#55

Maybe a good thing my 45 minute discussion with a lot of detail and science with Dana didn’t get put out there. What a complete cluster - totally the opposite of what was expected. Yes Agetron - dodged a bullet … and my initial annoyance of having prepared carefully for the interview, having her questions in advance … and not even a mention of anything conveyed. It’s disrespectful and rude. Don’t come and take up someone’s time when you aren’t going to use the content - when it is quality content. Anyway - think I dodged a bullet … but the quality of the end product isn’t what it could have been.

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#56

Welcome!
See previous discussion here as well:

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#57

I took rapamycin for several years at a low dose (2 mg a week) for anti-aging purposes and experienced serious infections that caused permanent damage. In my experience, the potential side effects are often downplayed. I would encourage others to carefully consider the risks before taking this medication.

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#58

Can you please share more details… what other things you were taking at the time, and more details on the exact nature of these infections, and how you measured and identified any permanent damage?

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#59

I began taking Rapamycin about five and a half years ago at a dose of 2 mg once a week, along with metformin and MitoQ (a more advanced form of fisetin). After roughly a year, I increased the dose to 6 mg once a week. Shortly afterward, I developed a severe upper respiratory infection, something I had never experienced before. Fortunately, it resolved without causing permanent damage, and I returned to the 2 mg dose.

Later, while still on Rapamycin, I contracted herpes and experienced an unusually severe outbreak. From what I’ve learned, the intensity of the initial outbreak often dictates the severity of future recurrences, and since then, I have faced frequent, relentless outbreaks. I believe this is due to the immunosuppressive effects of Rapamycin.

A few years later, I intermittently combined dasatinib and quercetin with my 2 mg weekly dose of Rapamycin. Unfortunately, I ended up needing urgent care at the hospital due to a serious infection that caused some necrosis. After discussions with specialists, we concluded that the immunosuppressive effects of these medications were likely responsible. This outcome was unexpected, particularly for someone middle-aged and otherwise healthy.

Based on my experience, I believe there needs to be greater awareness of the potential risks associated with these medications, especially Rapamycin and metformin. For me, these treatments did more harm than good.

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#60

Well, our goal here at the site is to identify all the benefits as well as the downsides to any new potential longevity therapeutic, so I appreciate you sharing this information in the detail you have. I encourage everyone who visits here to do the same.

Perhaps some medical professionals here can jump in and ask relevant questions that might help us understand the likelihood that rapamycin contributed towards the risk of getting these bacterial or viral infections, and their severity. We’ve had other reports here of similar issues: Too many bacterial infections, have to stop, low WBC

While I think its a small minority of users, I do think its a risk and its important for us to figure out ways to measure, mitigate / obviate and counteract (if possible) these risks.

When you got these infections did you typically stop rapamycin or continue taking it?

Did you get any blood tests done before or after the infections, that might reveal any issues; for example were white blood cell counts too low? I remember Dudley Lamming suggesting to us that a good way to track and measure our immune system strength may be via tracking TREGs, but I’ve yet to find an inexpensive way to get this tested.

TREGs (T-cell Regulatory Test) (Test details ), Labcorp TREGs test
Test TREGS on the same day you test Trough Sirolimus levels to see if there is significant disruption to your immune system.

I definitely do think that there are risks with rapamycin (though low) and I think it would be great if, as a group, we can work towards identifying factors that increase or decrease these risks. I’m sure, for example, that infection risks for medical professionals who regularly see sick patients and work in hospital environments, may be at a higher risk than a software engineer who works at home alone most of the time; simply due to exposure risks to potential infection agents.

I saw this post on X / twitter recently and it also surprised me - so I do agree that there are issues that we are still discovering with rapamycin. While we don’t hear of these reports often, its important for us to try to learn about the issues, identify the frequency, and identify ways to lower the risks.

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Source: x.com

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#61

I really encourage people to do blood tests. In my case I was surprised to see that the half life of rapamycin was 82.5h. That might look not too far from the 62h generally cited but because it’s an exponential clearance it means that the rapamicyn is going to accumulate if I take it every week.

I was also taking 6mg per week but, to avoid that accumulation issue, I now take 12mg every other week instead.

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#62

I was surprised by this comment. Did it have any follow up please (I´d check ti myself but Twitter is down on my country)?

