44 replies to this topic

[malbecman]

I"ve not had time to read the whole thing, its pretty lengthy and I've just gotten back to work after the holidays. But it looks like a pretty thorough review
of many of the in vitro and in vivo studies and overall is arguing about the u-shaped curve of resveratrol's beneficial effects at low, medium and high doseages.....


Dose Response. 2010 Mar 18;8(4):478-500.
Dose-dependency of resveratrol in providing health benefits.

Mukherjee S, Dudley JI, Das DK.

Cardiovascular Research Center, University of Connecticut Health Center, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-1110, USA.
Abstract

This review describes the dose-dependent health benefits of resveratrol, a polyphenolic antioxidant that is found in a variety of foods, especially grape skin and red wine. Resveratrol provides diverse health benefits including cardioprotection, inhibition of low-density lipoprotein, activation of nitric oxide (NO) production, hindering of platelet aggregation [32] A.A.E. Bertelli, D.E. Giovannini, R.L. Caterina, W. Bernini, M. Migliori and M. Fregoni et al., Antiplatelet activity of cis-resveratrol, Drugs Exp Clin Res 22 (1996), pp. 61-63. View Record in Scopus | Cited By in Scopus (111) and promotion of anti-inflammatory effects. Studies have shown that at a lower dose, resveratrol acts as an anti-apoptotic agent, providing cardioprotection as evidenced by increased expression in cell survival proteins, improved postischemic ventricular recovery and reduction of myocardial infarct size and cardiomyocyte apoptosis and maintains a stable redox environment compared to control. At higher dose, resveratrol acts as a pro-apoptotic compound, inducing apoptosis in cancer cells by exerting a death signal. At higher doses, resveratrol depresses cardiac function, elevates levels of apoptotic protein expressions, results in an unstable redox environment, increases myocardial infarct size and number of apoptotic cells. At high dose, resveratrol not only hinders tumor growth but also inhibits the synthesis of RNA, DNA and protein, causes structural chromosome aberrations, chromatin breaks, chromatin exchanges, weak aneuploidy, higher S-phase arrest, blocks cell proliferation, decreases wound healing, endothelial cell growth by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor, and angiogenesis in healthy tissue cells leading to cell death. Thus, at lower dose, resveratrol can be very useful in maintaining the human health whereas at higher dose, resveratrol has pro-apoptotic actions on healthy cells, but can kill tumor cells.

PMID: 21191486

[hamishm00]

I guess one of the key questions is what constitutes a high dose and what is a low dose. I've been tracking this discussion for a few days now on alt.sci.life-extension.

On this group Paul Wakfer says: "I have access to the full paper from which is it clear that the horm[e]tic "sweet spot" will vary somewhat depending on the purpose intended for the resveratrol. While most of these valuable dose results are from cellular experiments and are given as micromolar amounts, the paper does maintain that the amount of resveratrol in 1-2 glasses of red wine per day would generally be a beneficial dosage, and that it would take 1.75 -3 liters daily to reach those higher levels where the resveratrol would usually have negative effects. It therefore seems clear that the beneficial daily amount is only a few mg and that 250mg would be in the harmful area for many desired effects. Since I am currently taking about twice that amount daily, I will immediately be taking measures to greatly reduce my dosage of resveratrol."

Is this also the case for what we have been discussing recently: resveratrol fighting back sarcopenia by resveratrol inducing mitochondrial biogenesis - is there a hormetic response for this as well?

The full paper is: Here

Based on this paper, are there any good reasons at all to be taking anything but a few milligrams of resveratrol daily if you are otherwise healthy?

Edited by hamishm00, 03 January 2011 - 06:02 PM.

[maxwatt]

FWIW, here are the blood serum levels Boocock found in human volunteers after administration of 0.5, 1, 2.5, or 5 g of resveratrol:


AUCinf (ng h/mL) 223.7* 544.8 (57.2) 786.5 (36.2) 1,319 (59.1)
Cmax (ng/mL) 72.6 (48.9) 117.0 (73.1) 268.0 (55.3) 538.8 (72.5)
Tmax (h) 0.833 (0.5-1.5) 0.759 (0.5-4.0) 1.375 (0.5-4.0) 1.500 (0.67-5.0)
(for Cmax, the number in parentheses is time, in minutes, to Cmax)

Link to Boocock's Paper

The mean average (Cav) and peak plasma concentrations (Cmax) of the parent molecule [resveratrol] across the four dose levels ranged from 8.4 to 52 ng/mL (0.04-0.23 μmol/L) and from 73 to 539 ng/mL (0.3-2.4 μmol/L), respectively

By comparing these to the concentrations seen in rodents or the molar concentrations in the in vitro sudies in this paper, we should be able to get a handle on what is a high versus a low dose.

