#45

As an immunologist and someone that treats angioedema every day I can tell you this:

  1. Anyone on ACE-inhibitor should look out for angioedema.
  2. There is NO EVIDENCE that low dose (non-immunosuppressive) rapamycin given in relatively healthy people will significantly increase that risk.
  3. Epinephrine will NOT treat ACE induced angioedema, anyone that develops it should rush to the ER.

I try to stay in my lane, it just happens that all forms of angioedema is what I do.

I wouldn’t argue with you about the best pub in London or parliament procedures.

6 Likes
#46

I think the only point I disagree with you is point 2. That depends on the definition of “low dose”.

I don’t think 6mg with GFJ is necessarily low dose.

I live in Birmingham, but I was a member of the UK House of Commons Procedure Select Committee for 10 years.

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#47

Hi @Candleflower Yes. There was one study mentioned on this site that said too low of a dose of Rapamycin can stimulate MTOR instead of deactivating it. It was fairly recent but I am having difficulty finding it here on the site as I read it in passing. Maybe someone reading this can point you in the right direction?

#48

@Candleflower

Per Copilot:

Yes, a too low dose of rapamycin can result in partial inhibition of mTOR (mechanistic target of rapamycin), which might not fully suppress its activity. This partial inhibition can lead to incomplete effects on mTOR signaling pathways, potentially affecting mTOR-mitochondria cross-talk²³.

In some contexts, low doses of rapamycin have been observed to trigger hormetic effects, which are beneficial stress responses that can activate anti-aging pathways². However, the exact outcomes can vary depending on the specific dose and the biological context.

If you’re considering rapamycin for any health-related purpose, it’s crucial to consult with a healthcare professional to determine the appropriate dosage and monitor its effects. Do you have any other questions about rapamycin or related topics?

Source: Conversation with Copilot, 10/2/2024
(1) Hormetic effect of low doses of rapamycin triggers anti-aging cascades … Hormetic effect of low doses of rapamycin triggers anti-aging cascades in WRL-68 cells by modulating an mTOR-mitochondria cross-talk | Molecular Biology Reports.
(2) Does Rapamycin Work For Longevity? - Life Extension. Does Rapamycin Work For Longevity? - Life Extension.
(3) Effect of Chronic Administration of Low Dose Rapamycin on … - PLOS. Effect of Chronic Administration of Low Dose Rapamycin on Development and Immunity in Young Rats.
(4) Targeting mTOR for cancer therapy - Journal of Hematology & Oncology. Targeting mTOR for cancer therapy | Journal of Hematology & Oncology | Full Text.
(5) Recent advances and limitations of mTOR inhibitors in the treatment of … Recent advances and limitations of mTOR inhibitors in the treatment of cancer | Cancer Cell International | Full Text.
(6) Pharmacology of mammalian (mechanistic) target of rapamycin … - UpToDate. UpToDate.

4 Likes
#49

Thanks Chris, I’ll take it up to 4 then.

#50

I think you are referring to this for low dosage increasing rather than decreasing MTOR - Top 5 - Which Currently Available Longevity Interventions Do You Think Are the Best - #201 by Jonas

@Candleflower

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#51

It’s worth pointing out that the effect is in tissue culture.

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#52

“downstream signaling actually increases”

What does it mean in plain English? Is MTOR decreased or increased?

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#53

Yes. That’s what I was referring to. Thanks @Bettywhitetest

#54

You and me both - I’d like to know too. It seems almost a throw-away response on Twitter but the researcher, David J Glass MD may have published something that covers his thinking. If I find it I’ll let you know.

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#55

I had been on 5mg siro per week, then started 500mg of metformin, IR eww… Then, I realized that IR was not what I wanted and moved to ER, then to 1,000mg ER then to 1500mg ER metformin, no issues.

I wonder if that person written about lost 5% of weight out his backside due the trying to take1500mg of Metformin at one sitting.

Btw, recently I doubled my Rosuvastin from 10 to 20mg daily, My lipid profile is excellent, so why? Rosuvastatin is anti-proliferative and I have prostate cancer. No negative effects that I can detect, no muscle issues, no tendon issues and lately I’ve been progressively increasing weights at the gym.

