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Chemical Biology

Curcumin Will Waste Your Time

I really enjoyed reading this article in J. Med. Chem. on curcumin. (Update: here’s the take over at Practical Fragments). That’s a well-known natural product, found in large quantities in turmeric root (which is where most of the yellow color comes from). It has, over the years, been a hit in many, many assays, and I would not want to guess how many derivatives of the structure have been prepared along the way. There is an entire web portal that attempts to bring together all the publications (thousands) and patents (hundreds) relevant to the field. More than that, a quick search will reveal that there are plenty of people ready to sell you curcumin tablets in every variety, for a list of ailments longer than most people’s legs. Everything from Alzheimer’s to upset stomach – curcumin is good for what ails you, apparently.

So what do you get when you look closely at the molecule and its activities? Well, for one thing, curcumin’s stability and pharmacokinetics are absolutely terrible. It’s less than 1% bioavailable, and its half-life under physiological conditions is measured in minutes. This makes a person wonder how it can be such a wonder drug. The authors of the current paper, indeed, state that “To our knowledge, (it) has never been shown to be conclusively effective in a randomized, placebo-controlled clinical trial for any indication“. How about as a lead compound, a hit from an assay? The situation is just as 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.

In cell, tissue, and animal assays, it falls into the category of “Invalid/Improbable Metabolic Panacea” (IMP), a term that’s been used for natural products that seem to have all sorts of weakish activity all over the place. Unfortunately, the literature is full of reports of curcuminoid compounds as actives for all sorts of specific molecular targets (this latest review goes into several of these). Taking the properties and activities all together, though, these efforts would seem to be largely – and almost certainly completely – wastes of time and money. What’s worse, it appears that from 2001 on there are at least 135 registered clinical trials using the stuff. The review goes into four examples for which details are available, all of them complete wipeouts, and those would seem to serve as good proxies for the rest given that no curcumin trial has ever reported any convincing positive results.

The paper ends with a very sensible set of recommendations for anyone doing natural product bioactivity research (and indeed, these are also high recommended for anyone screening any set of compounds. They are not new – everyone should know this stuff. Check your compound’s solubility and aggregation under the assay conditions. Check its stability and purity. See if the activities you’re getting make any sense given those numbers. Check the selectivity data, and not just against something that’s very close to your target. Use biophysical methods (several, preferably) to confirm that your compound is really hitting the target, or some target – don’t just rely on cellular readouts without digging further. And so on.

These things are a pain in the ass, of course. They take more time, more effort, and more money. They will slow down your publication plans, and often enough they will invalidate your entire line of inquiry and you may have to find something else to do or come up with a completely new idea. It’s no mystery why so many labs slide over many of these tasks, because they’re really annoying. You should only follow these recommendations if you care about your research being valid and reproducible, and if you’d like it to lead to something useful. But if you just want to bang out some publications, scoop up some money, and fill the scientific literature with more waste products, then carry on as before. There are lots of experiments you can do with curcumin.

94 comments on “Curcumin Will Waste Your Time”

  1. anonymous says:

    There was lot of irrational exuberance from every one with the sole objective of getting funded and boy this was well funded project by you name it NIH, NSF, etc.! The Indian concept of ayurveda surmises that it has some medicinal properties. May be, but then you just have to incorporate in all your Indian cooking. Turmeric itself is not poisonous (curcumin’s structure with beta-diketone, phenol reveals its fast clearance from the blood) but the synthetic variation maybe, if it worked. But then we may never know.

    1. Calli Arcale says:

      “The Indian concept of ayurveda surmises that it has some medicinal properties. ”

      Mind you, ayurveda says the same thing about lead. There was a big to-do a few years back about the FDA seizing some ayurvedic remedies that the press described as “contaminated with lead”. Which was inaccurate. Lead wasn’t a contaminant. It was the main ingredient.

    2. wzis says:

      That’s not true. I have been taking curcumin capsules for more than a year. It improved my short time memory, improved the symptoms of gingivitis, the longvida one even improved my hearing and I also can feel it improved my cerebrovascular,reduced the risk of getting stroke,

  2. Hap says:

    Did they reference Chemjobber’s list of chemical-free products with their title?

    1. Chemjobber says:

      NB it’s not just my list; my coauthor Dr. Goldberg should not be forgotten.

      1. Hap says:

        I forgot who the other author was at first. Sorry.

      2. M. Welinder says:

        Your list is missing Helium. That, by and large, has not participated in anything chemical since alpha decay created it and it grabbed the nearest two electrons.

        1. Allen says:

          It’s all about the right incentive. But merely existing is an excluding criterium for that fine list.

  3. charlie says:

    I remember in the 1970s making turmeric balls to put on an uncle’s body as he lay dying of lung cancer.

    (And mind you, I come from a family of physicians!)

    I actually take a turmeric supplement. Tiny little pill. I do think it changed the amount of gray in my hair.

    My only issue is when I cook with tumeric (and I am indian) I use about 5x the amount that is in the pill. I like the taste and color but hate the clean up – the stuff gets everywhere.

