“Curcumin for monoclonal gammopathies. What can we hope for, what should we fear.” My comments on the Vermorken study, 2012, in three parts.

March 25 2013 postINTRODUCTION. You may remember my March 28, 30 and April 1 2010 posts about a study by Vermorken et al on the possible dangers of taking curcumin. If you don’t, then please have a look at the three rants…I mean, at the three POSTS, before proceeding any further:

March 28, 2010: http://margaret.healthblogs.org/2010/03/28/a-word-of-caution-against%E2%80%A6another-word-of-caution-part-1/

March 30, 2010: http://margaret.healthblogs.org/2010/03/30/brussels-sprouts-instead-of-broccoli-part-2/

And then, the clincher. April 1, 2010: http://margaret.healthblogs.org/2010/04/01/

Well, here we go again…

About two years after the first study, here is another one, available for free online:http://goo.gl/oqzE9 (click on “PDF” to download the full text). This 2012 study has an ominous question contained in its title: “What can we hope for, what should we fear?” Uhm, what should we “FEAR”???!!! Holy cats! Now I’m scared! ;-)

Naaaah, let’s not panic. It’s just one of those eye-catching titles…Let’s see if it really means anything…

This time, even though you can read the full study on your own, I decided to go through it with you almost step by step, only skipping the stuff that I didn’t find as interesting or that we already know (what MGUS is, blablabla) and adding my own comments, right or wrong as they may be. In case it’s not obvious, I’m annoyed…but also as cool and calm as a purring cat (see photo)… 😉

CHAPTER ONE. I actually agree with a few things these authors write. First and foremost: it’s not a good idea for EVERYONE to take curcumin, the active ingredient of the spice turmeric. For example, I wouldn’t take it if I were trying to get pregnant (either gender)…or if I had gallstones…Or if I had any of the medical conditions listed on my Warnings and Side Effects page…

And I also agree with them that curcumin probably isn’t going to help all cancer patients. I mean, it’s just like anything else. We’re all different, so it makes total sense that some of us will do well or even really well on curcumin, whereas others won’t.

That said, let’s get down to business.

The first thing we read in the abstract is that curcumin is considered to be safe for healthy people but possibly not for those with MGUS: Curcumin might be helpful for some but certainly not for all patients with monoclonal gammopathies. Intriguing statement. I agree, sort of. As I said earlier, if you have gallstones, e.g., you shouldn’t take it, since curcumin increases bile production (but if you don’t have gallstones, curcumin will prevent their formation…).

Then we get to the study’s “Introduction,” which gives us an idea of what the main argument is going to be: The anti-inflammatory activity of curcumin comes, however, at a price: immunosuppression.

Aaaaaah, immunosuppression. Well, since I’ve discussed my own (lack of!) immunosuppression in a recent post (March 22nd), I won’t use myself as an example here. Just go have a look at that post, if you haven’t read it…

Skip skip skip.

The introduction ends with this statement: Because myeloma is a devastating incurable condition while MGUS and SMM are often asymptomatic, patients with a high-risk MGUS and with SMM are candidates for preventive strategies. It is absolutely essential for a preventive approach that it does not itself increase the risk of progression.

Again, I agree. The problem is that conventional treatments don’t fall into that “won’t increase the risk of progression” category. Conventional treatments are harsh, very harsh, and let’s not forget that the International Myeloma Working Group is NOT in favor of an “early intervention” approach, since there are no benefits. Indeed, there are many potential hazards (loss in quality of life, etc.).