Just looking at one of the studies cited in the review,

, resveratrol enhances proliferation when used at low dose (0.1–1 (g/ml) and induces apoptosis and decreases mitotic activity when used at high dose (10–100 (g/ml

I wonder if the "high" doses are attainable via oral administration. It will require going through Das' paper study by study to determine if human serum levels overlap the range of deleterious effects.

Edited by maxwatt, 03 January 2011 - 06:43 PM.
Link to paper

[malbecman]

Here is also a link to a table with all the studies cited in the paper, it's a pretty nice summary of most of the in vitro and in vivo work so far.


http://www.ncbi.nlm..../t2-drp-08-478/

[maxwatt]

Here is also a link to a table with all the studies cited in the paper, it's a pretty nice summary of most of the in vitro and in vivo work so far.


http://www.ncbi.nlm..../t2-drp-08-478/

It certainly is nice having the doses in tabular form. First pass, none of the in vitro concentrations for any of the reported effects, either positive or negative, were obtained in blood serum in Boocock's human volunteers, even at a dose of 5 grams! And average serum levels were considerable less than the peak plasma level of 539 ng/mL (2.4 μmol/L) measured at the extreme response range of a five gram dose. Are people looking an nano-grams and interpreting it as micrograms? Did they go blind counting leading zeroes?

The rodent studies, with doses in mg/kg or percent body weight, are not readily translatable to human equivalents. We know that rodents' CYP and sulfotransferase enzymes are much less efficient than in human, so the "official" equivalences based on relative body mass or surface area do not hold; the rodents' serum levels will be much higher at the putative equivalent dose.

I would appreciate other eyes looking at the numbers, but I suspect this paper is much ado about nothing: there is an inverted U-shaped response curve, and too much of anything can be bad, but the doses most people take do not begin to exceed it.

[niner]

I've been impressed by Das' work in the past, but I feel like he's run off the rails a bit here with all the red wine concern. I couldn't find the part where they recommend dosages in terms of "red wine", but I think that Fig 3 and Fig 4 contain the money shots. The "low dose" regimen where cardioprotection was observed was at 2.5 and 5mg/kg bw, and enhanced damage from ischemia was seen at 25 and 50mg/kg. If you simply take the mouse numbers and apply them to a 70 kg human, "low = 175-350 mg/day, and "high" = 1.75 - 3.5 gm/day. If you take into account the blood levels seen in dose ranging experiments with humans and mice, the amounts for humans might even be increased, though that is a speculative game. There was a big to-do over this at a cardiac conference a year or two ago, and there are probably more than a few heart patients using low dose resveratrol as we speak. I doubt we will see any good data on ischemia protection in humans any time soon. FWIW, I'm taking about 300 mg. That's only an estimate, as I've just dumped RG powder into a hardgel cap, and it's so fluffy that it doesn't pack well. (I need a flow agent..)

I don't know what they're smoking over at sci.life-extension.

[mikeinnaples]

Then you got formulations like Anthony's product that should bump up levels over powder quite a bit. Taking 250mg of that atm and I suspect I should still be in the 'low' range with that, and most definately not in the 'high' range.

[shaggy]

From the tabular format...

1 mg/kg bw Induces atherosclerosis in case of hypercholesterolemic rabbits. Wilson et al. 1996

Woah... this is worrying, is it not?

[maxwatt]

From the tabular format...

1 mg/kg bw Induces atherosclerosis in case of hypercholesterolemic rabbits. Wilson et al. 1996

Woah... this is worrying, is it not?

It would be worrying if I were a hypercholesterolemic rabbit. They fed them a diet they are not metablically equipped to deal with to induce hypercholesterolemia, so drawing conclusions as o causality is not staight-forward. We do not know the dose equivalent for rabbits, and it is a fairly old study from 1996. I have yet to find a recent study with similar results, though I tried.

