July 9 2007 post. Reading through an MD Anderson 2005 study on plant polyphenols and chemosensitization (abstract: http://tinyurl.com/2k3pea), I came upon piperine, and it seemed a good time to write a post about this spicy alkaloid ingredient of black pepper which enhances the bioavailability of many compounds, including my beloved curcumin. I should mention once again that curcumin, from all accounts, is poorly bioavailable. There are quite a few studies on this topic. One of them, a 2002 study (http://tinyurl.com/2y8gp6), concludes that curcumin is avidly metabolized by human intestinal tissue. And this could be a major reason for its poor systemic availability. And a 2005 study (http://tinyurl.com/2tlgwm) on curcumin and colorectal cancer patients states the following: Taken together, the results presented here and elsewhere suggest that whilst orally ingested curcumin has low systemic availability, it furnishes sufficient levels in the human intestinal tract to cause pharmacodynamic changes commensurate with intestinal chemoprevention. The low systemic availability of curcumin might be considered a disadvantage because it precludes the use of curcumin as a chemopreventive agent for target organs distant from the gastrointestinal tract. Note: these cancer patients were given three different doses amounting to less than 4 grams a day, which is less than half the amount of curcumin I am taking, AND this particular experiment lasted only one week. But even a dose of 3,600 mg was found to have positive effects in the colorectum.

I found a not-too-technical explanation for what happens to curcumin once it is ingested in an article written by Dr. Richard Beliveau and published in the London Free Press in March 2007: as soon as it enters the intestine, the molecule is quickly modified by an enzyme called UDP-glucuronosyltransferase, which triggers its elimination, without it having had the chance to exert its numerous anti-cancerous and anti-inflammatory effects. In the presence of pepper however (and therefore, of piperine), the UDP-glucuronosyltransferase activity is blocked, which allows the turmeric to be better absorbed. This effect of piperine is quite remarkable because it increases by almost 2,000 per cent the concentration of curcumin in the blood, thus allowing it to reach sufficient concentrations to produce its effects. [ ]

Piperine and bioavailability. A study published in 1985 (http://tinyurl.com/3dpp53) concludes that piperine is a potent inhibitor of drug metabolism. A 1998 study (http://tinyurl.com/329d2d) examines the bioavailability of curcumin in animals and humans, and concludes that piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects. But an even more interesting study (http://tinyurl.com/2zz8mm), published in 1997 on oral drug bioavailability in humans, reminds us that one of the factors involved in the first-pass effect is food, which can inhibit or enhance the absorption of drugs. I confess that I had to look up first-pass effect (or first-pass metabolism ), which simply means that after a drug is swallowed it is absorbed by our digestive system and goes into the liver, which may metabolize it and change it to the point that only a small unchanged amount will be bioavailable (which is apparently what happens to curcumin). This study gives us a list of some inhibiting foods, such as smoked foods or cruciferous vegetables. Hmmm. Interesting. Garlic instead seems to have no effect on drug metabolism. But, and this was the most interesting bit for me, the study brings up something I already knew, but only vaguely: Constituents of grapefruit juice also result in reduced first-pass metabolism, especially for drugs that are CYP3A substrates. Again, this dietary effect is more pronounced in the intestinal epithelium than the liver. A similar, but more generalized, phenomenon also appears to be associated with eating piperine- and capsaicin-containing spices. In fact, some time ago I read that MM patients doing chemotherapy should avoid eating grapefruit. But, in the case of curcumin-takers, reducing the first-pass effect with grapefruit might work quite well. So, how about swallowing curcumin with a big glass of grapefruit juice? I have actually done this in the past, whenever I have been able to buy organic grapefruit. A 2004 study (http://tinyurl.com/2z8bjg) shows that piperine enhances the bioavailability of EGCG in mice by inhibiting glucuronidation and gastrointestinal transit. Glucuronidation, by the way, is a chemical process used by the body to expel a variety of molecules, including drugs and pollutants, as well as substances like curcumin and EGCG. Therefore, inhibiting this process means that these compounds are better absorbed. So far, so good. The study concludes that piperine inhibits small intestinal glucuronidation of EGCG, which may result in increased absorption, and that piperine may also slow the GI transit of EGCG, thus increasing residence time in the intestine and allowing for greater absorption. [ ] The increase in plasma bioavailability for EGCG may improve its cancer preventive activity in vivo.

