155 replies to this topic

[niner]

As announced 7 January 2008, the Sirtris Phase 1b clinical study in human patients with Type 2 Diabetes was conducted using a daily dosage of 2,500-5,000 mg resveratrol (proprietary formulation) per day. That's more than anyone in this thread discussed taking. No significant adverse effects were reported.

This contradicts anecdotal accounts in this forum of joint pains, etc. caused by taking high does of resveratrol. It would be interesting to discover how many of the people reporting these symptoms would have done so if they had not first read other accounts of such side effects here. Is there any scientific basis for concluding that resveratrol consumption above a certain threshold causes joint pain? Animal studies with which I'm familiar point to the exact opposite conclusion.

One lesson learned from comparing the discussions in this thread dating back almost a year to the published results in the human study is that it is very difficult for layman to judge an appropriate dosage for resveratrol consumption. And that's not surprising.

However, it is worth noting that this study was only conducted over a 28 day period.

On the contrary, a number of us are taking doses in that range. For example, the previous posting in this thread by tintinet mentions taking 5+g/day. I think that the members of this forum, which includes a number of scientists and a couple physicians, have done an impressive job of exploring the formulation and dosing of resveratrol. Joint and tendon pain is a relatively common phenomenon, so it would be pretty easy for one or two cases of that to be ignored in a 28 day study. I think that the members of this group are on to something with the recognition of this effect, and if you have followed the forum for a while you will have seen a number of hypotheses floated as to the molecular mechanisms involved. I'm not sure that studies of typically sedentary animals are the best place to look for this sort of problem.

[TianZi]

Hello Niner,

I'm not a biologist, chemist, or physician. I'm only an attorney. But I believe I'm still able to glean something of value from reviewing the available reliable reports and articles on resveratrol.

The specific animal studies to which I referred showed markedly improved motor coordination in mice dosed with resveratrol, as demonstrated by the ability of dosed mice to perform significantly better walking across a narrow, rotating wooden rod as compared to the control group. A different study showed marked improvements in endurance in mice, judging from performance on a treadmill. If I recall correctly, the dosage was quite high in proportion to the body weight of the mice.

Although I speak from the perspective of a layman, I doubt mice suffering from acute joint pains would have performed better on a treadmill test for endurance, let alone demonstrate improved ability to walk across a narrow, rotating rod!

Granted, mice aren't people. Further, they can't (yet? ) tell us whether they are suffering from joint pain. Nonetheless, humans and mice are approx. 99% identical genetically, and mice have proven a generally reliable measure for predicting outcomes of drug interventions in humans. The studies mentioned two paragraphs above cast doubt on the proposition that "high" doses of resveratrol will cause joint/tendon/muscular pain in humans. More importantly, I am not aware of any study of resveratrol use on human subjects that has reported joint pain as a side effect experienced by participants. That doesn't mean the question is settled, but it seems to me most sensible to value the present lack of any evidence for this negative side effect in the available pertinent scientific literature (known to me) over anonymous anecdotal accounts on an internet forum.

Cause and effect can be difficult to pinpoint. I suffer from tendinitis and sometimes severe joint pain, and I don't take resveratrol. It would be improper for me to conclude from this that my not taking resveratrol caused my joint and tendon pain. Joint pain is a normal symptom of aging (and/or vigorous exercise), and presumably, many of the members of this forum are just entering that lovely stage of their life where joint pain rears its ugly head.

With that said, I believe representatives of Sirtris have mentioned to the press that certain substances mixed with resveratrol can produce negative side effects, but did not elucidate what precisely those side effects were, nor the nature of said "other substances."

Edited by TianZi, 10 January 2008 - 07:55 AM.

[maxwatt]

Hello Niner,

I'm not a biologist, chemist, or physician. I'm only an attorney. But I believe I'm still able to glean something of value from reviewing the available reliable reports and articles on resveratrol.

The specific animal studies to which I referred showed markedly improved motor coordination in mice dosed with resveratrol, as demonstrated by the ability of dosed mice to perform significantly better walking across a narrow, rotating wooden rod as compared to the control group. A different study showed marked improvements in endurance in mice, judging from performance on a treadmill. If I recall correctly, the dosage was quite high in proportion to the body weight of the mice.

Although I speak from the perspective of a layman, I doubt mice suffering from acute joint pains would have performed better on a treadmill test for endurance, let alone demonstrate improved ability to walk across a narrow, rotating rod!

Granted, mice aren't people. Further, they can't (yet? ) tell us whether they are suffering from joint pain. Nonetheless, humans and mice are approx. 99% identical genetically, and mice have proven a generally reliable measure for predicting outcomes of drug interventions in humans. The studies mentioned two paragraphs above cast doubt on the proposition that "high" doses of resveratrol will cause joint/tendon/muscular pain in humans. More importantly, I am not aware of any study of resveratrol use on human subjects that has reported joint pain as a side effect experienced by participants. That doesn't mean the question is settled, but it seems to me most sensible to value the present lack of any evidence for this negative side effect in the available pertinent scientific literature (known to me) over anonymous anecdotal accounts on an internet forum.

Cause and effect can be difficult to pinpoint. I suffer from tendinitis and sometimes severe joint pain, and I don't take resveratrol. It would be improper for me to conclude from this that my not taking resveratrol caused my joint and tendon pain. Joint pain is a normal symptom of aging (and/or vigorous exercise), and presumably, many of the members of this forum are just entering that lovely stage of their life where joint pain rears its ugly head.

With that said, I believe representatives of Sirtris have mentioned to the press that certain substances mixed with resveratrol can produce negative side effects, but did not elucidate what precisely those side effects were, nor the nature of said "other substances."

Good points. Sort of a negative placebo effect. Everyone has joint or tendon pain from time to time, one person says "I have joint pain", and everyone attributes it to the resveratrol they take. I take resveratrol not to have joint pain.

As for negative side effects from other substances with resveratrol, both quercetin (250 mg) and luteolin (between 50 and 200 mg) taken with resveratrol, resulted in more joint pain for me than I had been trying to prevent. I believed this was due to their metabolites competitively inhibiting SirT1.

