Well, looks like we've got a bit of news in the science world. Check out this study currently in press (accepted, but not printed yet). Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance.
Let me post some excerpts (they are using "Male ICR mice, 8 weeks of age", btw):
"Quercetin feeding for 7 days resulted in an increase in PGC-1α (Figure 1A) and
SIRT1 mRNA (Figure 1B) in slow-twitch muscle and in the brain (P<0.05). We found
approximately a 100% increase in PGC-1α gene expression in the soleus muscle with both doses
of quercetin and a 50% and 100% increase in the brain following 12.5mg/Kg and 25mg/Kg
quercetin, respectively (Figure 1A). SIRT1 expression increased almost 200% in the muscle
with both doses of quercetin and by 50% and 100% in the brain following 12.5mg/Kg and
25mg/Kg quercetin, respectively (Figure 1B)."
Firstly, we see quite vividly the activation of Sirt1, as PGC-1alpha was doubled in abundance - and its abundance is directly controlled by Sirt1 activity as we've seen for resveratrol (blocking of Sirt1 activation of PGC-1alpha abolishes many of resveratrol's effects, for instance. PGC-1alpha is an essential step in the pathways activated by resveratrol and now quercetin).
"Mitochondrial DNA Content
The relative amount of soleus muscle and brain mtDNA was determined using RT-PCR.
Using cytochrome b as the target gene for mtDNA and β-actin as the internal control for nuclear
DNA, relative mitochondrial number was determined by an increase in copy number of mtDNA
per diploid nuclear genome. mtDNA was approximately doubled in the muscle and brain
following 7 days of feedings with the 25mg/Kg dose of quercetin (P<0.05), but there was no
change with the 12.5mg/Kg dose (Figure 2)."
As expected, mitochondrial biogenesis is stimulated, just as with resveratrol. Both quercetin and resveratrol are working through the same pathways here at least. This proves quite nicely that quercetin does not inhibit Sirt1, for which there has been no evidence in vitro, or in vivo, that I know of. Only with a fluor de lyse Sirt1 assay system (not using whole cells, but recombinant Sirt1) and a quercetin metabolite - a system that has been proven to give completely false results; as with resveratrol where that system showed direct binding to Sirt1, but then it was later proven that resveratrol does not bind Sirt1 and it was an artifact caused by the fluor de lyse fluorophore interacting with resveratrol (thus my hypothesis that it acts through Nampt).
Yes, there is no evidence that quercetin inhibits Sirt1 (that I know of), but instead was one of the two molecules screened out back in the day as a Sirt1 activator, with resveratrol being the other. And here we see in vivo absolutely that quercetin does not inhibit Sirt1, but is activating it apparently (we see this elsewhere too). How it's doing its activation though is an unknown.
"Treadmill Performance (Maximal Endurance Capacity)
In order to test the effects of quercetin on maximal running capacity, mice were fed
quercetin (12.5mg/Kg or 25mg/Kg) or placebo for 7 days prior to the run to fatigue; for these
experiments, the treadmill was operated at a fixed speed and grade (36m/min; 8% grade) Short-term
feedings of both doses of quercetin were associated with increased exercise capacity
(Figure 4) (P<0.05). The 12.5mg/Kg dose increased run time by 36% and the 25mg/Kg dose by
37%."
Again as expected, stamina increased, like we saw with resveratrol, once more suggesting the same pathways are activated by both to some degree.
Now, quercetin is different from resveratrol. Though they have many overlapping effects in vivo, they also have differing effects, and quercetin especially is known to have other roles than activating Sirt1 (Nampt?). For instance, from the paper:
"Quercetin, like caffeine, has been shown to be
an adenosine A1 receptor antagonist in vitro (1) and in vivo (unpublished data from our
laboratory) which is at least partially responsible for the psychostimulant and ergogenic effects
of caffeine (1, 5, 7, 9). Therefore, in addition to its effects on mitochondrial biogenesis,
quercetin may enhance exercise tolerance through its activity as an adenosine A1 receptor
antagonist in the brain."
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So, the reason for posting this is to show we don't need to worry about taking resveratrol and quercetin together. In fact, the two have been shown to be powerful synergizers. Moreover, quercetin is quite potent at inhibiting the metabolizing enzymes that target resveratrol (though some percentage of deconjugation of resveratrol during uptake into living cells means it is hard to estimate what the real impact of those metabolism enzymes on resveratrol bioavailability is), theoretically increasing resveratrol's bioavailability significantly. Now we can expect the two to work together in Sirt1 and PGC-1alpha activation.
From reading the literature, I do not believe quercetin is near as potent as resveratrol. It appears resveratrol may be far more potent at kicking on the pathways than quercetin in absolute terms, in that resveratrol gives longer lasting, more consistant and profound physiological benefits in vivo, than quercetin does. This may reflect different start points in the activation of the Sirt1 pathways, and/or additional pathways. Quercetin for sure has other pathways by which it affects the body, as the final quote from that paper illustrated. Furthermore, quercetin has not been shown to mimic CR, as far as I know, again differentiating it away from resveratrol - also again implying quercetin acts farther down the pathway while resveratrol acts higher up (Nampt) where more branches of other pathways will be activated. That doesn't mean quercetin won't also mimic CR, as there is now a chance for that, but it has not been observed, as far as I know.
Quercetin is no replacement for resveratrol. But together, much greater benefits than either alone may be gained, this data suggests. Until we have actual in vivo studies with both of them specifically, we cannot know absolutely, but all evidence points that way so far.
Edited by geddarkstorm, 18 February 2009 - 04:48 AM.
