19 replies to this topic

[MatthewK]

I just spent two hours trying to read and understand what dosage and method of resvertrol I should take - and now I'm really confused.
There is a tremendious amount of confusing information that is rapidly unfolding. Maybe it's too slippery to catch right now. 50% vs 99%, amount. method, concern of side effects???

Could someone who follows all this, who feels themselves to be fairly objective, summerize what an intelligent resveratrol regime should be. Or maybe summerize the various schools of thought.

My company wants me to recommend a 'science-based' supplement plan for them. I'm trying to keep it as simple as possible but still significant.

[krillin]

Could someone who follows all this, who feels themselves to be fairly objective, summerize what an intelligent resveratrol regime should be. Or maybe summerize the various schools of thought.

99%, in a HPMC solution, dose titrated by individual users, treat diarrhea from high doses with Gatorade G2 or homebrew equivalent. I haven't actually received my HPMC yet, so I'm taking the word of others.

[tintinet]

Could someone who follows all this, who feels themselves to be fairly objective, summerize what an intelligent resveratrol regime should be. Or maybe summerize the various schools of thought.

99%, in a HPMC solution, dose titrated by individual users, treat diarrhea from high doses with Gatorade G2 or homebrew equivalent. I haven't actually received my HPMC yet, so I'm taking the word of others.

I have some HPMC, but I don't know that I can attribute any subjective effects to using it. I use 99%+ pure extract or synthetic trans-resveratrol these days. I hope it's beneficial, but, after all, who really knows at this point. I'd think a science based program would likely include medical-legal concerns and avoid advocating anything at all, BTW.

[Forever21]

Yeah I am very confused too. I dont know where to buy and what to buy.

[DukeNukem]

Well, rather than waiting on the sidelines waiting for ALL the facts to be be sorted out (we're still waiting for all the facts on age-old aspirin!), you might at least get started with at least 100mg a day, equal to about 20 glasses of good quality red wine. If there's any benefit to resveratrol at all, 100mg will impart at least some benefits, and likely at minimum the benefits attributed to the French Paradox.

It's a pretty safe bet that at worst, resveratrol at this dosage is merely harmless. Yet, there's reasonable odds that it's highly beneficial, too. I give extremely low odds that resveratrol is harmful. All indicators seem to point in the other direction.

[MatthewK]

Dukenukum,

This is good advise. I'm placing my first order soon.

What about thoughts of more, naturally complex mixes such as adding muscadine grape seed in addition to these more pure and extracted reservatrol loads - just to cover the hundred of little details we might not be aware of.

[DukeNukem]

Dukenukum,

This is good advise. I'm placing my first order soon.

What about thoughts of more, naturally complex mixes such as adding muscadine grape seed in addition to these more pure and extracted reservatrol loads - just to cover the hundred of little details we might not be aware of.

I think this is smart. While most of the studies appear to rely on pure resveratrol, it can't hurt to cover your bases with a more thorough approach.

[sUper GeNius]

I might have missed it, but has there been any consensus formed here as to the proper dose for humans based on the June 4th study?

"A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice"

[maxwatt]

I might have missed it, but has there been any consensus formed here as to the proper dose for humans based on the June 4th study?

"A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice"

No.

The situation is more complicated. A recent paper by Guarante (Sinclair's mentor) found caloric restriction does not activate Sirt1 in all tissues.
Extrapolating mouse dose to human dose by body mass and metabolic rate is complicated by the difference in conjugation of resveratrol in mice and men. It was originally thought humans needed about 1/5th the amount per kilo of body weight than mice, but Boococks paper that Hedgehog, Niner and others analyzed, showed that humans need five times as much to achieve the blood levels mice do.

We also do not have enough data points. We have mice on about 5 mg/kg a day, and we have mice on 20 mg/kg a day, and on 400 mg/kg a day.

5 mg/kg --> gene expression similar to CR
20 mg/kg --> over-fed mice remain healthy (but why was the paper on health-diet mice not published?)
400 mg/kg --> inactive rats became athletic, with the endurance of a trained rat. (Rat weighs more than a mouse, so this number would be different in mice.

Perhaps the different metabolic rates and conjugation rates between mice and men cancel and mouse dose and man dose are the same per kilogram for the same effect?

