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Too much resveratrol is not a good thing


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#1 maxwatt

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Posted 06 January 2007 - 01:26 AM


I found a toxicology study of resveratrol; Rats receiving 300 mg/kg of body weight were not harmed, but at higher doses there were adverse effects: clinically significant renal lesions, including an increased nephropathy, renal tubule dilatation, papillary necrosis, acute pelvic inflammation, dehydration, anemia .....

They conclude that the maximum safe dose for rats was 300 mg/kg under the conditions of this study. Using a metabolic scaling factor to account for rats' faster metabolism and smaller size, this would translate to 50 mg/ kg in a human, or 3.5 grams daily for a 70 kg human (about 168 pounds.)

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Toxicological Sciences

ToxSci Advance Access originally published online on August 25, 2004
Toxicological Sciences 2004 82(2):614-619; doi:10.1093/toxsci/kfh263

Resveratrol-Associated Renal Toxicity
James A. Crowell*,1, Peter J. Korytko, Robert L. Morrissey, Tristan D. Booth and Barry S. Levine
* Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland 20892–7322; Toxicology Research Laboratory, University of Illinois, Chicago, Illinois 60612–7353; Pathology Associates, a Charles River Company, Chicago, Illinois 60612–7353; and Royalmount Pharmaceuticals Inc., Montreal, Quebec, Canada H4P 2T4

ABSTRACT

Resveratrol, (3,5,4'-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic, antiviral, and beneficial cardiovascular and cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg trans-resveratrol per kilogram body weight per day for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg per kilogram body weight per day. These included increased clinical signs of toxicity; reduced final body weights and food consumption; elevated BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts. Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, were observed. Diffuse epithelial hyperplasia in the bladder was considered, equivocal and of limited biological significance. No histological effects on the liver were observed, despite the clinical chemistry changes and increased liver weights in the females. Effects seen in the group administered 1000 mg resveratrol per kilogram body weight per day included reduced body weight gain (females only) and elevated white blood cell count (males only). Plasma resveratrol concentrations in blood collected 1 h after dose administration during week 4 were dose related but were relatively low given the high dosage levels; conjugates were not measured. Under the conditions of this study, the no observed adverse effect level was 300 mg resveratrol per kilogram body weight per day in rats.
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The entire paper can be found here: http://toxsci.oxford...t/full/82/2/614
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#2 velopismo

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Posted 06 January 2007 - 02:02 AM

Too much water will kill you even quicker. Fortunately I can't afford anything close to 300 mg/kg of resveratrol. I will also point out that the mice in the Resveratrol endurance study received 400 mg/kg for 15 weeks with no adverse effects and more then a few positive effects.
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#3 deftndumb1

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Posted 06 January 2007 - 02:05 AM

Pity they didn't also test at, say 500mg/kg. The mice in the Auwerx's cell study showed the big metabolic changes at 400mg/kg, but not so much at 200mg/kg, as I recall. That 300mg/kg No-adverse-effect falls frustratingly in between.
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#4 marting

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Posted 06 January 2007 - 02:29 AM

Hi!

I would like to give it my aging dog - 6 yrs (around 30 kiloes, a dobermann) any idea what I should aim for? For excample, maybe one capsule of the most potent one from NSI which is also the recommended dosis for humans would be too strong? Opt for a less potent one but still with good absorption capabilities I imagine is an alternative - or maybe half a capsule of the one for NSI a day if it would not lead to problems with oxidation etc, diminsh the absorption capabilities etc.

any comments would be appreciated

Br

Martin
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#5 kylyssa

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Posted 06 January 2007 - 03:31 AM

Hi!

I would like to give it my aging dog - 6 yrs (around 30 kiloes, a dobermann) any idea what I should aim for? For excample, maybe one capsule of the most potent one from NSI which is also the recommended dosis for humans would be too strong? Opt for a less potent one but still with good absorption capabilities I imagine is an alternative - or maybe half a capsule of the one for NSI a day if it would not lead to problems with oxidation etc, diminsh the absorption capabilities etc.

any comments would be appreciated

Br

Martin


I don't know about resveratrol dosages for dogs but the supplement routines that I give my cats are based on the amounts given per kilogram of weight in beagle studies (no good cat studies) that I've slightly tweaked over the years. I've had very, very good results with these regimens. Perhaps you should look for dog studies on resveratrol and model your dosage based upon those with good results?
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#6 emitecaps

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Posted 06 January 2007 - 05:51 AM

Resveratrol is roughly 30% bioavailable in rats but perhaps near zero in people. This aside there's also a human to rat equivalent dose ratio of 1:6 I believe or perhaps it's the otehr way around. Don't forget to factor that in as it can greatly affect the toxic amount.

But as previously stated everything is toxic given the right dose hence why there's an LD50 for every chemical. It's not hte chemical itself but rahter the dose that determines lethality.
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#7 velopismo

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Posted 06 January 2007 - 07:01 AM

Pity they didn't also test at, say 500mg/kg. The mice in the Auwerx's cell study showed the big metabolic changes at 400mg/kg, but not so much at 200mg/kg, as I recall

I've carefully read the study and I can not find any results from the 200mg/kg mice. Does anyone know if the lower dose results were published or discussed anywhere?
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#8 deftndumb1

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Posted 06 January 2007 - 12:02 PM

I've got the same problem: They mention the group fed 200mg at the outset of the study(page 2), but all the data they show thereafter are for the 400mg group.
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#9 deftndumb1

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Posted 06 January 2007 - 12:44 PM

In the earlier Nature study by Sinclair there were two dosages tested as well, and only the results of the higher doses were published:

"Cohorts of middle-aged (one-year-old) male C57BL/6NIA mice were provided
with either a standard diet (SD) or an otherwise equivalent highcalorie
diet (60% of calories from fat, HC) for the remainder of their
lives. To each of the diets, we added resveratrol at two concentrations
that provided an average of 5.260.1 and 22.460.4 mg kg21 day21,
which are feasible daily doses for humans. After 6 months of treatment,
there was a clear trend towards increased survival and insulin
sensitivity. Because the effects were more prominent in the higher
dose (22.460.4 mg kg21 day21, HCR), we initially focused our
resources on this group and present the results of those analyses
herein. Analyses of the other groups will be presented at a later
date."
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#10 maxwatt

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Posted 06 January 2007 - 02:18 PM

Hi!

I would like to give it my aging dog - 6 yrs (around 30 kiloes, a dobermann) any idea what I should aim for? For excample, maybe one capsule of the most potent one from NSI which is also the recommended dosis for humans would be too strong? Opt for a less potent one but still with good absorption capabilities I imagine is an alternative - or maybe half a capsule of the one for NSI a day if it would not lead to problems with oxidation etc, diminsh the absorption capabilities etc.

any comments would be appreciated

Br

Martin


Well. a rat weighs about 200 grams, and your doberman weighs 30,000 grams. To account for metabolic rate differences (an approximation, there can be other factors, like biochemistry) raise the ratio to the 1/4 power:

(30,000/200)^0.25 = 3.8

So divide the rat dose per kilogram by 3.8 to get your dog's dose per kilogram.

Edited by maxwatt, 06 January 2007 - 11:39 PM.

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