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Metformin (Barely) Extends (Mean) Lifespan

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#1 Michael

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Posted 31 July 2013 - 07:51 PM


Metformin once again fails to live up to hopes, as it did once before ((1), and this post on the previous competent metformin lifespan study), tho' this new disappointment is not as severe.

I had been told some time ago that Rafal de Cabo and colleagues had gotten life extension out of their lower dose of metformin, and assumed that this meant something at least as impressive as rapamycin (which, unlike metformin, is pretty grossly toxic and self-evidently inappropriate for self-experimentation). I went to various online pharmacies several times, gazing indecisively at the proferred pills of uncertain provenance, and almost bought the stuff, generally pulling back because I hadn't seen the results, and because of the obvious possibility that a person already on CR might already be maxing out these pathways (tho' I thought this not very likely, since humans are clearly not as eat-your-young hungry as mice on 40% CR are), or that people on CR might be put at risk by doing so (eg, by inhibiting gluconeogenesis when we have no other source of energy, leading to a hypoglycemic crisis (tho' these are not reported for diabetics on metformin)). I also considered buying a bunch just in case there was a rush on the stuff when the study came out.

I guessed I should'a realized when one of the authors told me that it was coming out in Nature Communications and not Nature that the result wasn't going to be earth-shattering.

This (2) really isn't much of anything: they got a 4-6% increase in MEAN LS depending on the mouse strain, and no increase in max; moreover, "male mice treated with 0.1% metformin in both longevity studies did not show any major difference in pathologies at 115 weeks of age nor obvious causes of death in the necropsies compared with SD-fed animals."

Based on two different allometric scaling methods and some reasonable-seeming assumptions about body weight and food intake that turned out to be pretty damned good guesses, I'd calculated that the 'low-dose' Met that got life extension (0.1% of diet) was significantly lower than a standard starter dose for diabetics (and thus probably low-risk). Yet say that even the 'low-dose' metformin "yielded a concentration of 0.45±0.09 mM in serum and 0.49±0.06 nmoles mg−1 protein in the liver ... which is considerably higher than seen in the serum of diabetic patients treated with metformin [my emphasis]". Granted that high-dose metformin shortened life, it's not at all clear to me what rational basis one would have for determining a dose for self-experimentation.

"Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake." I think I'll keep eating healthily and exercising, and wait for something a bit less trivial.

References

1: Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB.
Metformin supplementation and life span in Fischer-344 rats. J Gerontol A Biol
Sci Med Sci. 2010 May;65(5):468-74. doi: 10.1093/gerona/glq033. Epub 2010 Mar 19.
PubMed PMID: 20304770; PubMed Central PMCID: PMC2854888.
http://www.ncbi.nlm....les/PMC2854888/

2. Alejandro Martin-Montalvo, Evi M. Mercken, Sarah J. Mitchell, Hector H. Palacios, Patricia L. Mote, Morten Scheibye-Knudsen, Ana P. Gomes, Theresa M. Ward, Robin K. Minor, Marie-José Blouin, Matthias Schwab, Michael Pollak, Yongqing Zhang, Yinbing Yu, Kevin G. Becker, Vilhelm A. Bohr, Donald K. Ingram, David A. Sinclair, Norman S. Wolf, Stephen R. Spindler, Michel Bernier & Rafael de Cabo
Metformin improves healthspan and lifespan in mice
Nature Communications 4, Article number: 2192
doi:10.1038/ncomms3192
http://www.nature.co...ncomms3192.html
Published 30 July 2013
PMID 23900241‎

Edited by Michael, 07 February 2014 - 08:05 PM.

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#2 James Cain

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Posted 31 July 2013 - 08:38 PM

As usual, thanks for that shrewd analysis, Michael.

This is a very good point:

Granted that high-dose metformin shortened life, it's not at all clear to me what rational basis one would have for determining a dose for self-experimentation.



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#3 Andey

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Posted 01 August 2013 - 08:05 AM

First study shows that CR rats group also didnt increase MAX lifespan but you forgot to mention it ) Metformin rat group didnt show any decrease in glucose or affect insulin numbers and shows that may be study fail in metformin administration way or this rat strain is unresponsive for it. So if I would start use metformin and glucose levels would decrease for me than this study is completely useless in my case. (I think its a case for majority of people)

I found your posts in general are very biased against anything other than CR.

