In my November 22nd post, I mentioned a newly published MD Anderson study, co-authored by Prof. Aggarwal (abstract: http://tinyurl.com/35w4mn). Thanks to Sherlock (grazie mille!), I was able to read the full study, which I have read but must read again, as it is filled with so many significant details etc. My original post turned out to be too long, so I will divide it into chapters, at least two.
Titled Bioavailability of Curcumin: Problems and Promises, the study was published in the November 14th issue of Molecular Pharmaceutics. It begins with an overview of curcumin, which, as we know by now, has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. Additionally, the hepato- and nephro-protective, thrombosis supressing, myocardial infarction protective, hypoglycemic, and antirheumatic effects of curcumin are also well established. Even at high doses, up to 12 grams a day, curcumin is well tolerated. I know I have written all this before, but I think it’s good to go over known information sometimes.
Curcumin’s main problem, as we (again!) know, is bioavailability: studies over the past three decades related to absorption, distribution, metabolism and excretion of curcumin have revealed poor absorption and rapid metabolism of curcumin that severely curtails its bioavailability. The serum levels of curcumin are extremely low. Let us keep in mind, though, that the UK Phase I Clinical Trial of Oral Curcumin (full study: http://tinyurl.com/32kwok), which tested regular curcumin (C3 Complex without bioperine) on patients with advanced colorectal cancer, ends with the following statement: The findings of the study presented here lead us to conclude that the systemic pharmacological properties of a daily dose of 3.6 g of curcumin are suitable for its evaluation in the prevention of malignancies at sites other than the gastrointestinal tract. 3.6 grams. Very little, compared to the 8 grams that I am taking. This Phase I clinical trial in fact showed that consumption of 3.6 g of curcumin daily generates detectable levels of parent compound and conjugates in plasma and urine, where the parent compound was curcumin, of course. The study contains headache-causing (for a non-scientific brain!) amounts of details, but, unless I am much mistaken, a few are lacking, which I would be curious to know, for instance: 1. what time of day was curcumin taken by the patients and 2. did they take it on a full or empty stomach?
Speaking of time of day, as I was reading through the description of all the studies cited by the MD Anderson team, a BIG question popped into my head. Relevant or not, here it is. Remember my November 11th post on circadian rhythms, in particular the part about human versus rat testing? Well, here’s a memory refresher: Despite this evidence of variation, drug research is almost always done during daylight hours, when the humans leading the studies are awake and alert. And in the animal testing stage, it’s almost always done with mice and rats, which are nocturnal â‚¬”the middle of our day is the middle of their night. This can lead to gross misestimations of the effectiveness and toxicity of a drug intended for humans. My question: could circadian rhythms possibly affect the curcumin testing being conducted on mice and rats? And what about the curcumin testing on humans? What if these tests were conducted at different times of the day and night? Would there be differences in the results? My feeling is that there would be. Take a look at this sentence in the MD Anderson study: the serum levels of curcumin in rats and in human are not directly comparable. Hmmm. Well, okay, that makes sense on all sorts of levels, of course, even though I enjoy a bite of cheese probably as much as a mouse does 😉 , BUT could this divergence also be due, at least in part, to daylight testing on nocturnal animals? Another point. We don’t know what time of day or under what circumstances the human subjects in these trials took their dose of curcumin. And, for instance, we are informed that some folks developed diarrhea but others didn’t. Did both groups take curcumin at the same time? All this information would indeed be interesting to have. Okay, I realize that I’m in over my head here, and that my suspicions may turn out to be irrelevant rubbish. I must read the MD Anderson study again, and look up all the studies, one by one (yeah, that’s likely to happen… 😉 ). Ok, enough about circadian rhythms.
The MD Anderson researchers point out that the issue of curcumin levels found in body tissues has been relatively ignored. Interesting, I thought. One of the few studies dealing with body tissues dates to 1980 (abstract: http://tinyurl.com/3a93ko). I quote from the MD Anderson study: after oral administration of 400 mg of curcumin to rats only traces of unchanged drug were found in the liver and kidney. At 30 min, 90% of curcumin was found in the stomach and small intestine, but only 1% was present at 24 h. The team points out also that Although many curcumin analogues are found to show improved biological activity over curcumin, specific evaluations of structural analogues and/or derivatives of curcumin to show improved tissue and plasma distribution are lacking. More studies are needed!
There is lots more, including mentions of substances we can take to enhance the bioavailability of curcumin and novel bioavailability methods, some of which I have mentioned in previous posts. But this post is getting to be too long, so I will stop here for now. In chapter two, I will discuss glucuronidation! 😉