Terra Sigillata

Curcumin for Cancer: Part Two

ResearchBlogging.orgYesterday, we began discussing why the health care consumer should be wary of dietary supplement promotions based solely on “scientific research” cited from studies done on isolated cells in Petri dishes, pure enzymes, or other systems far removed from whole animals or whole humans.

There are many barriers to absorption of compounds from herbs, supplements, and prescription drugs, and the body’s capacity to metabolize xenobiotics (and externally administered compound) is quite robust. For a compound to become a drug, it must sometimes be modified chemically to circumvent the metabolic processes our physiology has evolved over a few million years.

My oncology colleague, Orac, also posted on another example whereby the a somewhat reverse might occur: a compound may show no activity against cancer cells grown in culture, yet be useful (in rodents harboring human tumors, so far) because it disrupts a process required for cancer development in vivo that does not always exist in simple Petri dish studies (the ability of a tumor to produce factors that create its own blood supply, known as angiogenesis).

Today, I’d like to follow up on a more simple concern: that the doses of an herb or dietary supplement may not achieve sufficient concentrations in the body to mimic the seemingly miraculous effects observed in cell culture studies. To illustrate this point, I will use peer-reviewed published data that also appears on the website of a company that sells herbal and dietary supplements.

i-09e70920b904b7a26501b21a09d45543-Curcuma root.jpg Yesterday, we spoke of curcumin, a chemical highly prevalent in Curcuma longa, a member of the ginger family (Zingiberaceae) whose roots look like ginger but contain this characteristic yellow-orange color. Curcumin is also known as diferuloylmethane or turmeric yellow, derived from an Indian spice made from extracts of the roots that is also used in traditional Indian Ayurvedic medicine. (Photo courtesy of Jardin botanicos Mundani on the Spanish island of Mallorca).

It is rare for a herbal or dietary supplement company to conduct, much less publish, the results of the bioavailability of their products. For dietary supplements, these studies are not required by the US Food and Drug Administration or by any federal regulatory authority in the world. By “bioavailability,” we mean a study as to what fraction of a given oral dose actually makes it into the bloodstream. While measuring bioavailability, scientists also conduct more sophisticated calculations to determine the peak blood concentrations, when they occur, and how quickly the body clears the substance.

However, one company that markets curcumin products has done just that, and even provided us with their original data from both rat and human studies (they have also supported a clinical trial of another of their herbal products, with a negative outcome but, again, the company had the guts to lay their product out there for critical evaluation). The animal and human data presented below actually appear in a peer-reviewed 1998 paper in the journal, Planta Medica, a common journal for publication of such studies.

i-63f6d3be15a249976307bbff7aa5b2fd-Rat curcumin PK.gif

In this first case, illustrated above, groups of 6 rats were given curcumin at a dose of 2 grams per kilogram body weight or together with another compound (Bioperene brand of piperine, a black pepper constituent purported to increase bioavailability). The peak blood concentration of curcumin in this study averaged 1.35 micrograms/mL and the “enhancer” substance increased that to 1.80 micrograms/mL. (The precise numbers and other pharmacokinetic data are listed in a table that accompanies the graph here.) Blood levels returned to zero at 5 hours after dosing.

Of course, animal studies raise many questions. How do these doses compare with those that must be taken by people? Do rats handle the compound in the same manner as people? Would I really have to take 2 grams per kilogram body weight? (I am 214 lbs, or 97 kg – does that mean I have to take 194 grams of curcumin per dose??? – Note added 6 Oct: my toxicology colleagues remind me that a factor of 7 is usually used when comparing human doses to rat doses due to rodent metabolic rates; hence, the 2 g/kg for a rat would be comparable to 0.3 g/kg for a human, and the 194 grams I quote would translate to about 28 grams for a person my size, still a whopping dose). And how does 1.35 or 1.80 micrograms per mL compare to those concentrations required for anticancer effects in Petri dish studies?

Well, what readers probably care most about is what happens in humans, and the company provides us with that information.

i-8545f267d5f5046b8a0200ba56b34f23-Human curcumin PK.gif

In this case, human subjects (eight per group) were given 2 grams of curcumin alone or together with 20 mg of piperine. Unlike the rats, humans show virtually no curcumin in their bloodstream (peak concentration of 0.006 micrograms per mL). However, those also taking the piperine-containing product had average peak blood concentrations of 0.18 micrograms per mL but, even in this case, blood levels were almost zero within one hour of taking the dose.