[niner]

1 mg/kg bw Induces atherosclerosis in case of hypercholesterolemic rabbits. Wilson et al. 1996

Woah... this is worrying, is it not?

It would be worrying if I were a hypercholesterolemic rabbit. They fed them a diet they are not metablically equipped to deal with to induce hypercholesterolemia, so drawing conclusions as o causality is not staight-forward. We do not know the dose equivalent for rabbits, and it is a fairly old study from 1996. I have yet to find a recent study with similar results, though I tried.

Yes, I'd be inclined to ignore this study, since it's never been replicated in any system to my knowledge. It's such a low dose and there isn't a mechanistic explanation, so it's most likely erroneous.

[health_nutty]

It seems like the dosages have come full circle.

[hamishm00]

Since I quoted Wakfer in a recent post, it is fair that he's quoted in a follow up post he has made on alt.sci.life-extension:

I decided that I could not wait any longer and quickly read the paper myself. Here is the text of the summary conclusion of the paper:

"There are numerous plant-derived natural components, vitamins and minerals whose daily allowance requirement are safe and promote good health when taken at a low dose. When the same substances are taken at a high dose, they become toxic and produce adverse effects to the cells at the subcellular levels. Similarly resveratrol is good for health but the health benefit of resveratrol is dose-dependent. Low doses resveratrol protect health from different types of diseases, while high doses resveratrol can be detrimental for health. However, high dose resveratrol may be required in pathological conditions such as destroying cancer cells."

The low beneficial dose is 2.5-5 mg/kg body wt for a rat, which I translate into about 0.6-1.2 mg/kg for a human. At dosages more than 10 times the low dose, the beneficial effects are less and some negative effects begin. As sufficiently high dosages resveratrol is liver toxic, but these doses are way beyond anything anyone has been taking, AFAIK.

As soon as I can reorganize my supplements, I will reduce my dosage to below 50 mg daily.

--Paul Wakfer

[maxwatt]

Since I quoted Wakfer in a recent post, it is fair that he's quoted in a follow up post he has made on alt.sci.life-extension:

I decided that I could not wait any longer and quickly read the paper myself. Here is the text of the summary conclusion of the paper:

"There are numerous plant-derived natural components, vitamins and minerals whose daily allowance requirement are safe and promote good health when taken at a low dose. When the same substances are taken at a high dose, they become toxic and produce adverse effects to the cells at the subcellular levels. Similarly resveratrol is good for health but the health benefit of resveratrol is dose-dependent. Low doses resveratrol protect health from different types of diseases, while high doses resveratrol can be detrimental for health. However, high dose resveratrol may be required in pathological conditions such as destroying cancer cells."

The low beneficial dose is 2.5-5 mg/kg body wt for a rat, which I translate into about 0.6-1.2 mg/kg for a human. At dosages more than 10 times the low dose, the beneficial effects are less and some negative effects begin. As sufficiently high dosages resveratrol is liver toxic, but these doses are way beyond anything anyone has been taking, AFAIK.

As soon as I can reorganize my supplements, I will reduce my dosage to below 50 mg daily.

--Paul Wakfer

The problem is he is assuming a 4:1 equivalency in rat dose per kilogram to human dose per kilogram body weight. This is the ratio used for toxicology studies, determined by estimated metabolic rate inferred from factors such as relative body mass and surface area as stand-ins for metabolic rate. It does not take into account different efficiencies for enzymes that process a substance. Humans have much more efficient CYP and sulfotransferase enzymes than do rats and mice. A more accurate equivalency can perhaps be determined by looking at the blood serum levels measured after a given dose of the substance, and distinguishing oral administration from injection (which gives much higher peak values for a given dose.) See my earlier post, above. While it is wise to err on the side of caution, nothing in these papers indicates a human dose of less than two or three grams will be problematic -- and that is still somewhat conservative. Das is being alarmist IMO. Paul usually is much more critically discerning; I am surprised at his response.

On the other hand, I don't recommend everyone go out and take 2 grams of resveratrol a day. If you intend to use this substance, you should have a clear idea of what benefits you expect from it, you should start with a low dose and gradually increase to your target dose, and ideally you should have some means of measuring your response. If it doesn't work stop using it. This applies to any supplement.

