Metformin is a biguanide class drug used to treat diabetes mellitus. Like most of you will know, the ins/IGF-1 pathway is not only malfunctioning in diabetes mellitus but it also influences the rate of aging. This of course leads us to the speculation that anti-diabetic drugs could delay aging as well. Several trials have been conducted and they found that metformin significantly increased the lifespan of mice. Female outbred SHR mice who were given 100mg/kg metformin in their drinking water had an 37,8% increase in mean lifespan, 20,8% increase in the last 10% survivors and a 10,3% in maximum lifespan compared to control mice [1]. Also the closely related drugs butformin and phenformin extend the lifespan of mice and furthermore decrease the incidence of spontaneous tumors. Butformin caused a 9% increase in medium lifespan and 1,6 fold reduction in spontaneous tumors. Phenformin had no significant effect on mean lifespan but increased the maximum lifespan by 3 months and decreased tumor incidence by 1,3 fold [2,3]. In the C3H/Sn mice however phenformin did increase the mean lifespan by 24% and the maximum lifespan by 26% while reducing the incidence of spontaneous tumors by fourfold [4]. In another trial, the treatment of C3H/Sn mice with 2mg phenformin per mouse for 5 days a week prolonged the mean lifespan by 21,1%, the lifespan of the last 10% survivors by 28,4%, increased the maximum lifespan by 26% and reduced the incidence of mammary adenocarcinomas by fourfold. Phenformin however didn’t extend the mean lifespan of LIO rats in the same study but it did increase the lifespan of the last 10% survivors by 10,1%, the maximum lifespan by 9,8% and attenuated the development of spontaneous tumors. Butformin was also tested in the same trial and it increased the mean lifespan of female LIO rats by 7,3%, the lifespan of the last 10% survivors by 12%, the maximum lifespan by 5,5% and decreased tumor incidence by 49,5% at 5mg per rat per day [5]. Phenformin had no significant effect on food consumption [6] ruling out the possibility that lower food intake caused the increase in lifespan and decrease in tumor incidence. However, I think that metformin could function as a CR mimic [7]. Metformin activates LKB-1which activates AMPK [8]. AMPK activates TSC1/TSC2 which then inactivates Rheb. Rheb probably activates Torc1 but inhibits Torc2 (Torc is a complex that consists of the well know mTOR combined with mLST8/Gbl, PRAS40 and Raptor in Torc1 or Rictor in Torc2) [9]. This also links this pathway to the discovery of rapamycin as a life extension drug [10] previous year because rapamycin also inhibits Torc1 but not Torc2 [11].
That’s why I decided to start taking metformin, 210mg each morning. Metformin is quite save, I would say about as safe as taking aspirin. But you have to use it in right way just like with aspirin.
What are the things that you have to keep in mind? First of all, metformin bought on the internet is probably fake. Never take that! Secondly, it inhibits the absorption of B12, so you should supplement this. It appears that about 10% but in some studies up to 30% of the people who take metformin experience a reduction in B12 absorption [12-15]. Deficiencies in B12 can lead to neurological problems. It also appears that calcium supplementation reverses the malabsorption of B12 [16]. Third, never take too much and don’t take it if you have kidney-, heart- or liver insufficiency, before an operation or before undergoing a scan that involves the injection of iodinated contrast fluid. In these cases metformin can cause lactic acidosis [17-20]. The incidence of lactic acidosis is estimated to be about 0,03 cases in 1000 patient years [21]. Salpeter et al. found, after reviewing 274 published reports and controlled trials, no cases of fatal or nonfatal lactic acidosis in 59,321 patient-years of metformin use and estimated, using poison statistics, that the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 5.1 cases in the metformin group and 5.8 cases in the non-metformin group who used other glucose lowering strategies [22]. Therefore some say that the withdrawal before a surgery or scan is not needed [23-25]. However, because I’m talking about metformin as a life extension drug in non-diabetic people it is advisable to better be safe than sorry and thus stop using metformin at least 48h before a scan or operation. Alcohol could increase your risk of lactic acidosis [26], so don’t take metformin just before of while drinking alcohol. Fourth, experiencing gastrointestinal symptoms like diarrhoea during the first couple of days is normal. About 10 to 30% of the patients experience non-specific gastrointestinal symptoms [19]. Fifth, always check if metformin doesn’t interfere with other drugs that you take.
I hereby also promise you to write a paper about the possible use of metformin to slow aging.
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