Edited by Andey, 01 August 2013 - 08:06 AM.

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#4 Michael

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Posted 01 August 2013 - 03:25 PM

First study shows that CR rats group also didnt increase MAX lifespan but you forgot to mention it )

I raised and addressed that issue, as well as the lack of effect on glucoregulation that you mention below, in the post I linked. Don't make assertions about what I haven't addressed when you haven't looked at the materials where I address them.

Metformin rat group didnt show any decrease in glucose or affect insulin numbers and shows that may be study fail in metformin administration way or this rat strain is unresponsive for it.


That wasn't a crazy hypothesis at the time the rat study came out. However, (a) it's at least equally reasonable, and on first principles more so, to expect that there would be no effect on glucoregulation in nondiabetic animals: indeed, metformin has no effect on glucoregulation in obese women with normal glucose tolerance(1) and only modest effects on fasting glucose in normal-weight, normoglycemic men(2); and (b) in the new study, metformin did lower HbA1c and improve OGTT and ITT (despite not lowering fed or fasting glucose measures — consistent with its primarily anti-gluconeogenic action), and it still had no meaningful effect on lifespan.

I found your posts in general are very biased against anything other than CR.


I think an objective reading would be that I am against things that don't actually work when tested, and also against hype about things that haven't been proven or that are pumped up on flimsy evidence. I was cautiously optimistic that metformin might extend lifespan for many years (see eg. here and here, and more recently here), and still held out hopes about it after the failure in rats, in large part for the very reasons you mention. We now have one study reporting no effect in longevous nondiabetic rats, and two independent studies (by Spindler and by de Cabo, reported jointly in the new Nature Communications paper) finding that it has a trivial effect in two strains of longevous nondiabetic mice. I think it's clear at this point that self-experimentation by healthy nondiabetic humans cannot be regarded as a rational risk.

References
1: Binnert C, Seematter G, Tappy L, Giusti V. Effect of metformin on insulin sensitivity and insulin secretion in female obese patients with normal glucose tolerance. Diabetes Metab. 2003 Apr;29(2 Pt 1):125-32. PubMed PMID: 12746632.

2: Fruehwald-Schultes B, Oltmanns KM, Toschek B, Sopke S, Kern W, Born J, Fehm HL, Peters A. Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabolism. 2002 Apr;51(4):531-6. PubMed PMID: 11912566.

Edited by Michael, 07 February 2014 - 08:03 PM.

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#5 Andey

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Posted 01 August 2013 - 05:23 PM


1: Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB.
Metformin supplementation and life span in Fischer-344 rats.
First study looks compromised for me. You cannot expect to show wheather metformin mimicking CR effects or not in setup where you cant get almost any effect from CR itself. I cannot draw any conclusion based on this, only that money and efforts are not well spent on this study.

Unfortunatly I cannot see full text of second study but Abstact part looks rather promising
"Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging.."
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#6 Kevnzworld

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Posted 01 August 2013 - 05:47 PM

Unfortunatly I cannot see full text of second study but Abstact part looks rather promising
"Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging.."


As a middle aged male that can't and won't live a CR lifestyle, I will continue to take metformin . The above reinforces that opinion.
The anti cancer effects of Metformin are also impressive. It has helped me lower my post prandial glucose levels and HbA1C.
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#7 drtom

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Posted 03 August 2013 - 07:01 AM

I am also a non-diabetic, middle-aged male. I do practice Alternate Day Fasting, but also take 250mg metformin.
I find it does affect my plasma glucose level although I am more interested in the other effects, such as increased AMPK activity and reduced inflammation.

#8 garcia

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Posted 04 August 2013 - 12:37 PM

drtom, do you take the 250mg in one dose or split between two doses? Presumably you half a 500mg tablet to get the 250mg? Have you tried any other dosages? I too am interested in the AMPK activity and reduced inflammation (rather than glucose reduction). Many thanks.