So, how does this compare to the cell culture data? Well, we must first compare apples and apples and convert concentrations from micrograms per mL to the more commonly used term of “molarity” using curcumin’s formula weight of 368.39. A peak concentration of 0.18 micrograms per mL corresponds to a concentration of 0.488 micromolar – let’s round up to 0.5 micromolar for simplicity.

Now let’s examine the data from a typical, high-quality peer-reviewed paper from an excellent cell biology laboratory at a major US academic cancer research center. I pick this 2004 paper from the journal, Blood, the official journal of the American Society of Hematology, because it is freely available and discusses curcumin treatment of both tumor cells in culture as well as multiple myeloma cells isolated from actual patients.

i-291edb44c376a5dae2e4ed45a7de35fc-curcumin multiple myeloma.gif Figure 5. Curcumin activity. Curcumin inhibits the growth/viability of human multiple myeloma cell line U266 and bone marrow CD138+ multiple myeloma cells (A-D). Cell line U266 (A) or enriched CD138+ cells (2 x 104/0.1 mL) from bone marrow aspirates of multiple myeloma patients (nos. 7, 9, and 10) (B-D) were cultured in the absence or presence of the indicated concentrations of curcumin for 24 hours, and cell viability was measured by MTT assay (A-B) or standard trypan blue dye exclusion method (C,D) as described. Curcumin inhibits the expression of Bcl-2 and Bcl-XL proteins in human multiple myeloma cell line U266 (E) and bone marrow CD138+ multiple myeloma cells (F). A total of 2 x 106 U266 cells (E) or CD138+ multiple myeloma cells (F) were treated with curcumin (50 µM) for the indicated times, prepared the cytoplasmic extracts, resolved the 50 µg cytoplasmic extracts on 10% SDS-PAGE gel, electrotransferred on a nitrocellulose membrane, and probed for Bcl-2 and Bcl-XL by Western blot analysis. {beta}-actin was used as a loading control. Values represent the mean ± SD of triplicate cultures.

These data show that even continuous exposure of at least 10 micromolar curcumin is required to have any detectable effects in killing multiple myeloma cells and that 50 micromolar is better, although in no case does that very high concentration eradicate the tumor cells in any of the experiments.

So, what would be the effect on these cancer cells of 0.5 micromolar curcumin for barely the length of one hour as shown earlier in the human pharmacokinetic study? Almost nothing. Even if the myeloma cells were exposed continuously to 0.5 micromolar curcumin, this is still 1/20th to 1/100th the concentration required to have any weak effect. In other words, taking 2 grams of this curcumin/piperine product for cancer is about as much use as taking a sliver of a baby aspirin tablet for a major headache, except that most headaches are unlikely to be potentially fatal.

Even those rats in the first series of studies, those taking an astronomical 2 grams per kilogram body weight, would achieve a maximum blood concentration of roughly 5 micromolar.

Hence, the dose recommended by this excellent herbal manufacturer is unlikely to have any effect on this cancer.

Other papers by the laboratory cited here and others have concluded that curcumin concentrations have to be above 20 micromolar to see any effects across any variety of cancer cell lines, alone or in combination with chemotherapy (an entirely different and more risky proposition that we won’t discuss here.)

Well, couldn’t you just increase the dose? Try and take 40 grams of curcumin product, perhaps. Pharmacokinetic dosing is such that increasing dose by 20-fold does not necessarily lead to 20-fold increases in blood levels, so there is no way to know how much of this curcumin product must be taken to achieve blood concentrations consistent with cancer cell growth arrest or cell killing.

And that’s without even getting into whether you would have to take 40 grams every hour, even if you could afford to do so. Besides, do you know what 40 grams looks like? That is the equivalent of 80 tablets of your typical 500 mg analgesic (warning: do not take 80 tablets of any analgesic under any circumstance.).

So, yes, curcumin might be a promising anticancer compound but only if you could literally shovel quantities of it into the bloodstream. So, what should be done? Remember, I do this kind of work for a living and am a big proponent of natural products as a source of anticancer drugs.

Well, it turns out that this very same laboratory group is approaching the problem by taking curcumin as the starting material and construct dervatives (sometimes called “semi-synthetic” compounds) that retain the action of curcumin but that are more potent. While more work remains to be done, this approach is more likely to result in compounds that can be given at reasonable doses and realistically achieve biologically-effective concentrations in the body.

In the meantime, to continue marketing curcumin, even in a highly-bioavailable form, is misleading and gives false hope to patients.

At the very least, it is a tremendous waste of money.