    1. JSR says:

      Wait, more gray or less gray??
      (asking for a friend…)

  4. Janitor says:

    Another nice little tur* for Mr Ramaswamy to polish…

    1. David says:

      You can’t polish a tur*… but you can roll it in glitter

      1. Docrailgun says:

        The Mythbusters proved that you can polish a ball of human waste.

        1. Not gonna put my name on this says:

          Depends on how much Indian food you’ve had.

        2. rws says:

          I don’t think they used human waste. Not sure what kind.

          At least I hope not.

  5. Peter Kenny says:

    It’s certainly useful to see the medicinal chemistry of a natural product reviewed in this manner and, for me, the poor chemical stability of curcumin would rule out its clinical development. Nevertheless, I would challenge the following statement by the authors (I have not included the references):

    “Curcumin Is a PAINS. PAINS, or pan-assay interference compounds, are compounds that have been observed to show activity in multiple types of assays by interfering with the assay readout rather than through specific compound/target interactions. Many compound classes have been codified and identified as PAINS or potential PAINS. Compound 1 exhibits all known PAINS-type behaviors: covalent labeling of proteins, metal chelation, redox reactivity, aggregation, membrane disruption, fluorescence interference, and structural decomposition.”

    The basis for my challenge is that the original PAINS study was performed on results from a panel of six AlphaScreen assays so it is not accurate to claim that PAINS “have been observed to show activity in multiple types of assays”. Secondly, I would challenge the authors to present evidence of any of the PAINS in the original study showing any of the “PAINS-type behaviors” in the six AlphaScreen assay panel of the original study.

    I have linked the first of a series of five blog posts as the URL for this comment

  6. lynn says:

    Thanks. Very useful reference to direct prospective authors to when I review the inumerable papers on the wonders of curcumin as an antibacterial.

  7. PF9 says:

    Nice article, but I echo Pete’s comments on PAINS. To me, as a computational chemist, it screams Do the experiment! As a journal editor, what a nice rebuttal article to cite on the numerous in silico studies on cumins I get.

    1. Peter Kenny says:

      When focusing on a single compound like this, it’s probably best to simply present the (experimental) evidence and not get too distracted by the PAINS dogma. I would argue that this article is actually weakened by reference to PAINS and it would have been more authoritative if it had made no reference to PAINS. One problem with using the term PAINS is that it is often unclear what it should be taken to mean. Nevertheless, J Med Chem makes specific provision the occurrence of PAINS in manuscripts. As public service, I have provided some guidelines for dealing with PAINS-related reviewer criticism and have linked these as the URL for this comment.

    2. Derek Lowe says:

      Definitely do the experiments – but do the ones to shore up your belief that such a compound is doing what you think it’s doing. I think that the proper response to seeing a PAINS-like structure should be to move said compound up to the top of the experimental queue for aggregation, etc.

      1. Peter Kenny says:

        Hi Derek,

        There is certainly no suggestion that we should ignore concerns about screening hits based on their chemical structures or historic screening data. That said, I think we should stop using the term PAINS because it’s not clear what it means. In J Med Chem guidelines for authors, calling a compound a PAINS seems to mean that its molecular structure matches one of the substructural patterns in the original PAINS article although I will put it to the editors that this could have been made clearer. The curcumin article featured in your blog post talks about both PAINS and potential PAINS. I would argue that to describe a substructure associated with frequent hitter behavior in a panel of 6 AlphaScreen assays as showing pan-assay interference represents extrapolation of data analysis outside its applicability domain.

        It has been recognized for almost as long as HTS has been around that it produces a certain amount of crap. The challenge has always been to demonstrate in an objective manner that what we believe to be crap really is crap. The danger of posed by studies such as the original PAINS article is that they lull us into thinking that our beliefs are grounded in fact. I’ve linked a blog post on the need to make a clear distinction between what we believe and what we know.

  8. JAB says:

    As a natural products chemist, I couldn’t agree more….potency and specificity are the only way to fly!

  9. Lane Simonian says:

    The problem with curcumin is indeed its very low bioavailability. There are several researchers trying to get around that problem employing everything from nanoparticles to nebulizers. Whether anything will come of this remains to be seen.

    Curcumin is such an enticing compound because of its antioxidant capabilities.

    Other methoxyphenols such as ferulic acid, eugenol, sinapic acid, syringic acid, and vanillin have their own challenges, but because of their antioxidant and anti-inflammatory qualities they will continue to receive attention.

  10. Emjeff says:

    Bioavailability and pharmacokinetics matter. If the compound is not absorbed, I can’t see how it has any activity beyond a local GI effect. Any systemic effect attributed to a compound with <1% bioavailability is either incredibly potent, or magical. Same for a short half-life, UNLESS you can show through its pharmacology that it has long-lasting downstream effects.

    1. Diver dude says:

      Well, the gut is pretty firmly connected to the CNS and the immune systems. I’m not supporting curcumin, merely suggesting that a local GI pharmacological effect can have wide systemic repercussions.

