Triglyercerides and Insulin (with a touch of cholesterol)

So we wrapped up first round (6 weeks; 4mg once per week, then 2 week wash out). Ran the labs. Triglycerides and Insulin both shot up. Chol a little bit. We’ve read about “benevolent starvation diabetes” effects, etc. Any thoughts? Is it transitory? Also read about 20 week period to normalize. What’s the mechanism (lipolysis release from fat cells, etc)? Thanks…just checking if others have seen the same thing. HbA1c and glucose didn’t change but clearly the metabolic, adipose pathway is in flux. T also dropped.


@IndigoNaturals - Just for clarification and I am sure you did this, but both labs were fasting? How much is a big jump on Triglycerides and insulin? How much of a drop was your T and are you on or off TRT? Any other variables that would explain changes - diet, exercise or sleep. Thanks for sharing!

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Thanks for reply!! fasting. mine: insulin 6.8-8.7. Spouse’s (female) 2 to 12! Now, she was taking glucose control from pendulum (akkermansia and butyrate driving probiotics) before (which she stopped) so her normal is probably around 8. triglycerides 190 to 240. Always had an issue there. Low T which finally went back up (bioidentical sublinguals - free from 60 to 211) but dropped back after rap (44). Everything else is pretty stable. Glucose didn’t change (around 7). Thinking of testing again in 2 months to see if it’s a panic response from metabolic pathway (famine signals) similar to CR and fasting which mirrors same responses. T drop makes sense since mTOR inhibition is change from growth/reproduction to housekeeping but I don’t want to lose effects of T. If results still show in 2 months, I’ll prob switch to 2mg/once per week and test. That’s still .3mg daily equiv…just below the .5mg/daily tests that showed results. May have to stretch it out further for less flux. We need a database of individual results so we can start to see patterns. Thanks again!



My triglycerides have been stable and fluctuated between 109 and 57 for the last 7 years (12 years on Rapa).

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@IndigoNaturals - Overall I would not consider most of the changes you noted as clinically significant even though some may meet the criteria of statistically significant. Your plan is good since we are making this stuff up as we go. Labs are part of our journey, but not an absolute. Fish oil has worked well for many to lower triglycerides and may be an option. Make sure your testosterone levels are troughs since easier to predict than peak.

My approach, not everyones, is to have highest priority for Health Span or quality of life. If I get extra for Longevity then great! I have noticed a significant decrease in what I subjective consider as symptoms of aging. Lower joint pain, improved exercise recovery and feeling of well being all better on Rapa and worse off - just subjective. If I did not get any of these, then tougher for me to stick with it for longevity alone.
Keep us posted!

@David how long have you been taking Rapa? Do you take a break from it at all?

at what point did you start noticing positive effects?

was there an initial flux in the beginning?

Decided to continue through 2nd period with same protocol (6 weeks at 4mg and 2 week washout) and then retest just to rule things out. Will post when completed. Thanks!

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@Basil_Dev - I am on my 5th month which is a rookie on this site:) I did have a break when I got COVID about 6 weeks ago and felt like I took a break when I tried a compounded version of Rapa.

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@IndigoNaturals - I think you bring up a great point and might be worth a separate thread of why we check labs on Rapa and what people are doing with that information. It would be interesting to see what Dr. Green does with all of the labs he is getting and what adjustments he is making when he gets that information. My guess is that most of the time nothing is done with lab changes like yours and rarely some glucose and or cholesterol control modalities are added. Some of the lab changes we are noticing may not have anything to do with health risks associated with those changes. If I told you that I am using a modality that increases inflammation resulting in muscle soreness and joint pain along with stimulating mTOR, then first response may be stop the modality. If I told you I am talking about exercise then most say that this is acceptable response.

Looking forward to hear more about your journey. I like the concept of a wash out period. I would think our sites longest user of Rapa, @LaraPo, would have some valuable feedback on labs, adjustments based on those labs and washout periods.

