Evidence Update: Biologic Plausibility of Curcumin (Turmeric) Very Low

In 2013, I wrote about the burgeoning popularity of the spice turmeric as a medicinal herb. At the time, my conclusions were:

Overall, there is no compelling clinical evidence in humans supporting any use of curcumin or other turmeric compounds…There is virtually no clinical research in companion animals, and what there is does not support claims of benefit from turmeric compounds. Finally, the limited research to date suggests a few potential risks but the significance of these is unclear.

Since then, there have been many additional in vitro or lab animal studies, but no significant clinical trials in companion animal species. The pre-clinical research continues to find interesting biological activity of curcumin and other turmeric compounds which might, or might not, lead to clinically useful effects. At this point, there isn’t much new evidence that supports altering my previous conclusions.

However, one new review has looked at the biologic plausibility of curcumin, which is one factor in assessing the potential medicinal applications. This paper, somewhat surprisingly, suggests that the basic biochemistry of curcumin makes it unlikely to be a clinically useful remedy.

Nelson KM. Dahlin JL. Bisson J. et al. The Essential Medicinal Chemistry of Curcumin J. Med. Chem. 2017;60:1620?1637.

The authors review the pre-clinical and clinical trial literature for curcumin with an eye to features that would make the compound a better or worse candidate medicine. They conclude that its basic biochemical features make it unlikely to be useful but highly likely to generate false positive results if not tested with a clear understanding of its properties:

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.

Curcumin…has shown excellent promise in early testing (in vitro), even though this testing may have been bedeviled by design problems that led to several misfires. The structure of 1 suggests that it might be unstable in a biological setting, and in fact, it is: both its in vitro and in vivo stabilities are abysmal…relative to commercial drugs.

To our knowledge, [curcumin] has never been shown to be conclusively effective in a randomized, placebo-controlled clinical trial for any indication. Curcumin is best typified, therefore, as a missile that continually blows up on the launch pad, never reaching the atmosphere or its intended target(s).

While these failures would normally end further research on its use as a therapeutic, they apparently have not deterred researchers interested in its development.

Given its low systemic bioavailability, we remain highly skeptical that an oral dose of 1 can ever be effective in human clinical trials that are translated from reports of in vitro activity… the lack of any observed efficacy of oral curcuminoids in clinical trials where it was given in high doses does not bode well for these alternative hypotheses of therapeutic efficacy.

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.

While such an analysis does not entirely preclude curcumin eventually being a useful remedy, it does reduce the likelihood of this, especially given the failure of any dramatic clinical trial results suggesting a significant real-world benefit.

This entry was posted in Herbs and Supplements. Bookmark the permalink.

7 Responses to Evidence Update: Biologic Plausibility of Curcumin (Turmeric) Very Low

  1. Sarah says:

    Strange then, that Royal Canin has based it’s Mobility C2P+ Diet off of turmeric.

    https://www.royalcanin.co.uk/products/dog/canine-veterinary-diet/mobility-c2p/

  2. skeptvet says:

    Not really strange, just a company responding to a potential marketing opportunity. Even when the evidence is weak, or non-existent, supplements find their way into commercial diets, grain-free diets are widely marketed, and so on because companies respond to what consumers seem likely to want. Of course, as I’ve pointed out there is some pre-clinical evidence that turmeric might have anti-inflammatory effects, so it’s not out of the question it could be useful, it just seems unlikely based on what is known so far.

  3. Paul says:

    “Even when the evidence is weak, or non-existent, supplements find their way into commercial diets, grain-free diets are widely marketed, and so on because companies respond to what consumers seem likely to want.”

    Yup my experience as well. But I also would like to add that Vets have kind of helped people “want” grain free diets because it’s easier for a Vet to say the dog is sensitive to grains then to explain that there may be so many other things making the patient itch or have loose stool and that the work involved to narrow it down takes time and effort.

    So Vets have kind of helped move trends in what is added or subtracted to foods just by the virtue that they are Vets and people listen.

    The worst thing is that since I don’t have the DVM behind my name my advice about nutrition and such for dogs is taken as less than a Vet even though I’ve done the work to get an MS in small animal clinical nutrition. But it’s just an issue I need to deal with.

