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A Low Dose of Dietary Resveratrol Partially Mimics CR


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#61 krillin

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Posted 08 July 2008 - 02:21 AM

For a person 150lbs, 68inchs and wants 4.9mg/kg this FDA calculator says you need a dose of 334.09mg of

Based on a rat model that took 50mg/kg you get a plasma concentration of 548ng/mL and if you scale it down you could assume you get a plasma concentration of 53.68ng/mL if you give a rat a 4.9mg/kg dose.

Assume that the boocock paper (human plasma data) is correct which in a 500mg dose they achieved a 72ng/mL level. If we assume the average person in the study is 150lbs or 68kg then the dosage per kg is 7.4mg/kg. This also achieves a higher plasma concentration then what is seen in the rat model. If you do the conversion you need to take about 350mg dose to achieve a plasma concentration of 53ng/mL.

The FDA formula suggested 334mg human dose would be equivalent. So IMO it is pretty close

This math assumes lots of things.... (mainly weight of a person and of the rats they used)

If this calculation is correct, the rat's higher metabolism is almost exactly canceled out by its lower conjugation of resveratrol, so we don't even need a conversion factor to apply rat studies to humans. So here's a range of results to expect.

5 mg/kg: replicate the effects of CR on gene expression for about half the genes affected by CR, but not enough to activate SIRT1
20-25 mg/kg: overcome effects of bad diet (PMIDs 18356487, 17086191), NFkB inhibition (Maxwatt's toe)
400 mg/kg: more mitochondria (PMID 17112576)

Wait, something's funky here. Hedgehog, if you're reading, where did you find that rat data? Marier's rats at 50 mg/kg had a Cmax of 6.6uM, while 548ng/ml * (4.386nM/ng/ml) = 2.4uM. So Marier's rats are hitting three times the Cmax on the same dose. They were dosed orally, so I don't see where the discrepancy comes from. Marier is http://pmid.us/12065739

Comparing large oral doses of resveratrol between rats and humans, looking at Cmax, I get:

Marier (rat) 6.6 uM/50 mg kg(-1) = 0.132
Boocock (human) 2.4 uM/71 mg kg(-1) = 0.0338

0.132/0.0338 = 3.9 So the rats are seeing a Cmax that is 4 times that of the human Cmax on the same mg/kg dose. So to see the blood levels of rats getting 5mg/kg, we probably want more like 20mg/kg, or ~1.4 g/day. That's not too hard to do. Overcoming a bad diet? A bit over 5 grams per day. More mitochondria? If it really takes 400mg/kg to do it in rats (it might take quite a bit less), then at 1600mg/kg, a 70 kg human would need to eat 112 grams a day, which is decidedly not on for most of us. In reality, I think the more mitos application probably takes a lot less. Sirtris has a trial going for MELAS, a mitochondrial defect disorder. If the goal there is to generate more mitos, then we should be able to find out the dose they used in the trial eventually.

Krillin bows his head in shame. Almost all of the studies I cited used mice, not rats. (PMID 18356487 was the only rat one.) As penance I shall do the calculation for mice.

PMID 14760392 gave mice 240 mg/kg and got a Cmax of 32 uM. 32 uM/240 mg kg(-1) = 0.133

OMG! Rat and mouse resveratrol mg/kg dosages are identical.




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