Edited by maxwatt, 08 January 2011 - 06:01 PM.

[FedAce]

At what dose does RES promote Cancer like Lymphoma ?? and what is considered Low dose ??? and what happens at Medium dose ?

[maxwatt]

At what dose does RES promote Cancer like Lymphoma ?? and what is considered Low dose ??? and what happens at Medium dose ?

I thought the post before yours answered your questions on dosage.

We have no evidence of cancer promotion at any dose in vivo. Cancer promotion in cells in culture was seen at much higher concentration than can be achieved from oral administration.

[FedAce]

At what dose does RES promote Cancer like Lymphoma ?? and what is considered Low dose ??? and what happens at Medium dose ?

I thought the post before yours answered your questions on dosage.

We have no evidence of cancer promotion at any dose in vivo. Cancer promotion in cells in culture was seen at much higher concentration than can be achieved from oral administration.

Max, do you know or recommend any other supplements to fighting aging or to improve brain function other than RES ? thank you so much

[maxwatt]

Max, do you know or recommend any other supplements to fighting aging or to improve brain function other than RES ? thank you so much

My own belief is that metformin could help a lot, though it is a prescription medicine. It is readily obtainable, especially if your blood sugar is a little high. The dangers of lactic acidosis seem to be greatly exaggerated. I am not using it myself at this time, but am considering it.

Curcumin is showing great promise, I know people are working on increasing its bioavailability. Tetrahydrocurcumin has extend the lifespan of healthy mice on a standard diet and won the study's author the Hayflick award for 2006. This was overshadowed by Sinclair's showmanship for reseratrol. I am planning to experiment with this one. I think it's been neglected. Telomerase activators would be on my list if there were stronger evidence for them, Other potential beneficial polyphenols include myricetin (reduces glucose by the same mechanism as metformin) and luteolin (anti cancer, induces SIRT1, may augment the effect of resveratrol via sulfotransferase inhibition.)

Caution: just taking polyphenols isn't guaranteed to make you live longer. Even if several of them are helpful, taking them together may cancel out their effects. It's not been studied, and I do not believe in magic or intuition somehow bringing about an elixer of life. In fact, just ensuring you get an adequate magnesium intake may do more for your longevity, or taking a methyl folate supplement if you have the MTHFR genetic polymorphism. I take both.

[FedAce]

Max, do you know or recommend any other supplements to fighting aging or to improve brain function other than RES ? thank you so much

My own belief is that metformin could help a lot, though it is a prescription medicine. It is readily obtainable, especially if your blood sugar is a little high. The dangers of lactic acidosis seem to be greatly exaggerated. I am not using it myself at this time, but am considering it.

Curcumin is showing great promise, I know people are working on increasing its bioavailability. Tetrahydrocurcumin has extend the lifespan of healthy mice on a standard diet and won the study's author the Hayflick award for 2006. This was overshadowed by Sinclair's showmanship for reseratrol. I am planning to experiment with this one. I think it's been neglected. Telomerase activators would be on my list if there were stronger evidence for them, Other potential beneficial polyphenols include myricetin (reduces glucose by the same mechanism as metformin) and luteolin (anti cancer, induces SIRT1, may augment the effect of resveratrol via sulfotransferase inhibition.)

Caution: just taking polyphenols isn't guaranteed to make you live longer. Even if several of them are helpful, taking them together may cancel out their effects. It's not been studied, and I do not believe in magic or intuition somehow bringing about an elixer of life. In fact, just ensuring you get an adequate magnesium intake may do more for your longevity, or taking a methyl folate supplement if you have the MTHFR genetic polymorphism. I take both.

Thank you Max. I will look into Curcumin. but I cannot recommend Metformin for you. Currently this is a Prescription medication for Type 2 Diabetic patients. and yes Lactic acidosis is rare in younger patients. but in Older patients with Kidney failure, it is a real danger. and actually manufacturer states Metformin is contraindicated in patients with renal failure. and if you are not diabetic, i highly recommend against using this. It can lower your sugar and put you at risk for Hypoglycemia which means low sugar. That can cause you to faint or feel dizzy and that is very dangerous if happens when you are not expecting it like whlie you are driving for instance.

