Krister Kauppi: My rapamycin journey notes

I am just interested in quantifiable data. Id really like to know what Rapamycin changes inside us. Specifically I am interested in biomarkers related to autophagy and inflammation as I feel that Rapamycin may have the most benefits in those areas and it’d be nice to quantify.

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how do you ensure quality? Most of them from China.

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I remember seeing something that indicated that MRI can be used to pick up autophagy levels, but I cannot track that back at the moment.

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By testing, NootropicsDepot use an in-house lab.

Thank you for your work. I missing and important point after your journey with rapamycin. Except for more energy, are you noticing anything else that justify taking it? Thank you.

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No luck on that, and it sounds like its a long way away (like a decade): See this thread: Measuring Autophagy in Body and Brain, Comparing Autophagy Activators

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I will write a post on that but the biggest improvement is probably dental health. When it comes to energy levels they are high so no improvements there and I don’t want more energy. Too much already :slight_smile:

Easier weight loss is also one other thing I noticed. But I will write a post around this in some weeks to summarize everything.

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You are relatively young so the resulting benefits of taking rapamycin of course will not probably become apparent until you are older. Much like changing the oil in your automobile will not produce any immediate benefits, but your automobile will last longer.

I was 80 years old when I started taking rapamycin and have experienced many benefits.

One of the things that is still controversial is how much rapamycin suppresses the mTORC2. My own evidence is that rapamycin slows wound healing. But, on the other hand, it seems to prevent infectious diseases.

You would think because I am old I would be more susceptible to viral infections. I know that some people have experienced mouth sores or acne from rapamycin. I have not.
The source of infectious diseases for me would be from the gym that I go to that has a large membership and we are all in danger of transferring “germs” from the equipment we use.
The other source of infectious diseases that I encounter is shopping, especially at large grocery stores where who knows how many infected people have handled the shopping cart or even the products.

I am not a germaphobic so I am not as cautious as some people. In the two years that I have been taking rapamycin, I have not gotten any infectious diseases. I don’t know how rapamycin retards wound healing, yet seems to prevent viral infections.

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I think Rapa is “exercise” for the immune system hence it makes it stronger and thus we are less susceptible to infection over time.
(Just my hunch - nothing to back this up).

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I have a Ping Pong partner whom I play with nearly daily. Last week, he got Covid and I didn’t, despite spending more than an hour every day together to play a game where we all touch the same sets of balls constantly. A good data point?
What would a retrospective study on COVID-19 incidents reveal about the rapamycin population compared to the general population?

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In general it is believed Rapa helps protect you from viruses and weakens you to bacteria. This is similar to how other organisms work. They can become stronger against viruses but in the process become weaker to bacteria and vice versa.

I believe this video details that.

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I recall being told this is why people get bacterial lung infections after being sick with a cold or flu. The body optimizes for virus defense and becomes more vulnerable to bacterial inflection. Oddly I’ve stopped getting sick all together. Sinus rinsing and nasal breathing was the big lever; rapa seems to have been the final piece.

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I was at a conference few weeks ago, major covid outbreak followed, some 200+ people getting covid, I was in close contact to many that got ill or had symptoms and I was sure I was gonna get it too. But it passed me. Is it rapamycin? It might be. I also tend to get less colds lately or I have a sense of developing a cold, but next day I am clear…,

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What DeStrider writes about rapa making you vulnerable to bacterial infections is certainly true in my case. I got a minor pneumonia; my lymphocytes - T, B as well as NK - were reduced greatly after rapa.

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What was your rapamycin dose?
My lymphocytes reduced on 6mg/week/6months but really insignificantly.

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Went down to 1 mg still reduced lymphocytes, somewhat. Possibly combination with another med could have played a role will try again when lymphocytes have recovered.

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Many things cause pneumonia. Viral pneumonia is the most contagious. Maybe rapamycin actually helped you to have a mild case?

Relevant question, however it must have been been bacterial since it was rapidly cured by an antibiotic. But it was extremely mild, mainly a persistent coughing.

I have been taking Rapamycin now for more than one year and these are some of the effects and insights that I have noticed during that time. If it’s due to Rapamycin or placebo I don’t know but these are the things that I have noticed.

:one: A subjective feeling of improved dental health, less plaque and changes in saliva. Two different dental hygienists have both said that there was not much dental plaque to remove. On top of this I feel that my dental health has improved and my saliva has changed in some way. To strive to keep dental health up seems also according to many studies to be an important thing for longevity (pubmed: 14765890, 36150950). I’m very curious to see the results from the RAPID clinical trial where the effects of Rapamycin on periodontal disease will be tested. The trial will be led by Jonathan An and will be started this year.

