Australian MGUS-curcumin clinical trial

March 13 2009 post The MD Anderson curcumin myeloma clinical trial is not THE only one. Yep, that’s right. Another trial is being held right now in Australia. Well, okay, technically, it’s a MGUS, not MM, curcumin trial, as we will see in a second.

 

Let’s see, you can access the PDF file that provides some information about the trial (an interesting read, by the way), but for some reason it doesn’t seem to work unless you do a Google search (for instance, the words curcumin myeloma clinical trial Australia should bring up the correct Dove Press article).

 

OR you can click on this HTML link: http://tinyurl.com/crkjy3. Then click on the PDF link at the top of that page. You can then download the PDF file onto your computer.

 

OR (!) you can do another Google search for the title of the study “The potential role of curcumin (diferuloylmethane) in plasma cell dyscrasias/paraproteinemia.” I’m very sorry that I cannot provide a direct link (as I said, it doesn’t work, not for me anyway). But this search operation will take only a few extra seconds of your time.

 

If you don’t want to go to the trouble, though, then just read the following synopsis. The abstract tells us that Preliminary results from our pilot study show a drop of between 5% and 30% serum paraprotein in patients taking curcumin compared with patients on placebo. Thirty percent??? Holy cats and dogs! That’s Giovanni Allevi music to my ears…sweet!

 

The Australian researchers favour early intervention in MGUS patients to reduce the paraprotein load. I am in favour of that, too, but only if said intervention is made with non-toxic natural extracts. As in this case.

 

Toward the end of the article, we get to the relevant part: We are conducting a single blind randomized controlled pilot study on 25 patients with paraproteinemia. Entry criteria included patients defined as having MGUS ie, the presence of a serum paraprotein (greater than 8 g/L and less than 40 g/L) with the exclusion of multiple myeloma. These patients are being monitored for a 6 month period of curcumin or placebo therapy.

 

I almost got teary when I read what followed: Curcumin or placebo is being administered orally as a 2 grams twice daily regimen. After one week on curcumin, there has been a drop of between 5% and 30% serum paraprotein in some patients, compared to controls […]. After 3 months of curcumin therapy, these reduced levels have remained suppressed. These exciting findings have prompted a double-blind, randomized, controlled trial. The benefits of the fall in paraprotein is uncertain. How long these reduced levels will remain suppressed and what the clinical benefits are, remain to be seen. As a natural product, it has exciting potential in the treatment of plasma cell dyscrasias. Only TWO grams of curcumin??? YAY!!!

I say, this is very exciting news indeed. Another trial! Plus, the preliminary results are bloody excellent. Hoppity hop! Needless to say, I have a million questions that I hope will be answered soon. For instance, I wonder what type of curcumin these patients are taking, how they are taking it, blablabla. Rest assured, as soon as I have any news, I will post it. Good or bad, as always…but hey, how could it not be good?!!!

Update. September 10 2009 postThis afternoon I received a Google Alert about a new study on curcumin and myeloma. I got so excited that I could barely finish reading the abstract! (see: http://tinyurl.com/mc8vth)

The abstract informs us that 26 MGUS patients were given a daily dose of four grams of curcumin. Hmmm, come to think of it, these must be more results from the Australian MGUS-curcumin trial that I posted about on March 13 2009. Yes, I am sure of it…same names, same hospital. Well, well.

Let’s go directly to the results, which show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen.

I’d never heard of this urinary peppy thingy, so I had to look it up. I found a study that explains its significance for myeloma patients: http://tinyurl.com/lqls9e Basically, it is a sensitive and specific marker of bone resorption in multiple myeloma. High levels of urinary N-telopeptide of type I collagen, or NTx, are found at advanced stages of disease. Okay, so the lower, the better.

But hey!, have a look at the Conclusions: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation. Well, I’ll be…! Just knock me down with a Tetris tile! Oh, I can’t wait to read the whole shebang…!!!