Then the corresponding doses for the above effects for a 70 kg man would be 350 mg, 1400 mg ? Rats are different than mice, don't know their blood levels or conjugation rates so I've not guessed as to the human equivalent dose for athletic effects in couch potatoes.

We don't know what happens in between these doses; what happens at doses of 10 mg/kg, 15 mg/kg? Or 30?

I use arthritic symptoms to titrate my dose. I take enough to alleviate the symptoms, but not more than I need to get the maximum effect. This is roughly 2 grams, roughly 27 mg/kg. But different people have different rates of conjugation. Most Asians get higher blood levels from the same relative dose as Westerners due to less efficient glucuronidation and sulfonation enzymes, for instance. Some people can't drink coffee in the afternoon or they don't sleep that night while others have an after-dinner coffee and have no trouble sleeping. YMMV. I can't recommend my dose to anyone else except perhaps to my genetically similar brother. I only know it controls my arthritis. I have no idea if this dose will make me live longer or not.

For that matter, no one knows if Caloric Restriction will increase his life span. It may improve the possibility of living past 120, but only if something else doesn't get you first. Walford practiced CR assiduously, yet died in his seventies from Parkinson's complications if I recall correctly. He was remarkably fit for his age until near the end, though.

Edited by maxwatt, 22 June 2008 - 01:32 PM.

[dachshund]

FYI - Dr. Walford died of ALS. Living into his 70's was pretty remarkable with this disease.

[Luna]

Any idea how to get reverastrol in Israel?

[sUper GeNius]

Thank you for the thorough summary Maxwattt.

[hmm]

I use arthritic symptoms to titrate my dose. I take enough to alleviate the symptoms, but not more than I need to get the maximum effect. This is roughly 2 grams, roughly 27 mg/kg. But different people have different rates of conjugation.

MaxWatt, thanks very much for your synopsis. I was hoping you would be willing to provide an additional explanation along the same lines. My understanding is that your current preferred method of administering RSV is by mixing powder into a small amount of vodka to micronize the powder and then pouring in a solution of HPMC mixed with water to make sure the micronized RSV particles can be dispersed (and remain dispersed) from each other. Can you summarize the advantages of administering with this method as opposed to, say, putting the same amount of powder in your mouth and just washing it down as quickly as possible with a glass of water? How much more RSV is making it into your blood stream and how much longer is it staying in there, for example? Using the wash-it-down-with-a-glass-of-water method, how much RSV do you think you would need to take in order to achieve the same benefits to your big toe that you currently get?

Edited by hmm, 22 June 2008 - 06:08 PM.

[tom a]

Perhaps the different metabolic rates and conjugation rates between mice and men cancel and mouse dose and man dose are the same per kilogram for the same effect?

OK, this is a point I have never understood.

Why is it not reasonable to assume that these two rates don't effectively cancel each other out?

My understanding (small, certainly) of how metabolic rates might affect the correct dosage would suggest that far lower levels of a chemical in the blood in a human being would be the best match to the overall effect of that chemical in the case of, say, a mouse. Apparently, when first targeting drug mg/kg dosage levels for human beings, that's the way it's done, following FDA protocol.

So the question is, why is resveratrol a chemical that should be treated differently from other drugs in this respect?

(Is the argument that, at a given mg/kg, the "total area under the curve" over time is less for human beings in the case of resveratrol than for a mouse, whereas with other drugs it is typically more, since it takes more time to metabolize in a human being? What's the argument?)

[niner]

Perhaps the different metabolic rates and conjugation rates between mice and men cancel and mouse dose and man dose are the same per kilogram for the same effect?

OK, this is a point I have never understood.

Why is it not reasonable to assume that these two rates don't effectively cancel each other out?

My understanding (small, certainly) of how metabolic rates might affect the correct dosage would suggest that far lower levels of a chemical in the blood in a human being would be the best match to the overall effect of that chemical in the case of, say, a mouse. Apparently, when first targeting drug mg/kg dosage levels for human beings, that's the way it's done, following FDA protocol.

So the question is, why is resveratrol a chemical that should be treated differently from other drugs in this respect?

(Is the argument that, at a given mg/kg, the "total area under the curve" over time is less for human beings in the case of resveratrol than for a mouse, whereas with other drugs it is typically more, since it takes more time to metabolize in a human being? What's the argument?)

