27 replies to this topic

[proteomist]

I hope that subtitle is taken as the gentle, friendly ribbing I intend [lol]. There's been lively debate on here recently as to appropriate resveratrol dosage. Some of those opposed to these dosage levels have speculated that people taking 1000mg or more a day may be doing so at grave peril to their health, or are otherwise 'crazy' to do so. Some others have taken a conservative, measured wait-and-see approach and are reserving judgement. Others, anxious to get the benefits of Sirt1 activation without waiting, have speculated that appropriate doses are on the 1-5 gram scale, based on the published literature and have been experimenting at those levels.

Well, add Sirtris to the 'crazy' list. Their Phase Ib trials for resveratrol against diabetes were conducted with either 2.5g or 5g per day of SRT501, the resveratrol formulation they claim yields substantially elevated blood levels as compared to plain resveratrol. So we're talking about levels you might get with roughly 5-50 grams per day. Their study for MELAS, a mitochondrial disorder, were conducted with five grams per day.

So, who else want to join the >1000 mg club?

Edit: Hat-tip to Paragon for noticing these dosage indications in the Sirtris IPO Roadshow, and Malbecman for posting the link to the presentation in the first place.

Edited by proteomist, 11 May 2007 - 09:38 PM.

[Anthony_Loera]

I love the title to your post... I almost fell off my chair...

Anthony

[shifter]

Well in my opinion those dosages are still new territiory for humans, and so far from what i've read, the resveratrol does not work in humans the way it works in other animals. Its not cheap either, and I think I can divide the money for supps better than just resveratrol.

I cant wait to see what longivenex prices will be with a 1000mg+ supplement though.

Also maybe if everyone starts taking 5grams instead of 100-500mg as the norm the share price might shoot up (if its on the stockmarket).

[sUper GeNius]

I hope that subtitle is taken as the gentle, friendly ribbing I intend [lol]. There's been lively debate on here recently as to appropriate resveratrol dosage. Some of those opposed to these dosage levels have speculated that people taking 1000mg or more a day may be doing so at grave peril to their health, or are otherwise 'crazy' to do so. Some others have taken a conservative, measured wait-and-see approach and are reserving judgement. Others, anxious to get the benefits of Sirt1 activation without waiting, have speculated that appropriate doses are on the 1-5 gram scale, based on the published literature and have been experimenting at those levels.

Well, add Sirtris to the 'crazy' list. Their Phase Ib trials for resveratrol against diabetes were conducted with either 2.5g or 5g per day of SRT501, the resveratrol formulation they claim yields substantially elevated blood levels as compared to plain resveratrol. So we're talking about levels you might get with roughly 5-50 grams per day. Their study for MELAS, a mitochondrial disorder, were conducted with five grams per day.

So, who else want to join the >1000 mg club?

Edit: Hat-tip to Paragon for noticing these dosage indications in the Sirtris IPO Roadshow.

Holy sh't! I'm gonna have start growing the stuff...

[malbecman]

Thanks for the hat-tip. Glad someone made it through the whole presentation; I havent quite found the time yet.

I couldn't believe your post and/or the dosages Paragon noticed Sirtris is using.

Fall off my chair indeed......

[Brainbox]

Is this presentation available on the net ?

[lucid]

My understanding is that the phase 1b results will not be available until the second half of 2007. If the results are out already, does anyone have a link?

[proteomist]

It's available here in the link in the first post.

Is this presentation available on the net ?

[tintinet]

Ha! I've come close: ~ 3 grams/day for a bit. But I've since tapered down to about 1.5 grams/day.

[paragon]

Thanks. I wish I could consistently stay on a few grams per day; I've tried it a few times, and after a while the quality and duration of my sleep deteriorate. This is not so uncommon, as I've seen others report the same side effect on here.

[proteomist]

I think it will be really interesting to hear what the reported side-effects are when they present the results of the trials. Maybe we'll learn that some of the things users have reported have shown up there as well. And maybe there will be effects we are unaware of, due to small sample size or the requirement of formal diagnostic tests. Then again, maybe we'll here these things are quite rare.

Thanks. I wish I could consistently stay on a few grams per day; I've tried it a few times, and after a while the quality and duration of my sleep deteriorate. This is not so uncommon, as I've seen others report the same side effect on here.

