The phenomenon of different effects, especially, helpful versus harmful effects, seen at different dosages, is also known as
hormesis. A review of the evidence for hormesis in resveratrol was published here:
http://www.ncbi.nlm....pubmed/21115559However, some differences attributed to differences in dosage may in fact be due to differences in experimental design or execution.
This is a fundamental problem in science, identifying which correlations or associations are accidental coincidences, and which are examples of a fundamental, cause-and-effect relationship. It's a crucial question, especially for someone trying to decide whether to take resveratrol, and at what dose.
A classic discussion of the issue is the paper by Herbert Simon, “Spurious correlation: A Causal Interpretation,” Journal of the American Statistical Association, Volume 49, Number 264, 1954, pp. 467-479.
One example may be the question of
apopotosis, or programmed cell death. Does resveratrol increase or decrease apoptosis? There is evidence for both, and we might be tempted to conclude that the difference is due to dose, an example of hormesis. However, I think there is another explanation, and the story is illustrated nicely in the context of a single paper:
http://www.ncbi.nlm....pubmed/21541654"Pro-apoptotic versus anti-apoptotic properties of dietary resveratrol on tumoral and normal cardiac cells."
Looking at numerous studies that report an effect of resveratrol on the rate of apoptosis, I see a common theme. If the cells in question are in some way defective, if they are tumor cells, or cells which have been intentionally damaged by the experiment, for example, by the introduction of oxidative stress, then the rate of apopotosis increases. The bad cells die. However, if the cells in question are normal healthy cells, the rate of apoptosis decreases. The good cells live.
This was the finding in the cardiac cell study referenced above. Resveratrol increased apoptosis for the tumor cells and decreased it for the normal cells.
I call this a "theme" rather than a "fact" because there are exceptions, and we have to look at the total design of the experiment to try to understand and perhaps explain them. For example, resveratrol seemed to promote, rather than retard the growth of breast cancer cells, but only when they were transplanted to a severely immune deficient mouse. Other researchers, working with other kinds of mice showed an opposite effect.
One reason why the dose of resveratrol may be especially important is its low bioavailability. Resveratrol is broken down quickly by the liver, so very little may get a chance to circulate through the bloodstream for an extended period. At higher doses, bioavailability improves in a nonlinear fashion. It is as if the liver gets too busy to process everything at once, so a fraction of the dose is able to circulate for a longer period.
The effects of higher doses might be achieved at lower dose levels through the use of other substances that enhance bioavailability. Piperine has increased the bioavailability of resveratrol in an experimental animal:
https://www.ncbi.nlm...pubmed/23620848https://www.ncbi.nlm...pubmed/21714124
Edited by cudBwrong, 21 May 2013 - 01:51 PM.