(Chimpanzees and humans are said to be 99% genetically identical. I believe mice are much less so, maybe not more than 85%. I'm sure it depends on how you count.)

[TianZi]

Hi Maxwatt,

Since I've no background in biology past whatever I may have learned in high school, I checked to see if my memory of the degree of similarity was correct. Based on a San Francisco Chronicle article I found entitled "Of Mice and Men" (linked below), on a letter-by-letter basis 85% of the genes of mice and men are identical. However, mice and humans both have about 30,000 genes - and share 99% of them.

http://www.sfgate.co...mp;type=science

[ajnast4r]

Upped my dose to 2200mg last night, up from 1,200 mg. am crawling out of my skin today, thinking that the t-res isn't reacting too well with Paxil. I wonder if the Paxil metabolism is being slowed? I have some screwy enzymes to begin with I think, as I was first on Zoloft, a dose so small that the doctor said she starts children on it, and I could not tolerate it at all.

you are playing with fire my friend. i suggest you rethink things a little bit. rsv is a selective cytochrome p450 inhibitor, which is what metabolizes paxil... this combo is gonna leave you with abnormally high levels of paxil in your system, and most likely cause you some serious problems. it also may inhibit serotonin and nor epinephrine uptake in and of itself... which would make it QUITE incompatible with paxil.

WHY you would not research this before megadosing ANYTHING, especially when you are taking such a potent prescription medication, is beyond my ability to understand.

Edited by ajnast4r, 10 January 2008 - 03:53 PM.

[missminni]

Re: joint pain
IIRC the people complaining of joint pain were also running excessively.
There was an issue of the degree of running and the anti-inflammatory action
of the res resulting in joint pain. It wasn't the res itself causing the pain.

[niner]

Hello Niner,

I'm not a biologist, chemist, or physician. I'm only an attorney. But I believe I'm still able to glean something of value from reviewing the available reliable reports and articles on resveratrol.

The specific animal studies to which I referred showed markedly improved motor coordination in mice dosed with resveratrol, as demonstrated by the ability of dosed mice to perform significantly better walking across a narrow, rotating wooden rod as compared to the control group. A different study showed marked improvements in endurance in mice, judging from performance on a treadmill. If I recall correctly, the dosage was quite high in proportion to the body weight of the mice.

Although I speak from the perspective of a layman, I doubt mice suffering from acute joint pains would have performed better on a treadmill test for endurance, let alone demonstrate improved ability to walk across a narrow, rotating rod!

Granted, mice aren't people. Further, they can't (yet? ) tell us whether they are suffering from joint pain. Nonetheless, humans and mice are approx. 99% identical genetically, and mice have proven a generally reliable measure for predicting outcomes of drug interventions in humans. The studies mentioned two paragraphs above cast doubt on the proposition that "high" doses of resveratrol will cause joint/tendon/muscular pain in humans. More importantly, I am not aware of any study of resveratrol use on human subjects that has reported joint pain as a side effect experienced by participants. That doesn't mean the question is settled, but it seems to me most sensible to value the present lack of any evidence for this negative side effect in the available pertinent scientific literature (known to me) over anonymous anecdotal accounts on an internet forum.

Cause and effect can be difficult to pinpoint. I suffer from tendinitis and sometimes severe joint pain, and I don't take resveratrol. It would be improper for me to conclude from this that my not taking resveratrol caused my joint and tendon pain. Joint pain is a normal symptom of aging (and/or vigorous exercise), and presumably, many of the members of this forum are just entering that lovely stage of their life where joint pain rears its ugly head.

With that said, I believe representatives of Sirtris have mentioned to the press that certain substances mixed with resveratrol can produce negative side effects, but did not elucidate what precisely those side effects were, nor the nature of said "other substances."

TianZi, you are very correct in saying that mice aren't people. Although we "share" most of our genes, nearly all of them are non-identical homologs. They differ in various, sometimes critical amino acids, and sometimes they don't work the same way. Sometimes in mice there will be gene duplications where you will find a large family of related genes while in humans there is only one. This could also work the other way around. To a first approximation, mice are like people, which is quite an eye-opener to people who think that humans are not animals. However, they are only so-so when it comes to testing drugs. Their primary advantages are that they are cheap and most (but not all) people don't have enormous ethical concerns over experimenting on them. Still, they are so different from humans that there is no way you could ever get a drug approved for use in humans on the basis of a mouse test. There is a very long list of treatments that worked in mice but failed in humans. There are probably some promising treatments that failed in mice but would have worked in humans, but we'll have to rediscover those at a later date.

As you know from your legal training, you can't prove a negative. It is an even longer stretch to say that mice not showing a side effect means that humans will also not experience it. The placebo effect argument is a good point, although I'm pretty sure that some people have seen the effects stop when they stopped resveratrol, then resume when dosing resumed. There is still a lot of room for placebo effects here, and I suspect that some of the positive results that have been reported are also that.

[niner]

Upped my dose to 2200mg last night, up from 1,200 mg. am crawling out of my skin today, thinking that the t-res isn't reacting too well with Paxil. I wonder if the Paxil metabolism is being slowed? I have some screwy enzymes to begin with I think, as I was first on Zoloft, a dose so small that the doctor said she starts children on it, and I could not tolerate it at all.

you are playing with fire my friend. i suggest you rethink things a little bit. rsv is a selective cytochrome p450 inhibitor, which is what metabolizes paxil... this combo is gonna leave you with abnormally high levels of paxil in your system, and most likely cause you some serious problems. it also may inhibit serotonin and nor epinephrine uptake in and of itself... which would make it QUITE incompatible with paxil.

WHY you would not research this before megadosing ANYTHING, especially when you are taking such a potent prescription medication, is beyond my ability to understand.