But, there is a possibility that it could also still present some risks besides simply not working against cancer cells.

In the next part of this series, we will discuss the properties of this “bioavailability enhancer,” the black pepper component called piperine, and discuss why it by itself might be of danger, especially if taken with other drugs.


Bharti, A.C. (2004). Nuclear factor- B and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood, 103(8), 3175-3184. DOI: 10.1182/blood-2003-06-2151

Comments

  1. #1 anjou
    October 4, 2006

    Hi Abel–
    Great post– really helped me “understand” all the complicated issues involved in the work you, and others, do in the field of herbs and cancer treatments!!

    anjou

  2. #2 dlamming
    October 4, 2006

    Really, with curcumin you picked a bad target. Curcumin will be tested in a variety of clinical trials (and I believe some have already been done) for a variety of conditions. See this link if it works, or search for “curcumin” at clinicaltrials.gov. So in truth, we’ll know if it really does beat cancer (ie, colon cancer) in the not-too-distant future.

  3. #3 anjou
    October 4, 2006

    Dlamming– perhaps I didnt read Abel’s posts the way you did. From my reading, he seems quite positive about research being done in this area– after all– it is his line of work. Rather he is disparaging how supplement companies misuse early positive data and snooker vulnerable patients into believing that if they buy their product, or sprinkle tumeric on their breakfast, they are helping their disease.

  4. #4 Abel Pharmboy
    October 4, 2006

    Dlamming – yes, I am very aware of the PK and efficacy trials that are planned or are currently recruiting subjects here, in Israel, and elsewhere. However, I am concerned that, with the exception of the actual PK study at Mass General (using 4 gm doses of curcumin with piperine or silybin), that the efficacy studies are putting the cart before the horse or, in most cases, hooking the cart up to a lame horse.

    For example, if we already know that certain doses of a specific curcumin formulation do not produce adequately high and/or prolonged plasma levels of compound, the efficacy studies are likely to fail – not because curcumin doesn’t work, but because the doses are subtherapeutic.

    Sadly, ignoring the need to conduct proper human pharmacokinetics studies with specific, quality-controlled formulations of botanical supplements prior to clinical efficacy trials is quite common in this field and has led to negative efficacy outcomes for herbs that may very well have been effective. I posted on this at the old blog back in February on this very point regarding a negative saw palmetto trial outcome.

    I would love for nothing more than curcumin or any inexpensive supplement to prove to be an important adjunct in treating cancer. But, the studies must be done correctly, the outcomes represented accurately, and the claims be realistic and evidence-based if the industry and advocates hope to garner the support of sympathetic scientists like me, much less the open-minded oncologists with whom I work.

    Faulty studies and outrageous claims only serve to hurt the cause of therapeutic natural products.

  5. #5 Jeanene
    October 4, 2006

    Abel’s reply to Dlamming can be further supported by considering the early trials of high-dosage vitamin-C in cancer treatement. The issue of dosage efficacy in terms of plasma concentrations was not adequately addressed at that time. Three decades later, NIH researchers recognize the oversight and have reopened the necessary research to confirm or refute the role of high-dose intravenous vitamin-C in cancer treatment.

  6. #6 Jeanene
    October 4, 2006

    Besides any potential direct effect of curcuminoids on cancer cells, the possibility of indirect and/or synergistic effects also require investigation. WIth respect to curcumin, a key issue is role of inflammation in cancer development, and curcumin has been identified as an effective antiinflammatory. Whether the most effective therapeutic role of curcumin lies in prevention, suppression, or cure remains unclear. Careful and comphrehensive scientific study are required to resolve this question.

  7. #7 Emily
    October 5, 2006

    Abel, this is superb. Most people don’t think about bioavailability issues, and you’ve articulated them very clearly.

  8. #8 Renee
    October 5, 2006

    How apropos that that you’ve been discussing curcumin. Just today, when I was leafing through Glamour magazine, and then this month’s Family Circle, there were small blurbs about curcumin and what else, cancer.

    In the Oct Glamour, on p. 181, there’s one paragraph about how curry is good for fighting diabetes, heart disease and cancer, because of the curcumin content. There’s a quote from a researcher, Bharat Aggarhal Ph.D, of the MD Anderson Cancer Center in Houston (http://www.mdanderson.org/departments/expther/display.cfm?id=DD472022-195D-4B73-855872401E0646BB&method=displayFull&pn=BCF512C7-24BA-464C-B62521340EEC2781, about the good effects of eating curry-containing foods. He also suggests that a person can take a 500mg curcumin pill if they want to protect their health.