And that’s what my own position is: don’t poke the sleeping dragon (=myeloma). Conventional treatments (in my opinion, and obviously I am referring to MGUS and SMM situations) have a high “poke-the-dragon” risk. Too high…again, in my opinion…

But I do agree with what the authors say about the current impossibility of identifying patients who would benefit from taking curcumin. There haven’t been enough clinical trials, they say. I’d like to add that there will probably NEVER be enough clinical trials, which in most cases are sponsored by the big pharmaceutical companies… Curcumin simply isn’t profitable enough, so it gets essentially ignored by big pharma… And that is why I am extremely thankful for the persistence and dedication of researchers such as Terry Golombick (Australian curcumin-MGUS trial). (FOR THE RECORD: I wrote this post over the weekend, that is, before Dr. Golombick left a comment on my March 22nd post… :) )

CHAPTER TWO. Then we get to this statement: It should be kept in mind that in multiple myeloma, so far, no significant activity of curcumin has been noted in clinical trials in which the validated endpoints used for other myeloma drugs [17] were applied to adjudicate efficacy of therapy.

You know, the more I think about it, the more I believe that this sort of comparison makes no sense whatsoever. How can you possibly compare an incredibly toxic, poisonous substance that kills everything in sight (good and bad cells alike) to a natural, nontoxic extract that inhibits or kills only bad cells but that clearly isn’t as strong or as fast or as effective or as well absorbed?

Just a quick aside: I was actually shocked to read some official recommendations for the handling of chemo drugs. It gave me an idea of how toxic these substances are. Here are a few of the randomly picked websites I looked at: http://goo.gl/fOizv (a guide on how to administer, handle and dispose of chemotherapy) and http://goo.gl/P6qu4 (the story of a healthcare worker exposed to chemotherapy).

Curcumin, on the other hand, has no handling problems. You can rub it all over your body or EAT it. In other words, it won’t harm you in any way, oh, except it might stain your hands a bit (so wash ‘em in very warm water after taking your daily dose!). Huge difference, I’d say.

The problem is that we are impatient. We like and want quick fixes. Conventional drugs, when they work (sometimes they don’t, and that should be noted), have the potential to bring down our paraprotein levels quickly, etc. etc. etc. With curcumin, there are no quick fixes. By the way, before you get your knickers tied in a knot (love that expression!): I’m not implying that anyone should go off chemotherapy and take curcumin instead. That’s not my point, here.

My point is: we just can’t compare honeybees to Godzilla ( = that was the first image that popped into my silly mind…).

The real issue for me is how to increase the strength and efficacy of curcumin without turning it into something toxic (which might risk waking up the dragon!). If that could be achieved, then we could use the above-mentioned endpoints.

As things stand now, though, we just have to be content with the small improvements in our markers or with being stable. Of course, stable is always good!!! :)

March 27 2013 postCHAPTER THREE. Now we’ve reached paragraph 2.3, titled “Curcumin does not influence the paraprotein level in all patients.” The authors suggest that curcumin might not act directly on the abnormal plasma cells. It could act indirectly on secondary mechanisms that play an increasingly important role in later stages of MGUS. One of these secondary mechanisms is IL-6, a close friend of myeloma, as we know.

Another interesting statement: Increased C-reactive protein- (CRP) and erythrocyte sedimentation rate- (ESR) values (indicators of systemic inflammation) that can be increased in myeloma as well as MGUS are independent prognostic factors for survival in myeloma [24,25]. 

Vermorken and his team then suggest that curcumin might be beneficial to MGUS and SMM folks who have increased CRP and/or ESR, adding that long-term use of curcumin reduces CRP.

This suggestion is repeated in the following paragraph (no. 3), by the way: Not all patients with monoclonal gammopathies have increased levels of CRP or ESR but these levels are indicators for prognosis. If indeed like in SLE the activity of the BAFF pathway would be correlated to CRP or ESR [30] in some or all patients with monoclonal gammopathies, curcumin could be helpful and CRP and ESR would be very useful indicators for success of intervention.

I have something to say on this particular issue. I have seen a decrease in both of these markers over the years. My CRP has always been in the normal range, but compared to the pre-curcumin period, it has decreased more than 10% (and, in some tests, even more than that).