Paxil is metabolized by P450-2D6, and is subsequently glucuronidated and sulfated, like resveratrol. There are a number of P450's, and it matters a lot which one you are inhibiting or being metabolized by. They are not typically interchangeable. Resveratrol is a weak inhibitor of 1A1, and a very weak inhibitor of 1A2. At physiological concentrations of resveratrol, neither of these would likely be a factor in any case, and definitely not with paxil. It's conceivable that resveratrol was acting in some way to slow the conjugation of paxil, but that's probably a long shot. There's a sizable population of people who have a less effective 2D6, but this would be completely separate from resveratrol issues.

[wydell]

quote]

Good points. Sort of a negative placebo effect. Everyone has joint or tendon pain from time to time, one person says "I have joint pain", and everyone attributes it to the resveratrol they take. I take resveratrol not to have joint pain.

As for negative side effects from other substances with resveratrol, both quercetin (250 mg) and luteolin (between 50 and 200 mg) taken with resveratrol, resulted in more joint pain for me than I had been trying to prevent. I believed this was due to their metabolites competitively inhibiting SirT1.

(Chimpanzees and humans are said to be 99% genetically identical. I believe mice are much less so, maybe not more than 85%. I'm sure it depends on how you count.)

To be fair, all of the positve effects reported here could also be placebo based. There are no good human studies (positive or negative) that I am aware of. I don't consider Sirtirs studies to be indicative of what resveratrol does in humans because they are not testing plain old resveratrol in those studies. While sirtris drugs may be effective, plain resveratrol may not be effective. I am not negative on Res. I take it. But I am not a firm believer either. (There goes the placebo effect for me . . . I guess.)

[ajnast4r]

Paxil is metabolized by P450-2D6, and is subsequently glucuronidated and sulfated, like resveratrol. There are a number of P450's, and it matters a lot which one you are inhibiting or being metabolized by. They are not typically interchangeable. Resveratrol is a weak inhibitor of 1A1, and a very weak inhibitor of 1A2. At physiological concentrations of resveratrol, neither of these would likely be a factor in any case, and definitely not with paxil. It's conceivable that resveratrol was acting in some way to slow the conjugation of paxil, but that's probably a long shot. There's a sizable population of people who have a less effective 2D6, but this would be completely separate from resveratrol issues.

i understand that... but i still think hes playing with fire in a major way. if 2g rsv made him feel like hes crawling out of his skin, something is going on.

i personally do not think the possible benefits of rsv are worth the possible damages of mixing it with ssri's.

[sUper GeNius]

Paxil is metabolized by P450-2D6, and is subsequently glucuronidated and sulfated, like resveratrol. There are a number of P450's, and it matters a lot which one you are inhibiting or being metabolized by. They are not typically interchangeable. Resveratrol is a weak inhibitor of 1A1, and a very weak inhibitor of 1A2. At physiological concentrations of resveratrol, neither of these would likely be a factor in any case, and definitely not with paxil. It's conceivable that resveratrol was acting in some way to slow the conjugation of paxil, but that's probably a long shot. There's a sizable population of people who have a less effective 2D6, but this would be completely separate from resveratrol issues.

i understand that... but i still think hes playing with fire in a major way. if 2g rsv made him feel like hes crawling out of his skin, something is going on.

i personally do not think the possible benefits of rsv are worth the possible damages of mixing it with ssri's.

I was very nervous that day. I do no know whether it was the t-res, a bunch of coffee, Benadryl rebound, or just me. I get nervous sometimes. Sometimes more, sometimes less.

The next day I felt fine, and have ever since. I continue to take t-res, but only 1.5g. I'll take my time and go back up later.

[niner]

Paxil is metabolized by P450-2D6, and is subsequently glucuronidated and sulfated, like resveratrol. There are a number of P450's, and it matters a lot which one you are inhibiting or being metabolized by. They are not typically interchangeable. Resveratrol is a weak inhibitor of 1A1, and a very weak inhibitor of 1A2. At physiological concentrations of resveratrol, neither of these would likely be a factor in any case, and definitely not with paxil. It's conceivable that resveratrol was acting in some way to slow the conjugation of paxil, but that's probably a long shot. There's a sizable population of people who have a less effective 2D6, but this would be completely separate from resveratrol issues.

i understand that... but i still think hes playing with fire in a major way. if 2g rsv made him feel like hes crawling out of his skin, something is going on.

i personally do not think the possible benefits of rsv are worth the possible damages of mixing it with ssri's.

I was very nervous that day. I do no know whether it was the t-res, a bunch of coffee, Benadryl rebound, or just me. I get nervous sometimes. Sometimes more, sometimes less.

The next day I felt fine, and have ever since. I continue to take t-res, but only 1.5g. I'll take my time and go back up later.

If you feel fine on 1500mg, I kind of doubt that another 700mg would have you crawling out of your skin. Also, Paxil is probably the most sedating of the SSRIs, so nervousness wouldn't be something I'd expect from it, though paradoxical reactions are common with these things so I couldn't rule it out. With all the pills most of us have rattling around, the likelyhood of taking two of something or missing something start to get significant; something to consider.

[DukeNukem]

>>> I don't plan on taking any resveratrol as a supplement until more studies are completed.

The younger you are, the more reasonable is this approach. Anyone over 40, though, time is running out, and I'd recommend taking some chances. RSV seems to be a very safe bet, given what we currently know, and also based on the long history of low dose RSV via red wine.

At minimum, I'd recommend 250mg daily, just to capitalize on the heart protective and cancer resistant properties of this molecule.

Edited by DukeNukem, 12 January 2008 - 04:05 PM.

[zawy]

I think the Paxil discussion is interesting because in the last 3 days of taking 300 mg 3x/day, i feel a little jittery or "jazzed" in a way that is not yet annoying. I'm 140 pounds on calorie restriction (1700/day), so this is like 1.5 g/day for a lot of people. I'm not sure i would enjoy taking 2 g/day. I'm using 50% country life. It feels very much like the zoloft i tried for two weeks, except not nearly as bad. "jazzed" describes it well. I just did a circuit training session of 10 reps of 15 different exercises in a record speed of 8 minutes. I'm working 12 hrs/day instead of my usual 8. I'm skipping the my usual morning coffe/tea/cocoa because i don't need anymore jazz than this. My joints and tendons would probably suffer from being overly jazzed and doing too much. From what i saw of the joint posts, it doesn't seem to have reached the level of evidence yet. It would be good if someone read all the posts and summarized the claims. One person posting several times could make it look like it's more than the actual number of people.