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Don’t think so. Looked at data for 10 years. 109 was the highest I had for triglycerides. My HDL is also very good, while LDL is always abnormally high.

Maybe some people need washout periods and others don’t?

I’ve only been on Rapa for a couple of months. When I get my labs in a couple of months, if I find any problems with triglycerides/LDL/HOMA-IR, I’m not sure what I’ll do.

Adding interventions such as metformin and statins to fix the problem reminds me of the old rhyme about the old lady who swallowed a fly, then swallowed a spider to catch the fly, etc…it just doesn’t sit well with me.

I really don’t want to stop taking rapamycin, so maybe 10 weeks on 8 weeks off like Matt Kaeberlein mentioned in his latest video is an viable option.

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I just saw your post. Similar to you, my colleague also experienced an increase in his fasting insulin and drop in his testosterone. More details in this thread:

I hope others will routinely monitor their fasting insulin / HOMA-IR and testosterone levels, and report their results in this forum. It seems that rapamycin can cause a deleterious change in these metabolic parameters.

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In this study, rapamycin Alone reduced HOMA-IR and inflammation.

Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice


Great read, thanks.

I have used a wide variety of rapamycin dosages, generally speaking trying to reach the threshold of undesirable side effects. Maybe I need to define what I think are any undesirable side effects. Actually, it is quite easy: Anything that drives my blood panel results outside of the normal range is undesirable to me.

Quoting Dr. Mikhail V. Blagosklonny:

“I defined anti-aging dose of rapamycin as highest dose that does not yet causes side effects. If significant increase of LDL is viewed as side effects that needs treatment, then dose of rapamycin should be reduced. By definition, so simple. LDL will drop. Nothing else.”

On examining my blood results from the time I started in November 2021 with 5 mg weekly with EVOO I can see that everything looked better at the lower dosage.
I have not been happy with my blood panel results on the higher dosages that I am taking now.
Before I get my next blood panels, I am going to go back to the 5 mg/weekly dose and see if that improves my results.

Also, I guess it’s best to stick with metformin. I have been on and off again with metformin.
From the article you cited::

“Although broad use of rapamycin as a generalized antiaging treatment has been contraindicated by its immunosuppressive and hyperglycemic effects, recent research indicates that immunosuppressive effects can be attenuated, and potentially reversed, by alternate treatment schedules and lower doses than used for organ transplantation”

"This study demonstrates that the hyperglycemic effects of rapamycin can be managed with antihyperglycemic co-treatments such as metformin and that the benefits of rapamycin are enhanced by such co-treatment."

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I am up and down about my feelings on dosing. I’m sort of in the middle now at about 6-8 mg’s per week.

I’m thinking that walking right after meals and the soleus push-ups will make meds like metformin and acarbose unnecessary while avoiding any known and potential side effects.

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I’m thinking that it is true for smb who’s not on Rapa and who wants to avoid T2D and stay overall healthy. With Rapa it seems not enough. I’ve been trying very hard (diet, 0 sugar, 0 deserts, exercising 7/7, walking after meals, etc) and my FG is always borderline. Feel like I need a little push with Metformin, may be a pulse low doze when I take Rapa.

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Metformin has a whole laundry list of beneficial effects as been discussed elsewhere in the forums. I take it for these other benefits not because it lowers my blood glucose.
I only waver because of my age and I don’t want to take the edge off of the resistance training I do. It wasn’t until I reached age 80 that I started to weigh the benefits against possible inhibition of muscle gain. My personal recommendation, and not medical advice, to anyone under ~75, you ought to be taking it.

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I taper my Metformin usage and that seems to work best. I take 1 g on the day I take Rapa and for the next two days. Then I go down to 500 mg for 2 days. Then I stop taking Metformin the last two days. I do this because my body tells me I am taking too much Metformin later on in the week. (I get feelings of hypoglycemia)

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