[maxwatt]

...

Thank you Max. I will look into Curcumin. but I cannot recommend Metformin for you. Currently this is a Prescription medication for Type 2 Diabetic patients. and yes Lactic acidosis is rare in younger patients. but in Older patients with Kidney failure, it is a real danger. and actually manufacturer states Metformin is contraindicated in patients with renal failure. and if you are not diabetic, i highly recommend against using this. It can lower your sugar and put you at risk for Hypoglycemia which means low sugar. That can cause you to faint or feel dizzy and that is very dangerous if happens when you are not expecting it like whlie you are driving for instance.

Thanks for your concern. I would only use it with my doctors' help,and use of a glucose meter.

[FedAce]

...

Thank you Max. I will look into Curcumin. but I cannot recommend Metformin for you. Currently this is a Prescription medication for Type 2 Diabetic patients. and yes Lactic acidosis is rare in younger patients. but in Older patients with Kidney failure, it is a real danger. and actually manufacturer states Metformin is contraindicated in patients with renal failure. and if you are not diabetic, i highly recommend against using this. It can lower your sugar and put you at risk for Hypoglycemia which means low sugar. That can cause you to faint or feel dizzy and that is very dangerous if happens when you are not expecting it like whlie you are driving for instance.

Thanks for your concern. I would only use it with my doctors' help,and use of a glucose meter.

Is it worth that much to you ? Are you Diabetic ? No reputable doctor will give you Metformin unless you have a diagnosis of diabetes. I cannot see why metformin is so good that you are risking hypoglycemia. people can die from it. and dangerous low blood sugar is different for every patient. Some patients i have seen go into fainty spells at sugar around 70 even. and some people Blood sugar of 70 is perfectly fine to them.

[mikeinnaples]

Thank you Max. I will look into Curcumin. but I cannot recommend Metformin for you. Currently this is a Prescription medication for Type 2 Diabetic patients. and yes Lactic acidosis is rare in younger patients. but in Older patients with Kidney failure, it is a real danger. and actually manufacturer states Metformin is contraindicated in patients with renal failure. and if you are not diabetic, i highly recommend against using this. It can lower your sugar and put you at risk for Hypoglycemia which means low sugar. That can cause you to faint or feel dizzy and that is very dangerous if happens when you are not expecting it like whlie you are driving for instance.

If you are older WITH kidney failure or if you have renal failure it is contraindicated. Your recommendations is absolutely silly not to take it unless these specific conditions apply to you. The increased risk for hypoglycemia is also extremely low, to the point of it being a non issue for most healthy people.


Edit: You are basically telling someone without renal failure and without kidney failure that they shouldnt take a LE drug with considerable upside because it is contraindicated for people that have renal or kidney failure. There are other valid reasons for someone not to take Metformin, but this argument of yours absolutely is not one of them.

Edited by mikeinnaples, 12 January 2011 - 01:17 PM.

[mikeinnaples]

Is it worth that much to you ? Are you Diabetic ? No reputable doctor will give you Metformin unless you have a diagnosis of diabetes. I cannot see why metformin is so good that you are risking hypoglycemia. people can die from it. and dangerous low blood sugar is different for every patient. Some patients i have seen go into fainty spells at sugar around 70 even. and some people Blood sugar of 70 is perfectly fine to them.

Again, this is absolutely silly and only a doctor in the stone ages wouldn't write a script for metformin given good reason, reasonable dosage, and bi-annual blood work. Good reasons being the following: pre-diabetic conditions, diabetes, PCOS, and off label use for both cholesterol and to reduce long term cancer risk. Metformin is one of the safest and most tested drugs on the market and it absolutely safe for most people. As long as you are under the supervision of your doctor or getting your own blood work done, there is absolutely no reason whatsoever not to take Metformin for life extension purposes. Lactic Acidosis is a non factor in non diabetics and hypoglycemia is a non issue for the vast majority of healthy people taking metformin for LE purposes.

[maxwatt]

Agree with Mike. I believe aspirin is more risky than metformin for most people, and it wouldn't receive FDA approval if it were introduced today.

More on metformin in this thread, HERE.

Edited by maxwatt, 12 January 2011 - 01:34 PM.