If that fellow had gone from 1,000 mg ER/SR metformin to 1500 milligrams IR Metformin, well, there goes one’s appetite and many would spend a lot of time sitting in contemplation, after that.

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#56

If you have prostate cancer, try taking dutasteride (or alternatively finasteride) as 5ar inhibitors have shown to reduce the incidence of prostate cancers.

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#57

Thanks for the links.

#58

Thanks for the link!

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#59

Sadly, it’s far too late for that. I have a T3 0/0 tumor that’s about 4 years old. I followed all the advice CDC/the task force and so on: "More risk to do digital + PSA and stopped getting checked about 4 years ago when I turned 70, just about the time it started. Thanks a lot CDC.

Yes, finasteride would be good for those at risk. I did not think that I had any risk factors, no family history of any cancer. I got it from Agent Orange, as a college kid I sprayed defoliant under power lines. 1 gallon of 2-4-5-T (or D?) to 55 gallon kero. I came home wet to the skin, every day.

I’ll do Orgovyx with Abiraterone, then hit it with 25 sessions of IMRT then get high-dose brachytherapy and that should give me a 80+% survival rate out to about 12-years.

I’ve been taking a bunch of anti-proliferative stuff, and I think worked because there were no distant mets.

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#60

Sorry you got prostate cancer, and I hope you’ll beat it 100%, but don’t you think getting cancer at 70 of something you did at 15 is realistic? If agent Orange was the culprit, I would think you could have gotten other cancers much sooner/faster? I know about 6 people that died of various cancers before or around 48-62 of age (all working in construction as painters), and obviously there is plenty of fumes and chemicals used in painting. But they got cancer much faster than 50 years, more like within 10-20 years working in such jobs.

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#61

Do you mind sharing what your PSA is showing?

#62

I agree - and no medications of any type help ACE-I angioedema. I see a lot of my colleagues giving epinephrine, steroids, h1/h2 blockers. The more “clever” ones try TXA, FFP and icatibant. Sadly none of this helps. It’s all time and airway management, and making the decision to place an airway or wait and see.

As the mechanisms are totally different, getting angioedema from rapamycin (which I’ve never seen) is an independent item from ACE-I and taking both together would have no feasible mechanism to increase risk of either item causing Angioedema. The risk would be additive with the highest risk being the ACE-I and the lower risk being Rapamycin being the cause of angioedema if one were to develop it while on both.

3 Likes
#63

I think this may happen with ARBs like Losartan as well.

#64

To prove a linkage between my cancer and Agent Orange (AO) (2-4-5-T / 2-4-5-D) conclusively would be difficult. As time goes by it might actually be provable if there is a genomic change that is linked to dioxin. (Note: Neither compound are carcinogenic, but both contained dioxin).

If I had been military, in an area where AO was used then my cancer would be presumed to be caused by AO by the VA.

“Complications from Agent Orange exposure were life-threatening and caused death. Over 300,000 U.S. veterans and over 400,000 Vietnamese people died from exposure to Agent Orange from 1962 to 1971.Feb 10, 2023”

Even if my cancer could be linked to AO, it would be difficult to sue the manufacturer since the US government forced (really, it was a mandate) nine different manufacturers to create it.

The take-away is, probably I’ll never be able to conclusively link it to my exposure.

As for time-linkage, “The mean time from exposure to Agent Orange was 407 months.” Therefore, the median likely age that I would have developed CaP from AO would be around age 54. So, it could be that AO was not the cause. Or it could be that I’m simply farther out on the bell curve.

I’m quite happy to have developed CaP nowadays, as the state of medicine twenty years ago was pretty awful, compared to today, which is, if nothing else, much “gentler.”

There is no history of prostate cancer (or any cancer) in my family history. I never smoked and I do find it interesting that for many years I have taken Rosuvastatin and have used Celecoxib, both which are anti-proliferative.

My PSA when discovered was 54.10. It is metastatic, but locally, not distant.

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