#9 Kevnzworld

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Posted 07 September 2013 - 07:57 PM

I take 500mg of Metformin CR twice per day. My latest fasting glucose measurement was 86, whereas it had always been low 90's before. There are a lot of factors which can influence FBG readings obviously.
It's also good to measure fasting insulin and HbA1C, glucose tolerance, and post prandial glucose to get a more complete picture.
Metformin is one of the most prescribed drugs in history worldwide, and it maintains a relatively good safety profile. I started out with half my current dose to determine my personal tolerability before increasing to my current dosage.
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#10 Kevnzworld

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Posted 19 December 2013 - 08:10 AM

" NIH researchers find diabetes drug extends health and lifespan in mice"
This study was published July 2013

Quote" on a standard diet with no metformin. The 1 percent metformin treatment had the opposite effect. These mice had a 14.4 percent shorter lifespan compared to the control group, likely due to kidney failure. The lower metformin dose did not seem to cause any negative effect on the renal system.
A battery of tests performed with male mice taking 0.1 percent, 1 percent, or no metformin starting at middle age, revealed a clear health benefit of the 0.1 percent treatment. These mice had improved general fitness and weighed less than the control group mice, despite consuming more calories. Metformin increased their use of fat for energy. Mice on metformin tended to preserve body weight with age, a characteristic associated with increased survival in other studies. They had a lower incidence of cataracts, a common health problem in the strain of mouse. Not surprisingly, metformin prevented the onset of metabolic syndrome. It had similar effects as calorie restriction on genes in the liver and muscles, which induced longevity-associated activity in the mice. Metformin also appeared to have some antioxidant effects in the mice."

http://www.nia.nih.g...d-lifespan-mice

Edited by Kevnzworld, 19 December 2013 - 08:13 AM.


#11 Kevnzworld

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Posted 19 December 2013 - 04:10 PM

" NIH researchers find diabetes drug extends health and lifespan in mice "
July 31 2013

I left out the quote that included the % lifespan increase. The study was conducted only on middle aged male mice.

" In this study, researchers found male mice on a 0.1 percent metformin treatment had a 5.83 percent increase in lifespan compared to control group mice on a standard diet with no metformin. "

http://www.nia.nih.g...d-lifespan-mice
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#12 Andey

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Posted 19 December 2013 - 04:56 PM

Thanks

" In this study, researchers found male mice on a 0.1 percent metformin treatment had a 5.83 percent increase in lifespan compared to control group mice on a standard diet with no metformin. "

not bad for "barely extends" )
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#13 InquilineKea

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Posted 28 December 2013 - 09:23 AM

Does anyone know if its effects on healthspan are greater than its effects on lifespan? I wouldn't be surprised if it improved healthspan more than lifespan.

Though this quote is telling (and suggests no improvement in healthspan). I'll add that I know that Rafel de Cabo published a study showing that CR increases healthspan but not necessarily lifespan (and I also talked to him, where he basically said that to me).

This (2) really isn't much of anything: they got a 4-6% increase in MEAN LS depending on the mouse strain, and no increase in max; moreover, "male mice treated with 0.1% metformin in both longevity studies did not show any major difference in pathologies at 115 weeks of age nor obvious causes of death in the necropsies compared with SD-fed animals."


One thing I'm confused about: I know that metformin works better in diabetics than non-diabetics. Yet - metformin's primary effect is that it suppresses gluconeogenesis (though upregulating AMPK is another mechanism too). Shouldn't gluconeogenesis be highest when blood sugar is lowest? i know that this may be dysregulated in diabetics, but this would also make it seem like metformin's effects would be strongest when glucose levels are lowest (aka in non-diabetics). And we know that hypoglycemia is a rare side effect of metformin.

==

Anyways - I'm wondering - is metformin even worth taking if I normally have glycated hemoglobin values at around 4.9-5.0? I suppose I could just try and test it after a month of taking it.

Edited by InquilineKea, 28 December 2013 - 09:27 AM.


#14 Kevnzworld

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Posted 28 December 2013 - 11:28 PM

Does anyone know if its effects on healthspan are greater than its effects on lifespan? I wouldn't be surprised if it improved healthspan more than lifespan.