    2. Dr CNS says:

      Active metabolites formed in the gut, which are themselves absorbed?
      I am not saying that is the case with curcumin, but compounds may have pharmacological effects without themselves being absorbed. Prodrugs, for example…

      I also agree with Pete. Some generalizations have been made too quickly… and with too few data.

      I worked in a project where a racemic hit contained a PAINS fragment. Yet, after resolution, one enantiomer was active in vitro at the target, and the other was not. I thought this was ruling out the activity was due to aggregation in the in vitro assay.
      I am curious what folks think… can aggregation be enantiospecific?

      Thank you.

      1. tlp says:

        If you had a chiral counter-ion in the assay mixture, why not? That’s how chiral resolution works, isn’t it?

  11. JACS ASAPS says:

    “You should only follow these recommendations if you care about your research being valid and reproducible, and if you’d like it to lead to something useful. But if you just want to bang out some publications, scoop up some money, and fill the scientific literature with more waste products, then carry on as before.”

    modern organic methods, anyone?

  12. Wavefunction says:

    It’s worth noting that one of the leading researchers on curcumin, Aggarwal from MD Anderson, has come under fire for some very suspicious results and papers (you can look him up on Retraction Watch). Curcumin reminds me of resveratrol. It probably has some beneficial effects but these are likely limited, local and dependent on longtime chronic exposure (as in your daily food regimen).

    1. YMD says:

      “Very suspicious results” is putting it mildly. Nineteen papers by Bharat Aggarwal have been retracted and a total of 65 of his papers face allegations of fraud. His research is largely responsible for the hype around curcumin and it turns out that it is basically all based on faked results.

  13. JG858 says:

    On the other hand, curcumin is great at detecting boron in water!

    1. Derek Lowe says:

      Probably its most reliable use, when you get down to it.

  14. rtw says:

    Curcumin is something quite a lot of people diagnosed with Colon Cancer take as an adjudicate supplement, mostly because many studies have shown that people (Indian mostly) that have a diet high in Tumeric seem to derive some benefit and lower rates of colon cancer than those that don’t have this in their diet. I think many of those studies are probably not likely due to a causative effect yet it persists. Correlation especially in many of these studies does not equal causation! But lots of colon cancer patients use it anyway. As Derek has indicated, innumerable studies have been initiated but clinically they have ended up being a bust, therapeutically speaking. A recent paper in Science Signaling:

    Seems to support the idea that curcumin does have some effect on inflammation via NF-κB signaling and use at lower than that expected dosage to outright kill cancer cells, in combination with something like a PD-L1 inhibitor might be clinically useful and should be investigated.. (Their words not mine). They used cell-based, biochemical, and proteomic assays using human cancer cell lines of various types, T cell co cultures, and an immunocompetent mouse models to come to this conclusion.

    So like as not this sort of stuff with continue.

  15. Chad Irby says:

    Turmeric is a significant mood-altering substance.

    When I eat a good curry, it makes me feel better, at least…

    1. milkshaken says:

      turmeric must be the explanation why I feel so sleepy after lunch in a good all-you-can-eat indian buffet

      Every time I see chalcone-like motiff in HTS hit, I groan with pain (and I used to work on Sutent compounds for several years)

    2. Passerby says:

      It’s probably because turmeric is a mild laxative.

    3. michael valentino says:

      Yes. Nothing beats a good curry. And a good placebo is worth its weight in gold.

  16. ZK says:

    Just wondering how to compare results from curcumin to that from turmeric. Turmeric activities may come from other constituents.

  17. gippgig says:

    I found that curcumin from tumeric, even 95% pure, upset my intestines (anecdotal evidence, but the result seems clear). Be forewarned.

  18. Nicholas Yee says:

    As a younger chemistry student (3rd year, looking good for a masters) what specifically is bad about “coordinating metal ions” within the body? I have a slight textbook familiarity with chelation therapy for heavy metal poisoning, and have used EDTA before, but i have hardly any pharmacology or toxicology background.

    I’m guessing it makes essential metals like iron and magnesium unreactive within the systems they usually work with, like Fe with myoglobin and hemoglobin. Am i wrong?

    1. Hap says:

      Coordinating metal ions means that when you test curcumin in the presence of metal ions, you might be seeing the effect of the metal ions in the assay rather than the effect of curcumin (for example, In that case, you would be seeing something as a hit that really isn’t.

    2. Derek Lowe says:

      Hap’s right. Another complication is when an enzyme in an assay needs a metal cofactor, like magnesium, and the drug substance is yanking it away. You see a deactivated enzyme and think “Aha! I have an inhibitor compound!” when all you have is a metal chelator.

  19. Duncan Purvis says:

    Perhaps formulating curcumin correctly and using it to treat IBD, where a local gut activity could provide a benficial effect, might provide a route to showing efficacy? , Mutalik et al., 2016: Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin.

