ADME Properties of Resveratrol

Diet and Nutrition
1

I was digging around some articles and came across this one:

Asensi, M.; et al. Free Radical Biology & Medicine, Vol. 33, No. 3, pp. 387â??398, 2002

[quote]
Abstract:
The relationship between resveratrol (RES) bioavalability and its effect on tumor growth was investigated. Tissue levels of RES were studied after i.v. and oral administration of trans-resveratrol (t-RES) to rabbits, rats, and mice. Half-life of RES in plasma, after i.v. administration of 20 mg t-RES/kg b.wt., was very short (e.g., 14.4 min in rabbits). The highest concentration of RES in plasma, either after i.v. or oral administration (e.g., 2.6 ± 1.0 μM in mice 2.5 min after receiving 20 mg t-RES/kg orally), was reached within the first 5 min in all animals studied. Extravascular levels (brain, lung, liver, and kidney) of RES, which paralleled those in plasma, were always < 1 nmol/g fresh tissue. RES measured in plasma or tissues was in the trans form (at least 99%). Hepatocytes metabolized t-RES in a dose-dependent fashion (e.g., 43 nmol of t-RES/g � min in the presence of 20 μM tRES), which means that the liver can remove circulating RES very rapidly. In vitro B16 melanoma (B16M) cell proliferation and generation of reactive oxygen species (ROS) was inhibited by t-RES in a concentration-dependent fashion (100% inhibition of tumor growth was found in the presence of 5 μM t-RES). Addition of 10 μM H2O2 to B16M cells, cultured in the presence of 5 μM t-RES, reactivated cell growth. Oral administration of t-RES (20 mg/kg twice per day; or included in the drinking water at 23 mg/l) did not inhibit growth of B16M inoculated into the footpad of mice (solid growth). However, oral administration of t-RES (as above) decreased hepatic metastatic invasion of B16M cells inoculated intrasplenically. The antimetastatic mechanism involves a t-RES (1 μM)-induced inhibition of vascular adhesion molecule 1 (VCAM-1) expression in the hepatic sinusoidal endothelium (HSE), which consequently decreased in vitro B16M cell adhesion to the endothelium via very late activation antigen 4 (VLA-4).[/quote]

Basically, what I got out of the article was that resveratrol has decent oral bioavailability, but due to the 1st pass effect, will become metabolized very quickly. In the discussion, the authors stated that keeping an aqueous solution of resveratrol in the mouth for 1 min was quite effective in spiking blood serum levels of it. But they also stated that resveratrol has a very short half life in the blood stream (14 min).

So, for those who are knowledgeable about such things (such as Bill Roberts), my questions are:
-Since it has such a short half life, will it really be that effective at aromatase inhibition and acting as a SERM?
-If so, then if someone were to supplement with resveratrol such as Rez-V, should we instead keep the tab in our mouth for a bit to vastly enhance absorbtion (as gross as that sounds)? I suppose you can just suck on some peanut butter/grapes to get the resveratrol out of there…haha.

Thanks guys!

2

I’m not sure about your first question, although I’d like to find out myself. As for your second one, one capsule of Rez-V is equivalent to about 28 liters of wine, if the values of resveratrol in red wine listed on Wikipedia is to be believed. You would need to consume an absolute ton of peanuts or grapes in order to get close to those levels of resveratrol.

Also, I believe that Rez-V is absorbed in the small intestine, meaning that you would have to break open the capsule to try to absorb in in your mouth. I’m not saying that it won’t work, but if I’m right about it being absorbed in your intestines and not your stomach, your stomach acid will destroy the resveratrol that you don’t absorb.

I’m kind of getting ahead of myself though. We should probably wait for an expert before trying to figure things out.

3

Well, fortunately the time course in man is not as short as in the rat:

http://cebp.aacrjournals.org/cgi/content/full/16/6/1246

If wishing more total effect, I would use more doses per day, for example two. However users seem happy with one dose per day. I even know a person who experiences too much effect (side effects characteristic of abnormally low estrogen) from one dose per day. But certainly most don’t find one dose per day to be excessively effective.

I wouldn’t recommend using the Rez-V under the tongue. While I haven’t tried the Rez-V that way, I’m familiar with the taste of the excipient. It is very soapy-tasting. At any rate, likely only an added few milligrams could be absorbed that way.

I don’t consider myself an expert on the exact topic of resveratrol but I had thought of resveratrol’s anti-estrogenic effects as being much more in the SERM category than as an effective anti-aromatase. With regard to partial reduction of estradiol’s effects at the estrogen receptor, a pulsatile pattern of having some hours of more such activity and other hours of little to none winds up averaging out. Obviously not to a high overall level, but to about (not exactly the same) as a more consistent level totalling the same area under the curve.

4

Does it matter what source it comes from?

5

Trans-resveratrol is trans-resveratrol.

Whether the delivery system makes a difference, I would think it most likely does. I wasn’t involved in that project and don’t have whatever proprietary information there may be on it. On those things that I have been involved in testing with that delivery system that had low bioavailability, not one wasn’t very considerably improved, though.