    In the Oct. 1 issue of Family Circle (p.111), Prof. Aggarwal turns up again, this time being quoted about how consuming curcumin is one way to decrease the risk of developing breast cancer. The article states that women in India have a lower incidence of this cancer (19/100,000 persons) compared to women in the US (101/100,000 persons) because of all the turmeric in Indian food. I’ll leave it to others to comment on this comparison.

    Now, Glamour and Family circle magazines aren’t peer-reviewed, but they are widely read and have been around for years; nearly every supermarket and drugstore carries them. And they’re not into alternative medicine per se; the magazines, like all women’s magazines, believe they’re doing women a service by publishing this information, no matter how speculative it is. On the other hand, it’s not clear if the magazines even realize how speculative the research on curcumin is at this time. However, it’s articles like these that get mainstreatm readers all fired up about curcumin, or whatever the latest cancer-fighting craze is.

    I’m not certain if Prof. Aggarwal is being quoted accurately, or if he’s been misquoted. And since I’m not a cancer researcher, I can’t tell from the MD Anderson webpage above how legitimate his work is.

    Sorry for the length.

  9. #9 Abel Pharmboy
    October 6, 2006

    Emily: Thank you so much for the comments; that is high praise coming from the author of such an excellent health information blog.

    Renee: Thank you for the heads-up; the length is fine given the important content of your comments. Prof. Bharat Aggarwal is the real deal: a highly-regarded scientist recognized for many basic science contributions to the natural product literature. In fact, the Figure 5 I cite above from the Blood paper comes from work of his laboratory. More technical readers will also note that Dr. Aggarwal was one of the discoverers of tumor necrosis factor while he was employed at Genentech in the mid-1980s.

    However, I cannot comment on how he is represented in the popular media, but it does seem that the PR dept/press office of his institution does tend to oversell and overrepresent his excellent work. FYI, I have also had personal experiences where popular journalists have over- or under-interpreted my own comments; in general, you as the subject do not get to give a final approval on interview content that appears in the popular press.

    Let me make perfectly clear that Houston’s M.D. Anderson has been one of the nation’s leading academic cancer hospitals and research centers for decades. I even interviewed there for a postdoctoral fellowship in my younger days. But, realize that part of their mission is to communicate their services to the general public. A quick review of some of their website information reveals, IMHO, an occasional overselling of some excellent science and medicine being done there.

    However, you’d have to ask Dr. Aggarwal himself as to how accurately Glamour and Family Circle magazines have represented the information he provided in his interviews. What I can tell you, as a cancer researcher, is that he is a highly-cited scientist with an impressive output of excellent, peer-reviewed work. How that work is interpreted, however – in the popular press, by herbal manufacturers, and by his institution’s own PR writers – is an entirely different story.

  10. #10 Karl Schwartz
    October 6, 2006

    The MD Anderson FAQ About Curcumin page gave me the impression that the author is promoting rather than objectively testing a hypothesis.

    A statement from the page: “Epidemiological evidence indicate that incidence of certain cancers is less in people who consume curcumin than in those who do not.”

    Clearly, there are many factors involved in cancer risk in specific populations, such as age, ethnicity, other exposures, other foods, etc.

    Statement: “Although there are numerous companies that supply curcumin, people need to be careful that they are buying the genuine product. The Sabinsa Corporation is one wholesale supplier that sells high-quality curcumin. You can also buy “Super Curcumin” from Sabinsa that contains BioPerine?, a phytonutrient that enhances bioavailability.”

    Is the author prescribing an herbal product? That the author is recommending doses and brands for patients to purchase infers that bioavailability and clinical questions have been answered. While I don’t know of any problem or risk from taking curcumin, I know that it can do harm when a patient with a cancer delays or avoid treatment based on a strong belief. I think the FAQ page fosters this belief. That this hypthothical information is posted as shown on an MD Anderson website make it all the more concerning.