  20. Raisin-In-The-Rum says:

    The authir is wilfully ignorant of the fact that curcumin has demonstrated clinical efficacy in many human conditions, from relieving inflammation in ostheoarthritis, to decreasing polyp number and size in people with familial adenomatous polyposis (polyps which eventually become tumors).
    The authors of his quoted study even have the presumption to claim IN VIVO results are ‘likely false’! There is no way a substance gets into 135 clinical trials while being useless, yet people like that think everyone else is an idiot except them. This is simply smug despair, so they don’t have to think about optimistic possibilities (out of fear of being disappointed).
    Fast metabolism problems have been overcome by using eg glucuronidation inhibitors like like piperine. Oral availability has improved through other adjuvants, including other components of turmeric. If a molecule has ‘weakish’ (by whose definition?) activity or bioavailability, it means it’s not being used correctly, or aggressively enough.
    This review article shows which studies of curcumin have succeeded, and how it is being made into a more convenient drug with a better lifetime and availability.

    1. Hugo says:

      Bringing up a review article from the “scientist” with the most retractions in history doesn’t really reinforce your point…

    2. Derek Lowe says:

      Exactly. You are quoting a known fraud, whose papers are being pulled from the literature because they have been faked. Wake up.

  21. Anon says:

    Invest in Watson to search the literature for potential drug candidates with its artifcial intelligence, and I’m sure curcumin would jump right out. That’s the problem with AI: Put shit in and you *still* get shit out. Except that you pay millions to be told it’s the best of all candidates.

  22. Insilicoconsulting says:

    Here go the doubter’s brigade railing against things unncecessarily. Yes turmeric is not curcumin but is one of the best known and most abundant compounds in turmeric. Curcumin is not bioavailable yadaya true. How did this advance our knowledge of medchem or the chances of new drugs being discovered?

    Turmeric is indeed a constituent of indian food and home cooks use it sparingly. In particular combos, We were supposed to drink Milk+turmeric in our childhood for throat infections. These days when i get a sore throat or a bacterial infection, I just take a teaspoonful with water, gargle and gulp it down. Works for my throat. Along with salt water gargling and , eucalyptus oil inhalation for sinuses. Shall we invest 500 mUSD in clinical trials so skeptics will be satisfied?

    Again this is for turmeric not curcumin which probably has all non-drug like properties but is a good anti-oxidant etc. (even for wounds)

    I am tired of this all negative posts. We are intelligent enough to figure out what is nonsense. No need to repeat it ad nauseum or or snigger at home remedies that may be placebos but worked anecdotally or as placebos before modern industrial medicine appeared, just this last century.

    1. Derek Lowe says:

      Perhaps all the efforts that have gone into curcumin over the last ten or twenty years could have advanced medicinal chemistry if they’d been directed towards something else? If you come up with some Doubter’s Bridgade stickers, I’ll be glad to put on one.

      1. Insilicoconsulting says:


        It’s not just about curcumin. Maybe its useless. But repeatedly blogging about such failures doesn’t do any good. Just as repeatedly talking about food babe doesn’t. Most folk try out home remedies because there are no good alternatives. Have anyone found a great oral drug cure for sinuses lately? Childhood viral infections? IOr repeated infections in polluted countries like ours that makes taking antibiotics each time a non-option? That’s when such measures are used. And as I quoted curcumin or not, turmeric works in throat and sinus infections. Why not write a post that points out those positive points and then say that curcumin is probably not what makes it work and other compounds should be investigated? And speculate which ones?

        Why not compare the reasonable looking symmetric structure and reason in which of the myriad claimed indications, it could work from a medchem viewpoint? I have seen similar structures albeit with much better bioavailability come up in anti-cancer SAR’s and diabetes SAR’s.

        Our ancestors had to make do with what nature gave them since organic chemistry and understanding of drug mechanisms is a very recent development (relatively). Why not think about what your expertise could do to make it work? Thus the talk about the badge. Being scientific is not beating the drum that every layperson has always been wrong. We saw where it got us with Trump’s supporters.

        1. Hap says:

          The structure (or the mixture) is not the problem – it’s the unwillingness to actually test that the lead does what is seen in the original assays and to look at what the structure might do (or is known to do) chemically and to try to eliminate those reactivities as the mechanisms of action. If you ask a question, you ought to be willing to listen to the answer. Not liking the answer is not relevant. If we’re immune to data, then we’re FUBAR. Reality doesn’t care about our egos or identities – it is, whether or not we believe it, and its enforcement is without appeal.

          As a side note, if the lead is claimed to have both an activity and its converse, it ought to make one start questioning what is happening with the lead.

        2. Lane Simonian says:

          Studies such as the one discussed in this article don’t really get us very far. The question is whether curcumin does not work (outside of gastrointestinal inflammatory diseases perhaps) because of its low bioavailability or it does not work for other reasons. If the answer is the former, then the compound should continue to be studied. What can be done or has been done to increase it bioavailability? Does the combination of curcumin with piperine make a difference? Do the other compounds in turmeric make a difference? And are similar compounds with greater bioavailability effective in the treatment of diseases caused by oxidation and inflammation? The intent of studies like this seems to be as conversation enders. Instead, they should be conversation starters.

