According to an ad in my local paper’s supplement, cayenne, baking soda and H2O2 are wonderful as well. Not only do they cure many diseases–famed physician and herbalist Dr. John Christopher reported “In 35 years of medical practice I have never lost one heart attack patient”–but they are also handy for home cleaning, even rust removal and elimination of blood stains!! Even better, while one single book costs $17 (sorry, each miracle cure/cleanse has it’s own special book), you can get all three for ONLY $30!!! I hope hardnose is around to learn about this screamin’ deal! hardnose, let me know if you need the mailing address.

    BTW, the secret to avoiding death from heart attack is to administer “a “precise [alas, unspecified] dose of cayenne–once you are suffering from a heart attack! God, er, information, bless these people who realize the value of “alternative medicine”. May the Force be with you, hardnose!!!!!!!!!!!!!!!!!!!!!!

  8. SteveAon 13 Jan 2017 at 7:17 am

    It would make a great story…

    We’d been searching for the cure to such-and-such for years, and it was right here under our noses all the time. We only had to reach out and open the kitchen cupboard…Oh, the irony.

    I think that’s the appeal of this kind of thing. It also plays to the folksy “what do those guys in white coats know?” narrative.

    My mother once bought a book on vinegar, which apparently cures and cleans EVERYTHING.

  9. Willyon 13 Jan 2017 at 9:29 am

    I remember the vinegar thing too. Just think: cayenne, vinegar, baking soda, H2O2, and curcumin–the trifecta, er, quint-fecta? Well, some kinda “fecta”, fer shure.

  10. zorrobanditoon 13 Jan 2017 at 12:02 pm

    Bouncing of what DevoutCatalyst said, my physician recommended Arnica (a homeopathic ointment) for some ailment or other, and now it regularly appears on her “list” of “medications” I am taking.

    Now this woman has a medical degree, she is a very successful general practitioner, and surely she knows (and surely she should know) that I will get about as much benefit from Arnica as I would get from bacon grease.

    But why why why is what we want to know. Why did she tell me to use this stuff? Surely it is harmless (one hopes), but is that the bar? That’s it? Just that a recommended remedy should do no harm? It doesn’t have to actually accomplish anything?

    I haven’t yet had the heart to challenge this. Either she really believes that Arnica will accomplish something, in which case I’m wondering about the quality of care I am getting otherwise, or she will admit that she thinks I’m a moron.

    “My mother once bought a book on vinegar, which apparently cures and cleans EVERYTHING.”

    This idea regularly appears on facebook.

  11. tmac57on 13 Jan 2017 at 2:02 pm

    My anecdotal evidence is that curcumin can cure the blandness of chicken and white rice…just sayin’

  12. Surakyon 13 Jan 2017 at 10:05 pm

    Because curcumin is not bioavailable, it is not responsible for whatever benefits it supposedly has in traditional remedies.

    Yet people are assuming that if we could make it bioavailable, it really would be a remedy.

    … watch it turn out to be really toxic with no medical benefits.

  13. locutusbrgon 16 Jan 2017 at 1:45 pm

    @zorrobandito
    As an orthopedist I am dismayed by the anecdote from devout catalyst as well as your anecdote. I have heard my partner offer a known homeopathic cream sold at whole foods for knee pain. 🙁
    Physicians are human beings. There are many reasons that good physicians bend to this type of messy thinking.
    Medical training is a foundation, some people are driven by conformation biases or a case of the shruggies-as steve would say-Whats the harm? people. Some feel the the placebo effect is beneficial and an integral part of helping patients deal with chronic illness. Most stop short of openly recommending quackery, but not all.
    So the bar is complicated.
    I ask them questions like” do you really think you would use a knee arthroplasty model, with this level of evidence supporting it? So why are you recommending this cream” and such… trying to get them to think. It doesn’t always work the medical model invariably induces conflict of opinion.
    encouraging the best evidence standards is all we can hope for.

  14. djjosh21on 16 Jan 2017 at 8:39 pm

    Sorry, can someone explain why improving the bioavailability is not a good idea? If say the majority of the molecule has an effect at the cellular level in in vitro studies, then let’s say for example adding a hydroxyl group at some part of the molecule that does not interact with its receptor improves its bioavailability (maybe through solubility or whatever). Then what’s to say the in vitro effects observed in previous studies will not be observed at the organismal level? Yes there will be other complicating factors beyond bioavailability and getting past the liver, but how can we know unless it’s tried?

  15. tb29607on 17 Jan 2017 at 12:06 am

    dj

    I would be willing to bet someone is trying to do exactly what you have suggested. Looking through the posts it seems that the concern (or at least the only one that makes sense to me) is that ” bioavailability enhanced curcumin” would be made available and marketed to the public without proper testing. If it proves to have the anti-inflammatory properties being advertised, it may work too well and cause people to become immune compromised for example.

  16. tb29607on 17 Jan 2017 at 12:19 am

    locutusbrg,

    I have also listened to colleagues spout off the benefits of the in vogue, magical, all-natural, cure alls and I agree it is distressing.
    Most recent one in my area is a water ionizing system to reduce our “acid levels”. People are spending thousands on the things and don’t even know that to reap the “benefits” you have to drink the water within a couple of hours of it being “treated”. A dermatologist is promoting that one.
    And a pediatrician is on the copper/magnetic bracelet for arthritis band wagon.
    Far too many people in our profession seem to adopt their own brand of “woo” and blindly cling to it.
    I have gotten so that I only address the potentially harmful ones.

  17. Lane Simonianon 17 Jan 2017 at 12:52 am

    djjosh, this really is the direction that the research on curcumin is going in.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882399/

    Between ineffective due to low bioavailability and being a pro-oxidant at high doses (which is generally but not always a negative) lays the potential of curcumin. Whether that potential can ever be reached is impossible to determine at this point.

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