The FDA's Human Equivalent Dose calculations are used for setting an upper limit on dose for the first time a drug is ever used in a human. Only then can you measure a blood level and begin to titrate the dose for the effect desired, after carefully looking for toxicities. One of the many differences between mice and men is that mice have a more rapid oxidative (Phase I, P450) metabolism, therefore many compounds get chewed up faster in mice. Resveratrol doesn't happen to get metabolized by P450s, so that may be one reason it's not following the "rule". The reason that I put rule in quotes is because these guidelines are not meant to be predictive, they are meant to avoid toxic surprises the first time you put a drug in a human. No one cares if the drug doesn't reach a high enough blood level the first time it's in a human, but they care a lot if the human dies because the level got too high, and there was an unsuspected toxicity.

[tom a]

The FDA's Human Equivalent Dose calculations are used for setting an upper limit on dose for the first time a drug is ever used in a human. Only then can you measure a blood level and begin to titrate the dose for the effect desired, after carefully looking for toxicities. One of the many differences between mice and men is that mice have a more rapid oxidative (Phase I, P450) metabolism, therefore many compounds get chewed up faster in mice. Resveratrol doesn't happen to get metabolized by P450s, so that may be one reason it's not following the "rule". The reason that I put rule in quotes is because these guidelines are not meant to be predictive, they are meant to avoid toxic surprises the first time you put a drug in a human. No one cares if the drug doesn't reach a high enough blood level the first time it's in a human, but they care a lot if the human dies because the level got too high, and there was an unsuspected toxicity.

So I take it your claim is that, once you establish that, say, you've achieved the same blood levels in human beings as in mice with a drug (and, assuming as well, have the same area under the curve over time), then the very different metabolisms of mice and men should otherwise make little difference in the effects of that drug, typically?

[niner]

The FDA's Human Equivalent Dose calculations are used for setting an upper limit on dose for the first time a drug is ever used in a human. Only then can you measure a blood level and begin to titrate the dose for the effect desired, after carefully looking for toxicities. One of the many differences between mice and men is that mice have a more rapid oxidative (Phase I, P450) metabolism, therefore many compounds get chewed up faster in mice. Resveratrol doesn't happen to get metabolized by P450s, so that may be one reason it's not following the "rule". The reason that I put rule in quotes is because these guidelines are not meant to be predictive, they are meant to avoid toxic surprises the first time you put a drug in a human. No one cares if the drug doesn't reach a high enough blood level the first time it's in a human, but they care a lot if the human dies because the level got too high, and there was an unsuspected toxicity.

So I take it your claim is that, once you establish that, say, you've achieved the same blood levels in human beings as in mice with a drug (and, assuming as well, have the same area under the curve over time), then the very different metabolisms of mice and men should otherwise make little difference in the effects of that drug, typically?

Not exactly. There are a lot of differences between mice and men, and many of them might alter the effects of a drug. My only claim is that absent any better sources of information, setting the dosage in humans to match the blood level in rodents would be a good start if you want to duplicate the effects seen in the rodents.

[sUper GeNius]

So Niner, how much are you taking?

Edited by FuLL meMbeR, 23 June 2008 - 04:36 AM.

[niner]

So Niner, how much are you taking?

At the moment, none, but that's because I ran out. I was about to order some more when some scumbag got my credit card number and charged a bunch of weird stuff. I'm back in business now, so I should probably get back to ordering. I will probably shoot for about a gram a day, taken as a single dose. Maybe as much as two grams, in two doses. I'd like to buy Anthony's micronized powder, and put it up in HPMC. The micronized stuff is kind of pricey for me though, so I'll either make do with regular 99% or maybe try milling it myself. I already have most if not all of what I need to make a simple ball mill. I had been doing the now classic Everclear/Miralax method, but I finally bailed out on that because the taste was just too horrid. I think that the taste was due not just to the Everclear but also to the ultra-micronized resveratrol. I'm hoping that regular micronized resveratrol (around a micron) will taste ok. I suppose it could always be capped. The most recent thing I've been doing is throwing a fairly large spoonful (2 gm?) of 99% in a yogurt, berry, and vegetable smoothie.

[mikeinnaples]

You should ditch the everclear and just got with some potato vodka. You wont taste the alchohol at all.