The results for my ESR have been even stronger. It used to be in the upper 80s (mm/hour). Yikes. How did my blood even circulate??? It must have looked like sludge, bleahyuuuuckgross. Anyway, in my most recent test results it had gone down to 34 mm/hour, close to the high end of the normal range = 25 mm/hour. That’s more than a 50% decrease…Uhm, did I just hear someone utter the word “significant”? ;-)

CHAPTER FOUR. Then we get to this (I highlighted two of the sentences): Since curcumin is helpful in chronic inflammatory states like autoimmune disease [42] the above suggests that curcumin could have a preventive effect on the development of MGUS in chronic inflammatory conditions. However, this is not easy to prove and would need long term monitoring of large groups of patients. Trials about prevention of the emergence of MGUS with curcumin in a context of chronic immune stimulation and low grade inflammation could be useful and should undoubtedly include measuring ESR as well as CRP with high sensitivity. It is important to note that curcumin concentrations in the inflamed target organs are perhaps not of determining importance. Crucial for a favorable outcome is probably the influence of curcumin on circulating immune cells. These could be confronted to higher curcumin concentrations in the gut and migrate to target organs. Relatively low doses of curcumin would therefore probably be effective.

Circulating immune cells, eh? Low doses would probably be effective? Hmmm. Very interesting…

In paragraph no. 4, the authors suggest that patients with high levels of circulating IL-6 would probably benefit (more than others) from curcumin intake. Then they add:We have so far seen that there are reasons for being hopeful about the potential of curcumin to be beneficial for prevention of monoclonal gammopathies in patients with inflammatory conditions. The influence on inflammatory symptoms could form early indicators of success. Yes indeed.  I am hopeful, too!

Immediately afterwards, they add: For high risk MGUS and SMM high doses are needed to provoke an effect on the paraprotein load and this, even more, obliges to anticipate the possibility of side effects. It is therefore mandatory to discuss reasons for potential concern. Ah, I have to comment on that. As you know, I’ve been on a high dose of curcumin for MORE THAN EIGHT YEARS now, and my side effects have been ONLY beneficial. Now, I won’t waste time writing out all the amazing and unexpected benefits I’ve had from curcumin, since I’ve written about many of them ad nauseam. 

However, one side effect that I haven’t mentioned very much is an aesthetic one: my rosacea, which used to be so bad that make-up hardly made a difference, and I just wanted to hide and never go out in public. Yeah, it was that bad. Well, to my amazement, my rosacea (inherited from my Dad, who has it, too) has completely cleared up. I do get the typical rosacea flushing now and again, but (YAY!!!) there are no more bumps, and my skin is soft and looks normal. Lookin’ good! :-)

April 3 2013 postCHAPTER FIVE. The part that really got my knickers tied in a knot is in paragraph 5.2…the part about immunosuppression: Patients with MGUS, but less so than those with myeloma, have an increased risk of infection. See my March 22 2013 post for my own experience…no point in going over it again.

Speaking of “again,” here the authors again (AGAIN!!!) bring up the case of ONE, SINGLE MGUS patient that they’d already used as an example back in 2010. You’ve got to be bloody joking. Boyohboy, you should have seen my face when I read this part. 8-O I mean, could they possibly have done no better than THAT, after TWO FULL YEARS of research (since 2010, I mean)??? Could they not have come up in the meantime with ANYONE ELSE, even a member of their own team forcryinoutloud!, to test their shaky-at-best theories on turmeric or curcumin (I wrote both because in their 2010 study, they seemed a bit muddled about the difference between the spice and its active ingredient)? If I had access to a lab, as they most certainly did, I’d be testing myself all the time and recruiting other people willing to be tested…I mean, you can do a lot in TWO YEARS. A lot…

Anyway, as they had already told us in 2010zzzzz, the above-mentioned patient’s daily intake of turmeric for intestinal complaints repeatedly led to bronchitis. Now wait a sec. Turmeric is used to treat bronchitis in Ayurveda, so this part makes subzero sense. But I’ve already written about this particular study (see my late March, early April 2010 posts), so I’ll leave it at that…

Oh wait, except I wanted to note that, while the authors of this study lament the fact that the Australian MGUS curcumin trial had only a small number of participants (25 or 26 MGUSers, as I recall…), it was perfectly okay for them to make pronouncements on the dangers of turmeric based on ONE SINGLE patient (= a guy with a long list/history of ailments, to boot…Just check out the 2010 case report…). So in the end we have, ah, let’s see: 26 cases versus…ONE?