Since these doses are unnatural, i would not combine it with a pharmaceutical without being very careful.

DukeNukem 250 mg/day orally is the same as the high-dose fish experiment when based on RESV/calorie consumed to adjust for the difference in metabolism of the two species. Other arguments i posted elsewhere say it may need to be adjusted to as high as 1 g/day. I think the 500 mg/day group is completely reasonable for great results and 2g/day is not at all insane in the absence of negative side effects. But based strictly on the fish results and using RESV/calorie consumed, even taking "only" 250 mg starting at age 30 (they began feeding it to the fish at 4 weeks which is 30% of the maximum 12 week lifespan) , don't be surprised if you live 56% longer in addition to avoid cancer and heart disease. Something like 10% lived up to the human-equivalent of 150 years.

I believe the RESV/calorie consumed is the most accurate comparison method because respiration is the result of calories consumed and the primary purpose of RESV is to decrease oxidation caused by respiration, probably allowing more viable cell divisions since it's been shown to work differently from CR (but not synergistically) which decreases time between divisions. RESV acts on SIRT1/FOXO3a to increase MnSOD to decrease the superoxide byproduct of respiration from complex 1 and 3 of the electron transport chain. I would be interested in seeing any research that contradicts this current state of knowledge. Be highly suspect of any claims of benefit from RESV that do not mention MnSOD as the key. I believe the majority of the benefits and gene expressions reported will be the result of the SIRT1/NAD+/FOXO3a that yields MnSOD action.

The reports of increased "testosterone" (aggression) could also be related to the "jazzed" feeling....which could be a serotonin increase. Hope we don't start hearing about a string of resveratrol people going on a shooting spree like 9 out of 10 of the all the shootings in the past decade that had an antidepressant SSRI involved. We hear nothing about that connection in the media....but believe you me that if a non-pharmaceutical starts doing the same thing, the FDA will shut distribution down in a heart beat.

Edited by zawy, 12 January 2008 - 06:10 PM.

[sUper GeNius]

Paxil is metabolized by P450-2D6, and is subsequently glucuronidated and sulfated, like resveratrol. There are a number of P450's, and it matters a lot which one you are inhibiting or being metabolized by. They are not typically interchangeable. Resveratrol is a weak inhibitor of 1A1, and a very weak inhibitor of 1A2. At physiological concentrations of resveratrol, neither of these would likely be a factor in any case, and definitely not with paxil. It's conceivable that resveratrol was acting in some way to slow the conjugation of paxil, but that's probably a long shot. There's a sizable population of people who have a less effective 2D6, but this would be completely separate from resveratrol issues.

i understand that... but i still think hes playing with fire in a major way. if 2g rsv made him feel like hes crawling out of his skin, something is going on.

i personally do not think the possible benefits of rsv are worth the possible damages of mixing it with ssri's.

I was very nervous that day. I do no know whether it was the t-res, a bunch of coffee, Benadryl rebound, or just me. I get nervous sometimes. Sometimes more, sometimes less.

The next day I felt fine, and have ever since. I continue to take t-res, but only 1.5g. I'll take my time and go back up later.

If you feel fine on 1500mg, I kind of doubt that another 700mg would have you crawling out of your skin. Also, Paxil is probably the most sedating of the SSRIs, so nervousness wouldn't be something I'd expect from it, though paradoxical reactions are common with these things so I couldn't rule it out. With all the pills most of us have rattling around, the likelyhood of taking two of something or missing something start to get significant; something to consider.

Maybe I took an extra Paxil that day? Hmmm. Maybe. Would have been increasing my paxil does 50%.

[ener555]

I was always wondering about those people who live in France drinking lots of Wine and living over 100. I think thats how scientists actually got the idea that there might be something in Wine that may increase your life span. Ofcourse it could also be that those people just live a way more relaxed lifestyle than most of us which could contribute to their high age.

Anyways I was thinking that if their old age is because of drinking lots of Wine, lets say about 1bottle a day (probably less), wouldn't they get way less Resveratrol than most of us? And they already seem to have a great benefit from it.

Wikipedia says that Muscadine Wines have about 14.1 - 40mg/l of Resveratrol so if they were to drink a whole bottle everyday they would get about 40mg of natural Resveratrol.

Now I don't know how comparable natural Resveratrol is to artificial but even with decreased bioavalibilty of the Resveratrol most of us take wouldn't even 500mg way exceed the 40mg those french people took by drinking Wine?

[sUper GeNius]

I was always wondering about those people who live in France drinking lots of Wine and living over 100. I think thats how scientists actually got the idea that there might be something in Wine that may increase your life span. Ofcourse it could also be that those people just live a way more relaxed lifestyle than most of us which could contribute to their high age.

Anyways I was thinking that if their old age is because of drinking lots of Wine, lets say about 1bottle a day (probably less), wouldn't they get way less Resveratrol than most of us? And they already seem to have a great benefit from it.

Wikipedia says that Muscadine Wines have about 14.1 - 40mg/l of Resveratrol so if they were to drink a whole bottle everyday they would get about 40mg of natural Resveratrol.

Now I don't know how comparable natural Resveratrol is to artificial but even with decreased bioavalibilty of the Resveratrol most of us take wouldn't even 500mg way exceed the 40mg those french people took by drinking Wine?

Yes Bill. Thanks for the Longevinex pitch...

[krillin]

It would be good if someone read all the posts and summarized the claims. One person posting several times could make it look like it's more than the actual number of people.

