Couldn't tell you exactly why and how, but Maxwatt could. My understadning is that
there are less steps in the process for it to get into their bloodstream, but I could be assuming that.
OK, it's not vital that I know, I'm just wondering. When Maxwatt gets here he can fill us in.
Why do dogs likely need less resveratrol than humans?
Like rodents, dogs have much less of the enzymes that conjugate resveratrol, that bind it to a sugar molecule or a sulfur group, so that it can be excreted from the body. Humans evolved with a predominantly vegetarian diet, and evolved the biochemistry to deal with many plant toxins. (Even hunter-gatherer cultures may get only 25% of calories from meat; Monkeys and gorillas can be as low as 5% animal protein, including insects.) Dogs are carnivores, and their lupine ancestors had no evolutionary advantage in developing these metabolic pathways. Mice are short lived creatures, reproducing rapidly, living fast and dying young. Their metabolic energy all goes into reproduction instead of into neutralizing slow-acting potential poisons in the plants they eat.
Niner and others have referenced papers showing a much higher blood serum level of resveratrol in rodents than in humans from equivalent doses. No pharmokinetic studies are available in dogs, so it is actually a surmise that dogs attain higher blood levels from an equivalent dose than do humans, but it seems likely.
Niner turned up other papers (Boocock
et al.) that showed a decreasing blood-serum to dose curve in humans, i.e. doubling the dose of resveratrol did not double the blood serum level of resveratrol in humans, though it did increase. The peak occurred at around 1 gram, and the level began to fall off rapidly at around two grams, but even at five grams there was an increase in human blood serum levels.
What does this mean? First, a given dose in mg/kg of body weight
might be more effective in dogs than in humans. Sirtris ran their SRT501 formulation phase II trials at doses of 2.5 and 5 grams, which makes me think they were aware of the dose/blood serum level curve. They did find greater efficacy at 5 grams. Another factor is AUC, or area-under-the-curve. Taking resveratrol more than once a day can result in higher average or continuous blood-serum levels, giving resveratrol more time to act on the body's cells, cancerous or otherwise.
Another complicating factor in all this is that blood proteins absorb resveratrol, and
may carry it through the blood and release it at the cellular membranes; in other words, blood serum levels may not tell the whole story.
Judging by the way you (thefirstimmortal) report feeling, you are going to survive past the October "Dead-line". You may outlive the doctors' predictions by a few months to a year, or you may achieve a state of complete remission. I think you are going to see complete remission. Resveratrol (and to a lesser extent curcumin and perhaps silymarin) induces apoptosis (suicide) in cancer cells; it activates the genetic machinery that has been turned off in cancer cells, that which makes a cell kill itself when it senses it is defective.
Edited by maxwatt, 10 August 2008 - 11:48 AM.