January 9 2008 post. I was waiting to read the full MD Anderson report before discussing the curcumin-myeloma trial results here, but Chris’ comment on yesterday’s post, on top of all the private messages I have received to this regard, made me decide this morning to go ahead and write a post even though, I repeat, I don’t have ALL the facts and numbers. I will certainly have more to say on the topic as soon as I read the full study, which hasn’t been published yet. In the meantime, for what it’s worth, here goes!

Oh, before proceeding, though, I wanted to mention that you can view Prof. Aggarwal’s ASH presentation on the International Myeloma Foundation’s website: http://tinyurl.com/yw4m7y One important thing he points out is that, even when as little as TWO grams of curcumin were administered to some of the myeloma patients in the clinical trial, after four weeks a downregulation of the evil (I added the "evil" part) transcription factor NF-kappaB was observed. After 24 weeks, no NF-kappaB could be detected in some of these patients. Not even a glimpse. And they were taking only two grams. How about that?

Prof. Aggarwal also says that cancer treatment requires the inhibition of more than a single pathway, which makes curcumin an ideal agent since it inhibits several different pathways involved in cancer progression. A key sentence: “Although this study was very interesting and we did find the downregulation of various markers for cancer in MM pts, no objective responses were noted. So, in the future, I think that it would be interesting to combine curcumin with some of the existing treatments.”

A few introductory comments of my own: we know from the huge number of studies published on curcumin that this biologically active compound has extraordinary anticancer properties in vitro. Frequently, however, extraordinary properties do not work as well, or indeed at all!, when applied in vivo. It’s one thing to inject curcumin directly into some cancerous cell cultures, quite another for us to swallow a capsule or pill and hope that eventually our myeloma cells will be blasted by enough active curcumin. As we know, when taken orally, most of the swallowed curcumin gets transformed into (probably) less powerful, perhaps even useless metabolites (first-pass metabolism etc.). The issue of bioavailability pops up, again.

So the big question is: how do we get enough still-active curcumin delivered right smack into our cancerous cells? Eh. Still working on that!

ASH abstract. Thanks to the kindness of someone who sent me the abstract presented by the MD Anderson curcumin myeloma trial researchers at the American Society of Hematology (ASH) meeting held in December 2007, I was able to read some of the preliminary clinical trial data.

The abstract tells us that the MD Anderson clinical trial (which is still recruiting patients, by the way) consisted of 29 myeloma patients with asymptomatic, relapsed/refractory, or plateau phase disease. They took curcumin capsules without bioperine, 2, 4, 6, 8, or 12 grams/day in two divided doses, OR curcumin capsules with bioperine, 10 grams, again twice a day. The abstract tells us that “At least 6 pts are enrolled at each dose level; 3 on the curcumin arm and 3 on the curcumin + bioperine arm.” Conclusions: “Of the 29 evaluable pts treated so far, no objective responses have been seen. Twelve pts continued treatment for more than 12 weeks and 5 (1 patient at 4 grams, 2 pts at 6 grams, and 2 pts at 8 grams dose levels) completed one year of treatment with stable disease.”

Key words: “stable disease.” These patients remained STABLE. My glass is half full, not half empty. Always. 

Most of the people with whom I have corresponded privately have focused on the “disappointing” trial results, that is, not one of these myeloma patients experienced a decrease in her/his myeloma markers. But that is precisely what I expected since my own results from my capsule experiments have been similar. So I am not disappointed. Not at all. Sure, it would have been great to see a decrease at least in one patient since I (myself) did experience a fluky IgG decrease in September of 2006 that may or may not be ascribed to my curcumin capsules with bioperine intake (update: my parents pointed out to me that the way I worded this last sentence makes it seem as though my September 2006 IgG decrease has been my ONLY decrease to date. That is not the case, of course. I have experienced decreases  while taking curcumin powder. So I thought I should clarify that I was referring to capsules here). I say "fluky" because at the time, pre-blog era, I wasn’t keeping good records on my intake, and when, months later, I repeated the capsule with bioperine experiment my results were stable, that is, there was no decrease. Hmmm.

Well, anyway, in my view, the following trial results are even more important than disease stability (which is important enough!): “Oral administration of curcumin significantly downregulated the constitutive activation of NF-kB (at 3 months a median reduction of 77%, p<0.0001) and STAT3 (69%, p<0.001), and suppressed COX2 (66%, p<0.0001) expression in most of the pts at each of the monthly time points.”

Check out those percentages! Accipicchia! Excellent! This means that curcumin is able to inhibit all the overly active transcription factors that make myeloma cells proliferate…and this happened IN VIVO! That is, in spite of its low oral bioavailability, curcumin was still able to inhibit these bothersome pathways in myeloma patients. In vitro translates to in vivo. That result is not at all disappointing but very very exciting. To me, at least. Oh, I can’t wait to read the full report.