Piperine and cancer. Piperine doesn’t merely increase the bioavailability of some compounds, but also seems to have some anti-cancer activity of its own. I will cite a few studies, including one (http://tinyurl.com/ypn47e) published in 2005 on lung cancer and piperine, which concludes: Our present results explain the understanding of unique association between anti-peroxidative effect of piperine and ultimately the capability of piperine to prevent cancer. It has anti-cancer properties also in the case of melanoma, according to this 2004 study in which (by the way) one of the inhibited cytokines was the infamous IL-6: http://tinyurl.com/37sl4b

Final considerations. The use of the conditional tense may result may improve in the above-mentioned 2004 piperine-EGCG study is interesting, and brings me to ask a few final questions, undoubtedly dictated by my ignorance and my non-scientific brain (so please forgive me!). What if it doesn’t matter if curcumin stays in the serum for an extended period of time? In other words, what if at least some of the anti-cancer effects of curcumin have little to do with its presence in the serum? If curcumin is so poorly bioavailable, how can one explain my test results, as well as those of other successful curcumin-takers? Another question: I have a MM listserv friend who is taking 12 grams of curcumin and discovering yellow stains €”corresponding to the head and trunk areas of her body €”on her sheets every morning. So, if curcumin is seeping out of her pores to the point of staining her sheets, what is going on? I have a lot of questions, but very few answers.


  1. dera Margaret
    I am also plagued with Mm , have been since 2003. have gone through various treatments , from Thalidomide with Dex , to Velcade with thal with Dex to Adryamycin with velcade with dex etc.. plus an SCT back in 2004.
    once more I am relapsing and my only options left are to take Revlimid with a few other things like Melphalan and dex if it does not work on its own . there are also talks of an sct followed by an allogeneic transplant from unrelated donor ( my brothers don t match. I am a unique piece ..). so I came accross your blog which I foind clever and very well documented and have started using Curcuma ( I bought a LARGE JAR ) and black pepper. for the past 3 weeks I have taken a tea spoon full of it , with pepper , at breakfast and after diner. yum..
    I am wondering wether you have any advice to provide me with , regarding exact dosage and what you would do in my situation. it does not mean I will follow it exactly( dont worry about your responsability in this ) BUT I am very interested in what you have to share .
    it s hard to measure such small quantities . any idea how much is 12 mgs of curcuma ?

    thank you so much for any idea u might have on the curcuma topic
    warm regards
    Marseille / france
    hope you are well and as happy as you sound 🙂

  2. A doctor whom purchases organic turmeric from me to use in his alternative cancer research has told me the therapeutic dose given in clinical trials is 10 grams. I believe this is fresh whole root. it could also be up to ten 500mg caps daily. He feels tincture liquid capsules are also more bio available than tablets. for what it’s worth. God bless and good luck.
    Aloha, Dean

  3. Thank you for such great information and research.We are not in agreement that you do not have a scientific mind. I think the greatest scientific mind is one that questions and postulates, then searches for the answer..In my opinion, what I read suggests that you have all that. I do not have MM or any obvious chronic diseases, but realize that chronic inflammation underlies all chronic diseases and aim to prevent this from happening. I now take a specially formulated curcumin supplement that has the addition of piperine..so the nutraceutical companies are catching up to your research:-)

  4. Hello Margaret
    I found your site after hearing Dieneke on BBC’s ‘The Food Programme’. My brother is receiving chemo for MM, so I was interested in the potential of turmeric, which I have used myself as an antibiotic/antiseptic.
    On Channel 4’s ‘Superfoods’ programme last night, a presenter was in India, investigating black pepper’s medicinal properties. She visited a researcher who has found that piperine enlarges the villi, by which nutrients are absorbed from the intestine; so this could also go some way explain the increase in bioavailability that it promotes.

  5. I started to take Curcumin plus piperine about 4 weeks ago and I have now strated to get diarrhea…
    The tablets are very strong, Turmeric Curcumin 2,510mg, and they have piperine iside the little tablets.
    Is it common to get loose stool from this little tablet.?
    I normally take it with D3, K2, and Astragalus root extract the first thing in the morning before breakfast.
    I then wake up around 3 AM with diarrhea…its been 4 days now. I have decided to not take the curcumin for a week and see what happens. I am not on any medication. I am otherwise healthy and have just had the colon test, so all normal down there in the large intestent…

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