I found these reports.

rhc124 1.2 g 50% hip pain
quarter 500 mg 50% achilles tendinitis
kenj 1.1 g 99% achilles tendinitis
alterego 1-1.5 g 99% exacerbated rheumatoid arthritis
matt unspecified dose ankle tendinitis
drmz 600 mg knees and ankles
enzyme 10 mg/kg hamstring tendinitis

[tintinet]

It would be good if someone read all the posts and summarized the claims. One person posting several times could make it look like it's more than the actual number of people.

I found these reports.

rhc124 1.2 g 50% hip pain
quarter 500 mg 50% achilles tendinitis
kenj 1.1 g 99% achilles tendinitis
alterego 1-1.5 g 99% exacerbated rheumatoid arthritis
matt unspecified dose ankle tendinitis
drmz 600 mg knees and ankles
enzyme 10 mg/kg hamstring tendinitis

I suppose you could add me: 5 grams/day 99%+ synthetic; 99%+ extract; and intermittently minor amounts 50% extract. Mild tennis elbow due to playing guitar.

[niner]

I think the Paxil discussion is interesting because in the last 3 days of taking 300 mg 3x/day, i feel a little jittery or "jazzed" in a way that is not yet annoying. I'm 140 pounds on calorie restriction (1700/day), so this is like 1.5 g/day for a lot of people. I'm not sure i would enjoy taking 2 g/day. I'm using 50% country life. It feels very much like the zoloft i tried for two weeks, except not nearly as bad. "jazzed" describes it well. I just did a circuit training session of 10 reps of 15 different exercises in a record speed of 8 minutes. I'm working 12 hrs/day instead of my usual 8. I'm skipping the my usual morning coffe/tea/cocoa because i don't need anymore jazz than this. My joints and tendons would probably suffer from being overly jazzed and doing too much. From what i saw of the joint posts, it doesn't seem to have reached the level of evidence yet. It would be good if someone read all the posts and summarized the claims. One person posting several times could make it look like it's more than the actual number of people.

Zawy, you are feeling the psychotropic effects of the 50% of the country life that is not resveratrol. Early in the 500 club thread, lots of people were reporting this kind of thing. If you switch to 98+%, it will go away.

Since these doses are unnatural, i would not combine it with a pharmaceutical without being very careful.

DukeNukem 250 mg/day orally is the same as the high-dose fish experiment when based on RESV/calorie consumed to adjust for the difference in metabolism of the two species. Other arguments i posted elsewhere say it may need to be adjusted to as high as 1 g/day. I think the 500 mg/day group is completely reasonable for great results and 2g/day is not at all insane in the absence of negative side effects. But based strictly on the fish results and using RESV/calorie consumed, even taking "only" 250 mg starting at age 30 (they began feeding it to the fish at 4 weeks which is 30% of the maximum 12 week lifespan) , don't be surprised if you live 56% longer in addition to avoid cancer and heart disease. Something like 10% lived up to the human-equivalent of 150 years.

Hold on there... There's no way we can extrapolate from these short-lived fish to humans. Humans have highly developed xenobiotic metabolism that seems to have evolved nearly specifically for getting rid of phytoalexins such as resveratrol. It certainly does a good job of it. These little fish probably have nothing of the sort, and mice appear to have a simpler, less effective version, at least based on the plasma levels achieved for a given mg/kg dose. When you compare blood levels of free resveratrol between mice and people for a given mg/kg dose, humans need about 4 times the mg/kg level to achieve the same blood levels. Applying the usual metabolic scaling rules would tell us that we'd need on the order of a tenth the amount as the mice. At this point in time, I'm not aware of any results that show a lifespan increase from resveratrol in mice eating a normal diet.

[zawy]

Thanks for the summary of the tendinitis reports. If you take a halogen flood light, 50 to 100 Watts and shine it on the tendinitis area, you can see an amazing immediate relief from pain. Healing time is theoretically 5 times faster. It needs to be bright enough that it makes the skin as hot as you can stand it and do it for 20 minutes as needed to eliminate the pain. You can use a zip lock bag of water between the bulb and skin to block the far-infrared heat that absorbs in the skin and causes pain from the heat. This is the same as LED light therapy that speeds healing with wavelengths from 630 to 880 nm (red to near-infrared) that penetrates blood and water better than other frequencies. It's not the heat that helps, but complex 4 of the electron transport chain (CCO) absorbs 50% of the energy in order to help the mitochondria convert output from the krebs cycle into energy for the proton gradient for ATP. Evolutionarily speaking, the light in this range makes up 30% of the energy from the sun and it kick-starts the cell into putting out more ATP for activity as might be needed in the daytime but not at night when the ATP needs to be reduced. The proteins that form the CCO proton pump were inherited from purple bacteria going all the way back to the evolution of mitochondria with only slight changes in various animals. I believe all varients have 2 copper and 2 iron atoms for doing the fuel-cell type reaction and "coincidentally" capable of absorbing the light at those atomic locations. The bacteria used the light-absorption properties of the pump for similar benefit. By kick-starting the last pump in the chain, it creates an electron vacuum in the other two pumps, complex 1 and complex 3. Too much of the light starts creating too many superoxides. Knowing all this is what made my eyes pop open when i saw the paper claiming it's not really what RESV does to SIRT1 but its assistance in creating more MnSOD that's important. The importance of MnSOD is that it counteracts the oxidation created by complex 1 and 3, so that now i had a possible way of applying more light for healing by using RESV to counteract the negatives of overdosing with light. The absorption spectrum of blood drops off so rapidly right where the CCO starts absorbing light, that I have to strongly believe that blood evolved so that CCO could still recieve light to kick-start ATP creation. If you suddenly jump naked into strong sunlight, you can see your respiration go up even before the heat has had time to have any effect. If you place 1 inch of water above your body to block the far-infrared heat so that it's much cooler, you can still see a sudden increase in respiration as demonstration of this effect.