Anyways - I'm wondering - is metformin even worth taking if I normally have glycated hemoglobin values at around 4.9-5.0? I suppose I could just try and test it after a month of taking it.

The study I quoted ( above ) demonstrated a significant health span improvement for the mice in the study
" These mice had improved general fitness and weighed less than the control group mice, despite consuming more calories. Metformin increased their use of fat for energy. Mice on metformin tended to preserve body weight with age, a characteristic associated with increased survival in other studies. They had a lower incidence of cataracts, a common health problem in the strain of mouse. Not surprisingly, metformin prevented the onset of metabolic syndrome. "

The study with male mice as well as other studies suggest a 5-6% increase in lifespan. I believe it's worth considering for its ability to inhibit cancer.

"New Users of Metformin Are at Low Risk of Incident Cancer
A cohort study among people with type 2 diabetes"
http://care.diabetes...32/9/1620.short
"Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission"
http://cancerres.aac...9/19/7507.short
"Metformin use and prostate cancer in Caucasian men: results from a population-based case–control study---
Metformin use was associated with a borderline significant decrease in the relative risk of PCa in Caucasians."

The studies that show Metformin's efficacy are primarily with type 2 diabetics given that's the population that it's prescribed to. I don't see why it wouldn't be as effective in non diabetics .

Edited by Kevnzworld, 28 December 2013 - 11:37 PM.


#15 InquilineKea

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Posted 29 December 2013 - 02:41 AM

Hmm.. good points.. those are a lot more convincing.. I'm considering getting some from bmpharmacy then...

The one issue is that I'm 93 lbs (BMI of 16.5). But I guess I'll see if it really hurts my appetite after taking it.

#16 tintinet

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Posted 01 January 2014 - 08:22 PM

It quite dramatically reduced my appetite for the initial 2 weeks after I started taking it at a relatively low dose (250 mg QD), but that effect diminished over time.

#17 albedo

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Posted 27 March 2014 - 04:44 PM

I take 500mg of Metformin CR twice per day.... I started out with half my current dose to determine my personal tolerability before increasing to my current dosage.

And at which time you take it Kevnzworld? Just before the two main meals or?

#18 Kevnzworld

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Posted 27 March 2014 - 04:53 PM

I take 500mg of Metformin CR twice per day.... I started out with half my current dose to determine my personal tolerability before increasing to my current dosage.

And at which time you take it Kevnzworld? Just before the two main meals or?


Yes. Before lunch and dinner. An update though. Metformin lowers NAD, so I think it's important to take some form of niacin. I prefer nicotinamide riboside , but nicotinamide is also ok. I take that in the AM. As has been written previously, Mefformin can deplete B vitamins and raise homocysteine , so take B12, methyl folate etc.
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#19 InquilineKea

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Posted 13 April 2014 - 04:34 AM

Couldn't metformin actually increase the rate of beta-amyloid accumulation? See http://pipeline.cora...imers_worse.php

 

Given the modest benefits of metformin, I'm not sure if we could recommend it until we can clear it of this association.

 

Also, Matt Kaeberlein seems pretty bearish on metformin's ability to increase lifespan (though he's a very pro-rapamycin person).


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#20 Kevnzworld

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Posted 13 April 2014 - 07:15 AM

Couldn't metformin actually increase the rate of beta-amyloid accumulation? See http://pipeline.cora...imers_worse.php
 
Given the modest benefits of metformin, I'm not sure if we could recommend it until we can clear it of this association.
 
Also, Matt Kaeberlein seems pretty bearish on metformin's ability to increase lifespan (though he's a very pro-rapamycin person).


Re: Metformin and Alzheimer's , there is this
" In summary, our data suggest a potential beneficial role of biguanides such as metformin in the prophylaxis and/or therapy of AD."
http://www.pnas.org/...793107.full.pdf
There aren't any published studies that I've found that have shown an increase in dementia or Alzheimer's in diabetics treated with Metformin vs other medications. There is a correlation with a decreased incidence of cancer in diabetics taking Metformin .
With all supplements and drugs there is always a risk/ reward trade off.
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#21 mikeinnaples

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Posted 15 April 2014 - 03:18 PM


Yes. Before lunch and dinner. An update though. Metformin lowers NAD, so I think it's important to take some form of niacin. I prefer nicotinamide riboside , but nicotinamide is also ok. I take that in the AM. As has been written previously, Mefformin can deplete B vitamins and raise homocysteine , so take B12, methyl folate etc.

