#1

73 yo male active physically daily30 minutes Pilates each morning and 5 miles daily walk average as well as 3x weekly pickle ball 2-3 hour sessions and skiing once a week and e-bike 600 miles annually.
I’ve stopped taking 5 mg weekly dose of rapamycin (Sirolimus) on 1/21/25 due to the sudden only 9 weeks between tests. increase in my Lipid Panel on 10/23/24 from 08/16/24 my cholesterol total went up from 176 to 210 and my LDL from 108 to 139 and also my hemoglobin A1c went from 5.8 to 5.9 hemoglobin A1c want to get this under control. My Apolioprotein B went from 87 to 104. On advice from a Doctor friend I started taking red rice yeast 1200 mg per serving along with CoQ-10. I will take a break from rapamycin until I retest my lipid and total cholesterol, and Hemoglobin A1c and Apolipoprotein B.
I had a recent CORONARY CALCIUM SCORE (AGATSTON UNITS): Total Score:172 BY VESSEL: LM:0 LAD:112 LCx: 10 RCA:28 D1: 23 The observed calcium score is at 47 % for subjects of the same age, gender, and race/ethnicity who are free of clinical cardiovascular disease and treated diabetes. McClelland RL, et al. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2006;113(1):30-37
Since I have family history of heart disease as my mother died of a heart attack at age 60. This is my concern with the sudden increase in my Lipid Panel and other bio-markers. I have an appointment with my Cardiologist on Wednesday to discuss but am also interested in your opinion. I take 25 mg Acarbose daily before my breakfast oatmeal or scrambled 3 eggs twice a week.Interested in hearing if others have had similar experiences and how to navigate this issue.

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#2

I have just started rapa a month ago, so I don’t know the impact on my lipids yet, will test sometime in March. But my lipids have always been trash TC 240-260, LDL 160-180. Atorvastatin 10mg/day initially was extremely helpful, but gradually failed, and now I’m almost back to my old numbers. I switched to self-prescribed pitavastatin 4mg/day since November 2024.

I’m 66. At 65 my CAC score was 0. I am expecting my lipids to be still not optimal, and I will then add bempedoic acid 180mg and ezetemibe 10mg, to try to crush LDL below 60 at a minimum.

My only observation for you would be to ask about the red rice yeast. That is just a more poorly dosed (less uniform) statin monacolin-K/lovastatin. If I were told to take red rice yeast, I’d probably just go on lovastatin directly, because at least you know the exact dose you are getting and in a pharmaceutical grade delivery system. But, if you are going on a statin, then there are many options. There are of course also non-statin drugs that can lower your ApoB/LDL. Some statins raise blood sugar and can even lead to diabetes, so I’d avoid those, but others do not do so. BA, EZ, and PCSK9i don’t derange your glucose.

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#3

I personally don’t know why anyone would take Rapamycin without metformin/sglt2 inhibitors and bempedoic acid/pcsk9 inhibitors/ezetimibe/statins.

Get your A1C under 5 and your APOB under 40 ASAP. Then add the Rapamycin.

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#4

The results from before rapamycin were already indicative of needing intervention. A non-zero CAC at any age and LDL > 100 should be treated. HbA1c in pre-diabetes territory despite physical activity should be treated.

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#5

“I personally don’t know why anyone would take Rapamycin without metformin/sglt2 inhibitors and bempedoic acid/pcsk9 inhibitors/ ezetimibe/statins.”

I do rapa (+ metformin) without bempedoic acid/pcsk9 inhibitors/ezetimibe/statins.

Why? Well, many little reasons, such as fearing starting statins too early and them no longer working well when I am old and may really need them, but perhaps the main reason is that I am still not properly informed on these issues, despite having soon digested several years worth of posts on this forum.

So, please, give me your best/worst beatdown/scolding on what I absolutely need to add now because otherwise I may better not do rapa because…

#6

Hi, and welcome to the site.

I’m not a doctor - but generally it seems you want to get your LDL down lower anyway, I recommend you review this thread: Saúde Cardiovascular

And your A1C is also higher than optimal - you really want to get it down to around 5.0 I think.

So - even aside from rapamycin I would work to get these numbers down. I had a similar situation; lipids and A1C slightly elevated even before rapamycin; added rapamycin and they went up about 20% when I’m on higher doses of rapamycin, closely spaced (e.g. weekly). Now I’m on a statin, bempadoic acid and Zetia and my LDL-C and APOB are under 50. Pill Splitting Ezetimibe and Bempedoic Acid to Save Money, Lower Side-effect risk

Even if I wasn’t taking rapamycin, I’d still target under 50 for APOB / LDL-C.