[FedAce]

Is it worth that much to you ? Are you Diabetic ? No reputable doctor will give you Metformin unless you have a diagnosis of diabetes. I cannot see why metformin is so good that you are risking hypoglycemia. people can die from it. and dangerous low blood sugar is different for every patient. Some patients i have seen go into fainty spells at sugar around 70 even. and some people Blood sugar of 70 is perfectly fine to them.

Again, this is absolutely silly and only a doctor in the stone ages wouldn't write a script for metformin given good reason, reasonable dosage, and bi-annual blood work. Good reasons being the following: pre-diabetic conditions, diabetes, PCOS, and off label use for both cholesterol and to reduce long term cancer risk. Metformin is one of the safest and most tested drugs on the market and it absolutely safe for most people. As long as you are under the supervision of your doctor or getting your own blood work done, there is absolutely no reason whatsoever not to take Metformin for life extension purposes. Lactic Acidosis is a non factor in non diabetics and hypoglycemia is a non issue for the vast majority of healthy people taking metformin for LE purposes.

You got it all wrong. I am not saying max shouldn't take it cause he is old or has kidney failure. If these conditions exist, it is an absoute contra-indication. but relatively healthy person should not take Metformin unless they are diabetic. BECAUSE, Diabetes is the only FDA approved indication for this drug. and It is a Prescription Drug. Only MD can write for it and then you can go get it from walgreens. Any reputable MD will not give it to you unless you have a diagnosis of Diabetes because that is the only FDA approved indication. and YES, doctors do use prescription drugs for Non-FDA uses, i KNOW. but to increase life span is not any medically indicated use. I thought you guys had some medical training but i see now that you guys know very little about medical world and how we operate. I too have read the benefit that Metformin might have on longevity and overall health. but metformin cannot be used for that purpose til there is a Good Controlled double blind study behind it. WHY ??? because Metformin is a Prescription drug not a health food or herbal product.

[mikeinnaples]

but relatively healthy person should not take Metformin unless they are diabetic. BECAUSE, Diabetes is the only FDA approved indication for this drug. and It is a Prescription Drug. Only MD can write for it and then you can go get it from walgreens. Any reputable MD will not give it to you unless you have a diagnosis of Diabetes because that is the only FDA approved indication. and YES, doctors do use prescription drugs for Non-FDA uses, i KNOW. but to increase life span is not any medically indicated use. I thought you guys had some medical training but i see now that you guys know very little about medical world and how we operate. I too have read the benefit that Metformin might have on longevity and overall health. but metformin cannot be used for that purpose til there is a Good Controlled double blind study behind it. WHY ??? because Metformin is a Prescription drug not a health food or herbal product.

First and foremost, the FDA is a bloated, mostly ineffective agency bogged down by bureaucratic red tape. I can tell you this first hand. While the FDA is absolutely needed and many of the controls it mandates are extremely good, it is not cutting edge by any means. Also, not everyone lives in the United States and this is not a United States only forum AND Metformin is a over the counter medication in many countries. Regarding the safety of this specific medication, it has with stood the test of time, millions of written prescriptions/patients, and libraries of research. I do understand your sentiment, but in the case of Metformin, it is silly. Its not like we are discussing a brand new drug that hasn't been tested. Take some time and read through the research that is out there, it might take a while as there is literally a library of it ....but it might change your mind.

Secondly, your statement that reputable doctors ONLY write scripts for Metformin for diabetes is silly blatantly wrong. Metformin scripts are being written by reputable doctors for off label use constantly for PCOS, fatty liver disease, and cholesterol (especially if combined with slightly elevated glucose ...but not high enough to deserve treatment outright). In addition, REPUTABLE doctors that are not stuck in the stone ages understand that the upside associated with reasonable Metformin usage greatly out weighs the downside, which is minimal. A GOOD doctor will recognize when a patient is determined to take a medication for off label use, and given the negligable risk, he/she will work with the patient to ensure proper lab work gets done.

FedAce ...are you an FDA employee? This is the only reasonable cause I have for understanding your responses.

Edited by mikeinnaples, 13 January 2011 - 01:26 PM.

[mikeinnaples]

FedAce -

One more thing. If step outside of the United States (remember this is not a USA only forum) and the reign of the FDA, can you tell me exactly what the difference is between Metformin and Resveratrol?