    I’ll end with a quote on scientific method:

    “He cannot permit himself any preconception as to what sort of results he will get, nor must he allow himself to be influenced by wishful thinking or any personal bias. All these things together give that “objectivity” to science which is often thought to be the essence of the scientific method.” – Percy W. Bridgman (From: Reflections of a Physicist, 1955)

    Karl Schwartz
    President, Patients Against Lymphoma

    Patient Consultant to the FDA/Oncologic Drug Advisory Committee (ODAC)
    Participant: NCI Progress Review Group for Blood Cancers (LMPRG)
    Participant: Biospecimen Access and Ethical, Legal, and Policy Issues Workshop (ELP)

    FAQ about curcumin: http://www.mdanderson.org/departments/cimer/display.cfm?id=b3aa8dbd-66c3-4a6e-a37c86ad3dce3ec9&method=displayfull&pn=915cd45e-7c37-4305-8e778e10de640e0c

  11. #11 anjou
    October 6, 2006

    You cant imagine how many times I have had to explain the confusion between correlation and causality on cancer support boards, not just on curcumin but a variety of topics. And, when this type of quote appears on the pages of a prestigious cancer center, , it makes it very very difficult to have folks accept a concept that is taught in statistics 101…….. Wonder if the folks who wrote this quote took the same stats 101 course, or did they miss it???????

    “Epidemiological evidence indicate that incidence of certain cancers is less in people who consume curcumin than in those who do not.”

  12. #12 carlo rapaccini
    October 7, 2006

    For colon cancer patients this research is interesting
    carlo

    Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences.

    Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ.

    Department of Oncology, RKCSB, LRI, University of Leicester, Leicester, LE2 7LX, United Kingdom. gg43@le.ac.uk

    Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy-beta-di-erythro-pentafuranosyl)-pyr[1,2-alpha]-purin-10(3H)one (M(1)G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M(1)G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days. Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M(1)G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 +/- 5.7 and 7.7 +/- 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace levels of curcumin were found in the peripheral circulation. M(1)G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M(1)G levels from 4.8 +/- 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 +/- 1.8 adducts per 107 nucleotides (P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution of curcumin outside the gut.

    Publication Types

  13. #13 CheeWai
    November 12, 2006

    Hi All,
    Yes, eventhough there is no clinical result on Curcumin and i believed sometime it is the only hope for us to try on something new and possible to the cure or at least delay the cancer progress.

  14. #14 Barbara
    February 6, 2007

    I found this study interesting:

    Per Dr Rowen

    Second Opinion Health Alerts are a complimentary
    e-mail service from the Second Opinion health
    newsletter written by Robert J. Rowen, MD.

    ******************************************************
    If Cancer Runs in Your Family, Read This …

    As you probably know, cancer runs in families. One of
    the most common cancers with a genetic link is colon
    cancer.

    Many people who get colon cancer have a condition call
    familial adenomatous polyposis (FAP). This is a genetic
    problem that causes hundreds of polyps in the colon.
    These polyps can eventually develop into colon cancer.

    A recent study found that FAP can be treated with nutritional
    supplements. In the study, researchers took five people with
    FAP and gave them 480 mg curcumin and 20 mg quercetin, three
    times daily for six months. Then they evaluated the size and
    number of polyps in their intestines and rectums.

    The number of polyps decreased in all five by an average 60+%.
    And the size of those that remained decreased by 51%. There
    were no side effects from the supplements.

    This was a small study. However, its results are compelling.
    Here, five people with extremely high risk for colon cancer
    saw their risk decline substantially. All they did was take
    these two cheap and common supplements.

    And because these two supplements are powerful anti-inflammatories
    and antioxidants, I wouldn’t be surprised if they also reduce the
    risk of other cancers as well.

    One final note: I’ve had great success over the years with vitamin
    A (100,000 IU daily) and folic acid (five mg, three times daily)
    supplements. They really help keep polyps from coming back.

    So if you have polyps or a family history of colon cancer, take
    vitamin A and folic acid, as well as curcumin and quercetin.
    You can find all four at any good health food store.

    Yours for better health and medical freedom,
    Robert Jay Rowen, MD

    Ref: Cruz-Correa, M., D.A. Shoskes, et al. “Combination Treatment
    With Curcumin and Quercetin of Adenomas in Familial Adenomatous
    Polyposis,” Clin Gastroenterol Hepatol., 2006, June 4.
    ************************************************************

  15. #15 chloe
    April 20, 2007

    1 The “10 micromolar curcumin” that you use as the target strength for the bloodstream was determined from this research: Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis
    where they say, “Suppression of NF-kappaB and STAT3 activation in MM cells by ex vivo treatment with curcumin (diferuloylmethane) resulted in a decrease in adhesion to bone marrow stromal cells, cytokine secretion, and in the viability of cells.”

    so, the “10 micromolar” strength is the strength that they found that was needed to kill cancer in a petri dish?

    Can you explain how you can assume that this will translate to the strength needed to kill cancer in the human body? Is it always a one to one direct relationship from strength needed in a petri dish to the strength needed in the blood plasma? I was a bit confused by this after Part 1, where you emphasize that what happens in a petri dish can be quite different from what happens in the human body.

