Would I need to take acarbose well away from my exercise so as not to blunt the response ? Does it work that way in the body ?
Hi Meg, unlike metformin, acarbose is not going to blunt the acute cytokine signaling that occurs after exercise that would stimulate muscle growth, nor does it prevent the mitochondrial biogenesis that you would typically see with forms of cardiovascular exercise. Additionally, it works on pathways independent of mTOR, so it does not impede protein synthesis. For this reason, we don’t have concerns about acarbose attenuating the benefits of exercise.
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Perfect. That’s helpful, and why I don’t want to mess with Rapa - I’m very much into my endurance and strength training at this stage of my life and don’t want anything to mess with that…! I appreciate the explanation of how Acarbose works
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Meg, I found your question interesting, I’m also interested in your comment about Rapamycin, how does this mess with workout?
Hey Steve, so maintaining muscle is a crucial component of the longevity equation for a multitude of reasons. We definitely do not want to impede the anabolic response to resistance training.
Rapamycin regulates cell growth through its inhibition of the mTOR pathway. The mTOR pathway plays a crucial role in muscle protein synthesis, which is essential for muscle growth and adaptation, particularly in response to resistance training. mTOR is activated by various stimuli, including resistance exercise and nutrient availability, such as amino acids—specifically leucine. The problem when it comes to aging is that mTOR becomes overly stimulated and results in the growth of unhealthy tissue and increased inflammatory signaling. This means we want to get a recalibration of mTOR to healthy and normal baseline levels, while not impeding on healthy anabolic activity.
This is where the intermittent dosing of rapamycin comes into play. Rapamycin prescribed for healthspan-promoting purposes, is typically taken once every 7 to 14 days. In this protocol, you should get a transient pulse of mTOR inhibition (promoting autophagy and diminishment of the pathological effects of senescent cells), and then mTOR levels go back to a normal level (normal anabolic behavior). When taking rapamycin on a day when you are doing resistance training you may be impeding the anabolic response to that training. However, you are not getting a sustained mTOR inhibition.
Matt Kaeberlein has spoken about his levels and how they relate to his workout routine in this Twitter thread:
Essentially for the transient period that the rapamycin is in your system, you may not want it to be a lifting day.
In my longevity protocol, I typically do resistance training Monday-Friday. Saturday I go for a hike and then Sunday is either an off day or I play tennis. I’ll take my rapamycin dose on Saturday so that it does not impede the anabolic muscle adaptations to resistance training on Monday.
The interesting thing is that as you get older, as mTOR activity becomes heightened, we lose our sensitivity to anabolic stimuli and it becomes harder to grow muscle. Essentially you lose mTOR sensitivity to anabolic stimuli (amino acids, resistance training, growth factors). It takes more and more amino acids and resistance training to have the same effects you would have when you had when you were younger. By intermittently taking rapamycin at this healthspan-promoting dosage frequency, the thought is that you can preserve your mTOR sensitivity and maintain your ability to grow muscle.
Professor David Glass has utilized mTOR inhibition as a way to preserve muscle mass and prevent age-related sarcopenia:
Healthspan did a research review on this:
Here is an additional narrative review on this subject:
Let me know if you have any questions regarding any of the above.
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This is so helpful, thank you for all of these links and for the very detailed response. I will take a look at the research - but this in general is in alignment with my understanding of how the mTOR inhibitors work and why I’m more interested in Acarbose at this stage of life . Between endurance work and strength work I don’t take any days off - I run 6 days/week, strength train 2-3 times a week and Ruck walk once a week. I don’t want to mess up any gains I stand to get at this stage of life !
Thanks Daniel, that was helpful. The way I interprete that, taking it once a week is not going to impact my weight lifting benefit. I just might plan the day I take it a run or bike vs lift day but not a big deal even if I do left.
Steve Rand
347-327-1968
Yes, thank you for the in-depth background on this. I weight train 5 days a week, speed walk daily with three of those days being a 45lb ruck. My original protocol was rapa + metformin, and though the bonus weight loss was nice at first, after about two months my gym gains halted, visibly and measurably. I dropped metformin and paired rapa with acarbose. It has been a little over a month and my gains are gradually returning. Additionally, the weight loss I enjoyed has stayed off.