In this article you will learn:
Why people take the prescription drugs Metformin and Rapamycin for antiaging
Understand the risks and benefits associated with these interventions based on the research
Get my personal take (disclaimer: I have not used Metformin or Rapamycin)
The Details:
Metformin is the commonly known type 2 diabetes drug and it was synthesized from French lilac in the 1920’s. Rapamycin is a unique anti-fungal and anti-bacterial substance produced by soil bacteria. It was discovered on Easter Island during a Canadian research expedition in the 1960’s, and it was predominantly used to help someone with an organ transplant by suppressing their immune system.
Both of these drugs have gained massive popularity in the last two decades for their potential anti-aging effects, with animal studies and research from people like Dr. David
Sinclair and others showing their significant ability to impact the specific metabolic pathways mTOR and AMPK. Don't worry if that sounds like gibberish, because we'll try to get a simple idea in this article.
Basically, the exact mechanisms of these two drugs and their effects on aging is not well understood because the pathways they affect are very complicated, but in general it is thought that they mimic the effects of fasting on the body. Your body has a “growth”
mode and a “safe” mode, and each gets triggered by various lifestyle choices and biological circumstances.
The mTOR (mammalian target of rapamycin) pathway gets activated by insulin, and since your insulin spikes when you eat (especially carbs), this tells your body to rev up many different processes related to growth and energy production because resources are present.(1)
The AMPK (AMP-activated protein kinase) pathway is another extremely complicated system that kicks into gear when your body is low on energy, fasting or under a stress of some kind.(2) Another way you've probably heard about this is "anabolic vs. catabolic," like in gym and lifting circles.
Despite their complexity, you can think of one as Yang and the other as Yin, or as a gas pedal and the breaks. This makes sense from the perspective of Duality, and what metformin and rapamycin do is basically fool your body into thinking it is in calorie-restriction mode... without the calorie restriction part. They put water on your metabolic fire, make your body believe it is fasting, and as a result they create a whole host of benefits not the least of which is extending life.
Unfortunately, both drugs must be obtained with a prescription and they are not without their considerations and lack of long-term data.
Metformin has been used as a diabetes drug for a while, and although current anti-aging trials in humans are underway and expected in the next few years, there is clinical evidence for many other positive effects on cognition and all-cause mortality.(3) It beneficially impacts the mitochondria along with the AMPK pathway. While these mechanisms aren’t fully understood yet, the effects are pronounced. Metformin studies in rats and other animals are pretty robust because it is an older drug, and the life extension potential is significant even if given later in life.(4)
Still, it is not without its considerations. Metformin may hamper your ability to absorb and utilize B12 while you are taking it, and it reduces the benefits of exercise.(5,6) If you are going to take metformin at a low dose for antiaging, it’s advised to take it on days you don’t exercise and only a few times per week, as well as with a bioavailable form of B12 for insurance against deficiency.
The other drug, rapamycin, is also only available by prescription and it’s harder to obtain. Quality control issues are a factor here, as some people find unlicensed sources overseas to get the drug without a prescription. There are a few doctors that will prescribe it for anti-aging purposes, but the general consensus is that there isn’t enough long-term data on its effects yet.
Proponents argue that the side effects of a low dose taken intermittently are rare and reversible, and that it’s impossible to overdose on rapamycin because no LD50 could be established (the amount at which 50% of the testing population in an experiment dies, or "lethal dose 50") or because there are no toxicities reported in the millions of cases where it’s been used over the years.(7)
It’s also thought that rapamycin’s immune suppressing effects may increase the likelihood of cancer, but some clinical research has shown that a low dose may actually inhibit some types of cancers.(8,9,10) Some research has also shown that a low dose increases immune function,(11) and many in the anti-aging sphere rave about its benefits.
Personally, I’ve never tried it, and while it’s very interesting, it is something that I will wait to see more data on. There are lots of clinical trials going on with rapamycin for anti-aging and I suspect in the next few years we will have at least some more short-term data on how to use it effectively. It’s not a drug that can be patented since the patent expired, so most likely you will also see new “rapalogs” or drugs that mimic rapamycin in
the near future.
In the end these kinds of interventions are very tantalizing, but remember that the science is still emerging. We still don’t even know how these drugs actually work, and with how complicated these pathways are in the body it is a gamble long term. Drug interactions, supplement interactions, the impact of toxins with these chemicals or even behaviors like fasting or exercise are all big unknowns when using these things.
Still, proponents argue that the potential benefit of living a longer, healthier life is well
worth any supposed risk compared to not taking it and dealing with the effects of aging.
The promise is definitely there, and these drugs may be something worth investigating once you’ve addressed your baseline deficiencies and toxicities through a complete nutrition program. In this way, you’ll at least have a proper foundation to experiment if that’s your choice and not risk going off the deep end with anything that you do.
If you do take rapamycin, it’s suggested to take a higher dose (like 6mg) once per week and then take a break every 2-3 months for 1 month. Organ transplant patients take 2mg per day, and the beneficial levels for anti-aging seem to be around half to a fourth of this amount daily. Taking a larger weekly dose achieves a high blood level and allows your body to process it without continued daily intake, which may or may not be better than taking a low dose every day.
Keep in mind that these are rough parameters and optimal dosing, timing and treatment length have not been established for rapamycin.(12)
References
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214394/
2. https://www.cellsignal.com/contents/science-cst-pathwayscellular-
metabolism/ampk-signaling/pathways-ampk
3. https://www.healio.com/news/endocrinology/20190829/metformin-may-hold-antiaging-promise-to-increase-health-span
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772077/
5. https://pubmed.ncbi.nlm.nih.gov/26583801/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880159/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/
8. https://pubmed.ncbi.nlm.nih.gov/15233824/
9. https://pubmed.ncbi.nlm.nih.gov/16249734/
10. https://pubmed.ncbi.nlm.nih.gov/16434506/
11. https://www.menshealth.com/health/a28440858/anti-agingrapamycin/
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401992/
