September 17 2007 post (scroll down for most recent entries). Last week a multiple myeloma listserv member posted a ScienceDaily article that initially puzzled me. The article (http://tinyurl.com/2k3acf) begins: Scientists report that a protein best known as a common marker of inflammation plays a key role in the progression of human cancer. The research, published by Cell Press in the September issue of the journal Cancer Cell, implicates C-reactive protein (CRP) as a potential target for cancer treatment. Well, that didn’t seem like breaking news to me. One of my regular blood tests measures my serum levels of CRP, and I know that it’s a myeloma marker. But then I read the showstopper: These results provide strong evidence that CRP is not just a marker for MM but is a critical regulator of myeloma cell survival.

Not good.

Reading on, this protein protects myeloma cells from the effects of chemotherapy and also enhances their production of IL-6 (an evil cytokine that protects myeloma cells from dying). So CRP and IL-6 work together to keep myeloma cells alive, in a sort of vicious circle. Also not good.

As I was reading this article and then the study abstract (http://tinyurl.com/2xop56), a question popped into my mind: are there any natural ways to decrease our CRP levels? The answer is YES. However, since this is a complex topic, both to understand and to investigate, and since my research has led me a bit astray (all over the place, actually!) given the overwhelming amount of information, I chose to post some of what I found out by degrees.

Let’s start with the C-reactive protein. What is it? In essence, it’s a protein produced by the liver and released into the bloodstream when there is an ongoing inflammatory process in the body. It is a non-specific marker for inflammation: an elevated CRP level indicates inflammation but won’t tell us where exactly it is located. So we might have high CRP levels due to a simple cold, arthritis or some type of infection.

The above-mentioned abstract reports that Elevated levels of C-reactive protein (CRP) are present in many disease situations including malignancies and may contribute to the pathogenesis of cardiovascular disorders. I didn’t know that an elevated CRP is a indicator also of cardiovascular problems, hypertension and other types of cancer (prostate, hepatocellular, e.g.) until I did research for this blog piece. Indeed, one interesting item that I came across is that people at risk of developing heart trouble or a stroke may, strangely enough, have normal LDL cholesterol levels but a high CRP. Quite an important recent discovery! Anyway, I double-checked my own CRP levels, which have never been above 9 mg/L (that is the normal range). The problem with this test, at least in Italy, is that it doesn’t quantify CRP. It simply reports that I have less than 9 mg of this protein in my blood. I prefer to have precise figures, so this test does not satisfy me at all. Besides, I noticed that in 2005 I had .5 mg, so at one point it WAS an actual number. Puzzling.

So we go back to the question of how to reduce CRP levels by natural means. I will give one example before stopping for the day (I have to get ready for my classes tomorrow). I found a couple of recent studies showing that one way to reduce CRP levels may be to increase our daily fiber intake. See: http://tinyurl.com/23hd2p and http://tinyurl.com/3xldst. That’s it for today!

November 10 2007 post: I recently read a study with a very long title, The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and C-reactive protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells (!), published in the European Journal of Pharmacology in February of 2007. The abstract can be seen here: http://tinyurl.com/26yy5q I was able to read the full study thanks to a friend (grazie, Sherlock!). As usual, I would be more than happy to forward the study upon request.

First, what are Chang liver cells? The online Dictionary of Cell and Molecular Biology tells us that these liver cells are derived from non-malignant human tissue. Now, I don’t want to get involved in a detailed explanation concerning inducible nitric oxide synthase, or iNOS, which is beyond my purpose here, anyway (phew!!!). Let it suffice to say that iNOS is linked to inflammation, and anything that inhibits it is good news. We already know about COX-2 (see my Ellagic Acid and Natural COX-2 Inhibitors Pages for more info) and CRP, and of course the ubiquitous NF-kappaB. Ah yes, and kaempferol is a natural flavonoid found in tea, broccoli, grapefruit and other plant sources. On with the study, then.

On page 222 we read that C-reactive protein (CRP) is an acute phase protein produced by hepatocytes whose serum elevation is considered as indicator of chronic inflammation and whose interaction with endothelial cells may be the mechanistic link between CRP and atherosclerosis [ ]. It is known that IL-6 induces CRP through a mechanism involving NF-kappaB [ ], but no study has until now documented potential effects of flavonoids on CRP expression in liver cells. Hepatocytes, by the way, are liver cells (for the more scientifically-minded, epithelial cells found in the liver that, among other things, have the function of helping to detoxify our blood).

Both quercetin and kaempferol reduce iNOS and COX-2: The present study indicates that both flavones reduce iNOS protein level in activated Chang Liver cells and that kaempferol was a slightly more potent inhibitor at low concentrations. COX-2 protein level was also reduced [ ] And, most importantly for our purpose, i.e., identifying substances that reduce CRP levels naturally: Our data show that both quercetin and kaempferol significantly reduce CRP protein level in liver cells and that this inhibition is concentration-dependent [ ]. SIGNIFICANTLY REDUCE? Well, I have been putting quercetin powder in my curcumin/chocolate mixture for other reasons (see my Bioavailability page for more information), but I am very pleased to discover that it may also be reducing my CRP levels.

The study ends: In summary, the present study indicates that the modulation of iNOS, COX-2 and CRP by quercetin or kaempferol may contribute to the anti-inflammatory effects of these two structurally similar flavonoids in the liver, via mechanisms likely to involve blockade of NF-kappaB activation. Sounds good to me!

March 30 2012 post: I wanted to highlight something that I learned this morning from a blog reader who sent me the link to a study (full text available online) showing that low levels of magnesium might increase our C-reactive protein (= CRP) levels. Ooooh, that’s not good at all! Many myeloma patients take magnesium for leg cramps and neuropathy…but now there’s yet another reason to take it. See: http://goo.gl/jrcph 

Excerpt: Among the 70% of the population not taking supplements, magnesium intake below the RDA was significantly associated with a higher risk of having elevated CRP. The lower the magnesium intake, the higher was the likelihood of elevated CRP. ‘Nuff said.