As promised, here is the chapter on glucuronidation. 😉 First, what IS it? According to Wikipedia, Glucuronidation, the conversion of chemical compounds to glucuronides, is a method that organisms use to assist in the excretion of substances that cannot be used as an energy source. Glucuronic acid is attached via a glycosidic bond with the substance, and the resulting glucuronide, which has a much higher water solubility than the original substance, is eventually excreted by the kidneys. So glucuronidation is used by the body usually to get rid of toxic substances.
What happens once we have swallowed curcumin? A blog reader has already explained this process to us, but let’s have a look at what the MD Anderson researchers write: Once absorbed, curcumin is subjected to conjugations like sulfation and glucuronidation at various tissue sites. They discuss a study published in Life Sciences in 2000 (abstract: http://tinyurl.com/3ybfhm): in rats, it would appear that orally administered curcumin is absorbed from the alimentary tract and present in the general blood circulation after largely being metabolized to the form of glucuronide/sulfate conjugates. Curcumin sulfate and curcumin glucuronide were identified in the colorectal tissue of colorectal cancer patients who ingested curcumin capsules. Metabolites, by the way, are substances produced during digestion. Okay, so once ingested, curcumin is transformed into these metabolites. But are these substances completely useless as far as cancer patients are concerned?
On page 7 we read the following: Whether curcumin metabolites are as active as curcumin itself is, unfortunately, not clear. While most studies indicate that curcumin glucuronides and THC are less active than curcumin itself, there are other studies which suggest that they may actually be more active than curcumin. THC is tetrahydrocurcumin, one of the major metabolites of curcumin. The section on curcumin metabolites concludes: “The lack of availability of curcumin glucuronides and related compounds contributes to a continued lack of clear understanding of the relative pharmacologic activities of observed curucmin metabolites.” So we don’t have a clear answer. Yet.
Are there ways of addressing all of the problems dealing with poor absorption, rapid metabolism and elimination? Sure there are! The MD Anderson team suggests that Nanoparticles, liposomes, micelles, and phospholipid complexes are other promising novel formulations, which appear to provide longer circulation, better permeability, and resistance to metabolic processes. So, no doldrums! (I like that word…)
The researchers examine studies on piperine, a known inhibitor of hepatic and intestinal glucuronidation. According to a 1998 study published in Planta Medica (abstract: http://tinyurl.com/2eb84u), in humans receiving a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine, however, produced 2000% increase in bioavailability. Conclusion: The glucuronidation inhibiting effect of piperine and the established lesser activity of curcumin glucorinides will indicate that inhibition of glucuronidation by piperine may be the major mechanism by which it increases the bioavailability of curcumin.
Quercetin is also mentioned. Yippeeeee! (I am already taking it, you see 😉 ). In a clinical study published in 2006, five familial adenomatous polyposis (FAP) patients with prior colectomy received curcumin (480 mg) and quercetin (20 mg) orally three times a day. The polyps decreased in number and size (60.4% and 50.9%, respectively) after approximately six months. See full study: http://tinyurl.com/3b46wd
Okay, all of this may sound discouraging, but it really isn’t, in my view. Of course, it’s also true that I don’t get discouraged easily! 😉 Seriously, though, in my opinion there are ways we can make curcumin more bioavailable. Some methods may work better for some of us, but the important thing is that those methods EXIST. On this topic…have a look at what this 2005 Clinical Cancer Research study (full study: http://tinyurl.com/2cugub) on head and neck squamous cell carcinoma (HNSCC) has to report: In the nude mice studies, we compared two different methods of delivery of curcumin: intratumoral injection and topical application of the curcumin paste onto the tumor. To our knowledge, we are the first to attempt in vivo studies using curcumin paste in nude mice. Use of this method of delivery could overcome the problem of low bioavailability encountered in studies of oral curcumin in colorectal and other cancers in mice and in humans. Now, ok, this method wouldn’t work with myeloma (but couldn’t curcumin be injected right into plasmacytomas?), but it sounds promising for solid tumour cancers and of course skin cancer. As you know, I have tested a few bioavailability methods on myself: some worked, some didn’t, and I am awaiting the results from my most recent tests so the jury is still out on my most recent experiment. A few days ago, though, Stefano suggested that I quit experimenting and start focusing instead on the methods that have already worked for me. He’s right. Besides, if my IgG level goes up anymore, I will have to adopt Don’s kitchen sink approach!
There is more food for thought in the MD Anderson study, but I need a change, so I will work on something different now. Speaking of working, drat, I still have to prepare my classes for tomorrow! YIKES! Ciao!