    3. This strength of curcumin that you are shooting for is “kill” strength, right? The strength needed to kill active cancer cells in the body. When they do the research with cancer cells in a petri dish… do they culture a certain number of cancer cells (can they do that?).

    If so, how do they translate the strength needed to kill X number of cancer cells in a petri dish into the strength needed to kill a tumor of Y cancer cells in the human body. if the person has a large tumor, wouldn’t they need a higher strength? or just a longer time of administration of the drug? Is there a formula that translates the kill strength needed to kill x number of cancer cells in a petri dish to the strength needed to kill y number of cancer cells in the body (you researchers have a formula for everything, don’t you ;))?

    Thank you.

  16. #16 chloe
    April 20, 2007

    don’t know what happened to the first part of my comment above, but I will repeat it here, since I can’t edit it into the comment above. The following should have been at the beginning of my previous comment. sorry:

    Abel, thank you for your explanation of the steps involved in researching a promising substance as a possible cancer.

    I do have a couple of questions about the strength of curcumin that you state is needed in the human plasma to be effective against cancer. I will quote here the statement I’m referring to:
    “These data show that even continuous exposure of at least 10 micromolar curcumin is required to have any detectable effects in killing multiple myeloma cells and that 50 micromolar is better, although in no case does that very high concentration eradicate the tumor cells in any of the experiments.”

    (and this continues with my comments above)

  17. #17 chloe
    May 1, 2007

    Bioperine (piperine) seems to have an anti-cancer effect of its own. Here is one study: Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells. there are other studies about piperine and cancer.

    Shouldn’t the strength needed to kill cancer cells in a petri dish have been determined by using both curcumin and bioperine? Isn’t there the possibility that the strength needed for both piperine and curcumin to kill cancer cells would be different than the strength needed for just curcumin alone, due to the addition of piperine’s own effect on the cancer cells in addition to just boosting the bioavailability of curcumin?

    Thanks.

  18. #18 Tony DeCaprio
    February 2, 2008

    If enormous amounts of curcumin are needed to substantiate a kill factor, how do we account for the very slight indication of prostate cancer existing to places like India and Mexico? Is there another factor involved, perhaps?

    Thank You.

    -TD

  19. #19 Abel Pharmboy
    February 2, 2008

    Hi Tony, great to know that my audience extends to extremely such an accomplished blues jazz guitarist!

    You raise a good point that reflects the difficulty in ascribing any one specific aspect of the diet to decreased cancer incidence. Those countries are likely to have diets that lower in meat, particularly in India, and/or lower in dairy (another dietary factor implicated in prostate cancer).

    With regard to Mexico though, you may be thinking more of cumin (from the seeds of Cuminum cyminum), a spice unrelated to curcumin (from the roots of Curcuma longa).

  20. #20 Tony DeCaprio
    February 2, 2008

    Hi Abel,

    Thanks for your reply, but it’s jazz guitarist. hehe)

    And could it also be the vitamin D factor? I mean lots of people here in USA are consuming less meat and less dairy, as well. Will these people be able to ward off the “original sin” of heredity? Some scientists seem to be suggesting (at least concerning India) it may be the combination of curry and cruciferous veggies, is why I brought this up. For example, is it true that prostate cancer rate is higher in North America due to the Sun’s output concerning vitamin D or is that another bit of mere conjecture?

    -Tony

  21. #21 Gianfranco Delorenzo
    October 14, 2008

    Hello, Abel and all.

    I’ve been reading your articles about curcumin with great interest. Thank you for posting them.

    I noticed that you haven’t yet replied to chloe’s inquiries. I wish you would, because I’m curious to know your answers.

    Thanks again to you and to all your readers who’ve added to my knowledge!

    Regards,

    Gianfranco

  22. #22 Charles Colenaty
    November 28, 2009

    Pharmboy,

    I obtained an enormous amouint of useful information from this post and the one preceding. I had been aware of the Bioperine experiments, but you blog finally provided a comprehensive review of the findings and their implications.
    In regard to the health effects ascribed to curcumin in the diets of the Indian population (which I understand also include low rates of Alzheimer’s and heart attacks), it is interesting to note that the dietary amounts of curcumin are actually quite small. turmeric is used as a spice and so large amouints are not consumed in a meal, and then curcumin only accoiunts for 5% of the turmeric.

    Sorry that you chose not to respond to Chloe.

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