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.
I guess this is enough to digest (again, no pun intended…) for today. I still have a pile of e-mails to answer, so I guess I’d better sign off now and go do that. I should also compile a list of New Year’s resolutions…
Today is Capodanno, i.e., the first day of the new year.
A culinary tradition that we gladly follow every year is eating lentils, which supposedly bring money and good luck. And in fact, my lentils appear to have worked very quickly since for the first time in years I won at tombola, which is bingo in English. Tombola is a traditional Xmas-New Year’s game in Italy. And we play for money! Well, okay, for change, really. Stefano won the first game, I won the second, for a total of perhaps ten euros. What a team! 
l’anno, which means “what you do on the first day of the new year you will do for the rest of the year!” So be really really careful about what you do today. Unless you like to iron, for instance, don’t do any ironing, or you will be ironing each and every day of 2008. And so on. Plan only FUN stuff for today! Yesterday, in fact, I did the laundry and other boring but necessary household chores so that today I could rest and have fun. I am about to go bake a batch of World Peace cookies (my hopeful wish for every year: world peace…!), and later we will play cards and probably another round of bingo. Bliss!
This photo will give you an idea of what I have been doing during these holidays, in addition to strolling around downtown Florence and eating eating and…more eating! It’s been a busy but restful holiday. Day before yesterday, Stefano’s aunt and uncle drove up from southern Italy to celebrate the New Year with us, and brought a TON of food. So we haven’t really had to cook at all, which has been fabulous.
) with rules and regulations and a statute. So hey, this is serious stuff. 
The title of my post today refers to part of a dithyrambic ode to wine known as "Bacchus in Tuscany" and written by the famous 17th century scientist and poet Francesco Redi. The ode celebrates the wine of Artimino, among others, and a translation of the verses I quoted is more or less: "but of that wine so pure/ that they harvest in Artimino/I want to guzzle more than a vat." Hehe. I couldn’t resist quoting these verses today, even though my post is mainly about a wedding reception that we attended…at Villa Artimino. This will all make sense in a second.
This photo, by the way, shows the detail of a frescoed ceiling. I liked this depiction of "Diligence."
Another name (!) of Villa “La Ferdinanda” is the "villa with one hundred chimneys" (villa dai cento camini), even though there are only actually 40 of these differently-shaped and sized chimneys. This photo shows a few.
In the background you can make out the small fortified Medieval village of Artimino. 
After dinner last night, Stefano and I were sitting at the table, chatting, when Peekaboo decided she had to check out the contents of my glass (water, what else?). I dashed to get my camera. 
This sequence gives a good idea of what happened (over and over…). Dipping her paw into my glass and shaking water all over the table wasn’t enough. She finally stuffed her silly little head into the glass. The third photo shows how much she appreciated my letting her have a drink (I should mention that our cats always have plenty of drinking water, the same water that we humans drink…). Needless to say, I got myself a new glass