1 Like
#63

Thank you Matterhorn, you bring valuable feedback. Anyone thinking of starting on rapa needs to be aware of possible risks, and some can be very severe. My takeaway is that if I find myself having persistent infections, or more serious infections, I have to re-evaluate the wisdom of staying on rapa. I’m not going to try to “tough it out”. The other big takeaway, is that polypharmacy is a seriously complicating factor. When I go on rapa (probably this November), I intend to stop various supps, like turmeric/curcumin, and take rapa away from most other meds on that day, and to add others only after 2-3 days (like carotenoids lutein, zeaxanthin, astaxanthin). We have very little data on interactions, and we all have unique health profiles and drug reactions. Caution is advised, and thank you again for your feedback.

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#64

Individuals often fixate on a certain item causing their adverse reaction or outcome. The majority of the time, in my experience, they end up being mistaken, but solidly convinced.
We’d need to know the details on such an individual’s claim, their full medical history, other meds, supplements, and importantly what % of the time were they under mTORC1 inhibition.
For all that we know, this individual could have been taking it daily.
There are adverse reactions to everything, from foods to environmental exposures, supplements and medications. It’s not a reason to have no one take what one person has an adverse reaction to.
I’m yet to have anyone have a significant adverse effect of rapamycin - and hope it stays that way.

6 Likes
#65

Yes.This is always the challenge with evaluating adverse events…

What (in the myriad number of things in our “environment” (food, supplements, medications, etc.) is causing the given issue. I know its a hard issue, made even more difficult because we have such extremely limited information and just was there is a placebo effect on the “positive” side of things, there is also the false attribution issue or coincidence issue that convinces people that X caused Y.

Maybe if we develop an “Adverse incidence” database for longevity drugs / therapeutics - as well as a positive / benefits incidents reporting mechanism, perhaps we can get a better handle on this - with the type of detail that you might see in a clinical study.

4 Likes
#66

I continue to be amazed by this story - even as low-key, cautionary and underselling of rapamycin as it was.

I didn’t realize it, but I just found out it was on the front page of The NY Times print edition. Wow - this will, I hope, help move longevity drugs and treatment more into the mainstream.

While I know many people here are disappointed the story was not as enthusiastic as most of us are about the potential for rapamycin to greatly improve people’s healthy lifespans… (and I fully agree with that sentiment) - I’m still glad that everyone here pitched in and share their stories and spoke with the reporter.

There is no question in my mind that the increased attention this type of story brings to field of longevity science will ultimately result in more investment in the field, more people working in the field, and faster progress. With a little luck even a rapamycin / longevity clinical trial might get done. Thank you everyone!

And yes, as you might expect, we’re getting more news media enquiries… so word seems to be spreading even faster now.

NYTimesSept25Rapamycin.pdf (2.6 MB)

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#67

I told my family about rapa and its potential help with neurodegenerative diseases (for some people some of the time). So, my sis in law asked her father’s doc about it for her father who has advanced parkinson’s. The doc refused and said it can make Parkinson’s worse and have negative side effects. So very frustrating when they don’t know that isn’t even true. What side effect for this immobile person are they even worried about. Makes me want to scream!

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#68

The story hit my instagram feed. I scrolled through some of the comments, and WHOA! There are so many unhappy people out there, which is pretty sad (who wants to live longer in this awful world, etc). Many more who seem angry and assume they know the details (only for rich people, etc). I didn’t see one person saying, hmmm, tell me more about this, I’m not convinced… etc.

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#69

Thanks for being willing to be in the article and sharing some of your story with us here. We all have different bodies, and we all can use therapies to help us with health - since many of us here take rapa.

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#70

Thanks for sharing your experience. A young (25yo) friend of mine, who has never used rapa, had the same (also shingles… Regular outbreaks of both for a few years now…). His first outbreak was just after he got his COVID vaccine. He never got COVID on the other hand. By any chance: did your first outbreak happen shortly after a COVID infection or vaccination?

1 Like
#71

If anything, T cell immunity is enhanced by Rapamycin, so I’d personally be happy that I was on Rapamycin - same thing for any of the viral illnesses.

I asked Vera-Health.ai … and got a good answer on this:
Rapamycin, also known as sirolimus, has a complex role in modulating T cell immunity. Its effects are context-dependent and can vary based on dosage and specific immune conditions.

Rapamycin primarily functions by inhibiting the mammalian target of rapamycin (mTOR) pathway, which is crucial for T cell activation, proliferation, and differentiation. This inhibition can lead to both immunosuppressive and immune-enhancing effects, depending on the circumstances.

One of the key ways rapamycin enhances T cell immunity is by promoting the generation of memory CD8+ T cells. These cells are essential for long-term immune protection and are particularly beneficial in the context of vaccinations, where a robust memory T cell response is desired for effective adaptive immunity. Rapamycin has been shown to improve the quality and longevity of antigen-specific CD8+ T cell responses, which can enhance the efficacy of various vaccines.

