44 replies to this topic

[mikeinnaples]

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.

Can* ...but won't in the vast majority of healthy people that take it.

The difference is this: Metformin has tons of research behind it and is, years of use by the general population, and proven to be one of the safest drugs out there. Resveratrol has very little actual human research behind its use.

[resveratrol_guy]

So I have a commonsense question related to the original topic of this thread. Namely, why are people so afraid of the purported apoptotic effects of resveratrol on the heart (nevermind the fact that they might not even occur, thanks to the lower-than-expected plasma concentrations that have been pointed out above)? Thanks to stem cell and other treatments, diffuse damage to the heart muscle is gradually becoming a solvable issue. But cancer remains the elephant in the room. I would much rather lose a little heart power output, than fully protect my heart, at the cost of protecting latent cancer cells as well.

For that matter, I even use resveratrol speculatively as a prophylactic postexposure treatment. For example, if I happen to get blindsided by intense paint fumes, or a burst of diesel smoke, I often elect to take an extra gram, which doubles my normal daily dose. I don't know how much statistical benefit this incurs to me, except to say that it's probably positive, particularly because it's much easier to stop a cancer when it's one or two cells, than when it's a tumor visible on an xray. Since I only do this roughly 1% of days, it doesn't make a meaningful difference to my longterm resveratrol intake. But it may, in fact, improve my longterm cancer prognosis. If you think about it, we all get the vast majority of our carcinogenic gene modifications from a tiny minority of our lives, so softening the impact of exposure spikes is of high significance to life expectancy, insofar as cancer is concerned. (I mean, is it any wonder that the oldest people in the world have a bias toward being country folk, as opposed to urbanites? But I digress.)

[Hamlet]

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.

My fasting glucose is 101 and I am going to ask my Dr. to prescribe metformin. What was your level?

If it lowers blood sugar from high normal to normal levels, that in and of itself would be life enhancing, would it not? If it also lowers cholesterol, another measurable benefit, that must also be life enhancing.

[mikeinnaples]

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.

My fasting glucose is 101 and I am going to ask my Dr. to prescribe metformin. What was your level?

If it lowers blood sugar from high normal to normal levels, that in and of itself would be life enhancing, would it not? If it also lowers cholesterol, another measurable benefit, that must also be life enhancing.

101 can give a doctor justification to write you a script in FedAce's words, ethically. Be aware though, that if you plan on getting life insurance at some point, say to fund cryonics, that you will want to delay getting a metformin script until after. The insurance won't give you a preferred rate if you are taking it unless you and your agent jump through some serious hoops, and then only if your doctor is willing to work with you and you are lucky. In other words, it could cost you quite a bit of money in the long run.

[Hamlet]

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.

My fasting glucose is 101 and I am going to ask my Dr. to prescribe metformin. What was your level?

If it lowers blood sugar from high normal to normal levels, that in and of itself would be life enhancing, would it not? If it also lowers cholesterol, another measurable benefit, that must also be life enhancing.

101 can give a doctor justification to write you a script in FedAce's words, ethically. Be aware though, that if you plan on getting life insurance at some point, say to fund cryonics, that you will want to delay getting a metformin script until after. The insurance won't give you a preferred rate if you are taking it unless you and your agent jump through some serious hoops, and then only if your doctor is willing to work with you and you are lucky. In other words, it could cost you quite a bit of money in the long run.

Thanks for the warning, I would not have thought of something so far out of left field (that's where lawyers do come in useful). Might a solution be to keep two doctor's around, one being your official "doctor of record" and another to write any scripts with potentially harmful ramifications such as you described?

[maxwatt]

...

Thanks for the warning, I would not have thought of something so far out of left field (that's where lawyers do come in useful). Might a solution be to keep two doctor's around, one being your official "doctor of record" and another to write any scripts with potentially harmful ramifications such as you described?

Bad idea. The doctor could lose his license, though it is unlikely.

This has come far afield from discussing resveratrol. Perhaps I should split the topic, into one on metformin, and put it under supplements? Any more such discussion, and I will.

[albedo]

Michael has clearly mentioned debunking of CR mimetic of resveratrol HERE. I still keep supplementing a lower dose following e.g. THIS study (4.9 mg/kg/day for mice) and applying the BSA (Body Surface Area) conversion ratio from mice to human. I think LEF uses the same conversion technique HERE (last table, just before the references). In my case (~78 kg) this gives (4.9 x 3/37) x 78 = 31 mg/d

I just wonder if I am completely wrong with the approach: not benefiting by CR mimetic and in other areas by a possible higher doses ! Comments ?

[maxwatt]

Michael has clearly mentioned debunking of CR mimetic of resveratrol HERE. I still keep supplementing a lower dose following e.g. THIS study (4.9 mg/kg/day for mice) and applying the BSA (Body Surface Area) conversion ratio from mice to human. I think LEF uses the same conversion technique HERE (last table, just before the references). In my case (~78 kg) this gives (4.9 x 3/37) x 78 = 31 mg/d

I just wonder if I am completely wrong with the approach: not benefiting by CR mimetic and in other areas by a possible higher doses ! Comments ?