Update. September 14 2009 post. The report is only six pages long but is packed with interesting information. There is so much good stuff, in fact, that it was difficult not to go ahead and print the whole thing! (I cannot do that, of course, for obvious reasons…)

It begins with a description of MGUS and how it differs from multiple myeloma, including this item of interest, which explains why the bone turnover marker is so important, even in MGUS: Although MGUS is largely considered a benign condition, a number of studies show that patients with MGUS are at increased risk of developing fractures even before progression to myeloma. Elevated bone turnover is an independent predictor of fracture risk, and a number of studies have shown elevated bone resorption and/or reduced bone formation among patients with MGUS and myeloma. Incidentally, in case you have MGUS and were a bit taken aback by the words “even before progression to myeloma,” don’t forget that the overall risk of progression MGUS-MM is a mere 1% per year.

Now read this: It is currently not possible to predict the course in any individual patient, and clinically symptomatic myeloma may not evolve for as long as 20 years. Whoa. I don’t think I have seen a sentence like that in any other study–clinically SYMPTOMATIC myeloma may NOT EVOLVE for…TWENTY years??? I had no idea…

The researchers note that matters are different for those who are in a high-risk group—e.g., with high levels of M-protein or heaps of evil cells in the bone marrow or an abnormal free light chain ratio or IgA and IgM instead of IgG.

Well, let’s get to the part about curcumin. First comes the description of the Curcuma longa plant and the various properties of its active ingredient, curcumin. We know most of this stuff, including the fact that Curcumin has also been shown to inhibit osteoclastogenesis and thus reduce bone turnover. And then we get to one of the reasons underlying this clinical study: Based on the antimyeloma cell activity and inhibition of osteoclastogenesis exhibited by this polyphenol, we postulated that curcumin will inhibit the action of abnormal plasma cells and affect the activity of osteoclast cells in patients with MGUS. This study offered the opportunity to test a possible preventative strategy with little risk.

Study participants: 26 MGUS patients, 16 men and 10 women over the age of 45, with less than 36 g/L serum M-protein (median: 20 g/L), less than 10% neoplastic cells in the bone marrow and no CRAB symptoms or evidence of metabolic bone disorder. They were separated into two groups in this single-blind cross-over pilot study, which means that group A patients were given curcumin at the start of the study and were then crossed over to placebo at the end of 3 mo. Group B patients were given placebo initially and then crossed over to curcumin.

Aha, here is a useful titbit: Patients consumed two tablets twice daily, i.e., 4 grams/d (this dose has been defined as the dose at which plasma levels of curcumin can be measured and pharmacodynamic effects showed in vivo) half an hour before food or 1/2 h after food and were crossed over at 3 mo after initiating therapy. Treatment continued for 6 mo. This leaves me with a question…were there any differences between the half-hour-before-meals group and the half-hour-after-meals group? I found no answer to that in the study.

Let’s keep going. During the study, two patients developed diarrhea and abdominal cramping and withdrew. Ah, but read this: nine out of twenty-six MGUS folks had a VITAMIN D DEFICIENCY. I highlight that little fact, since I have come to believe strongly in the importance of maintaining NORMAL vit D levels. The researchers make no comment about this possibly significant (or not) finding…so my next project is to have a look at the Tables to see what happens to the low-vitamin-D patients when they start taking curcumin…

In the results part of the study, we can read that half of the MGUS folks whose serum M-protein was more than, or equal to, 20 g/L, experienced a 12-30% decrease in their M-protein levels. And when they were switched over to the placebo group, two of them showed a rebound in their serum paraprotein levels. The less than 20 g/L folks instead did not show a response to curcumin, but their serum paraprotein levels remained stable throughout the study period (that might have happened anyway, of course…).

Now for the placebo group: In contrast to a decrease in serum paraprotein seen in patients initiating curcumin therapy, patients receiving placebo showed stable or an increase in their serum paraprotein levels. When they began receiving curcumin, though, two patients showed a decrease in their serum paraprotein (12.5% and 15%, respectively).

Now for some info concerning bone turnover: Although 73% of patients did not show a change in their uNTx levels while taking curcumin or placebo, 27% of patients showed a decrease in their uNTx levels while taking curcumin. uNTx is a bone turnover marker determined by a urinary test. Some patients, therefore, may show a decrease in bone resorption in response to curcumin. Some, not all…

Discussion: The present study shows that oral curcumin (a known inhibitor of tumorigenesis and osteoclastogenesis) is able to decrease paraprotein load and bone resorption in a select group of patients with MGUS. Fifty percent of patients with a paraprotein >20 g/L responded with a 12% to 30% decrease in their paraprotein levels while taking 4 grams/day curcumin orally. The placebo folks had no such decrease in their paraprotein levels.

