Thanks. I was wondering about that for a while. Funny.

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It’s been a while since I’ve updated this thread.

I am now alternating between 3 mg Rapamycin+ GFJ and 2 mg Rapamycin+ GFJ every other week.

I am now taking 500 mg Metformin daily as well as 180 mg Bempedoic Acid.

We’ll see how my lipids and HBA1C are when next I test.

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Why Metformin and not Acarbose and SLGT2i?

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I am also still taking acarbose 100 mg before each meal. I just noted the changes I made to my base regimen.

I am not taking an SGLT2 drug yet as I hope the daily Metformin will push my HBA1C levels back into normal zones. If not, I may try one.

I have stopped taking Ezetimibe for now because I want to test the effects on cholesterol by Bempedoic Acid first. After my next blood test, I’ll add it back in and then see what effect it has.

Very good questions! :slight_smile:

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I decided I don’t want to mess around with ApoB or LDL and have added Ezetemibe back in. Everything is going smoothly. I will be doing a full body checkup at the end of March with a full blood panel.

My father will be taking Bempedoic Acid + Ezetemibe as well, so we’ll see how his lipid panel is impacted by them. My father had to stop taking Rapamycin due to a bacterial infection in his tooth which simply rages out of control when he takes Rapamycin so he is going to have a root canal before he begins Rapa again.

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It’s been a while since I updated this, so here goes:

My father’s experience with Bempedoic Acid + Ezetimibe was a resounding success! His ApoB dropped about 40-50% from a high to a low risk. His inflammation (hs-CRP) also dropped from 1.2 to 0.57. I am now taking Bempedoic Acid + Ezetemibe as well. See below for more info:

I am currently alternating taking weekly 4 mg of Rapamycin + GFJ and 3 mg of Rapamycin + GFJ (14 mg - 10 mg Rapa equivalent). Currently, I am taking an off week as I have a bacterial infection and a mouth sore. Interestingly, the mouth sore caused shooting pain in the nearby molar, but since it has healed, the molar pain has gone away as well.

I have noticed that about every 3 weeks I develop a mouth sore, bacterial infection, or some other injury. I then stop taking Rapa for a week to allow my body to recover. I just finished a 3-day course of Azithromycin and Vitamin C to treat the bacterial infection (and as a mini-DAV experiment). It worked well and I will start taking Rapa again on Saturday.

I am still taking 500 mg of Metformin daily and Acarbose with my carb-heavy meals. I am having my body check at the hospital tomorrow so I should have new bloodwork results available in about 5-6 weeks. I’m really interested in seeing my new HBA1C and lipid panels!

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@DeStrider, thank you for sharing your experience.

Are you monitoring your fasting glucose levels with a Continuous Glucose Monitor? I have observed a consistent and systematic effect on fasting glucose levels (100-120 mg/dL) for 6-7 days following the administration of rapamycin (2 mg with grapefruit; 3 mg with grapefruit introduces some sort of glucose volatility on top in my n=1 case). In response to this observation:

  • I am introducing 800 mg of Metformin 1-2 days before and after taking rapamycin, as the effects of Metformin on glucose levels become noticeable after 3 days of intake.
  • I have decided to cycle rapamycin every three weeks to maintain stable fasting glucose levels for at least two weeks.

Currently, I view this glucose intolerance as part of the therapeutic effects of the starvation-mimicking drug rapamycin. (Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to; Mikhail V. Blagosklonny)

Therefore, I strongly recommend monitoring fasting glucose levels around the time of rapamycin intake to observe personal responses and decide on a regimen.

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Thanks so much for sharing all this information.

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I have just received my blood work results. This was on my protocol plus 500 mg Metformin and 140 mg Bempedoic Acid and 10 mg of Ezetemibe.

LDL cholesterol - 66 mg/dl (Down from 122 mg/dl)
HDL cholesterol - 46 mg/dl (Down from 54 mg/dl)
Total Cholesterol - 123 mg/dl (Down from 194 mg/dl)
Triglycerides - 84.1 mg/dl (Down from 101 mg/dl)

HBA1C - 5.4% (Down from prediabetic 5.7%)

Based on my father’s and my results, Bempedoic Acid and Ezetemibe do what they’re supposed to with a 45-50% decrease in LDL and ApoB.