  4. Pamela Mueller says:

    Oh Paul I feel your pain ha ha. I had (still have) a PhD in Animal Nutrition nobody cared two cents for my opinion or knowledge on nutrition. So I went and got a DVM and although I learned nothing new now everybody listens to me. Except dog breeders and those who read the Whole Dog Journal. Cause as we know the devout dog lovers who write that know more than any medical or scientific professional.

  5. v.t. says:

    But, Paul, don’t you know that vets only receive an hour’s worth of animal nutrition in their entire careers? (say the clients and woomeisters on the net)

  6. Paul says:

    I never understood that disparaging Vets about nutritional knowledge. I follow a raw feeding blog, because I have to see what new hells come from raw feeders so I can be ready to debunk them when customers ask, that always rails against “traditional” vets and their nutrition education. But anyway.

    I wish I had the time, and the stomach to do dissection, to just get my DVM just so I can say, “Hey, You SHOULD listen to me, I have a DVM too!” But alas I might have to finally break down and get my MS in small animal nutrition and display it prominently in my shoppe.

    I will say overall the vets in my area, barring a few who are close to being quacks, are quite good when it comes to overall practice and don’t always offer crappy advice. lol

  7. Carrie Spurgeon says:

    How interesting, thank you for this!

    The comment below, sorry it’s so long, was written by me last year. It was a dreadfully distressing time for us all. Sadly my elderly girl passed away 3 weeks ago, peacefully in her sleep, due to a brain aneurysm. A shock but happily she didn’t suffer, her stomach ulcer had healed nicely and she no longer showed any ill effects, but it could so easily not have been this way:

    ‘I’ve been giving golden paste to my older dogs for 8 months, both choc labs.
    A week ago my 10 year old suddenly started vomiting and went off her food, which isn’t her at all. She was also crying and very lethargic and had a runny tum. I took her to the vet and they ran blood tests which showed she had high liver enzyme values and a problem with her red blood cells indicating internal bleeding, she was also dehydrated but had no fever. They put a drip in and she had an overnight stay. I told them she’d had some acid reflux recently, so they prescribed Ranitidine.

    Back home she really didn’t improve much so she was booked in for sedation so they could scan and X-ray her to see if there was some sort of obstruction. Nothing was found. They changed her meds to Omeprazole as Ranitidine can cause nausea and said they thought she had a stomach ulcer. A week later he redid the bloods and found exactly the same problem with the results. She was booked in for 3 weeks time to check them again, our vet said if they were no better she’d have to have an exploratory operation to see if there was a tumour on her liver.

    Two days after this our other choc lab boy started vomiting too, exactly the same symptoms as our girl. I was confused, worried…well more than worried, was this some weird viral thing that presented without a fever? Unlikely!

    I was thinking about what was happening whilst cooking our dinner and my eyes were drawn to the turmeric powder. We’d used a new supplier and it was a much deeper shade, more of an orange than the last mustard colour powder we’d used before. I decided to google dangers of turmeric on dogs and came up with this about humans, I’ve only copied what applied to us but there were several other warnings:

    ‘2. Gallbladder Problems
    Research suggest that normal turmeric is helpful for the normal functioning of gallbladder by stimulating the release of different digestive mediators that stabilize the functioning of gall bladder ducts; however, high turmeric intake is also associated with aggravation of liver and gall bladder conditions. This includes inflammatory conditions of gallbladder (acute Cholecystitis) and gall bladder stones or duct obstruction. It is advisable to seek the help of a healthcare provider before using turmeric (even in recommended dosages) in all such cases to prevent pain and discomfort.

    3. Stomach and Gastrointestinal Problems
    Turmeric (also known as Indian saffron) usually does not cause any gastric irritation or inflammatory reaction when consumed as part of cooked curry (suggesting a small dose); however, individuals who consume turmeric for management of chronic inflammatory systemic conditions like rheumatoid arthritis and aching joints can develop turmeric induced gastric issues. Turmeric is slightly acidic in nature and is widely considered as a stimulant of gastric acid secretion. If you have a current history of dyspepsia or hyperacidity, it is strongly suggested to avoid turmeric in high doses. Individuals who smoke or use non-steroidal anti-inflammatory drugs are especially vulnerable to the side effects of turmeric (leading to dyspepsia, heartburn, indigestion, gastro esophageal reflux disease and peptic ulcers). It is indicated to consume a lot of water to minimize the accumulation of turmeric in high doses within the gastric lining. For best results, consume with food only.

