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Here is the Twitter Post.
On September 28th, I decided to stop rapamycin, ending almost 5 years of experimentation with this molecule for its longevity potential. I have tested various rapamycin protocols including weekly (5, 6, and 10 mg dose schedules), biweekly (13 mg) and alternating weekly (6/13mg) to optimize rejuvenation and limit side effects. Despite the immense potential from pre-clinical trials, my team and I came to the conclusion that the benefits of lifelong dosing of Rapamycin do not justify the hefty side-effects (intermittent skin/soft tissue infections, lipid abnormalities, glucose elevations, and increased resting heart rate). With no other underlying causes identified, we suspected Rapamycin, and since dosage adjustments had no effect, we decided to discontinue it entirely. Preclinical and clinical research has indicated that prolonged rapamycin use can disrupt lipid metabolism and profiles [1], as well as induce insulin and glucose intolerance [2] as well as pancreatic Beta-cells toxicity [3]. Despite anecdotal evidence of rapamycin slowing down tumor growth, its effect in inhibiting natural killer cells [4] do raise concern for anti-cancer immune surveillance and cancer risk in the longer run. Additionally, on October 27th, a new pre-print [5] indicated that Rapamycin was one of a handful of supposed longevity interventions to cause an increase/acceleration of aging in humans across 16 epigenetic aging clocks. This type of evaluation is the first of its kind, as most longevity interventions up to date have been tested against one or two aging clocks, leading to invisible biases and potential intended “cherry picking” of favorable clocks for the tested interventions. Longevity research around these experimental compounds is constantly evolving, necessitating ongoing, close observation of the research and my biomarkers which my team and I do constantly. Sources: [1] https://pubmed.ncbi.nlm.nih.gov/12177161/ [2]https://pmc.ncbi.nlm.nih.gov/articles/PMC3384435/#:~:text=(D)%20Chronic%20treatment%20with%20high,rapamycin%20induces%20Klotho%20%5B64%5D…. [3]https://diabetesjournals.org/diabetes/article/62/8/2674/34093/Evidence-for-Rapamycin-Toxicity-in-Pancreatic… [4]https://pmc.ncbi.nlm.nih.gov/articles/PMC4084728/#:~:text=In%20contrast%2C%20rapamycin%20significantly%20inhibited,cells%20in%20rapamycin%2Dtreated%20recipients….
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the hefty side-effects (intermittent skin/soft tissue infections, lipid abnormalities, glucose elevations, and increased resting heart rate).
I have not noticed these side effects in myself.
prolonged rapamycin use can disrupt lipid metabolism and profiles [1], as well as induce insulin and glucose intolerance [2] as well as pancreatic Beta-cells toxicity [3].
The first study (plasma lipids) involves transplant patients taking high doses (10mg/day).
The second study (glucose intolerance) involves “chronic high doses” and argues for “intermittent dosing”.
The third study (pancreatic cancer) involves transplant patients taking high doses (10mg/day)
These are arguments that chronic / high dose rapa could be problematic, not arguments against intermittent or low-dose rapa as we are doing.
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Cue the dozens of people complaining about his choice and how wrong it is, despite there being no clinical trial for rapamycin use in humans to improve longevity, and maybe one MR study that does.
I’ve had reservations for the following reasons:
- Infection risk
- Risk of cardiovascular, lipid abnormalities, possibly via increase of PCSK9, for some
- Cancer risk (?)
- Mice living in pathogen free environments
- Proponents dying from it, like the CR people, but there can be other reasons
Also it’s been tiring to have to tell people to STOP taking rapamycin if they have an infection. We have Matt Kaeberlein continuing taking rapamycin despite having an infection requiring antibiotics.
I’m looking forward to the development of better mTOR inhibitors though, without these side effects.
But I’m wondering about low dose rapamycin like 1-2 mg a week. I don’t like the seemingly random decision at 5 or 6 mg a week. Or @Dr.Bart mentioning 1 mg EOD (3.5 mg a week) seems interesting since it is a lower dose.
At the same time I think SGLT2 Inhibitors seem risky at 5% absolute risk for genital infections within study period, so maybe there aren’t that many interesting longevity drugs.
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This is why we need more studies. Personally I tried it because of periodontal disease and it incidentally seemed to help with my mild post-COVID syndrome.
