Krister Kauppi: My rapamycin journey notes

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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It’s frustrating to not know if a thing works or not but I feel the best thing I can do at the moment is to keep things on the safe side when it comes to Rapamycin. Hopefully one day we will get better data but until then I need to do qualified guesses about what may be the rough right direction. During this year I have quite many things I will work on to improve and I really hope also that the Rapamycin Longevity Lab can contribute to research and development of powerful potential longevity intervention cocktails.

I listened to a very interesting lecture on one of the Longevity Biotech Fellowship sessions during this week with Peter Fedichev. Below is one video with him and his theory of aging. It’s a very interesting one and a rough summary of it is that when the body is not able to recover from damage then things start to accumulate fast and we die. Naked mole rats are very good at recovering from damage. This is one reason according to him why they live healthy and long. If we can translate this to humans then we would be able to almost stop aging. This was very interesting because I thought stopping aging was harder to do than reverse aging. So I have changed my mind a bit on this topic and think Rapamycin is one important step in the right direction to stop (= slow aging dramatically) but we need much more bricks to achieve this. That is the goal with the Rapamycin Longevity Lab cocktails. I want us to be able to engineer those cocktails.

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I agree that homeostasis fails. I think it fails because of a failure of gene expression.

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Great analysis, both for your personal experience with rapamycin and how it relates more broadly to individual longevity.

I would offer 2 thoughts :

  1. At 69 I haven’t had any decline in strength. I have used rapamycin for only 2 years. I use similar measures as you - pull-ups, etc. My conjecture is that naturally high levels of testosterone have provided a buffer against decline. I will say my aerobic capacities are much more evident of decline. Instead of cruising at an 8-9 minute pace per hour when running, I now run at around 10 minute per hour pace. On the other hand I am still capable of running well under an 8 mile per hour pace - but my natural pace is just slower.

  2. Within your post and also on the forum, there is a continual bemoaning of the need for more data on rapamycin. I see it differently. We have quite a bit - looking at how it has been used on transplant patients as well as dog, cats, and the self-prescribers. Also, your excellent interview with Joan Mannick and strong evidence of rapamycin strengthening the immune system. We will always want more data, but I have a strong confidence in prescribing based on evidence given. You could look at a drug like aspirin, studied for a long period, and see the data still evolving. So I think this will be true of Rapamycin.

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@John_Hemming Interesting. Can you elaborate a little bit more on what specific failure of gene expression you are refering to?

@Bettywhitetest Big thanks for sharing your experiences in the field. Very interesting also around the aerobic capacity. It is not so much talk about that on social media. It feels more people are talking about avoiding sacropenia. But aerobic capacity is also to try to keep up as you point out.

Yes, I agree that we have a lot of data in field but there are so many questions that would be very interesting to get an answer on. I have a good feeling that we will get lot of great data when these trials and studies are starting to publish data (see link below).

https://twitter.com/KristerKauppi/status/1752285830884839611

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Most cellular logic occurs via the genome whether it involves transcription of mRNA and then translation into proteins or just the transcription of RNA from areas of the genome that are noncoding. This requires a certain amount of substrate and other metabolites such as acetyl-CoA.

This depends upon the energy levels of the cell, the efficiency of the mitochondria and the expression of the tricarboyxlate transport protein SLC25A1. These are the sorts of things that go wrong particularly as cells get older.

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