        3. Derek Lowe says:

          The authors of the review go into detail about pure cucurmin versus curcuminoid extracts, and they come to the conclusion that this complication just makes the literature on this topic ever more hard to interpret and/or worthless to build on. If you know of some reliable clinical data on turmeric helping viral infections, etc., I would be very glad to see it.

          I have never seen a structure like this turn into an actual drug. It is not “reasonable looking” at all. I don’t think I have enough expertise to make something like this into a workable therapy, and since art is long and life is short, I’m applying myself to other fields. If curcumin is what we’re left with as a good choice to do drug development on, we’re in a bad way.

  23. Paul Brookes says:

    Everything you need to know about Curcumin can be summed up as follows: “Bharat Aggarwal published lots of papers on it”.

    Google is your friend, if you don’t already know why he’s (in)famous. Unfortunately, the myth of curcumin lives on in part because the US Office of Research Integrity has yet to release findings of an investigation into Aggarwal, after more than 4 years. When (if) they do, I don’t imagine the effects on those promoting curcumin will be positive.

  24. “Everything from Alzheimer’s to upset stomach – curcumin is good for what ails you, apparently.”

    Including Type 2 diabetes, for which the effect disappears as reliably as it does for every other condition when the proper double-blind trial is conducted.

    I like curry, but not because I think it’s going to help my diabetes.

  25. STM says:

    Curcumin is a magic drug…just wait a few years and behold the abracadabra!

  26. Jeffrey says:

    erdure Sciences sells Longvida, a “highly bioavailable” formulated version of curcumin. Studies listed from their website:

    The purpose of this study was to determine the effects of oral
    supplementation of Longvida® 400 mg/days on muscle & ADL soreness, creatine kinase, and inflammatory cytokines following EMID. Subjects were randomly assigned to either curcumin or placebo (rice flour) and supplemented 2 days before to 4 days after EMID. Blood samples were collected prior to, and 1, 2, 3, and 4 days after EIMD to measure CK and inflammatory cytokines. Curcumin supplementation resulted in significantly smaller increases in CK (− 48%), TNF-α (− 25%), and IL-8 (− 21%) following EIMD compared to placebo. Continue Reading

    -Biomarkers: Curcumin supplement improves vascular endothelial function in middle-aged and older adults. Santos-Parker JR et al. Geront. Dec 2015. 55(Suppl 2): 195. DOI:10.1093/geront/gnv554.01
    -Longvida® Curcumin & Recovery from Muscle Injury, University of North Texas, Complete Awaiting Publication
    -Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations. Nahar PP et al. University of Rhode Island, J Med Food. July 2015. 18(7): 786-792. doi:10.1089/jmf.2014.0053
    -Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. Cox et al. Centre for Human Psychopharmacology, Swinburne University. J Psychopharmacol May 2015. (Vol 29)No 5: 642-651. doi: 10.1177/0269881114552744​
    -Anti-inflammartory effects of novel standardized solid lipid curcumin formulations. Nahar et al, J Med Food. 2014. 1-7.
    -Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. Cox et al 2014, J Psychpharm. 2014 Oct 2.
    -Curcumin (Longvida®) suppresses soluble tau oligomers and corrects molecular chaperone, synaptic and behavioral deficits in aged human tau transgenic mice. Ma et al, J Biol Chem. 2013 Feb 8;288(6):4056-65. doi: 10.1074/jbc.M112.393751.
    -Acute human pharmacokinetics of a lipid-dissolved turmeric extract. Shah et al. Planta Med 2012; 78-PH5
    -Diverse effects of a low-dose supplement of lipidated curcumin (as Longvida®) in healthy middle-aged people. Disilvestro et al. The Ohio State University. Nutr J. 2012. 26;11:79. doi 10.1186/1475-2891-11-79
    -Effects of Longvida® on soluble tau oligomers and cognitive and synaptic deficits. Frautschy et al. AAIC 2011, Paris France.
    -Human pharmacokinetics of chronic dosing of Longvida®: dose-concentration correlation. UCLA, 2011.
    -Acute human pharmacokinetics of 40mg curcumin (as Longvida®) leads to therapeutic blood levels. Shah et al. Manuscript submitted 2011.
    -Efficacy of Longvida® in stage III human trials, TATA Memorial Centre, Mumbai. Study ongoing.
    -Impact of Longvida® on soluble tau oligomers and behavioral and synaptic impairment. Ma et al 2011. Manuscript in publication.

  27. cysmuch says:

    “I have never seen a structure like this turn into an actual drug.” ibrutinib, anyone? tecfidera? those are drugs, very valuable drugs, last time I checked.

  28. cysmuch says:

    and by the way, ibrutinib was labeled as a “tool compound” never suitable to be a drug way back when. but it’s a drug now, so let’s stop with all the inferior chemical probe talk as well.