And then: Similar reductions in paraprotein have been seen with conventional antimyeloma therapies such as melphalan and dexamethasone. This is the first study, however, assessing the potential therapeutic effect of curcumin in MGUS patients.

The finding that only patients with higher serum paraprotein levels responded to curcumin is fascinating to me. The researchers suggest that this group may have an abnormal plasma cell clone that responds differently to curcumin or its metabolites. In vitro studies may help to differentiate a subpopulation of plasma cells that are curcumin responsive.

And here is more snack food for thought: The partial response rate (i.e., 50-75% decrease in paraprotein concentration) was 0% in both arms. In MGUS patients, the chance of a partial response are low because cell division is very slow. Even in smoldering myeloma, responses take much longer with a drug such as thalidomide compared with relapsed myeloma where cells are dividing more quickly. Indeed. 

The researchers conclude by stating that this pilot study has prompted them to commence a double-blind, randomized, control trial using higher dosages of curcumin in a larger cohort of MGUS patients with significant paraproteinaemia. Excellent. I am already looking forward to reading the results of the larger study!

5 thoughts on “Australian MGUS-curcumin clinical trial

  1. Rosey Faire

    Hi Margaret,

    Thanks for your very informative blog. In relation to the above entry, (Australian MGUS-curcumin clinical trial), I’m wondering if you’ve come across the letter that was published in response to this Australian trial which raised questions about curcumin’s possible effects on the Th1 response, especially in people with common variable immunodeficiency (CVID)? It was entitled “Is curcumin for MGUS without risk?” by Vermorken, Zhu & Van d Ven.

    Just wondering about your opinion on this, having done so much exploration about curcumin.
    Thanks again,
    Rosey Faire

    Reply
  2. Margaret Post author

    Hi Rosey, oh yes indeed. That letter infuriated me (I did a lot of research for NOTHING), that is, it infuriated me as soon as I discovered that the main conventional drugs used to treat MM also inhibit the Th1 response, but hey, you don’t hear anything about that, do you? Hah. Typical. For more information, have a look at my April 1 2010 post: http://margaret.healthblogs.org/2010/04/01/about-to-leave-for-rome%e2%80%a6and-a-few-random-thoughts%e2%80%a6/ I don’t think I need to comment any further.

    Reply
  3. Diana

    Hello Margaret,

    VERY good read! I live the in USA and have MGUS. Found it by a quirk blood test. Taking Super Bio Curcumin and now going to “up” the dose to the equivalent of 4 grams. Last numbers were stable. Had been going up. Going to read more posts to the right on this site. THANK YOU!! You make it very understandable to the layperson.

    Diana Whaley

    Reply
  4. Rosey Faire

    Dear Margaret,

    Your informative blog is a valuable resource for us. My husband’s MGUS paraprotein level is fairly low (4.6 g/L). We chased up this Australian MGUS-curcumin trial and because we live in Sydney we went for a second opinion to one of the authors – he suggested just monitoring for the time being because they didn’t find it made much difference unless the paraprotein level was higher. But we’re using a lot more turmeric in our cooking and have recently purchased Prof Aggarwal’s Healing Spices book which is wonderful – thanks to you.

    There’s a product here in Australia called Cumerone 1200 which I have been chasing up – it is more soluble in salt solution than straight curcumin since it is bound to a sugar group. It’s been tested with good results for osteoarthritis hand pain and I’ve been taking it for back pain. The research “proving” its higher bioavailability has to be taken with a grain of salt however – needs improvement.

    With yellow fingernails,
    Rosey

    Reply
    1. Marie

      Thank you Margaret . Wonderful information on turmeric and McGus . I have been McGus patient for 12 years . Bloods have been stable until recently … Protein is showing in the urine . Haematologist wishes 6 monthly bloods now to monitor it closely . I commenced curcumurin for my arthritis not knowing about the research on it and McGus . I live near Sydney , Australia . So looking forward to reading about the clinical trials in Oz and speaking to my haematologist about it all . Thank you again !

      Reply

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