January 2, 2008 post. As my good friend Sherlock and I are about to begin our BioCurcumax experiment (after we go to the hospital lab for blood tests next week), I am going to be spending a certain amount of time this week doing research on the general issue of bioavailability.

What follows is based mainly on info I gathered from various general websites. First of all, what does “bioavailability” mean, exactly? According to the Merck manual, “Bioavailability refers to the extent to and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action.” It essentially refers to how much of an ingested substance ends up being absorbed by our bodies. This is of fundamental importance because substances with poor bioavailability will be of little or no use to us. We know that curcumin is poorly absorbed, so one of our aims should be to increase its bioavailability. I am a big fan, no, a HUGE fan of curcumin, perhaps the world’s biggest fan of curcumin (okay, I am getting carried away, eh)…in sum, I think it’s one of the best anti-cancer substances that I have read about so far, but I also realize that it won’t work well if not taken “properly.” Speaking of which, it’s a shame we can’t take it intravenously! When a drug is administered intravenously, in fact, it is absorbed 100% because it does not pass through the stomach etc. Since Sherlock and I will be swallowing capsules of BioCurcumax, however, I have no interest in intravenous administration right now.

Let me proceed. As we have seen in previous posts, one reason for low bioavailability has to do with the first-pass metabolism (whereby a drug is metabolized before it reaches the bloodstream). The Merck manual tells us that “Low bioavailability is most common with oral dosage forms of poorly water-soluble, slowly absorbed drugs.” (for more info, see http://tinyurl.com/ywm4q8) In fact, curcumin, quercetin and parthenolide are not water-soluble (quick note: DMAPT, the leukemic stem cell killing parthenolide analogue, though, is water-soluble…).

There are many factors that influence how quickly and how well our bodies can absorb a substance. I found a good online reference titled “Basic Pharmacokinetics.” The chapter on bioavailability can be viewed here: http://tinyurl.com/yrn9hg Physical activity, age, biorhythm and emotional state, just to name a few items, can have an effect on bioavailability. And that explains why in vitro results do not always correspond to in vivo results. In fact, there is an entire section in “Basic Pharmacokinetics” that explains how this all works. Though interesting, it’s beyond the point of this post.

Another important factor is the “with or without food” one, which is a bit controversial as far as curcumin is concerned. I am on the side of the “empty stomach” takers, but some folks take curcumin with food for various reasons. And it’s also true that my current experiment is being conducted just before we go to bed, i.e., close to dinnertime, and at that time my stomach is not empty, since we tend to eat rather late in the evening in Italy.

“Basic Pharmacokinetics” tells us that “Food may also interact directly with drugs, either chemically (e.g. chelation) or physically, by adsorbing the drug or acting as a barrier to absorption. In general, gastrointestinal absorption of drugs is favored by an empty stomach, but the nature of drug-food interactions is complex and unpredictable; drug absorption may be reduced, delayed, enhanced or unaffected by the presence of food.” Actually, what I read here would seem to reinforce the empty stomach preference, since we don’t really want curcumin to remain in the stomach where it is subjected to fierce enzyme attacks.

This paragraph also made it clear to me why some substances have to be taken with lots of fluids: in order to dissolve and get them out of the stomach more quickly. Hadn’t thought of that. In fact, that would seem to be a good pointer on how to take BioCurcumax, Sherlock!

A few remarks on sublingual administration. As most of you know by now, I am testing a concoction of my own making, based on a blog reader’s suggestion. This involves the preparation of a mixture consisting of cocoa mass (100% chocolate), honey and quercetin and curcumin powders. Well, almost on a whim, a couple of months ago I began sticking gobs of this very warm mixture under my tongue. I guess I had read somewhere about sublingual (literally, “under the tongue,” from Latin) drug administration, and this bit of info had stuck in the back of my mind. And today for the first time I had a close look at the sublingual method, which would seem to be a VERY good way to take curcumin.

As I understand it, these gobs get absorbed into the epithelium beneath my tongue via the mucous membranes. Since the epithelium is covered with blood vessels, theoretically (at least) the curcumin-containing gobs are then able to enter the bloodstream very quickly. This would mean that curcumin is protected from the first-pass metabolism of the liver, which reduces its bioavailability (a lot, apparently). Taken sublingually, curcumin avoids being attacked by the hostile enzymes present in the gastrointestinal tract. Perfect! I had a gut feeling (no pun intended…) that this was a good way to take curcumin but didn’t really know why or how until today.