Rapamycin and risk of cardiovascular disease

I no longer believe I’ve had negative side effects from statins.

I was confused by the muscle soreness and occasional strains I get from work outs. But it doesnt seem that my pains are what is described as a statin side effect, so I’ve increased my minimum dose rosuvastatin from alternate days to daily in hopes for further lipid improvement. Doctor agreed.

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October 25, 2023RESEARCH ARTICLE

Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults: A Prospective Cohort Study

(Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults: A Prospective Cohort Study | Neurology) Higher triglycerides were tied to lower dementia risk, prospective data from the ASPREE trial showed. (Neurology )

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This just screams reverse causality. Is there a rpc trial looking at lowering triglycerides and dementia rates?

That probably an aberrant splicing issue

News > Medscape Medical News

Another Study Ties Statins to T2D: Should Practice Change?

Medscape, medical news

October 30, 2023
Again study showing increased risk of DM in patients on long-term statin therapy.

In the prostate?
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Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A US Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ , Ishak Mansi, MD, of the Orlando VA Health Care System, Orlando, Florida and colleagues, write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

Jill Crandall, MD, Albert Einstein College of Medicine, New York City, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, Emeritus, Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, Ohio, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”

Medscape Registration

The message seems pretty clear.

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The keywords here are " small increased risks". Everything seems to have some drawbacks.

Sadly there is no drug in existence that is perfectly tolerated by 100% of people taking it. We, as longevity pioneers, need to weigh risks against (potential) rewards.

For example, just check out rapamycin’s side effect profile. If it wasn’t for the potential 30% increase in lifespan, who in their right mind would risk the following side effects?

Sirolimus may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have any change in your mental state, decreased vision, weakness on one side of your body, or problems with speech or walking. These symptoms may start gradually and get worse quickly.

Sirolimus may cause serious side effects. Call your doctor at once if you have:

  • redness, oozing, or slow healing of a skin wound;
  • a new skin lesion, or a mole that has changed in size or color;
  • unusual bleeding or bruising;
  • sudden chest pain or discomfort, cough, feeling short of breath;
  • tenderness around the transplanted kidney;
  • signs of infection–fever, chills, painful mouth sores, skin sores, cold or flu symptoms, pain or burning when you urinate; or
  • low red blood cells (anemia)–pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

You should not use sirolimus if you have ever had a lung transplant or liver transplant.
Sirolimus may cause your body to overproduce white blood cells. This can lead to cancer, severe brain infection causing disability or death, or a viral infection causing kidney transplant failure.

Sirolimus Uses, Side Effects & Warnings (drugs.com)

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@AnUser I gave up Ezetimibe. My body can tolerate it fine, but it negates the cardio protective effects of Omega 3 fish oil which I take. ACM reduction was the same for taking Ezetimibe or Omega 3, so I kept with Omega. I will wait to see my next blood work and then decide what to do next. Probably Bempedoic Acid.

I’m really not having much luck with cholesterol lowering approaches!

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Do we know what type of serious brain infection this is? (the link seems to just be about general infection)

It prevents absorbtion of ALA, not DHA nor EPA. The cardio-protective effect is not dependent on ALA.

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Can you share more about this, is it N=1 experience (data vs subjective if so), mechanistic rational or seen in the trials?

I’m basing my decision off the information provided by @Joseph_Lavelle and followed by a couple studies I found by Google.

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There is no ALA in fish oil, that is a plant omega-3, they are different compounds.

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I take ezetimibe and fish oil still. I am trying to get both to work by cycling them in opposite cycles during day (AM Eze vs bedtime fish oil) and during week (stop eze and go heavy on fish oil Fri/Sat/Sun). The Eze half life is long but I’m trying).

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This is the study on Ezetimibe and Omega 3.

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Yes that is ALA, it is not the same as EPA/DHA. There is about a 1-10% conversion rate of ALA to EPA/DHA.

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Here is another study that shows that Ezetimibe reduces cardiovascular events in patients with low EPA, but has no effect on patients with high EPA. So, if you have a high EPA, Ezetimibe isn’t really effective.

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Friend, we are trying to help by exploring the different possible combos of drugs/supplements that you can take to lower lipids because you are not able to tolerate statins.

I couldn’t find it on a thread where you tried Pantethine.
I find it remarkable that it is so overlooked.

I tried it with 10mg of ezetimibe while stopping atorvastatin. It was just as good if not better than the atovastatin and ezetimibe combo.
So, the combo to try if you haven’t already tried it is: Ezetimibe+policosonal+Pantethine.

“Pantethine administration (standard dosage 900 mg per day) has been shown to significantly reduce serum triglyceride (−32%), total cholesterol (−19%), and LDL-C (−21%) levels and to increase HDL-C (+23%) levels.99,100 It appears to be especially useful in lowering blood lipids in diabetic patients.101–103”

“Policosanol significantly reduced levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C), as well as increased serum levels of high-density lipoprotein cholesterol (HDL-C”

“Policosanol Reduces Blood Cholesterol Levels by Inhibiting Sterol Regulatory Element-binding Proteins-1c and Fatty Acid Synthase”

“If so, it may be feasible someday to produce a tablet combining policosanol and ezetimibe that could reduce LDL cholesterol by about 40%, without side effects, and that could be recommended to virtually anyone whose LDL cholesterol levels were not already ideal.”

“Policosanol (PCO) supplementation is widely used in Central America and Latin America to treat dyslipidemia and manage cardiovascular burden”

https://www.sciencedirect.com/topics/medicine-and-dentistry/pantethine#:~:text=Pantethine%20administration%20(standard%20dosage%20900,C%20(%2B23%25)%20levels.

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