    1. HTSguy says:

      For the uninformed, how does curcumin resemble ibrutinib? To my untrained eye, ibrutinib looks like a typical kinase inhibitor with a reactive group at one end.

      1. Morten G says:

        Is it even that terribly reactive? I mean the alkene is in that nice conjugated system with the amide.

  29. RB Woodward says:

    Curcumin is just one of hundreds of small molecules in turmeric. Curcumin never was a viable “active component” of turmeric simply because it is not bioavailable. Curcumin is rapidly metabolized. It is conjugated to form glucuronide and sulfate secondary metabolites. No free curcumin is detectable in the circulation (The same is true for resveratrol, green tea catechins and most every polyphenol.) So, if there is indeed something beneficial in turmeric (or wine, tea and dark chocolate) it has not yet been identified. HINT: The “active component” is bioavailable and readily detectable in plasma…And, it most certainly is not a glucuronide or sulfate conjugate.

    1. Ram says:

      Unfortunately today’s reductionist scientist won’t understand you.

  30. Cysmuch says:

    @htsguy: ibrutinib contains a simple but obvious pains pharmacophore, something that would almost immediately rule it out for further development. Point being: molecules that fit the “wont ever be a drug” preconceived notion do in fact become drugs

    1. TB says:

      Ibrutinib was intentionally designed with a Michael acceptor to target a catalytic cysteine residue based on the co-crystal structure of the initial pyrazolpyrimidine scaffold. Such a covalent mechanism is attractive for anticancer agents that are given in very low doses and where the therapeutic index and hence safety profile is also low. If this compound were found as a hit in a HTS assay, then non-specific covalent inhibition would certainly be probable and most chemists would want some evidence that it possesses some useful level of selectivity before working on the scaffold. Among Michael acceptors, acrylamides are relatively weak compared to the corresponding vinylketones, vinylsulfones, vinylsulfoxides, and vinyl sulfonamides. In the case of ibrutinib, the selectivity is due to specific recognition with the target, which places the Michael acceptor proximal to a conserved non-catalytic, but sufficiently reactive cysteine. Likely the kinase also electrophilically activates the Michael acceptor through a H-bond interactions with the carbonyl (I haven’t read the literature and am just speculating). These factors together provide the selectivity.

  31. Haris says:

    In India turmeric used in curries as a spice. The procedure of cooking is adding turmeric and other spices to the boiling oil and mix thoroughly. Generally it is cooked in any cooking oil, and curcumin is readily soluble in almost all cooking oils. So the heat, and the presence of oil will increase the solubility of turmeric and hence it will increase the bioavailability. Turmeric also used in the dishes of chicken, meat, or fish, and the fat contained in it also increases the solubility of turmeric. In my experience, it is very difficult to remove the yellow color of turmeric from my hand after eating the turmeric contained food cooked in oil.
    Science is not myth, we want strong evidence, and proof to believe. So more research is needed on the efficacy of curcumin. In my opinion, the laboratory and real situation is entirely different. In real life we consume turmeric along with other spices, oils, fats, etc. and cooking is a chemical process. For example the presence of piperine will increase the bioavailability of curcumin.
    In the lab, curcumin will precipitate or aggregate very fast. This can overcome by dissolving curcumin in any organic solvent and dilute to the desired concentration by adding few microleters of concentrate curcumin in to the buffer solution in step wise and stir simultaneously.

  32. Helene Wallis says:

    Like Haris, I use turmeric as a food, not curcumin as a drug. Consumed with an oil or fat, to allow better absorption, and with freshly ground pepper to inhibit glucoronidation, it is indeed effective.

    The supplement industry jumped on the first few positive reports about curcuminoids and have used it as a cash cow ever since. That includes subsidizing university research that used their products (both Meriva and Longvida have been guilty of that). What does anyone expect when profit takes precedence over science?

    Turmeric, used in the traditional way or in some analogue to that, is as effective now as it has been for all the centuries it’s been in use. It was the low incidence of colon cancer and dementia in India that attracted western researchers to begin with. That wasn’t a laboratory artifact.

  33. srini says:

    sorry for your results with experiments.. still world doesn’t understand why citrus fruits are more immunity boosters than synthetic ascorbic acid.. same way., curcumin alone may not work in cell lines or animals. If you take root powder it works. we indians use whole root powder for cooking and health purpose and we very happy with it. keep all your publications and databases with you n cry for that. don’t spread nonsence news with your studies.

    1. Anonymous says:

      By most measures (life expectancy; general overall health indicators [incidence of various diseases]; quality of health care system; etc.), India is ranked far behind the USA.

      1. Jay says:

        Not sure what curcumin has to do with the fact that India ranks behind the US in life expectancy (which is more a function of poverty/malnutrition).
        But if India’s life expectancy is so poor, why is this INDIAN herb the #1 selling herbal supplement in America? Why are you spending $50M a year on curcumin.
        Granted I would rather spend that kind of money on turmeric than on American food like fries and hot dogs (which btw I wouldn’t even feed to an animal).