However, rapamycin’s impact on the primary immune response is more nuanced. While it boosts memory T cell responses, it can impair the function of effector CD8 T cells and macrophages, which are critical for immediate defense against acute infections. This suggests a trade-off between enhancing long-term immunity and potentially dampening immediate effector functions.

In the context of cancer treatment, rapamycin can enhance the antitumor efficacy of immunotherapies by promoting memory CD8+ T cell generation. However, its immunosuppressive properties necessitate careful application to avoid hindering immune responses.

Additionally, rapamycin’s modulation of mTOR signaling is crucial in balancing T cell quiescence and activation, influencing T cell differentiation and homeostasis. Emerging evidence also suggests that rapamycin can reduce chronic inflammation and improve antiviral T cell responses, as seen in HIV-1 infection models.

In summary, rapamycin can enhance T cell immunity primarily by boosting memory T cell responses, though this comes with the trade-off of possibly dampening immediate effector functions. Its application requires careful consideration of therapeutic contexts and dosing regimens to balance these effects effectively.

References

  1. Autophagy inducer rapamycin treatment reduces IFN-I–mediated Inflammation and improves anti–HIV-1 T cell response in vivo
    JCI Insight
    Mu et al.
    10 citations
    2022
    It is demonstrated that autophagy is directly linked to IFN-I signaling, which is a key driver of immune activation and T cell exhaustion during chronic HIV infection, and therapeutically targeting autophagic is a promising approach to treat persistent inflammation and improve immune control of HIV replication.

Open Access
Influential Journal
Show more
2. Immune Memory–Boosting Dose of Rapamycin Impairs Macrophage Vesicle Acidification and Curtails Glycolysis in Effector CD8 Cells, Impairing Defense against Acute Infections
Journal of Immunology
Goldberg et al.
29 citations
2014
It is found that functional CD8 T cell and macrophage responses to both viral and intracellular bacterial pathogens were depressed in mice in vivo and in humans to phorbol ester and calcium ionophore stimulation in vitro in the face of low-dose Rapa treatment.

Open Access
Influential Journal
Show more
3. Regulating Mammalian Target of Rapamycin To Tune Vaccination-Induced CD8+ T Cell Responses for Tumor Immunity
Journal of Immunology
Li et al.
81 citations
2012
The ability of a variety of rapamycin treatment regimens to regulate virus vaccination-induced CD8+ T cell memory responses and tumor efficacy is demonstrated and indicates that judicious application ofRapamycin can augment vaccine efficacy for chronic challenges.

Open Access
Influential Journal
Show more
4. Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment
Cancers
Hage et al.
26 citations
2021
This review presents the different classes of mTOR inhibitors and discusses their effect on immune cells by focusing mainly on CD8+ T cells and provides an overview of the different preclinical studies that investigated the anticancer effects of m TOR inhibitors combined to immunotherapies.

Open Access
Influential Journal
Show more
5. mTOR Signaling in T Cell Immunity and Autoimmunity
International Reviews of Immunology
Liu et al.
69 citations
2015
The mammalian target of rapamycin, a phosphoinositide-3-kinase-related protein kinase, acts as a rheostat capable of integrating a variety of environmental cues in the form of nutrients, energy, and growth factors to modulate organismal processes and homeostasis.

Influential Journal
Show more
6. Effects of Sirolimus treatment on patients with β‐Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4 + and CD8 + T cells
Journal of Cellular and Molecular Medicine
Zurlo et al.
5 citations
2023
Treatment of β‐Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN‐γ following stimulation with antigenic stimuli present in immunological memory.

Open Access
Show more
7. mTORC1 and mTORC2 as regulators of cell metabolism in immunity
FEBS Letters
Linke et al.
183 citations
2017
Findings show that the mTOR pathway integrates spatiotemporal information of the environmental and cellular energy status by regulating cellular metabolic responses to guide immune cell activation and generate a systemic understanding of the immune system.

Open Access
Show more
8. Rapamycin: could it enhance vaccine efficacy?
Expert Review of Vaccines
Nam et al.
12 citations
2009
It was reported recently that rapamycin, which is used as an immunosuppressive drug for organ transplantation, stimulates the production of memory CD8 T cells, which means thatRapamycin or related drugs could be used to enhance the efficacy of many types of vaccines.

4 Likes
#72

Thanks for the tip.

Our expertise in AI research has enabled us to build the highest-performing clinical decision support (CDS) tool on the market, achieving a 92% score on the US Medical Exam.

2 Likes
#73

Looks like one needs an invite. One can join a waitlist, however.

#74

It’s only for doctors.

1 Like