I believe the LEF tables underestimate the mouse/human equivalents. The FDA figures regarding surface area were developed to determine a hopefully safe human dose for drug testing. It does not take into account different levels of enzyme activity. Humans have much more efficient sulfotransferase enzymes than mice, and so metabolize resveratrol much faster than mice. (It is more complicate than this, but you should get the idea.) From studies of serum levels, it appears the highest peak serum level a human can attain at multi-gram doses is barely equal to the area under the curve of mice given given very large doses in Auzerx' study where the mice became highly athletic at an advance age.

Short answer, you may be missing out on some benefits, particularly greater stamina and not becomming subject to mitochondrial myopathy. You may be gaining some subtle benefits at those low doses, but we do not have reports or any dramatic benefits at those doses. When resveratrol first became available in quantity, some here tried to emulate the doses use in Sirtris'human studies at 2 to 5 grams, or an estimated mouse equivalent of the same amount. Most of these people have decreased their dose to something between 500mg and 2 grams, or hae even stopped taking resveratrol. I notice definite benefits at doses over 500 mg. If I take less, my arthritis symptoms become rapidly worse, and my stamina for aerobic exercise decreases. Perhaps younger, physically active people would not notice these things.

[albedo]

Maxwatt, thank you for your educated reply and sharing of personal experience.

Even if I am sure known to this community and mostly for my own reference I attach here Sinclair's booklet (probably necessarily cautioning doses higher than 250 mg/d in general) and a study on bioavailability and toxicity in humans. I might decide to test higher does than what I am taking.

My general feeling when considering "nutraceuticals" is that it is very difficult to scientifically proof effects of molecules present in our nutrition due to the complexity of scientifically sound and long term population studies and the interaction between different nutritional components (e.g. I was reading that in Europe the EFSA (European Food Safety Authority) rejected recently more than 80% of foods benefits claims). In particular for longevity, genetics will likely help to clarify the matter when you consider (I believe this is one of the areas where Prof. Auwerx is most active) that longevity might imply more that 700 genes!

Finally, while very far to have the discipline to practice CR, which I would like, I try at least to apply subjectively what Japaneses call "Hara Hachi Bu", basically eating at 80% of your hungriness plus take the bet of a moderate supplementation of researched components.

Attached Files

•  Resveratrol Sinclair.pdf   1.31MB   80 downloads
•  resveratrol.pdf   140.88KB   46 downloads

[albedo]

.... where RES can maybe cause some joint pain or dry skin which are minor at best....

Can you point to studies or anecdotes or why at all this can be a side effect of resveratrol?

[Anthony_Loera]

Albedo,

Sinclair is a good source, however his information comes from an ebook he published way back in November of 2009.

As of February 2011 we apparently have newer references regarding dosage, from the New York Academy of Sciences:

Currently 450mg or more a day is supported by the clinical data discussed in the Annals of the New York Academy of Sciences which highlights the many functions of resveratrol (Volume 1215, resveratrol and Health - pages 131-137).


Of course you would have known that back in February, if you would have seen Dr. V's blog on our website.

Cheers
A

Edited by Anthony_Loera, 11 April 2011 - 10:03 PM.

[maxwatt]

.... where RES can maybe cause some joint pain or dry skin which are minor at best....

Can you point to studies or anecdotes or why at all this can be a side effect of resveratrol?

He cannot reply, his posting ability is suspended due to abuse.

There have been many anecdotal accounts of joint/muscle or tendon pain in this forum, but no studies mention this as a side effect that I am aware of. We believe that improving one's vitamin D status eliminates such pain, as discussed in the topics dealing with joint pain.

Dry skin has been mentioned by only the above-quoted user that I recall, too small a sample to consider it a side effect.

[albedo]

Anthony_Loera, thank you for the information. Very interesting. I imagine I cannot have access to the study without registration, right? Any chance?

Maxwatt, thank you. Now that you say it I recollect this also from the LEF forum where I go more often. Just an additional anecdote: I also developed a small join pain which I attributed to a bad movement or overexercising (it is in the rotator cuff). Did some physio and special exercise AND optimized my Vitamin D blood level; it is going better. Maybe you are are on something .....



removed bold-face style

Edited by maxwatt, 16 April 2011 - 01:55 AM.

[maxwatt]

Just to footnote this thread, but paper malbecman cited to start this topic is one of those from Dr Dipak Das' lab, and is one of those cited in the University of Connecticut report as containing faksufued data,

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

[osris]

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.

 

According to the study cited in the first post here, low dosages of resveratrol could be dangerous, given as the study claims that: 

 

"at a lower dose, resveratrol acts as an anti-apoptotic agent".

 

https://www.ncbi.nlm...les/PMC2990065/

 

I wouldn't want to be taking something that might keeps cancer cells alive.