    4. Bleeding
    Turmeric may inhibit platelet aggregation, and thus, theoretically, may increase the risk of bleeding. It also affects the production of clotting factors from the liver and therefore must be avoided in patients who have a bleeding tendency or inborn error of clotting.

    5. Liver Problems
    High turmeric intake is associated with liver dysfunction that may present with indigestion and jaundice. Research studies in animals have confirmed the toxic effects of turmeric on animal hepatocytes and although no human study is currently available to suggest the possible mechanism of development of complications, it is recommended by healthcare provider to limit the intake under recommended dosages only. If you are suffering from a current medical illness that involves liver, it is better to avoid or totally eliminate turmeric from your diet.’

    My husband had just got home, I told him what I’d found and I googled some more during the evening whilst mopping up vomited water on a regular basis. Our boy, at 11.30 at night, suddenly vomited more water (another sign seems to be excessive drinking) but this time there was blood in it!

    Terrified I rang the vet, explained that my boy had the same symptoms as our girl and that I’d seen online that turmeric could be the problem (they know me and our dogs well lol) and we rushed to the out of hours surgery. Once there the vet said she’d been searching on her vet sites and this was a known problem and was getting more common as more people dosed their dogs on turmeric. She gave him an anti sickness injection in order to start giving him omeprazole straight away, declared him well hydrated and we came home at 1.00am. Apparently the bleeding wasn’t too much of an issue, it was caused by the stomach ulcer, she also asked me how long I’d been giving it, 8 months, but asked if I’d changed supplier at all, I said yes a month ago!

    So it seems both my dogs have a stomach ulcer directly due to giving turmeric!

    Part of me is cross with myself for not checking for dangers earlier, this stuff is actively being pushed as a cure for all despite no studies having been done. Luckily neither dogs were taking NSAIDS as well, the vet told me things would have been much worse if they had been. I stupidly got caught up in the hype!

    Another part of me is extremely thankful that I googled it and realised what was going on, if my boy hadn’t shown his symptoms when he did my girl could have had to suffer going through an operation for no reason, not good at any age but at ten there could have been serious complications.

    Another part of me is sad because I’ve had to see them suffer so much over the last week or so! I love my dogs, they are a part of my family and I, like anyone else who does so, hate seeing them so poorly! My boy is not eating much at all but I understand that he feels sick, even my girl, although much improved, is still occasionally vomiting up her food, she did so this morning. They both have weeks of meds to allow their ulcers to heal, it will be a slow progress, with more vet visits to check on bloods.

    The last part is annoyance that I’ve been lumbered with almost £1,000 of vets bills so far, if my girl had had the exploratory operation it would have been much more!

    Basically turmeric seems to work well as an anti-inflammatory, they were very sprightly whilst on it, but those that give it to their dogs, in order to prevent the liver problems associated with NSAIDS, should be made aware that because it works *it too* can cause the same problems! At least you know the tablets have a specified strength, with golden paste you have no such assurance! I was giving one teaspoon twice a day with their food, and my dogs are big labs, not fat (well my girl is a bit, although has lost weight recently of course) but big, chunky show types; my boy is 50.9kg and the vets say he isn’t overweight, he’s like a brown bear with the most enormous head. Goodness knows what would have happened if I’d given it to my 7 month old pup!

    I’m copying and pasting this reply on as many turmeric sites as I can find; if I only stop one dog going through what mine have been through then it will be well worth my time!

    Oh and the turmeric is now in the bin! ‘

    I have been copying this onto the numerous turmeric loving sites, but usually when I check back it’s been taken off. I really think more should be done to inform people about these dangers in both animals and in humans, I’m hoping you leave this on for all to see please.

    Thank you.

Leave a Reply

Your email address will not be published. Required fields are marked *

This blog is kept spam free by WP-SpamFree.