However, I agree with Attia and Kaeberlein about taking breaks from the drug. Cycling may be important, Johnson didn’t mention cycling off for several weeks.
One point though, isn’t Johnson taking like… 100 other supplements ?.. how in the hell did they “narrow down” to rapamycin. It is very possible that some of or combination of these supplements is exacerbating the side effects of rapamycin via direct or indirect action on m-tor pathway (or down the pathway), somehow potentiating the effect of rapamycin by reduced metabolism, synergy, etc. And of course other yet to be elucidated interaction with rapamycin.
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It does wonders for my inflammation. Will keep intermittent dosing, but continue my monthly breaks.
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one word (filler words due to word count requirement): lol
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He didn’t cite [5] for his claim about the study with “16 epigenetic clocks”. I looked and couldn’t find it on google, anyone find it?
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From what I remember, SGLT2i bring the genital infections in men to the level of women who don’t take it. And if you don’t have diabetes it’s close to zero. So the risk is very low.
Here: What's the Deal with Renewed Interest in Metformin? - #101 by Neo
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So now BJ is down to only using meme supplements and exercise? Next he’ll start going carnivore lmao.
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Right ?, that was the only intervention with the most evidence bad or good… but 100 other supplements most with scant data - NO PROBLEM.
NO NEWS IS GOOD NEWS for BJ I guess.
Can’t wait for the next Optispan episode…
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Michael Lustgarten only does diet + exercise. If we have longevity drugs coming it’s worthwhile to not take too high risks that might lead to something that can kill you, like infections (sepsis).
Ezetimibe
Acarbose
Taurine
Creatine
Astaxanthin
These seem low risk? What else?
Messing with the immune system seem particularly dangerous, based on the tail effect of infection, it’s no bueno?
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That is a rather useless reference… see this thread: The Effect of longevity interventions on epigenetic clocks (BioRxiv)
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No one else figured this out in the millions of years since humanity has been around. Just train and eat harder bro.
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Ahh, I literally mess with the immune system every day over the years in thousands of patients over past 25 years - saved lives, improved symptoms and outcomes.
Majority of medical problems are caused by dysfunctional immune system…
BTW, anytime you take an anti-inflammatory (aspirin) you are technically messing with the immune system
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It’ll be interesting to see if BJ improves in those parameters he attributed to negative rapamycin effects.
And it is clear that rapa has different effects on different people, at least according to anecdotal evidence, where not everyone on a given protocol gets mouth sores, lipid or glucose abnormalities, skin infections etc. For some it may be a matter of adjusting the protocol, but rapa may simply not be helpful for some people. Let us remember, that even though rapa was a positive in trials with mice, that was on a cohort level, and there were those who did not benefit for whatever reason. BJ may be someone for whom rapa is a net negative.
Of course, he does take a ton of supplements and interventions, so isolating the effects of just one seems like quite a challenge.
I’m keeping an open mind. I figure there is no way to know ahead of time whether rapa will be a net positive for my health, so I just have to experiment and see. The “see” part requires extensive measuring, recording and comparison, which is why at the moment I’m doing all the baseline tests and measurements before taking rapa, which I’ll start January 2025.
We’ll see. My only serious concern is the beta cell toxicity and the interstitial lung disease.
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They didn’t have linear regression, excel sheets, diet tracking, blood tests, association and mendelian randomization studies.
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With over 100 billion people having lived (with most of them in the past 1000 years) we would expect some freak who exercises and eats in a particular way to be noted for his longevity in history books.
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Too much war, pandemics, other infections, violence, low amounts of recordkeeping, and stuff like that. Most people were farmers and had deficiencies, why would you know about someone’s great great grandpa farmer who lived to 120? Did they even count how old people became or just guessed?
I think most people ate bread also or potatoes. Not much variety to show effect from diet?
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thanks, I remember that and thought that might have been what he was referencing but that doesn’t even say what he’s claiming. The study showed rapamycin no effect on the vast majority (14 or 15) of epigenetic clocks and slight acceleration in 1 or 2 depending on the dose.
Also I’m planning on taking cat’s claw because of that study. Doesn’t seem to have any major side effects so at worst I’m only losing like 60 bucks a year.
BTW what’s your take on Dasatinib?
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