[lucid]

In the video provided by the link, they say that the phase 1b trials are not yet completed and should be completed by the end of the year. But yes the effective doses in the trial are higher than the 1g resv dose. The results from the trial are not back though.

[sUper GeNius]

So, who else want to join the >1000 mg club?

Remember that we do not know what other medications/nutrients these subjects are taking, if any. Many of us here are taking numerous "experimental" substances besides t-res, as well as prescribed medications, i.e. statins, blood pressure meds, etc.

I think it would be very imprudent to take greater than 500mg dosages without regular blood testing. I take BP meds and Lipitor. I think I will be moving up to a gram of t-res, but I intend to get blood tests every month for the first 6 months. Then maybe I'll go to quarterly tests.

[edward]

I would consider higher dosages. Right now I am at 800 mg (400 twice a day). But my problem is that I have a large supply of 50% product which if I go even a little over 800mg I have emodin issues. I will need to buy something purer in order to go to a higher dosage and I haven't really looked into suppliers. Anyone have any suggestions (aside from group purchases) I don't need anything purer than say 80% with confirmed low emodin.

[xanadu]

Lets start a kilogram club. Who will take a kilo a day and live to tell of it? Pretty soon people will be spending so much time each day eating rsv that they wont have time for anything else. That's why I asked if you could bake with it for our more eager experimenters. I still wonder who will be the first to die of an rsv overdose?

Meanwhile, I sit on the sidelines happy with 40mg per day.

[Karomesis]

I hope that subtitle is taken as the gentle, friendly ribbing I intend biggrin.gif

[:o] [lol] it's good to have some frank gloating subtitles once in a while.


unfortunately for me, this means I have to refinance my house again to pay for JUST my resveratrol doses. [cry]

[tintinet]

Can't take it with ya, anyway!

[maxwatt]

Lets start a kilogram club. Who will take a kilo a day and live to tell of it? Pretty soon people will be spending so much time each day eating rsv that they wont have time for anything else. That's why I asked if you could bake with it for our more eager experimenters. I still wonder who will be the first to die of an rsv overdose?

Meanwhile, I sit on the sidelines happy with 40mg per day.

Sniping from the sidelines, more like it.

[sUper GeNius]

Lets start a kilogram club. Who will take a kilo a day and live to tell of it? Pretty soon people will be spending so much time each day eating rsv that they wont have time for anything else. That's why I asked if you could bake with it for our more eager experimenters. I still wonder who will be the first to die of an rsv overdose?

Meanwhile, I sit on the sidelines happy with 40mg per day.

Ahhh. Brings to mind the scene in Scarface where Tony Montana is snorting mountains of the stuff off of his desk. If the FDA outlaws t-res, maybe we'll see a remake, this time with resveratrol.

"Say hello to my little friend."

Or, "Hey, kid, come-mere. I got some knotweed that'll blow your socks off."

[xanadu]

maxwatt, someone has to be sounding the note of caution and prudence in this matter. We have lots of eager converts preaching the benefits and advocating higher and higher doses. All I'm saying is that this is a potent drug and needs to be treated with respect. It affects the DNA in your genes or affects the way that your DNA expresses itself. This is not something to be taken lightly.

Saying that the mice didn't die does not prove anything. The tests were for a limited period and there was no way to detect mood swings, neuropathy or other potential side effects. Also, we do not know for sure how a dose in animals translates into a dose for humans. We are on new and untried ground here. If even 1% or less have a terrible reaction to high doses, that's a good reason for caution. Someone could die from this stuff if they get too carried away.

[Anthony_Loera]

What I find interesting is the folks who are using a low amount of rsv, and being very critical here about folks taking a high amount.

I think it is strange as the folks who are taking a low amoung probably heard of resveratrol from "David Sinclair" or one of the other "Exclusive Consultants" (per the COO of Sirtis) listed below:





Now, this is the current track for Sirtis products:





Current human Study using their regular Resveratrol formulation SRT501 (check out the amounts!) RevGenetics looks great to me!:





And of course the current side effects of their regular resveratrol formulation on humans (SRT501 in green):




I find this very interesting, as RevGenetics was originally seen by other competitors as silly because we offered such a large amount in a capsule. Now I believe what will happen is that lots of other competitors are going to come out of the woodwork with a large dose product themselves, trying to match our 500mg capsule, or produce the 1000mg capsule using 98% (which we have done in small quantities... but it's still to expensive for most practical people).