[sUper GeNius]

I think the Paxil discussion is interesting because in the last 3 days of taking 300 mg 3x/day, i feel a little jittery or "jazzed" in a way that is not yet annoying. I'm 140 pounds on calorie restriction (1700/day), so this is like 1.5 g/day for a lot of people. I'm not sure i would enjoy taking 2 g/day. I'm using 50% country life. It feels very much like the zoloft i tried for two weeks, except not nearly as bad. "jazzed" describes it well. I just did a circuit training session of 10 reps of 15 different exercises in a record speed of 8 minutes. I'm working 12 hrs/day instead of my usual 8. I'm skipping the my usual morning coffe/tea/cocoa because i don't need anymore jazz than this. My joints and tendons would probably suffer from being overly jazzed and doing too much. From what i saw of the joint posts, it doesn't seem to have reached the level of evidence yet. It would be good if someone read all the posts and summarized the claims. One person posting several times could make it look like it's more than the actual number of people.

Zawy, you are feeling the psychotropic effects of the 50% of the country life that is not resveratrol. Early in the 500 club thread, lots of people were reporting this kind of thing. If you switch to 98+%, it will go away.

Since these doses are unnatural, i would not combine it with a pharmaceutical without being very careful.

DukeNukem 250 mg/day orally is the same as the high-dose fish experiment when based on RESV/calorie consumed to adjust for the difference in metabolism of the two species. Other arguments i posted elsewhere say it may need to be adjusted to as high as 1 g/day. I think the 500 mg/day group is completely reasonable for great results and 2g/day is not at all insane in the absence of negative side effects. But based strictly on the fish results and using RESV/calorie consumed, even taking "only" 250 mg starting at age 30 (they began feeding it to the fish at 4 weeks which is 30% of the maximum 12 week lifespan) , don't be surprised if you live 56% longer in addition to avoid cancer and heart disease. Something like 10% lived up to the human-equivalent of 150 years.

Hold on there... There's no way we can extrapolate from these short-lived fish to humans. Humans have highly developed xenobiotic metabolism that seems to have evolved nearly specifically for getting rid of phytoalexins such as resveratrol. It certainly does a good job of it. These little fish probably have nothing of the sort, and mice appear to have a simpler, less effective version, at least based on the plasma levels achieved for a given mg/kg dose. When you compare blood levels of free resveratrol between mice and people for a given mg/kg dose, humans need about 4 times the mg/kg level to achieve the same blood levels. Applying the usual metabolic scaling rules would tell us that we'd need on the order of a tenth the amount as the mice. At this point in time, I'm not aware of any results that show a lifespan increase from resveratrol in mice eating a normal diet.

Respectfully, then why do you take t-res?

[niner]

Since these doses are unnatural, i would not combine it with a pharmaceutical without being very careful.

DukeNukem 250 mg/day orally is the same as the high-dose fish experiment when based on RESV/calorie consumed to adjust for the difference in metabolism of the two species. Other arguments i posted elsewhere say it may need to be adjusted to as high as 1 g/day. I think the 500 mg/day group is completely reasonable for great results and 2g/day is not at all insane in the absence of negative side effects. But based strictly on the fish results and using RESV/calorie consumed, even taking "only" 250 mg starting at age 30 (they began feeding it to the fish at 4 weeks which is 30% of the maximum 12 week lifespan) , don't be surprised if you live 56% longer in addition to avoid cancer and heart disease. Something like 10% lived up to the human-equivalent of 150 years.

Hold on there... There's no way we can extrapolate from these short-lived fish to humans. Humans have highly developed xenobiotic metabolism that seems to have evolved nearly specifically for getting rid of phytoalexins such as resveratrol. It certainly does a good job of it. These little fish probably have nothing of the sort, and mice appear to have a simpler, less effective version, at least based on the plasma levels achieved for a given mg/kg dose. When you compare blood levels of free resveratrol between mice and people for a given mg/kg dose, humans need about 4 times the mg/kg level to achieve the same blood levels. Applying the usual metabolic scaling rules would tell us that we'd need on the order of a tenth the amount as the mice. At this point in time, I'm not aware of any results that show a lifespan increase from resveratrol in mice eating a normal diet.

Respectfully, then why do you take t-res?

Because all the cool kids are doing it! No, really, the list of positive effects seems to be pretty long. It did do some quite good things to Auwerx's mice, and if you have a habit of drinking from the deep fat fryer, there's a halfway decent chance you'll see a 30% increase in lifespan. I just don't think that what I'm doing today with resveratrol is going to make me live to be 150. (For that, I'll need alkalized water, H2O2 injections, and magnets...)

[sUper GeNius]

Since these doses are unnatural, i would not combine it with a pharmaceutical without being very careful.

DukeNukem 250 mg/day orally is the same as the high-dose fish experiment when based on RESV/calorie consumed to adjust for the difference in metabolism of the two species. Other arguments i posted elsewhere say it may need to be adjusted to as high as 1 g/day. I think the 500 mg/day group is completely reasonable for great results and 2g/day is not at all insane in the absence of negative side effects. But based strictly on the fish results and using RESV/calorie consumed, even taking "only" 250 mg starting at age 30 (they began feeding it to the fish at 4 weeks which is 30% of the maximum 12 week lifespan) , don't be surprised if you live 56% longer in addition to avoid cancer and heart disease. Something like 10% lived up to the human-equivalent of 150 years.

Hold on there... There's no way we can extrapolate from these short-lived fish to humans. Humans have highly developed xenobiotic metabolism that seems to have evolved nearly specifically for getting rid of phytoalexins such as resveratrol. It certainly does a good job of it. These little fish probably have nothing of the sort, and mice appear to have a simpler, less effective version, at least based on the plasma levels achieved for a given mg/kg dose. When you compare blood levels of free resveratrol between mice and people for a given mg/kg dose, humans need about 4 times the mg/kg level to achieve the same blood levels. Applying the usual metabolic scaling rules would tell us that we'd need on the order of a tenth the amount as the mice. At this point in time, I'm not aware of any results that show a lifespan increase from resveratrol in mice eating a normal diet.

Respectfully, then why do you take t-res?

