Just minutes after I had asked her, Sherlock sent me the full study…a blog reader did the same just a few hours later…then another blogging friend…so now I have three copies of the same study…fabulous! Thank you all!
Let’s dive right into the report, which 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!