We were the first to bring a 500mg capsule to the market, now we may be the first to do other interesting things as resveratrol becomes cheaper...


The Sirtis information is indeed great news for RevGenetics.


Anthony Loera

Edited by Anthony_Loera, 13 May 2007 - 10:16 PM.

[Brainbox]

I'm not a medical research professional, but how many promising drugs survive all the relevant tests that should be conducted before it can be labeled "effective and safe"? Could you please elaborate on that?

Ok, I'm also very eager to take T-Res. I'm in my 40'ties and willing to try a lot to stay healthy or become more healthy. But first I will wait for the test results of the healthy Sinclair mice before even thinking of these high doses. In my opinion that's a healthy starting point to begin with. Healthy discussion enables adaptation of standpoints. So, if you would like to convince me to take 1 gram or more of T-Res a day, and could be held liable for my well being, what would be your top 3 or 4 arguments for that? (Consider this a general question to all heavy T-Res users. )

Edit: What about the risk / benefit ratio as compared between general health enhancement products for already healthy individuals and medicine to treat illnesses for not so healthy individuals?

Edited by brainbox, 13 May 2007 - 11:07 PM.

[Anthony_Loera]

I'm not a medical research professional, but how many promising drugs survive all the relevant tests that should be conducted before it can be labeled "effective and safe"? Could you please elaborate on that?

Ok, I'm also very eager to take T-Res. I'm in my 40'ties and willing to try a lot to stay healthy or become more healthy. But first I will wait for the test results of the healthy Sinclair mice before even thinking of these high doses. In my opinion that's a healthy starting point to begin with. Healthy discussion enables adaptation of standpoints. So, if you would like to convince me to take 1 gram or more of T-Res a day, and could be held liable for my well being, what would be your top 3 or 4 arguments for that? (Consider this a general question to all heavy T-Res users. )

Ahh... that is quite the question!

Lets get to the meat of it... the words "...and could be held liable for my well being..." is the part I am referring to in your statement.

Answer to that bit...
I think these words are very broad in scope, and I am simply not a doctor who knows your medical history to ascertain what, if anything, resveratrol will do to you personally. Heck you might be a pregnant woman for all I know... and I then would have to say... don't take it! (Just like most supplement vitamin labels out there who also say the same thing about a pregnant woman.)

1- Is it safe? I believe it to be very safe, and no toxicity levels have ever been reported at that dosage, while 25mg has been shown to be easily flushed out of your system.
2- Have there been long term usage of resveratrol in humans? Only in Chinese medicine, and most folks here know how I feel about chinese medicine.
3- I take it myself and I am 35... I have taken it for 6-7 months now... without ill effects.

It may be that I am Alien, or an exceptional human (hehehe...) and resveratrol is simply great for me. But for you... I can't make medical decisions for you, sorry. All I can say is that, you and your doctor can both come to an agreement about taking a higher dosage and your doctor can definitely give you a weekly or monthly progress report if you so desire.

Anthony Loera

Edited by Anthony_Loera, 13 May 2007 - 11:23 PM.

[Brainbox]

Ok, let me narrow the liability bit somewhat. Suppose I'm a healthy man that is not pregnant.
For all I know that's a reasonable bandwidth, since most healthy individuals do not know anything about their medical background. Maybe it is wise to add to the argumantation what blood-markers should be tested on what intervals to eliminate the risk for individual complications to occur.

[Brainbox]

Regarding your edit: My doctor doesn't know anything about resveratrol and it's metabolic pathways. I think I know more about that already, but I don't know what blood-markers to look for.

[proteomist]

I'd like to remind people that the 'high' doses we're seeing used with resveratrol are only so high because it has very poor bioavailability and binds only weakly to Sirt1. Xanadu describes it as a 'very powerful drug'. I only wish this were true. It is a completely half-assed, gets itself laughed out of the gym weakling of a drug. A decent drug spends as much time bound to the target as resveratrol does at 40,000 fold lower concentration (1 nm EC50 vs 40 uM), and gets into the bloodstream at >50%, as compared to ~5% for resveratrol under good conditions.