With a positive CAC score - I’d be very aggressive on the LDL levels.

I’m not sure the best way to lower A1C. I’m sure others here will have suggestions.

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#7

I don’t understand why this would be a thing, I’ve heard Lustgarten say this as well but I don’t think I’ve ever heard of tolerance from a medication like statin with age.

More likely someone’s physiology changes with aging, lifestyle, that just means off treatment they would be even worse than they were in the first place. It has nothing to do with tolerance at the HMGCR receptor in the liver to a statin medication.

#8

@CronosTempi just wrote above: “Atorvastatin 10mg/day initially was extremely helpful, but gradually failed, and now I’m almost back to my old numbers.”

“More likely someone’s physiology changes with aging, lifestyle,” e.g. taking statins.

Anyways, even if the fear is unfounded, that is still far from saying that rapa should not be taken without statins. If that were the case, it should be one of the first things people see on this forum, like “Welcome to rapa, warning, don’t proceed with it before reading up on statins”.

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#9

I don’t think it gradually failed because of the statin itself.

The reason why statin isn’t automatically recommended with rapamycin is because it’s relatively rare to have an increase in lipids or glucose.

However as I’ve said before, using rapamycin while lipids are suboptimal is like rearranging the deck chairs on the titanic. You’re not going to live much longer or better when atherosclerotic plaques keep developing and destroy your brain (stroke) or heart (MI), and which has little to do with aging. Apolipoprotein B (ApoB)

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#10

I don’t know why my lipids went up again. The phenomenon of lipids rising with age is well established, so it’s possible that that’s what’s been happening in my case. I started on ator as I was turning 60. At first the effect was stellar, first year, then gradually worse, until the almost originally bad numbers when measured last October, age 66. Can I 100% exclude the statin becoming less effective, rather than age related rise in lipids? Well, few things in the body function can be stated as 100% certain, so no. All I have to go by are odds and statistics.

#11

This will most easily be resolved of a graph from a long term statin trial on LDL cholesterol levels but I couldn’t find any. First time I’m hearing this anyway so I’m very skeptical, and N=1 is rife with confounding factors.

#12

My LDL and ApoB went up a lot after starting Rapamycin. Taking Bempedoic Acid and Ezetemibe plus a low dose Atorvastatin brought them down to the 40-60 range. If you take Rapamycin you probably need BA (or low dose statin) and Ezetemibe at the very least to counter the effects on lipids. Just adding red yeast rice isn’t going to cut it, IMHO. Red yeast rice sold in the USA is required by the FDA to remove the cholesterol lowering ingredient which makes it impotent.

Pairing Rapamycin with Metformin should help with the HBA1C issues.

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#13

First off, to Lad_Lavicka: “73 yo male active physically daily 30 minutes Pilates each morning and 5 miles daily walk” DAMN!!

Next, this thread is scary. I’ve been using Rapa 4mg/week w/GF juice for awhile without any testing of lipids or what-have-you. I have an intense job, a side business and am the sole parent of a teenage boy, so not a lot of time for diving into PubMed and lipids which is why this community is invaluable.

So I asked my friend CGPT about Metformin & rapa:

“Whether taking Metformin alongside Rapamycin (4mg per week with grapefruit juice) is beneficial or necessary depends on your goals and individual health factors. Both drugs are often discussed in the context of longevity, anti-aging, and metabolic health, but they work through different mechanisms:

How Rapamycin Works
• Inhibits mTOR (mechanistic target of rapamycin), reducing cellular growth and promoting autophagy.
• May extend lifespan and improve age-related health markers.
• Higher bioavailability when taken with grapefruit juice, meaning a lower dose can achieve stronger effects.

How Metformin Works
• Activates AMPK, increasing insulin sensitivity and mimicking caloric restriction.
• Lowers blood glucose, reduces inflammation, and may have anti-cancer effects.
• Some studies suggest it has synergistic effects with Rapamycin in aging and metabolic health.

Is Metformin Necessary with Rapamycin?
• If you have insulin resistance or high blood sugar: Metformin could be beneficial since Rapamycin can sometimes cause mild glucose dysregulation.
• If you’re taking Rapamycin for longevity and general health: Metformin may add benefits but isn’t strictly necessary.
• If you’re lean, active, and metabolically healthy: Metformin might have little added benefit and could reduce the positive effects of exercise on mitochondria.

Potential Downsides of Combining Both
• Metabolic trade-offs: Rapamycin can slightly impair glucose metabolism, while Metformin improves it—balancing them is tricky.
• Nutrient absorption concerns: Metformin can reduce B12 levels, requiring supplementation.
• Exercise performance: Metformin might blunt some benefits of high-intensity exercise.