        1. Pennpenn says:

          Because it’s foreign and therefore exotic and therefore the credulous can easily be convinced that it’s either the healing powder of God or Satan’s crotch dandruff depending on who hawking it and how.

  34. Budding Med Chemist says:

    Looks like there’s been a response in ACS Med Chem Letters:

    Can someone with more knowledge on the subject (I’m a 2nd year grad student) point out details or flaws in one or the other side of this (or have I set myself up for a false dichotomy between the two)? On reading both, they both seem “right”. What is a learning med-chemist to think?

    1. Dr CNS says:

      That’s the fun part of medicinal chemistry: you have to decide what you think… and test it!

  35. KS says:

    I assume that you also tested it by actually trying it out for a longer period of time?
    Or maybe not… proving the article you wrote.
    I think I’ll stick with turmeric… as I (and the other members of my family) haven’t used any medicines in the past 5 years and solved literally everything with turmeric and other herbs. Including (me) a massive diaphragm-bil-stomach-duodenum inflamation. Just took a big dose of turmeric and the whole thing healed. It healed without strong chemical medication. My body did it on “just” an herb supplement.
    And you try to explain how it’s impossible that turmeric works? Nice try…

  36. Phil says:

    Funny. For me, curcumin is a life safer. I tried a lot of things to no avail but curcumin completely eradicates my “severe” general anxiety disorder and lifts my mood like im a new person. From little things that totaly stress me out (because im so burned out from my anxiety) to a normal feeling of being able to do things. All within 30mins after taking a capsule. We are all different and what works for one, might be useless for another. In that regard, such generalized articles might be of little help for anyone trying to gather information.

  37. Neil says:

    I’ve been taking Longvida curcumin at therapeutic doses (4-8g/day) for about 7 years now. I had very high systemic inflammatory blood markers (ACE, SED, HSCRP, and several others, all of which I’ve tracked very closely for these last 7 years), that had been individually rising year after year for 4-5 years until they all started to exceed the normal distribution. But, I was otherwise asymptomatic. I’m not overweight, I don’t smoke, I drink casually, but for additional reasons besides the blood work, my doc at UCLA thought I might be developing sarcoidosis (he had other sarc patients, so he was familiar with its etiology) and was about to put me on a low dose of Prednisone, when I did some research and asked if I could try some bioavailable curcumin instead. Seeing as how I wasn’t particularly acute, he agreed, and within 3-4 months of taking 8g/day, most of my blood markers cratered, not just by a little, but by halves, and quarters. I had a full course of blood work done nearly every month for 6 months. SED, ACE, HSCRP dropped to the low end of normal. My low D-25 rose, my high D1,25 dropped significantly. I had just previously had a liver ultrasound that showed pretty severe NAFLD, that 6 months later totally disappeared. The same tech gave me both tests and said that if it hadn’t been he giving me the tests, he wouldn’t have believed the initial Dx of NAFLD because I didn’t have a sign of it anywhere.

    I specifically did nothing different – not exercise, diet, work/life balance, didn’t change where I lived, nothing – just to make sure that as a single patient experiment, it was at least as consistent as possible. The results were hard to refute. I even went short periods where I would lower the dose, or stop entirely, and retest, and the markers rose quickly. I still seem to exhibit pressure on my entire inflammatory system, but the 4g/day maintenance dose of Longvida curcumin I take (it’s formulated with soy lecithin, so it’s much more bioavailable) I will be taking forever. I know there is still the correlation/causation conundrum, as well as confirmation bias, but it’s difficult to ignore that, at least in my body, it seems to work well. Yes, it can cause upset stomach for some, but it was never a problem for me.

    A lot of my initial research was from papers by B. Aggarwal, and I know what happened to him. It is a terrible stain on the research community and MD Anderson specifically. However, outside of Aggarwal, curcumin as a substance has been highly studied by lots of other researchers, and if I’ve found that, having read hundreds of these papers, that conclusions about the lack efficacy in humans are often because the trial did nothing to counter curcumin’s lack of water solubility, and thus, bioavailability. Or, many times the doses were very small, or for short periods. Besides the confirmation bias of science research in general, and Aggarwal, there’s still enough out there to demonstrate it has potential therapeutic value for a wide variety of people. Randomized human trials are, of course, the only way to really understand the efficacy of a product in humans, but one must remember that in any statistical analysis, the results are only related to what you test, all other things being equal. There are always unknown factors that, if not tested for (and how could they be, being unknown), don’t factor into the results. And, I’m not willing to entirely dismiss what is effectively an extremely lengthy longitudinal trial which Indian culture has engaged in with turmeric.

    For me, Longvida curcumin seems to work very well, but on principle, I’m not willing to give it a 95% confidence level. I’m happy to stick around 85%, which is enough for me to keep taking it in such large doses.