Grump…

So, let’s recapitulate: Vermorken et al use the same patient as an example in two separate studies written two years apart. I find that absurdly astonishing…beyond comprehension, really. So I’m going to repeat my question: is that the best they could do? In two years’ time, could they not find another patient or, better still, a group of curcumin-taking patients who developed some side effects that would prove their points on the dangers of this spice?

I guess not.

And that takes me to my next point. If we were to worry about everything that inhibits our T cells, thus depressing the immune system, we would have to stop aging, for one thing. Oh yeah, as we get older, our T cells decrease and are also not as effective as they used to be.

But, a bit more seriously now, we’d also have to avoid taking a lot of helpful medicines, including glucocorticoids. ”Oh yes, m’am, that’s really too bad about your pesky allergies and asthma, but you see, based on the perhaps-totally-unrelated experience of one single patient in the Vermorken study,  you should really avoid taking glucocorticoids because they might depress your immune system. And yes, you’ll just have to put up with the itchy hives and the wheezing, sorry!”

I mean, c’mon…

And another thought just popped into my mind. How come Vermorken isn’t worried about the clinical trials that are already testing or are about to test drugs such as lenalidomide (Revlimid) and dexamethasone, just to name a few, on smoldering myeloma patients? These are immunosuppressant drugs…tested on SMM folks. Now why isn’t Vermorken concerned about these drugs’ immunosuppressant effects, which I imagine would be far stronger than those of curcumin??? (See my April 1 2010 rant and rave on this topic.)

One of these trials, as you may recall, is the Spanish SMM chemo study (grrrrrr!!!). Well, I recently found an interesting bit of info that I want to share with you: the Mayo Clinic and the Spanish PETHEMA can’t even agree on which SMM folks are considered to be high-risk. No kidding. Check this out: http://goo.gl/2D7S3 Oh yeah, I’m angry. You can bet your favorite polka dot mittens on that. It’s a bloody disgrace…

And I say this with much regret, believe me. I wish it weren’t so. I really do. But what else can we conclude?

Okay, I’ll stop ranting for a second and get back to our topic at hand.

If you’re curious to know which conditions are treated by glucocorticoids, this page at Drugs.com will give you an exhaustive list: http://goo.gl/1f8Tx…from Acute Lymphocytic Leukemia to allergic reactions all the way to uveitis…oh, all sorts of ailments…

In a comment on my March 25 2013 post, Joao (thank you!) reminded us of the CAMP protein, which is vital to our innate immune system and, well well well quelle surprise (not!), is stimulated by…drum roll!!!…yes, you guessed it!, is stimulated by curcumin: http://goo.gl/ZjhLH Vitamin D stimulates CAMP, too, by the way. In fact, my intake of both (plus Nigella sativa) might explain why I am so healthy (knocking on wood, here!)…

So much for the issue of immunosuppression. I think I’ve said more than enough. ;)

CHAPTER SIX. On to paragraph 5.5. “Could curcumin induce a more malignant phenotype?” Wow, that’s a real eye-grabber. Let’s take a closer look.

Here the authors briefly discuss VEGF, which is a close friend and “feeder” of Mr. Myeloma. That’s precisely why VEGF is a target in conventional myeloma treatment. Unfortunately, though, at some point, myeloma cells become resistant to these anti-VEGF drugs. And these resistant buggers are more invasive. Okay, that’s clear.

But the authors imply that, since curcumin also inhibits VEGF, it might create resistant cells and a more malignant phenotype…just like those potent toxic conventional drugs. Huh? That’s all the “proof” they provide??? Just a hypothesis???