Because all the cool kids are doing it! No, really, the list of positive effects seems to be pretty long. It did do some quite good things to Auwerx's mice, and if you have a habit of drinking from the deep fat fryer, there's a halfway decent chance you'll see a 30% increase in lifespan. I just don't think that what I'm doing today with resveratrol is going to make me live to be 150. (For that, I'll need alkalized water, H2O2 injections, and magnets...)

I'm hoping for a healthy 105.

[maxwatt]

It would be good if someone read all the posts and summarized the claims. One person posting several times could make it look like it's more than the actual number of people.

I found these reports.

rhc124 1.2 g 50% hip pain
quarter 500 mg 50% achilles tendinitis
kenj 1.1 g 99% achilles tendinitis
alterego 1-1.5 g 99% exacerbated rheumatoid arthritis
matt unspecified dose ankle tendinitis
drmz 600 mg knees and ankles
enzyme 10 mg/kg hamstring tendinitis

I suppose you could add me: 5 grams/day 99%+ synthetic; 99%+ extract; and intermittently minor amounts 50% extract. Mild tennis elbow due to playing guitar.

I had very severe achilles tendonitis in 1998 when I was running, before I'd even heard of resveratrol.
What would one expect to be the rate of tendinitis in a random group of people?
Autoimmune diseases like rheumatoid arthritis can be exacerbated by Sirt1 activity; I would expect resveratrol not to be good in such situations.

[zawy]

What would one expect to be the rate of tendinitis in a random group of people?
Autoimmune diseases like rheumatoid arthritis can be exacerbated by Sirt1 activity; I would expect resveratrol not to be good in such situations.

I thought people were reporting less arthritis. From the tendinitis reports I saw, maybe half i had some doubt in the report. For example 2 were runners that said the RESV helped them increase activity.

niner wrote "...going to make me live to be 150. (For that, I'll need alkalized water, H2O2 injections, and magnets"

hahaha, good one, but don't forget the purpose of the 14-fold increase in MnSOD activity from RESV is to make more H2O2 out of O2-. Although i saw a report that increasing MnSOD directly reduced O2- whilst the cell's response kept the H2O2 low. And if you've ever stuck a super-strong magnet to an arthritic finger, you'll know that magnets relieve pain within 10 minutes and that the pain relief lasts for 2 hours (if the magnet stays in place). I doubt it heals, so i don't use them except for my wife's PMS (those industrial magnets cost $50 and they are extremely hazardous: erasing magnetic media, shattering if allowed to attract to each other, and are excellent pinchers of skin). If you ask an arthritic patient what their pain level is before entering an MRI and then ask again after, I bet you'll see a difference. The only anti-magnet reports I've seen involve foot insoles that don't have enough magnetism to hold a paper clip. I've looked for reports of pain relief from MRI but can't find any, so i'm a little skeptical despite the comments above. The MRI field is as strong as or stronger than a super-strong magnet. Polarity doesn't matter because cells don't know up down, right or left. In a strong-enough field, the electrons move in a circle with radius = m*v/q*B. The magnets i use are about 0.2 B (teslas, 2,000 gauss) beneath the skin. The charge and mass of an electron are 1.6E-19 C and 1E-30 kg. Velocity is ~800 m/s in the ~50 mV fields inside the electron transport chain and probably similar in hemoglobin oxygen delivery, which gives a radius of electron curvature to be 10 nm which is on the same scale as the protiens in the proton pump that are maybe 50 atoms wide. The 70 mV of nerve cells does not apply because it's moving heavy ions that can't be defelcted by the field.

All my comments on LED lights come from peer-reviewed journals and even the FDA approves the statement "For temporary relief of minor arthritic pain." One of the best articles shows pictures of rabbit retina with and without LED light after laser-induce injury. Low-level laser light therapy gets a lot more money in research, but it work no better than regular LED light (see Karu, et al). What's not published is that a $4 halogen light works the best because its wide-spectrum from black body radiation is the closest to the sun and you can get the necessary 4-6 J/cm^2 needed much quicker because it's more powerful/cm^2 than LED, LLLT, or the sun. 4 J/cm^2 to injuries beneath the skin means 100 to 1000 J/cm^2 is needed at surface. However, i have not yet seen pictures of any open wounds that have healed faster. Pain relief typically goes from 8 to 2 in any injury in 10 minutes with a strong-enough device. It's used in burn centers and at least a few pro-basketball teams use it for knees.

Edited by zawy, 13 January 2008 - 04:29 PM.

[zawy]

In a previous post I've showed that we need 2.7 to 3.7 times as much of the B-vitamins as fish, mice, and rats when the dose is based on dose/calorie consumed. The factor of 3.7 is based on assuming the RDA has the same factor of safety built-in as the B-vitamins supplied in the food of rats and mice. The factor 2.7 is based on comparing the RDA of niacin to the amount needed in fish to safely show maximal growth. If the RDA is twice as safe as assumed above, the factors are 1.3 and 1.8. But I want a safety factor at least as good as the RDA, so I believe 4 is a good factor for nutrients metabolized similarly to B-vitamins. This seems to me to be more accurate than the theoretical weight and suface area methods which give results either much more or much less than the above, depending on which method you use. Assuming RESV is metabolized and used like the B-vitamins, we need 500 to 1,000 mg/day to equal the high-dose group of the fish study. The important chart from that study is attached to this post. It shows no benefit from 24ug RESV / g food ( 40 mg RESV / 2000 calories using the factor of 4 above). It shows a 33% increase in lifespan when treatment began at 30% of maxiaml lifespan when using 5 times more ( 200 mg RESV / 2000 calories) and 56% increase at another 5 times increase ( 1000 mg RESV/ 2000 calories). Looking at the chart, one has to wonder if the same 23% increase will occur with another factor of 5 ( 175 years old at 5000 mg RESV / 2000 calories). By their method of food preparation (mixing larvae with RESV and a gel), i have to wonder how much of the RESV dissolved out of the food and into the water before consumption, so that such large quantities may not be needed. Also, they fed the fish only twice a day. Wouldn't they have quicker clearance? Overall i was really impressed with the quality of the article. It beats 95% of the medical literature in presentation and relevance. It's important to note that before this study, this species had never been observed to live beyond 13 weeks, and yet we have 50% of the high dose group going beyond that, still fertile with shockingly good histological results of the brain and active-avoidance measures. This research is 2 years old and involves fish you can buy off ebay. Why hasn't it been replicated 10 times by now?