 

 

This has several things wrong with it.

 

1. Metformin suppresses NAD(P)H Oxidase. That is not the same thing as NAD+ and is actually a very good thing. I think you need to reread the study you keep quoting because you are spreading things around that are not accurate. Metformin actually increases NAD+ levels.

 

2. I disagree with you about Nicotinamide being 'ok'. The general consensus seems to be that it is anything but ok. Nicotinic Acid, especially taken with aspirin is OK and actually increases NAD+ more in some cells than NR.

 

I do agree that it is important to take a methyl donor though, especially methyl-b12 if taking Metformin.
 


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#22 mikeinnaples

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Posted 15 April 2014 - 03:26 PM

Couldn't metformin actually increase the rate of beta-amyloid accumulation? See http://pipeline.cora...imers_worse.php

 

Given the modest benefits of metformin, I'm not sure if we could recommend it until we can clear it of this association.

 

Also, Matt Kaeberlein seems pretty bearish on metformin's ability to increase lifespan (though he's a very pro-rapamycin person).

 

Interesting read on that.
 

 

"The finding of a slightly greater risk of AD in association with metformin use in this large observational study is consistent with observations from a recent in vitro study, in which metformin was found to increase the biogenesis of Aβ protein.[11] By contrast, in other in vitro studies, metformin modified important steps in the biogenesis of neuritic plaques and neurofibrillary tangles or improved impaired neuronal insulin signaling,[9, 10] raising speculations about the potential to reduce the risk of developing AD, but all of these observations were made in cortical neurons of mice, and the results may not be applicable to humans." - source

 

Full article



#23 Michael

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Posted 29 June 2016 - 04:48 PM

Returning to the original topic of the thread: now the NIA's Interventions Testing Program (ITP) has now reported on its test of metformin to extend life in normal, nonobese, genetically heterogeneous mice — and, once again, it "did not significantly extend lifespan". More specifically, it modestly (+7%)  increased mean life expectancy in male mice, with no effect in females, and no effect on maximum lifespan (our best quantitative index of aging per se) in either gender.

 

Because the ITP study design incorporates testing of all agents at three independent competent universities, they also reported the results by individual study site: "Males treated with Met had site-specific changes of 13%, −1%, and 10% [in mean life expectancy] at the three test sites, but none of these was statistically significant ... There was no effect of Met on survival of female mice, either in the pooled data (Table 1, Fig. 3), or at any site".

 

Metformin supplementation has now failed to extend lifespan in normal, nonobese Fischer-344 rats (reference (1) in the opening post), and in normal, nonobese mice in five labs (the 3 labs in the ITP study, plus the two labs in reference (2) in the opening post). It just doesn't work as an anti-aging drug, folks.

 

On the other hand, amongst other important results, the same paper reports that adding metformin to rapamycin (a multiply-proven life-extending anti-aging drug) further enhanced the effect of rapa, in line with theoretical expectations from several previous reports.

 

Reference

1: Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, Fernandez E, Flurkey K, Hamilton KL, Lamming DW, Javors MA, de Magalhães JP, Marinez PA, McCord JM, Miller BF, Müller M, Nelson JF, Ndukum J, Rainger GE, Richardson A, Sabatini DM, Salmon AB, Simpkins JW, Steegenga WT, Nadon NL, Harrison DE. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell. 2016 Jun 16. doi: 10.1111/acel.12496. [Epub ahead of print] PubMed PMID: 27312235.

 


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#24 mikeinnaples

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Posted 30 June 2016 - 01:15 PM

7% increase in mean life expectancy seems significant to me even if this shows that it doesn't increase max lifespan.

 

What about all cause mortality? What about heath span? What about cancer risk? What about the fact that in some countries, like the US for example, the majority of the population is overweight and/or obese?

 

 

I know you have had a hard on for Metformin for quite a long time, but I think your hard campaign against it over the years is a bit of a disservice to people. I think most people moved on from thinking it s a CR mimetic or equivalent to Rapamycin quite a long time ago.