500 mg of Metformin also moved me out of prediabetes into a normal (optimal) zone.

Since Rapamycin raised both my HBA1C and LDL cholesterol, it seems that these two drugs do a great job of counteracting these bad side effects of Rapamycin.

This also probably explains why Metformin paired with Rapamycin helped mice live longer in the ITP trials. Since mice don’t die of heart attacks, but humans do, I’d wager we need to treat high cholesterol to optimize our lifespan further.

Summary: Rapamycin+Bempedoic Acid+Ezetemibe+Metformin is a winning combination N=2

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Update

Based on the PEARL trial results and my own experimentation with high dose Rapamycin, I have settled on a dose of 5-6 mg Rapamycin + GFJ + EVOO (17.5-21 mg equivalent) weekly. I am also taking 1 g of Metformin (500 mg morning, 500 mg night) + Acarbose (50 mg) with carb heavy meals.

For cholesterol, I am taking 140 mg Bempedoic Acid, 10 mg of Ezetemibe and 5 mg Atorvastatin (Lipitor).

I am adding Empagliflozin (12.5 mg) and added Metformin to help bring my HBA1C level back down. The 4.7 level I reported earlier was wrong, the correct value was 5.4 which is acceptable and my new short-term target.

I am concerned about my CRP score. Any good suggestions on how to lower this?

My ApoB is excellent. I am happy with it.

I have also added Telmisartan 40 mg to optimize my SBP which sits between 106-129. I am taking a total of 8 prescription medications and I am quite happy with the results so far.

My body weight has increased 1 lb. because I’ve been on vacation for the past 5 weeks and eating too well - Lots of fish and chips and prime rib. I’m back to Hong Kong and back to my healthy diet so I should see weight lose due to diet, exercise and Jardiance. I feel like I am more optimized for longevity and healthspan now.

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I think my protocol is why my CRP is normally below the measurement threshold the lowest of which is 0.15 mg/l.

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John - have you tracked your CRP over the years as you implemented your protocol? What factors do you think are the major contributors to your low CRP?

My CRP is at 0.90, and while not bad, I would like to get it much lower.

Looking at the list of factors that contribute to higher CRP:

Other suggestions to lower CRP:

How to lower high CRP levels: Focus on your risk factors

Since hs-CRP levels reflect the level of inflammation in the body, most ways to lower high CRP levels are focused on reducing underlying causes of inflammation. Making lifestyle changes to reduce inflammation is in your control, but other contributing factors (like autoimmune diseases) may need medical intervention. Due to their effect on inflammatory pathways, some medications may cause a reduction in CRP, such as:

  • Statins (commonly used for high cholesterol)
  • Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen and aspirin)
  • Corticosteroids (typically used to treat rheumatologic conditions like arthritis)
  • Metformin (commonly used to treat type 2 diabetes)
  • Vitamin or herbal supplements (e.g., fish oil, anti-inflammatory spices like turmeric and ginger)

There are also several ways that may help reduce high CRP levels naturally:

Eat anti-inflammatory foods

Certain foods are linked to higher levels of inflammation. Limiting or avoiding inflammatory foods like refined carbohydrates, fried foods, red meat and processed meat can help reduce CRP. Instead, focus on eating more anti-inflammatory foods like leafy greens, nuts, fatty fish and whole grains. Over time, an anti-inflammatory diet full of fruits, vegetables and fiber can help lower CRP levels.

Exercise regularly

In the short term, intense exercise like weightlifting or a long run might spike CRP levels. (That’s why it’s important not to exercise immediately before testing your CRP levels.) But in the long term, regular physical activity can have anti-inflammatory effects on the body. Exercise not only helps reduce body fat (which contributes to inflammation), but it can also help the body increase its production of hormones that fight inflammation.

Aim for 30 minutes of moderate exercise at least five days per week. This could include brisk walking, swimming, cycling or other cardio exercises that get your heart rate up. Strength training with weights two to three times a week also has anti-inflammatory health benefits.

Manage your weight

When your body is carrying excess weight, the surplus of macronutrients in the adipose tissues (i.e., body fat) can contribute to inflammatory effects in the body, causing the liver to produce more CRP. In other words, the more fat your body is carrying, the higher your risk of chronic inflammation and high CRP levels.