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[Hedgehog]

In a previous post I've showed that we need 2.7 to 3.7 times as much of the B-vitamins as fish, mice, and rats when the dose is based on dose/calorie consumed. The factor of 3.7 is based on assuming the RDA has the same factor of safety built-in as the B-vitamins supplied in the food of rats and mice. The factor 2.7 is based on comparing the RDA of niacin to the amount needed in fish to safely show maximal growth. If the RDA is twice as safe as assumed above, the factors are 1.3 and 1.8. But I want a safety factor at least as good as the RDA, so I believe 4 is a good factor for nutrients metabolized similarly to B-vitamins. This seems to me to be more accurate than the theoretical weight and suface area methods which give results either much more or much less than the above, depending on which method you use. Assuming RESV is metabolized and used like the B-vitamins, we need 500 to 1,000 mg/day to equal the high-dose group of the fish study. The important chart from that study is attached to this post. It shows no benefit from 24ug RESV / g food ( 40 mg RESV / 2000 calories using the factor of 4 above). It shows a 33% increase in lifespan when treatment began at 30% of maxiaml lifespan when using 5 times more ( 200 mg RESV / 2000 calories) and 56% increase at another 5 times increase ( 1000 mg RESV/ 2000 calories). Looking at the chart, one has to wonder if the same 23% increase will occur with another factor of 5 ( 175 years old at 5000 mg RESV / 2000 calories). By their method of food preparation (mixing larvae with RESV and a gel), i have to wonder how much of the RESV dissolved out of the food and into the water before consumption, so that such large quantities may not be needed. Also, they fed the fish only twice a day. Wouldn't they have quicker clearance? Overall i was really impressed with the quality of the article. It beats 95% of the medical literature in presentation and relevance. It's important to note that before this study, this species had never been observed to live beyond 13 weeks, and yet we have 50% of the high dose group going beyond that, still fertile with shockingly good histological results of the brain and active-avoidance measures. This research is 2 years old and involves fish you can buy off ebay. Why hasn't it been replicated 10 times by now?

i'll do it, I haven't read the study but how do you force feed a fish resveratrol?

[zawy]

Here is the fish study:
http://www.supercent...ol-lifespan.pdf

they give a little bit of info on how they did feeding.

I just tried 1-cup, 70 calories of blueberry blended with 200 mg RESV (50%, 400 mg total) to see if 5000 mg/ 2000 calories is consumable by lab animals and humans. It's completely tolerable but seems to take away the blueberry taste. My chihuaha loves blueberries, but the smell scared her away from the bowl. She showed fairly odd and funny behavior in approaching the bowl. Kind of like a skinny guy trying to approach a gorgeous woman in a bar. Strong desire mixed with fear. Approach, retreat, approach, retreat. With 98% it should be possible to mix it in animal food at 2500 mg / 2000 calories. I reduced the 50% to 1000 mg / 2000 calorie (4 times the maximum fish dose) , and she reluctantly consumed 1/3 of it. So there will probably be problems in feeding fish doses 5 times higher than the study. If they eat less, you have a calorie restriction confounder. You need 5 tanks of 30 fish each to do it right: 0, 24, 120, 600, and 2000 ug/g of food. Preferably, 2 tanks of 30 for each condition, so 10 tanks for a great little study. They have a tendency for aggression and canniblism, so it's not completely simple.

[Hedgehog]

Here is the fish study:
http://www.supercent...ol-lifespan.pdf

they give a little bit of info on how they did feeding.

I just tried 1-cup, 70 calories of blueberry blended with 200 mg RESV (50%, 400 mg total) to see if 5000 mg/ 2000 calories is consumable by lab animals and humans. It's completely tolerable but seems to take away the blueberry taste. My chihuaha loves blueberries, but the smell scared her away from the bowl. She showed fairly odd and funny behavior in approaching the bowl. Kind of like a skinny guy trying to approach a gorgeous woman in a bar. Strong desire mixed with fear. Approach, retreat, approach, retreat. With 98% it should be possible to mix it in animal food at 2500 mg / 2000 calories. I reduced the 50% to 1000 mg / 2000 calorie (4 times the maximum fish dose) , and she reluctantly consumed 1/3 of it. So there will probably be problems in feeding fish doses 5 times higher than the study. If they eat less, you have a calorie restriction confounder. You need 5 tanks of 30 fish each to do it right: 0, 24, 120, 600, and 2000 ug/g of food. Preferably, 2 tanks of 30 for each condition, so 10 tanks for a great little study. They have a tendency for aggression and canniblism, so it's not completely simple.

Resveratrol Treatment
Sample preparation for 120 mg/food: 1.2 mg/ml resveratrol stock
was prepared in 5% ethanol and stored at 4ºC in the dark. Frozen
Chironomus larvae were thawed, left to drip dry, and aliquoted
into portions of one feeding for 10 adult fish (1 g). 100 ml of the
1.2 mg/ml stock was added to each Chironomus aliquot, which
was left at 4ºC for 1–2 hr to soak. 5% gelatine was added to the Chironomus/
resveratrol aliquot,mixed, frozen, and stored at220ºC until
use. For feeding, the frozen gelatine/Chironomus cube was
thawed in water and fed to the fish. All uneaten food was removed.
Fish received 2 feeding per day. Control-fed fishes received the
same kind of food lacking resveratrol in the stock solution. The
food consumption was approximately of 50 mg (food)/g (fish
weight)/day.

I wondering what would happen if you solubilazed resveratrol with lecithin and just added it to the tank at a certain concentration. That experiment could be done. You could take a sample of the thank water resv concentration everyday to show that resveratrol is in the water. I would assume that resveratrol might be absorbed in the gills?