:two: One thing that I have noticed especially during the winter cold season is that many people around me have got the common cold or flu. My wife is also very seldom sick but she has got the common cold twice this year and also my daughter. I have just felt a little tickling in my throat for some minute when waking up but after that nothing more. So the symptoms, if it even is connected to the common cold, have been very mild. Other people who take Rapamycin have also anecdotally reported mild symptoms. This goes also well aligned with the research that Joan Mannick has done (pubmed: 25540326, 29997249, 33977284). I recommend listening to my podcast interview with her where she shares a lot of interesting information. The thing that I thought was extra interesting was that she found that many different antiviral genes were upregulated due to the mTOR inhibition effect (pubmed: 33977284). But I have also seen some anecdotal reports of people who have got more severe common cold symptoms or increased incidence of common cold. Why this happens we need more research on. One interesting thing I would really like to do is to compare my biomarkers with a person who has experienced this and try to better understand what may be the underlying cause.

:three: I see that my inflammation biomarker for high sensitive CRP has gone below 0.2 mg/L and stayed there. The average value is around 17.7 mg/L and the lowest registered value was 0.16 mg/L. I have also felt subjectively that less inflammation in my right shoulder which gets easily inflamed due to too much time in front of the computer. But I think it’s important to solve the root cause and not just decrease the symptoms when it comes to my shoulder problem. So this is one prioritized area for me to focus on to solve because this is something that impacts quality of life and probably also longevity in the long run.

:four: I feel that it’s somehow a bit easier to lose weight. Before I started taking Rapamycin my weight was around 76 kg and my current weight is now 73 kg. My current body fat percentage is around 14% and my target is to go down to 10-12%. I don’t feel that I have made any changes regarding my diet. I have also taken a pause during this year from extended fasting just to be extra cautious when taking Rapamycin and not overdo things. When looking at the research around Rapamycin and weight loss then there exists data on both animals and humans (pubmed: 24341993, 37191826) Some try to claim that the longevity benefits for Rapamycin is due to weight loss but I would say Rapamycin is not a great weight loss intervention. There are other interventions that work much better and no such intervention has come even close to the lifespan data in multiple species that exists on Rapamycin. So the mechanism of why Rapamycin works so well in extending both lifespan and healthspan in multiple species can not be explained by only weight loss.

:five: I have had a stubborn and quite big eyelid wart for many years but now it’s almost gone. I don’t know if this is because of Rapamycin or not but I started looking in pubmed for research studies and found some interesting things there (pubmed: 20346038, 17133572, 21876315). According to these studies it seems like Rapamycin may have a reducing effect on “cutaneous viral warts” in organ transplant patients. Very interesting but I don’t know if my wart is “cutaneous viral wart” or some other type of wart so it’s hard to say if this is due to Rapamycin or not. When I highlighted this in a previous tweet I got interesting anecdotal reports that some have experienced similar effects. So maybe there is something here for future research to look at.

Here are some of the side effects that I have noticed:

:one: I have seen a slight increase in levels of lipids which may be a potential side effect of Rapamycin. I have also heard others anecdotally report slight increases in their lipids. Why this happens to some people we don’t fully understand. Similar things may happen when people start practicing intermittent fasting, eating a ketogenic diet etc. One very interesting thing that Joan Mannick pointed out in my podcast interview with her was that higher lipids or glucose levels may indicate mTORC2 inhibition. Things point to that this type of specific mTOR inhibition is probably not good for longevity, at least if you are a mouse, (pubmed: 37142830) but more research is needed if the same thing applies to humans. I will dive more into this topic with future quests in the podcast. My main goal this year will also be to lower my lipids to much better levels. More on this in the future. Here are the three biomarkers pre and post Rapamycin that I keep an extra eye on.

ApoB: 1.05 g/L > 1.13 g/L
LDL cholesterol: 4.0 mmol/L > 4.6 mmol/L
Triglycerides: 0.47 mmol/L > 0.77 mmol/L

:two: Mild mouth sores four times during a period of a year. This is the most common side effect of Rapamycin but not all people get them (pubmed: 37191826). Why some get them and others don’t is still a mystery. The mouth sores that I have got have been mild and is something I can tolerate and live with.

:three: Three to four times I got some small acne pimples which I don’t usually get. This is also something that may happen for some people but I can tolerate and live with it. Why some people get it and some don’t is also a mystery. Organ transplant patients who take much higher doser and on a daily basis get them quite often (pubmed: 16781309).