The only reasons resveratrol is worth thinking about are that it's the best Sirt1 activator we have, in terms of safety and consumer availability, and Sirt1 activation appears to be a very good thing. But when proper Sirt1-agonizing pharmaceuticals come out, along the lines of the Sirtris NCEs, you'll be looking at 3-4 fold more Sirt1 activation than say 5 grams of resveratrol at 1%-10% of the dosage mass. Then I might start considering the possibility of getting too much Sirt1 activation (though honestly I expect the consequences will be quite favorable). In the meantime, I'm just worried about getting enough onboard to get my Sirt1 activity to 150 or 200 percent.

[sUper GeNius]

I'd like to remind people that the 'high' doses we're seeing used with resveratrol are only so high because it has very poor bioavailability and binds only weakly to Sirt1. Xanadu describes it as a 'very powerful drug'. I only wish this were true. It is a completely half-assed, gets itself laughed out of the gym weakling of a drug. A decent drug spends as much time bound to the target as resveratrol does at 40,000 fold lower concentration (1 nm EC50 vs 40 uM), and gets into the bloodstream at >50%, as compared to ~5% for resveratrol under good conditions.

The only reasons resveratrol is worth thinking about are that it's the best Sirt1 activator we have, in terms of safety and consumer availability, and Sirt1 activation appears to be a very good thing.  But when proper Sirt1-agonizing pharmaceuticals come out, along the lines of the Sirtris NCEs, you'll be looking at 3-4 fold more Sirt1 activation than say 5 grams of  resveratrol at 1%-10% of the dosage mass. Then I might start considering the possibility of getting too much Sirt1 activation (though honestly I expect the consequences will be quite favorable). In the meantime, I'm just worried about getting enough onboard to get my Sirt1 activity to 150 or 200 percent.

But what *are* the consequences of Sirt1 activation in humans? Does t-res activate other complexes in humans? How about humans taking several other experimental substances or experimental doses?

These are all very basic questions whose answers are pretty much uncertain at this time.

[proteomist]

The question of whether or not to activate Sirt1 is distinct from the question of what resveratrol dosage is required to do so. The decision to take resveratrol is predicated on the idea that activating Sirt1 is a good idea, based on what we know about the involvement of this enzyme in activating stress resistance pathways that are pro-longevity in experimental animals. If one believes this to be the case and wants to activate Sirt1, the question becomes one of what dosage is required to do so. My post was meant to address only the later point, on the assumption that Sirt1 activation is a good idea. I believe that it's very likely to be a very good thing, but the questions you raise are quite relevant, and I'd like to see them answered by ongoing research. In my opinion however, at this time the evidence is strongly in favor of Sirt1 activation being beneficial with very minimal downside.

I'd like to remind people that the 'high' doses we're seeing used with resveratrol are only so high because it has very poor bioavailability and binds only weakly to Sirt1. Xanadu describes it as a 'very powerful drug'. I only wish this were true. It is a completely half-assed, gets itself laughed out of the gym weakling of a drug. A decent drug spends as much time bound to the target as resveratrol does at 40,000 fold lower concentration (1 nm EC50 vs 40 uM), and gets into the bloodstream at >50%, as compared to ~5% for resveratrol under good conditions.

The only reasons resveratrol is worth thinking about are that it's the best Sirt1 activator we have, in terms of safety and consumer availability, and Sirt1 activation appears to be a very good thing.  But when proper Sirt1-agonizing pharmaceuticals come out, along the lines of the Sirtris NCEs, you'll be looking at 3-4 fold more Sirt1 activation than say 5 grams of  resveratrol at 1%-10% of the dosage mass. Then I might start considering the possibility of getting too much Sirt1 activation (though honestly I expect the consequences will be quite favorable). In the meantime, I'm just worried about getting enough onboard to get my Sirt1 activity to 150 or 200 percent.

But what *are* the consequences of Sirt1 activation in humans? Does t-res activate other complexes in humans? How about humans taking several other experimental substances or experimental doses?

These are all very basic questions whose answers are pretty much uncertain at this time.