Our esteemed moderator wrote:

"I personally do not take resveratrol at this time and have not changed my mind
as a result of this new research. I don't consider the potential benefits worth
the cost for me as evidence for benefits in those eating a healthy diet is still
lacking. -°Olafur]"

Yet the following quote from the abstract made me think there may be reason to
believe it may be worthwhile:

"Here we show that resveratrol shifts the physiology of middle-aged mice on a
high-calorie diet towards that of mice on a standard diet and significantly
increases their survival. Resveratrol produces changes associated with longer
lifespan, including increased insulin sensitivity, reduced insulin-like growth
factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and
peroxisome proliferator- activated receptor-gamma coactivator 1alpha
(PGC-1alpha) activity, increased mitochondrial number, and improved motor
function. Parametric analysis of gene set enrichment revealed that resveratrol
opposed the effects of the high-calorie diet in 144 out of 153 significantly
altered pathways"

[While these effects are all very interesting and beneficial it is particularly
important to note that they were found in mice on a high-calorie diet, not in
mice on a standard diet. In fact, in the study resveratrol was also given to
mice on a standard diet but no results were reported on the effects resveratrol
had on those mice. I suspect the reason for this is that the effects were not
significant since if they were then the authors, having a vested interest in a
company that is developing resveratrol, would surely want to publish that
results as benefit in healthy mice on a standard diet would be even better
reason for people to take resveratrol, giving the authors more money in their
pocket.

Looking at the full text article I can see that for a large majority of the
parameters, resveratrol supplementation in the mice on a high-calorie diet only
partially restored the levels towards the levels of the mice eating a control
diet without resveratrol. Only a few of the parameters were completely restored
or improved slightly beyond the levels of the control group. This is important
as there is a big difference between restoring harm in an animal caused by some
harmful treatment and further improving the condition of an animal that has not
undergone the harmful treatment and already has a healthy profile. The latter is
akin to fixing a car that ain't broke. So while these results indicate that
resveratrol may have great potential as a life-extension supplement, at the same
time they do not suggest that it will have much benefit for healthy humans
eating a moderate calorie diet. The main implications of the study is that
resveratrol supplementation is probably very beneficial for people who eat a
high calorie diet, have a high BMI or high bodyfat. For people that do not have
a high BMI or a high bodyfat, evidence for benefit from resveratrol
supplementation is less clear particularly when it comes to it's effect on
lifespan. -°Olafur]


If it is causing biological changes similar to those seen in calorie
restriction, then it is tempting to conclude it will produce the same effect:
increased longevity.

[Yes it is tempting but again these changes were only found in mice eating a
high-calorie diet and for most of the parameters it only partially restored
their profile towards that of the mice eating the standard diet. At the end of
the study the mice in the high-calorie group taking resveratrol had similar
survival curves as the mice eating the standard diet, which does not indicate
any lifespan benefit in people eating a moderate calorie diet. Unfortunately
more than 50% of the mice in the high-calorie group and the standard group were
still alive at the end of the study so whether resveratrol truly increases
longevity is not clear from this study. Hopefully the study is still ongoing and
further results will be published later.

Also note that I specifically said that I didn't consider the potential benefits
of resveratrol worth the cost for *me*. That does not mean I don't think it's
worth the cost for a lot of other people. Resveratrol is a bit expensive, at
least compared to most of the supplements I'm taking, but if I were older and
particularly if I had more assets then I would definitely take resveratrol, as I
think the risk of taking it is low. -°Olafur]


A similar approach was taken in a recent paper by Spindler "Use of microarray
biomarkers to identify longevity therapeutics" (PMID: 16441842
http://tinyurl.com/y3jnw2 ) which found metformin caused similar changes.

[In this study metformin produced gene expression profiles similar to that of
mice on CR and according to the full text this was seen in healthy mice. In the
resveratrol study, resveratrol also induced changes in gene expression that
resembled those of mice on CR, and even though the results were only seen in
mice on a high calorie diet they are still very interesting and suggest that
resveratrol may have similar effects in healthy humans eating a moderate calorie
diet, although probably to a lesser degree. Resveratrol however doesn't have
nearly as much in vivo or human evidence behind it as metformin does,
particularly when it comes to healthy humans. -°Olafur]


Of course caloric restriction is the most cost effective method of life
extension.

[In terms of money it sure is as you actually save money by eating less, but
cost can also include other things than money and clearly most
life-extensionists appear not to think it is that cost effective as otherwise
they would be practicing it. -°Olafur]


Max Watt (Richard Kaufman)

[Olafur made such an excellent response that I only have one thing to add. It
relates to an unpublished portion of an NIH study which was presented in a
poster at the Sixth International Symposium on Neurobiology and
Neuroendocrinology of Aging that I and Kitty attended in Bregenz Austria in July
2002. The poster contained graphs of the results of a mouse lifespan study using
metformin and 2-deoxyglucose (the results of the last were published as PMID:
15247056, 16399906). The graph showed a clear average and maximum life extension
effect from a dosage of metformin equivalent to about 1-2 grams per day for a
human. Although metformin seems to have little beneficial effect on my fasting
glucose and it may not have any effect in addition to CR, it has a good usage
safety record and I have been taking it constantly ever since that time, --Paul]