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#25 Michael

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Posted 28 August 2016 - 06:21 PM

All:
 

7% increase in mean life expectancy seems significant to me even if this shows that it doesn't increase max lifespan.


If you're not overweight, sedentary, and diabetic, eat a healthy diet (I don't mean a micromanaged health-nut diet — just not garbage) and have access to healthcare, you are guaranteed better results than this compared to your controls, and unlikely to gain anything further from metformin. And, again, the higher dose of metformin actually increased mortality in the same study. Do you really want to gamble that you're guessing the human-equivalent dose correctly? HED and allometric scaling give significantly different doses, just for starters.
 

What about all cause mortality?


All-cause mortality is captured by mean and by maximum lifespan. To be clear, lower all-cause mortality does not literally mean that something lowers death from every single possible cause of death — documenting that would be extremely difficult and would possibly extend into Zeno's Paradox: it simply means that it lowers the sum of all deaths without regard to particular cause.
 

What about heath span? What about cancer risk? What about the fact that in some countries, like the US for example, the majority of the population is overweight and/or obese?


Eat well and exercise ;) . We already know doing so works better than metformin for prevention of diabetes(1,3) and reduction of cardiovascular risk factors,(2) and adding metformin to lifestyle yields no additive benefits(3) — and this, using a relatively mediocre National Cholesterol Education Program step 1 diet. Cf. similar studies in other populations(4,5).
 

I know you have had a hard on for Metformin for quite a long time, but I think your hard campaign against it over the years is a bit of a disservice to people. I think most people moved on from thinking it s a CR mimetic or equivalent to Rapamycin quite a long time ago.


That's a curious way to put it. As documented above, I was quite optimistic for metformin for several years and almost started taking it — until the studies clearly showed that that optimism was misplaced. When the facts change, I change my mind. What do you do, sir?
 
References
1: Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009 Nov 14;374(9702):1677-86. doi: 10.1016/S0140-6736(09)61457-4. Epub 2009 Oct 29. Erratum in: Lancet. 2009 Dec 19;374(9707):2054. PubMed PMID: 19878986; PubMed Central PMCID: PMC3135022.

2: Diabetes Prevention Program Outcomes Study Research Group, Orchard TJ, Temprosa M, Barrett-Connor E, Fowler SE, Goldberg RB, Mather KJ, Marcovina SM, Montez M, Ratner RE, Saudek CD, Sherif H, Watson KE. Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study. Diabet Med. 2013 Jan;30(1):46-55. doi: 10.1111/j.1464-5491.2012.03750.x. PubMed PMID: 22812594; PubMed Central PMCID: PMC3524372.

3: Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V; Indian Diabetes Prevention Programme (IDPP). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006 Feb;49(2):289-97. Epub 2006 Jan 4. PubMed PMID: 16391903.

4: Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. PubMed PMID: 11333990.

5: Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997 Apr;20(4):537-44. PubMed PMID: 9096977.


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#26 Mike C

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Posted 29 August 2016 - 12:23 PM

http://www.ncbi.nlm....pubmed/25041462
Michael these rat studies may not be too impressive but this human study gained the attention of the current issue of Scientific American September 2016 as evidence that Metformin is indeed likely anti aging. Not only does it work to increase lifespan in diabetics when compared to healthy non diabetics but it also increases it when compared to diabetics who use other diabetic drugs indicating it does MORE then just control diabetes. This evidence is from HUMAN studies not RAT studies.
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#27 Michael

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Posted 29 August 2016 - 02:38 PM

http://www.ncbi.nlm....pubmed/25041462
Michael these rat studies may not be too impressive but this human study gained the attention of the current issue of Scientific American September 2016 as evidence that Metformin is indeed likely anti aging. Not only does it work to increase lifespan in diabetics when compared to healthy non diabetics but it also increases it when compared to diabetics who use other diabetic drugs indicating it does MORE then just control diabetes. This evidence is from HUMAN studies not RAT studies.

 

I've explained the flaw in that metformin study before. And, even if that flaw didn't exist, it was based on epidemiology, not a controlled trial.


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