[FedAce]

but relatively healthy person should not take Metformin unless they are diabetic. BECAUSE, Diabetes is the only FDA approved indication for this drug. and It is a Prescription Drug. Only MD can write for it and then you can go get it from walgreens. Any reputable MD will not give it to you unless you have a diagnosis of Diabetes because that is the only FDA approved indication. and YES, doctors do use prescription drugs for Non-FDA uses, i KNOW. but to increase life span is not any medically indicated use. I thought you guys had some medical training but i see now that you guys know very little about medical world and how we operate. I too have read the benefit that Metformin might have on longevity and overall health. but metformin cannot be used for that purpose til there is a Good Controlled double blind study behind it. WHY ??? because Metformin is a Prescription drug not a health food or herbal product.

First and foremost, the FDA is a bloated, mostly ineffective agency bogged down by bureaucratic red tape. I can tell you this first hand. While the FDA is absolutely needed and many of the controls it mandates are extremely good, it is not cutting edge by any means. Also, not everyone lives in the United States and this is not a United States only forum AND Metformin is a over the counter medication in many countries. Regarding the safety of this specific medication, it has with stood the test of time, millions of written prescriptions/patients, and libraries of research. I do understand your sentiment, but in the case of Metformin, it is silly. Its not like we are discussing a brand new drug that hasn't been tested. Take some time and read through the research that is out there, it might take a while as there is literally a library of it ....but it might change your mind.

Secondly, your statement that reputable doctors ONLY write scripts for Metformin for diabetes is silly blatantly wrong. Metformin scripts are being written by reputable doctors for off label use constantly for PCOS, fatty liver disease, and cholesterol (especially if combined with slightly elevated glucose ...but not high enough to deserve treatment outright). In addition, REPUTABLE doctors that are not stuck in the stone ages understand that the upside associated with reasonable Metformin usage greatly out weighs the downside, which is minimal. A GOOD doctor will recognize when a patient is determined to take a medication for off label use, and given the negligable risk, he/she will work with the patient to ensure proper lab work gets done.

FedAce ...are you an FDA employee? This is the only reasonable cause I have for understanding your responses.

I knew you were going to say that. of course, doctors write Off Label uses all the time, for ALL drugs not just metformin. but that is different than just giving metformin to someone for Prolonging life or for Health benefits. Do you get the difference ??? One is giving metformin for Known diagnosed DIsease that patient has like fatty liver, and the other is for patient that has nothing wrong and just wants to take it for Possible benefits like prolonging life or something like that. ONE is Legal and the Other is ILLEGAL. and to the physician who has taken the Oath, one is Ethical and the other is Not ethical. You had to have gone to medical school to understand this concept.

[FedAce]

FedAce -

One more thing. If step outside of the United States (remember this is not a USA only forum) and the reign of the FDA, can you tell me exactly what the difference is between Metformin and Resveratrol?

Huge difference. Metformin can lower blood sugar and cause you faint and get into accident and end up in hospital. where RES can maybe cause some joint pain or dry skin which are minor at best. RES doesn't cause lymphoma according to Max unless you take Mass quantity.

[david ellis]

I knew you were going to say that. of course, doctors write Off Label uses all the time, for ALL drugs not just metformin. but that is different than just giving metformin to someone for Prolonging life or for Health benefits. Do you get the difference ??? One is giving metformin for Known diagnosed DIsease that patient has like fatty liver, and the other is for patient that has nothing wrong and just wants to take it for Possible benefits like prolonging life or something like that. ONE is Legal and the Other is ILLEGAL. and to the physician who has taken the Oath, one is Ethical and the other is Not ethical. You had to have gone to medical school to understand this concept.

My doctor wrote me a metformin prescription because I had high normal blood sugar, does that cross the line? Just curious, because I would like to understand better the line between legal and illegal. I don't take metformin anymore because it upsets my stomach. I don't take any substance that makes me feel sick because of doubts that it truly is life enhancing.

[mikeinnaples]

ONE is Legal and the Other is ILLEGAL. and to the physician who has taken the Oath, one is Ethical and the other is Not ethical. You had to have gone to medical school to understand this concept.

Illegal in which country an unethical according to who? Medical school where? This isnt an american only forum.