Losing even a modest amount of weight can help lower inflammation and CRP. Focus on diet and exercise for safe, sustainable weight loss.

Avoid or quit smoking

Smoking triggers inflammation and damages blood vessels, raising your risk of several serious health conditions, including cancer, lung disease and heart disease, among others.

Giving up smoking can help lower CRP levels and inflammation. However, research shows that CRP levels may remain high long-term for those who quit smoking compared to those who have never smoked cigarettes.

Limit alcohol

Drinking heavily promotes inflammation. Moderate your alcohol consumption by limiting yourself to one drink per day for women and two drinks per day for men. Give yourself alcohol-free days each week to allow your body to recover.

Manage stress

Chronic stress takes a toll on the body and can raise inflammation. Make time for relaxing activities like meditation, yoga or deep breathing. Spend time doing hobbies you enjoy. Get enough sleep and connect with family, friends and other people within your support system. Managing stress can help control inflammatory responses.

The key to lowering inflammation is being proactive about your health. Get your CRP levels tested so that you know your baseline and talk to your doctor about your results to make sure you understand them and to see if additional evaluation or intervention is needed.

Source: What is a high C-reactive protein level? How to lower CRP

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You can see my CRP on this page and an explanation of the situation

https://citrate.science/2024poster/poster.html

I think it is a mixture of citrate (mainly) and melatonin. I think, however, that the reduction in inflammation also causes a reduction in WBC. Not that this is an issue.

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IMO: Since I have been tracking CRP for a very long time my history shows an almost random variation.
It may be a useful marker for the current state of your immune system, but other than that it is not a very helpful marker in predicting longevity.
If your CRP is constantly high over several tests, then maybe you have a problem.
One CRP measurement IMO is meaningless as a longevity marker.

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I agree that you need a number of measurements. You can see this on my chart.

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@John_Hemming Do you make up a mixture of different citrates? Ca, K, Mg, Na?

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@DeStrider Did you say why you added atorvastatin to the stack after your results were already very good?

Yes best look at the topic about this.

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I decided to add a low dose (5 mg) Atorvastatin because although my LDL and ApoB were just below 70 there was still research showing that there is some atherosclerosis at that level. However, at below 50, progression may stop and there may actually be some regression.

My 77 yo father also had an LDL and ApoB at the same level as me, but a CAC score of 352. His PCP put him on low dose Atorvastatin to try and lower the score and stop any progression. I decided to try a dose while visiting him and found I could tolerate Atorvastatin. After about 10 days on Atorvastatin, I had my blood work and I was quite satisfied with the new value.

Just below 50 seems like a sweet spot and I see no reason to lower it further.

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I have just recently finished my trial of Rapamycin at the following dosages - 4 mg + GFJ, 5 mg + GFJ, and 6 mg + GFJ a week. The reason I say 6 - 7 mg is because I took the dose on the back of a week of 5 mg, so there was some extra Rapamycin in my system that hadn’t cleared yet. I estimate that to be about 1-3 mg extra. These are all weekly doses. Here are the results:

6 - 7 mg + GFJ (21 - 25 mg equivalence) - Horrible hives (more than 50 mostly on the torso) for several days. It’s very itchy and annoying. It’s not what I want to do regularly. I won’t do this again.

5 - 6 mg + GFJ (17.5 - 21 mg equivalence) - Mild hives that lasted for several days. I had thought they were mosquito bites. Again, quite annoying but much better than at 6-7 mg.

4 - 5 mg + GFJ (14 - 17.5 mg equivalence) - 2 - 4 small semi-itchy hives that appeared on appendages. 2 acne pimples on the neck. This seems to be the level that works best for me, and I will maintain this level for now.

I did my bloodwork after the 6 mg + GFJ while I was in the US. My LDL and ApoB were still at 48 (due to statins, Bempedoic Acid and Ezetemibe) and my HBA1C was 5.8. So it seems that the various dosages at these relatively high levels do not significantly make lipids or blood sugar worse after the initial bump when I started taking Rapamycin. (When I first started Rapamycin, my LDL jumped to 120 from 67).

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