:four: During the first months when I started taking Rapamycin I felt minor tickling irritation in the ear and eye but this is not something I feel anymore. I don’t know if this is due to that my body has adapted to taking Rapamycin now or because of some other reason.

And here are some insights that I have got throughout this year thanks to this self-experimentation with Rapamycin:

:one: One important insight that I have got is that people tolerate Rapamycin differently. Some people may tolerate quite high doses without any big side effects and other people can not even take a low dose of it like 1 mg without experiencing side effects. There are also others that can not tolerate it at all. This highlights the individual complexity and the importance of individualized longevity protocols. This has made me quite skeptical of just copying other people’s overall longevity protocols. We can for sure inspire from each other’s longevity protocols but to copy-and-paste is most likely not a successful strategy.

:two: It is important to point out that there does not exist one single intervention today which is FDA approved for longevity. So much of the things that people try out in the longevity field is just based on qualified guesses. In many cases we don’t know for example what the optimal dose is or if the dose we take is effective or not. The same thing is with Rapamycin. I view Rapamycin as cutting-edge longevity interventions which we don’t yet have a lot of good human data on. The data in multiple species points towards a potential good longevity effect but it’s important to keep in mind that there are also risks connected to it. Because it’s still unknown territory I have prioritized quite high safety in my self-experimentation. My goal is to improve my longevity and not to do stupid things that conflict with this goal. Therefore I have done this self-experimentation for example under supervision of a physician. I have taken different tests before and during my self-experimentation to be able to follow progress. I read a lot around the topic and connected with many people who were self-experimenting with Rapamycin before I started. I eased up my dose of Rapamycin step by step instead of starting with the target dose directly because I didn’t know how my body would react to it. I have also got my Rapamycin from the local pharmacy because I have felt that it just increases the risk that something goes wrong if I got it from some other place. It’s not worth taking such a risk and getting bad quality for example. So safety has been important for me and not to just rush into something.

:three: Thanks to my high priority of safety in my self-experimentation with Rapamycin I have learned much more about self-experimentation and biomarkers. One thing that I really like is that I will do different tests every quarterly to follow up progress when it comes to optimizing my longevity protocol. Before I have done these tests once yearly but now I will get feedback loops more often which I see a big value in. For example now this year when I start to lower my lipids I can follow up things in a much better way with this approach. Maybe I will even add some more frequent tests in the beginning to see what effects the lipid lowering protocol will have that I try out. So I like that my self-experimentation has improved in different ways so I better can test if something works or not on me. It has helped me better understand myself and how I work.

:four: One important measurement when it comes to longevity is to stay physically fit and try to slow down the decline of it as much as possible. My goal is not to build lots of muscle or to have elite physical fitness. I’m quite satisfied with the peak fitness I have. Some improvements can of course be made but I will not do any major changes here when it comes to push things forward. My focus is more maintenance of what I have than doing major improvements. One thing that was good to see was that Rapamycin did not lead to a decline in my fitness. One indication that supports that is that every Sunday I do different tests and have done it for a couple of years. Max pushups just before I started taking Rapamycin was 50 and during my self-experimentation I did 54 which is my record. After one year with Rapamycin I achieved 53 max pushups. I have also felt good progress in the gym. One sad thing is that I don’t have cardio measurements but that is something I will try to add to my future measurements. Like VO2max. Here are some of the test values that I have:

Max pushups: 50 > 53
Max pull ups: 6 > 10
Max chins: 8 > 10
Grip strength (right): 40.9 > 45.4
Grip strength (left): 39.3 > 41.6

So lastly it has been a great self-experimentation year and I will continue to take Rapamycin until I get some data that shows that I would need to stop or change my dose regime. Next thing now is to continue to improve my longevity protocol step by step. More about that in the future.

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Nice work. What else are you doing simultaneously that may have separate effects or offsetting effects or compounding effects with rapamycin?

My personal journey has taken me away from away from many of my previous chemical interventions and toward lifestyle-like (perhaps traditional) interventions, such as measured sun exposure, red light / NIR light therapy, co2 tolerance training / hypoxia training, meditation/ deep breathing, zone 1 cardio (easy), non trad weight training (bar hang to failure, farmers carry, high rep body weight calf raises, shoulder front/back/top to failure, body weight core stability, etc).

I can’t isolate the benefit of rapamycin but believe it has made an important (but slow) contribution to my significant improvement in movement and brain function and reduction : elimination of pain and brain fog.

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