I have two observations to make:

1. if the conventional anti-VEGF (= anti-angiogenesis) drugs create more resistant and aggressive myeloma cells, then they should certainly not be used to treat myeloma…Translated, that means: no more thalidomide and analogues (the recently-approved-by-the-FDA pomalidomide/Pomalyst, lenalidomide…). No more bortezomib (Velcade) or other proteasome inhibitors. No more cyclophosphamide. No more zoledronic acid (Zometa)…ah, yep…Zometa inhibits the myeloma-feeding process of angiogenesis, too. Well, I’ll stop here. You get the gist.

2. now, if a hypothesis doesn’t need to be backed up by any tangible evidence (and in this particular case, as they did in paragraph 5.4 sigh, the authors bring forth no proof whatsoever that curcumin might induce a more malignant phenotype), does that mean that I can just blurt out any kind of crazy or random hypothesis about, well, about anything? What if I were to state that curcumin cures myeloma? Based on Vermorken et al, I don’t need to back up my statement with any proof. All I have to do is write a study about it.

Yes, of course it’s absurd. That’s precisely my point.

Sheesh.

Let’s keep going. I have a final clincher… :)

Conclusions. Vermorken et al continue to insist that there is a “dark side” to curcumin. There may well be, but it isn’t immunosuppression. And here we do have proof.

As for so-called “controlled clinical trials,” well, in a perfect world, I’d agree that these would be of the utmost importance. But we don’t live in a perfect world, to say the least. If you haven’t done so already, please have a look at my March 11 2013 post on “Publication bias.” The TED talk to which I link in that post is a real eye-opener…Obviously, this doesn’t mean that we should start testing potentially dangerous stuff on ourselves. It just means that we shouldn’t live with blindfolds over our eyes. We should be aware that negative data frequently doesn’t get published. That’s all I’m sayin’…

MY FINAL CONSIDERATIONS. I always find the “Conflict of Interest” part of a study most illuminating. Remember all the raging posts I’ve written about the Spanish SMM trial…remember how many of the physicians/researchers involved in that trial had incredibly obvious ties to Celgene, the maker of one of the drugs used in the trial (one of them, as I recall, was a Celgene employee, not even an MD!)? Yeah. My blood still boils when I see a reference to that trial, grrrr.

Well, as for this study, in addition to looking at the Acknowledgements, please don’t neglect to check out Prof. Andrès’ associations: “He has received several grants for lectures, studies or expertise from laboratories.” Hmmm, which laboratories? It’s worth it to list them all, methinks:

GlaxoSmithKline (that’s what GSK stands for), Amgen, Roche, Chugai, Vifor, Ferring, Sherring, Genzyme and Actelion…

Hey hey hey, lots of Big Pharma, here. Gee wiz. Is there anyone out there who has NOT been “contaminated” by big pharma money?

But, of course, “this work is free of any such association.” Of course it is. That malicious thought didn’t even pop into my mind. Or…

Did it?

 

1 Comment

  1. Just my interesting experience with curcumin, maybe others can relate their own stories. I have IgA MGUS. My Free Light Chains soared to over 250, that’s when I started taking curcumin. I started taking about 500 mg of Dr Best curcumin. In about 12 months, this reduced my FLC to about 170 and felt much better. Stayed on it for another 12 months and my FLC seemed to stabilize at about 170-175 range. Then I started a generic brand instead and stopped taking everyday. Over next 24 months, my FLC increased to about 260, so I started on Dr Best curcumin again at 800MG/day and in 12 months was able to reduce my FLC to 228. Headed in the right direction again . The only problem is, my IgA immunoglobulins keep rising (now at 1340, normal is 410) and I’m wondering if this has anything to do with my curcumin increase. Also, am I trading off lowering FLC for increasing levels of IgA Immunoglobulins? Is it strange that my Immunoglobulins and FLCs are moving in opposite directions? Am I doing more harm than good?

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