Many of you recently have asked me why it is we chose triacetyl resveratrol over other analogs and what makes triacetyl resveratrol so special in relation to normal resveratrol. I am going to give a quick summary of why it is triacetyl resveratrol is superior to the hydroxy form (normal Res).
One of the biggest problems of trans-resveratrol is the known low bioavailability of it. In vitro resveratrol exhibits absolutely amazing effects such as anti-aging, anti-tumor, anti-inflammatory, antioxidant, anti-estrogenic, immunomodulatory, and positive effects on bone. In vivo, however, these effects are not as well seen in most doses given in the laboratory. Although these effects are dose dependent it is very common for mega doses of the compound be given to rats to force plasma levels to rise by overpowering the effects of glucorinidation and sulfation. Together glucorinidation and sufation are the biggest threat to achieving high plasma levels of resveratrol. To combat this problem many people have used compounds such as quercetin and piperine to compete for the process. However, there are downsides to this process as well and it is more of a bandaid to a problem rather than a fix.
The second problem with resveratrol is that it is found in such small quantities in nature. Red wine has on average about 6mg per liter. To achieve 600mg resveratrol one would have to drink 100 liters of red wine, a feat only accomplished by maybe supersoldier and poppypants . One of the compounds that actually protects resveratrol is ethanol, but its use in dietary supplementation is impossible.
There have been scores of resveratrol analogs studied, each of which had an up side and a down side. It seemed as though pure resveratrol was the absolute best overall compound, but it is sort of a catch 22 since getting high enough plasma levels of resveratrol without mega dosing and breaking the bank was near impossible. Obviously IV and intrathecal administration is out as well. Compounds such as trimethoxy resveratrol shined in anti-tumor studies, showing a 10 fold decrease in tumor growth over resveratrol and more potent inhbition than many anti-tumor pharmaceuticals already on the market. The down side is that trimethoxy resvertrol exhibits close to zero antioxidant properties. Resveratrol itself exhibits antioxidant properties greater than vitamin e.
Our solution to these problems is simple. Create a compound that absorbs rapidly, resists breakdown, and returns to its natural form. Although triacetyl resveratrol itself exhibits many positive effects it is what happens to this compound in the body that will make it spectacular. First off is intestinal absorption. Resveratrol actually absorbs quite fast compared to many compounds, with absorption rates in vivo of ~ 70nm/s as opposed to the transport marker mannitol which absorbed at a rate of ~ 4nm/s. Since triacetyl resveratrol is much more lipid soluble than resveratrol it will absorb across these lipid membranes at a much faster rate, decreasing exposure to the enzymes responsible for glucorinidation and sulfation. The liver is the next point that triacetyl resveratrol will meet and although some will get broken down, it is well known that acetyl groups resist breakdown better than hydroxy groups. Ester hydrolysis will occur in the body and the product of ester hydrolysis is pure resveratrol. This will allow the highest levels of pure resveratrol to enter the blood stream.
Triacetyl Resveratrol: R1,R2,R3 = COCH3
Resveratrol: R1,R2,R3 = H
Another good article is Enhancement of the oral bioavailability of phenyto...[Biol Pharm Bull. 1998] - PubMed Result.
Enhancement of the oral bioavailability of phenyto...[Biol Pharm Bull. 1998] - PubMed Result
Ch20: Hydrolysis of Esters (from picture above)