Bottom Line

If your blood sugar is normal and you don’t have metabolic issues, Metformin may not be necessary. However, if you have prediabetes, diabetes, or insulin resistance, adding Metformin could be beneficial. If you’re unsure, tracking fasting glucose, HbA1c, and insulin levels could help determine whether Metformin would be helpful alongside Rapamycin.“

I get blood tests regularly at Kaiser. Based on the community’s experience, what should I ask to be included in the blood test analysis? Fasting glucose, HbA1c, and insulin level? Can these be tested with an “at home” diagnostic test?

Thanks for sharing this information & your experiences.

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#14

And lipids (LDL-C, etc.).

I go to the local LabCorp office every few months to track this sort of thing. I would start with the CBC (or something similar from Kaiser):

and the A1C:

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#15

My friend Dr. Alex is a long time functional Health advocate and advised me the following along with interpretation of my October 26,2024 CBP 9 weeks after starting on 5 mg Sirolimus weekly and 25 mg Acarbose daily as recommended by Healthspan. Comparing it to my CBP on August 16, 2024.
Here’s my take:

  1. CBC–elevated MCV (mean corpuscular volume=size of red blood cells). When enlarged, often caused by low Vitamin B12 and Folate. However, with the B Vitamins a B Complex is advised b/c they work in concert. My favorite: Active B Complex by Integrative Therapeutics.

  2. Lipids: because of your mother’s early heart attack, you are considered to have a positive Family History. Your Cholesterol is the sum of your HDL (H for happy), LDL (L for lousy) and your Triglycerides/5 (so a smaller contributor). Having an HDL of 61 ia considered protective, but many physicians want your LDL to be <=100. That is over-simplistic since we know that HDL and LDL are both made up of different “fractions”, some good, some bad, so you have to go beyond the mere number. Quest offers a better look by ordering:

  • Cardio IQ with Inflammation (#94220)
  • Oxidized LDL (#92769)
  • Cardio LP-PLA2 (#94218)
  • Cardio IQ(R) MPO (#92814)
  • F2-Isoprostane/Creat (#92771)
  • ADMA/SDMA (#94153)
  1. Your HgbA1C (hemoglobin A1C), a measure of average blood sugar over a 3 month period is in the “pre-diabetic” area. You need more information, as this often results from “Insulin Resistance”. There are 2 ways of investigating:

a) Get a 3-hour Glucose Tolerance Test (which measures your blood glucose fasting and then each hour for 3 hours after a drink of glucose. However, the important thing is to get your physician to write for Insulin levels to be done at the same time as each blood draw–fasting, 1-hour, 2-hour and 3=hours post glucose drink). This additional test is rarely done in my experience and needs to be specified. Then, each time your blood is drawn, you need to double check with the phlebotomist that the insulin was done as well as the glucose.

b) Get a fasting blood test for glucose and insulin. Then eat a breakfast that includes some starches (bagel, toast, potatoes, jam, jelly, pancakes or something like that) and then repeat a glucose and insulin blood test 2 hours after the start of the meal.

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#16

Thank you for sharing and expanding on the other potential issues to be aware of when taking rapa. You’re lucky to have such a knowledgeable friend to assist you on this journey.

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#17

Regardless of and unrelated to rapamycin, your LDL/apoB are too high esp given that CT Ca score. That is not a reason not to take rapamycin but is a reason to treat your lipids and lower risk. Would go right to crestor and titrate up aiming for LDL<70 at least. Might want to also check your LPa as a separate risk factor. If high, would push the numbers even lower. But don’t give up on rapamycin.

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#18

You can lower your weekly dose, for example 2mg per week.

#19

@Lad_lavicka Good for you getting on top of this! You are doing great with the exercise so keep up the good work there!

I agree with others you need to push your LDL and A1C lower. I have a little different perspective though. I’d recommend going straight to pcsk9i with your family history and your lipid profile. You can then add to that (ezetimibe, low dose statin, Bempedoic acid) as needed. You’ll need to ask a lipidologist or perhaps your internist for a prescription and it will likely need pre-authorization from your insurance but you can emphasize your family history, A1C, and CAC score to write a convincing letter. You can also apply for a copay card and get the price down to quite reasonable levels. I believe I pay $30 every 3 months.

Also, I’m not a fan of metformin based on the mouse studies and it’s mechanism of action. For dropping A1c I’d start with an SGLT2i like Empagliflozin. 25 mg daily. Reassess in 3 months and tweak as needed. I’d only use Metformin if you are overweight and have type 2 Diabetes.

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#21

A strict Ketogenic diet will definitely lower your HbA1C, but may raise your lipids.