    1. Brian Herwood says:

      Thank you for pointing out that many studies from others than the infamous Aggarwal have concluded that curcumin(s) with something else that makes them bioavailable work in human studies. I just went to and looked up the abstracts of 15 studies on curcumin, all positive to a degree for various conditions, and none of them were Aggarwal’s work. I have also recently dropped allopathic meds for simple conditions like BPH & minor arthritis and used Ayurveda instead – after researching combinations and dosage. It takes a month or more to start, but stuff works – curcumin, Boswellia, Ashwagandha, and so on.

    2. Judith says:

      Hi Neil,
      I have recently discovered that I also have NAFLD which has puzzled both me and my docs. I am going to attempt a course of Curcumin but would like to know the specific preparation that you took because clearly there are absorption and bioavailability issues. Can you possibly share the brand name? Thanks

  38. Tony says:

    Regular curcumin has about 1% bioavailability but advanced compounds like the one used in Longvida brand about 20%. It’s been proven to penetrate the blood-brain barrier and bind to beta-amyloid plaques and has succesful double-blinded, placebo controlled studies to back it up.

  39. tapcity says:

    Turmeric, especially infused in kambucha, loosens the joints. I’m 64 and I play basketball with young guys, and it is so. Pain levels provide my proof. Isolating constituents of a proven folk medicine isn’t invariably wise not for products nor for in vitro testing neither.

  40. DK says:

    The problem with scientists is that they succumb to the 95% confidence level trap. Oh I get it, fail to follow that and you’ll never survive a defense.

    But hey, learned a valuable lesson from a chemist many years ago….even bad data can tell you something useful. But the tendency is to quickly find a “flaw” and then knee-jerk reaction dismiss the study/data in its entirety. So many big brains stifled by self-imposed narrow-minded thinking that would be right at home in a John Birch Society meeting!

    Don’t discoveries happen when someone thinks outside of the box and steps out of their comfort zone?

  41. haris says:

    A recent article on the interaction of curcumin with DNA.

  42. David Klasovsky says:

    However, numerous lines of evidence have indicated curcumin’s ability in human participants to modulate multiple cell signaling molecules such as pro-inflammatory cytokines .

  43. hoops says:

    There are hundreds of trials suggesting major associations with reductions in inflammation and plaque devlopment but they’re all wrong because it’s not understood how they work given low bioavailability and its unpredictable behavior it’s all lies?

    Couldn’t it just be that you only need a little and what we call undesirable behaviors are maybe actually beneficial in ways not known?

    1. Derek Lowe says:

      There are not hundreds of well-controlled trials, though. And one thing that the history of drug discovery tells you is that without well-controlled blinded trials, you can fool yourself in a dozen different ways.

  44. Leeza says:

    My mother was unlucky enough to have Primary Amyloidosis and secondary Multiple Myeloma. She was.dx when she nearly bled to death after her spleen ruptured. She had amyloid plaques in her liver too.
    She had bone marrow biopsies and DNA testing all conclusive of the disease named above. Chemo put her into heart failure and she was sent home on hospice at 79lbs, on oxygen with heart and kidney failure. After a more than a month not being on chemo I found an article/ study about MGUS and curcimin on the web site. In followed this study and informed the oncologist of what I was doing. ( Insert eye roll) but month by month my mother’s free kappa light chains started to decrease. Within 1 year she was in what he called ” A complete and massive remission”. It has been a year and a half now and she is up to a 100lbs and can walk 3 miles . I would be more than happy to give the author of this article a full release to speak to my mother’s oncologist .

    1. Peter Robinson says:

      Please which brand of curcumin did you give to your mama ?
      Many thanks.

  45. Erik Johansson Andersson says:

    Please explain to me why this article fails to mention the various forms that increase the bioavailability of Curcumin.

    1. Derek Lowe says:

      The article I’m blogging about does. But most of the trials of it don’t seem to bother.

  46. mewebtech says:

    I read this Blog very nice

  47. Deborah says:

    This is a cynical article that lacks details and continues to strengthen that dangerous pharmaceutical hold over our health. The author leaves out Curcumin MERIVA – which has been shown in many credible, scientific studies to aid in healing, reduce inflammation, pain and to also help lower risk of Alzheimer’s. I urge everyone to do their research before listening to a single and out of touch article like this. Ibuprofen and many other anti-inflammation meds harden our blood vessels and cause many health problems that I doubt many traditional doctors and scientists will tell you about. This article is out of touch. You and your health deserve better.

    1. Moses says:

      Agreed. Not only that, the article is very misleading particularly from a therapeutic application. While the author may be experience/educated in research, he lacked due diligence with regards to the improvement of therapeutic benefit of curcumin when combined with other foods and supplements.

      Additionally, curcumin IV therapy, which circumvents the bio-availability argument, has tons of evidence-based research to prove its therapeutic benefits. I’ve personally seen patients riddled with hand crippling arthritis, begin to freely and painlessly move, flex, and extend their hands and fingers during and after IV administration of curcumin.

      1. Derek Lowe says:

        References for the i.v. administration evidence?

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