I generally agree with the main thrust of the article, however, I do have one comment in relation to:
“Before taking any supplements, you should optimize lifestyle factors for a longer lifespan and improved health.”
My experience has been that Rapamycin has been a critical enabler to me “optimizing lifestyle factors”. I was exercising regularly but the pain that induced made it very difficult to do day to day tasks and I was waking up constantly at night. After taking rapamycin all that pain is pretty much gone so now I can exercise freely again. Since rapamycin isn’t a pain killer I am fairly sure this isn’t just masking anything.
First let me say you handled what was, on reflection, a fairly inflammatory post with incredibly good grace. I apologise for making the discussion personal. FWIW fitness is all relative, for example I am one of the least successful athletes in my friendship group (that includes an Olympic silver medalist in rowing).
Secondly, let me illustrate one reason why adaptation to training might be important. Say you have an individual who decides to start cycling. At first he can maintain 200w for an hour but after 6 months of training he’s able to average 300w. However say the same individual is also taking metformin so now, after 6 months, he’s only able to average 250w:
300w x 60 mins =~ 1080 calories
250w x 60 mins =~ 900 calories
So you can see that being fitter allows you to burn greater calories per unit time.
Thank you for your post. It really means a lot to me. Truly. I can see that you are a very intelligent and interesting individual and I feel like I can learn a lot about the me I want to be from you.
I can completely understand why you and any other athletic individual would shun Metformin. And honestly I’ve been thinking about ditching it if acarbose will work for me better. But right now, I need something to keep my blood sugar levels in check and Metformin has done the job for me. Dropping 20 pounds would be better though.
We’re all in this together on this longevity journey and I am always looking for ways to improve my life and the lives of others. Thank you for your comments and insights. Whenever I see your comments, I usually end up ditching a supplement I am taking.
My mates call me a COC (cut old ) - rude buggers (only mid fourties’ too).
FWIW I’ve been taking Metformin for a little over a year and have noticed zero difference in my athletic performance (Oura, Apple Watch tracking - not overly sophisticated I’ll admit). In fact, I’m feeling great and my numbers are better now then they were before Metformin. However, that could also be the Rapa I started 6 months ago….
Anyways - I’m glad you guys kissed and made up. Takes a lot for someone to do that, especially in a public forum - respect
Regardless of your thoughts on metformin, it still keeps showing up in new studies as a probable life extender with properties beyond its glucose-lowering effects.
I am not currently taking metformin, but I may take it up again.
“Metformin and rapamycin are gerotherapeutics under intense investigation for their potential to delay many facets of aging to ameliorate physiological deterioration and potentially increase the quality and length of life”
Maveric, your perspective is echoed by Dr. Peter Attia, and as someone who prioritizes exercise and nutrition above other longevity-promoting interventions, I get where you’re coming from. But gotta meet people where they are, and after that, nudge them to where they (presumably) need to be.
This is the interesting question as to the balance between nutrition and supplementation. I am quite heavily into taking additional chemicals (which are all found in natural food) to skew my metabolism in a particular direction.
I don’t think doing this is practical doing normal foodstuffs.
I’ve also read the research on Metformin and muscle growth/performance and have a couple of comments:
First, part of the idea of how Metformin could affect performance and muscle growth stems from its ability to curb MTOR. The exact same question has been raised about Rapa and it has been suggested that it may have the same effects. I know that there is at least one researcher that has suggested that a similar study be done on Rapa.
Second, if Metformin did have this effect I can’t help but wonder if it has to do with the reduction in testosterone that it causes. You need testosterone and protein to build muscle and medications like Metformin and Acarbose both have studies suggesting that they lower testosterone. Granted, the findings seem to differ based on sex, but larger scales studies could illuminate this. I know from doing my own bloodwork that Metformin does decrease my testosterone.
Since finding about AgelessRX site, I am now able to subscribe to Metformin and Rapamycin. However I had to fill out a questionaire about my health before being allowed to get Metaformin. As fo Rapamycin I had to have blood work done before I was enrolled in their Rapamycin trials. So I agree being healthy is a requirement before taking such experimental drugs. Im 75 and my BMI is 23. I bike ride 90 minutes at least four times a week and when I can’t go for a ride, I get my walking in. I also have a diet that excludes most sugary items and lots of vegetables and a little meat. It’s working for me so Im happy to be part of the Anti Aging experiment.
The effect of metformin on muscle growth through mTOR inhibition is likely to be insignificant. Notice that metformin has been used by millions of people for decades, yet nobody has noticed any effect of metformin on muscle mass gains. The chances of its mTOR inhibitory effects having any significant effects on muscle mass gains is even smaller when you consider that people taking rapamycin generally don’t notice any negative effects on muscle gains even though rapamycin is a far stronger mTOR inhibitor than metformin.
Regarding testosterone. There was some study that showed a small reduction in testosterone in men taking metformin, but that’s just one study. Probably most studies show no effects and again people have been using it for decades and nobody noticed a reduction in testosterone so it is unlikely that it will have significant effects on it. Anyways, if it is reducing mTOR and testosterone slightly, that’s likely to be beneficial for longevity for most people so I am personally not concerned with either of these effects and would particularly welcome the potential mTOR inhibitory effects.
The main concern I have with metformin is that it might inhibit complex I of the respiratory chain leading to impaired adaptions to endurance exercise. That’s something that has more potential to be harmful for longevity, not just for exercise performance. But again, if we consider the millions of people that have taken metformin for decades, if it had a significant effect on endurance in a significant portion of people taking it, people would know by now from experience. The fact that nobody seems to have noticed such an effect can only mean the effect must be really small. Perhaps small enough to be of no concern.
One thing I wonder about as a possibility is that the complex I inhibition might have a more significant effect in older adults because they are the ones that are likely to have experienced an age-related decline in complex I activity. Younger adults might be able to tolerate slight complex I inhibition better than older people. That’s just my speculation though. I haven’t seen any research on it.