I have been self experimenting on myself with various rapamycin dosage regimens and I started with high doses, up to 20mg with grapefruit juice bi-weekly. At the time, Dr. Blagosklonny was advocating higher doses with increasing age with manageable side effects. I have been titrating down ever since. I am currently taking 5mg/weekly with EVOO. Since I have started taking rapamycin my blood markers have not been as good as they were before I started rapamycin. My epigenetic age on the Levine spreadsheet became worse right away.
I have some blood tests scheduled at the end of this month and if there is no significant improvement over my last tests I will be reducing my intake of rapamycin to 1mg/daily for a week and then one week off.
I am thinking that rapamycin may not be the panacea for aging that we have been led to believe. Or, maybe, the doses I have been taking are just too high for me.
I would not say there is a single solution to mitigate aged based deterioration. There are a number of interventions. One is rapamycin.
Mike Lustgarten has a simple philosophy, does a variable positively or negatively impact ‘big picture biomarkers?’. This is the second thread today where we have objective data that Rapamycin is pushing markers in the wrong direction. I’ll ask again, does anyone have longitudinal data showing rapamycin having a positive effect on any biomarker? For example, monthly data for A1c before, during and after rapamycin treatment?
I think quite a few people have positive data on MCV. My view is that Rapamycin causes an improvement in mitochondrial quality. However, I think it causes a short term increase in glucose levels. The big question (to which I have no answer) is how long the increase in glucose lasts. This will depend upon how much is in the blood for how long (dosage, bioavailability, half life etc).
As far as I am personally concerned my HbA1c and glucose returned to a good level once the rapamycin dropped out of my system.
I can give extracts of any biomarker I measure on an almost weekly basis from May 2022 if you want.
I have a broader protocol objective and I am happy that my cellular health is improving.
For example Cystatin-C
8/6 0.73 mg/l
See the chart in this tweet:
CRP:
or DunedinPACE
YES and YES and YES, I experienced a sustained rise in baseline glucose level ( I have a continuous glucose monitor) a few weeks after starting rapamycin. In my case it subsided after a few weeks to previous basal glycemia (4.5) spontaneously.
@vishnu I also have a fasting glucose which is too high with rapamycin. As I have a continuous glucose monitor I can see that it’s totally unrelated to the meals and it’s not at all an insulin resistance issue. During the nights my glucose is around 80-90 but then 1 hour or 2 before my waking time the liver cranks up the glucose production and the level goes up (It’s called the dawn phenomenon). All that is perfectly normal so far but the issue is that the glucose continues to rise and rise until 105-115 which is very high in a fasted condition.
I’m eating low carbs/keto so I’m totally powered by burning fat and ketones as a more efficient fuel than glucose so my cells don’t really use it and it stays there until either, I go for a run, which will bring it back to around 90 or, I eat, in which case the glucose goes up and then down when the insulin kicks in.
At some point, I was also worried about insulin resistance so I did an NMR blood test to check and as you can see in my post below my insulin resistance is so low it’s off the charts (literally)
How to interpret Very high LDL and TC on rapa but with conflicted risk assessment?
BTW in addition of high glucose I also have high LDL but again the NMR blood test above says it’s low CVD risk so I’m not really worried about that one.
Anyway if somebody has suggestions to reduce that hepatic glucose generation that would be welcome.
Basically I need to find the equivalent of Settings/Liver/Glucose-Generation/Level and set it to 90. 
Right so we have mounting evidence now that @DeStrider was right a few months ago, for most people, rapamycin should be used in conjunction with a diabetes medication.
It depends because, as I said in the previous post, the excess glucose is generated in the liver, not ingested.
BTW I use acarbose to reduce the post prandial spike so I don’t have any meaningful glucose spikes after the meals. I hoped that preventing those glucose spikes would help, as some studies did found out that using acarbose reduced the morning glucose spike but maybe it was for people eating a standard diet while I’m already eating low carb/keto.
So far I didn’t tried metformin because I’m a runner and metformin can be an issue but maybe I will try at some point.
I would be interested to know what people take in similar cases.
Here is a relevant paper: Rapamycin-induced glucose intolerance: Hunger or starvation diabetes
I am sure that rapamycin suppresses other glands in the same way. This is the price of longevity
I use 1g of Metformin on the day of Rapa dosing and 500 mg on the day after. If I take it on days after that, I get hypoglycemia (too low blood sugar). So, this may be a useful yardstick for you.
Metformin undergoes renal excretion and has a mean plasma elimination half-life after oral administration of between 4.0 and 8.7 hours .
Most likely doses were too high. IMO, if taken for a long time, doses have to be pretty low. I’m on Rapa for a long time, at one point took 1mg every day for years, developed small cyst on my pancreas. Now take 2-3mg every 7-10 days and feel much better. Even that low dose requires breaking from time to time imo. Unfortunately there’s no clear guidelines on that. Even Blagosklonny did not know.
Rapamycin doesn’t reverse aging, it slows it down over the long run. You can’t rely on short term changes in biomarkers to determine whether it’s working or not. If it was working you shouldn’t expect to notice anything for years. Any short term changes in biomarkers are neither prove nor disprove that it works. Epigenetic age tests are also very unreliable and can be changed quickly by things that have nothing to do with aging.
Problem is we don’t really have the big picture biomarkers. As an example, we have no biomarker of autophagy, but that doesn’t mean interventions that increase autophagy aren’t doing just that and that isn’t beneficial for aging.
Note also that long term effects will not necessarily be reflected in short term variations. As an example, lets say rapamycin would have positive effects on aging of the kidneys overall. It could also at the same time influence some of the enzymes or hormones that control glomerular filtration rate (GFR) in the short term leading to reduced GFR making you think it’s making your kidney health worse when it’s actually doing the opposite. Most of the changes that you want to see with rapamycin are not going to be easily detected by any blood tests because they happen gradually over many years. So if you see some changes in the short term, they are often not the changes that tell you anything about its main effect on aging.
I don’t rely on anything but keeping my biomarkers in the “normal” range. This was the goal long before rapamycin came along. It would be ridiculous to ignore high glucose and lipid levels if your goal is a long health span.
I don’t rely on anything but keeping my biomarkers in the “normal” range. This was the goal long before rapamycin came along.
That’s a mistake. Biomarkers are important, but you also have to do what evidence suggests is likely to be healthy for you, totally regardless of whether you can measure it or not. Don’t get me wrong, it’s great to measure things if you can, but if you had no access to any ways to measure your biomarkers or progress, it would still make sense to do tons of things for your health like exercising, eating your vegetables, getting good sleep and more. I very much disagree when some people say that what you can’t measure you can’t change. That’s absurd. You can of course change things if you can’t measure them, you just can’t be as sure as to what exactly changed and how. In that case you have to rely more on evidence from the literature to predict the changes.
It would be ridiculous to ignore high glucose and lipid levels if your goal is a long health span.
Agreed. It would be equally ridiculous to assume that biomarkers are usually your best guide as to what is good for you or not. We can measure tons of things with blood tests, but truth is, currently available biomarkers aren’t even scratching the surface as far as detecting the changes the things you do have on your body. As an example, if you give mice rapamycin for one month and measure a whole bunch of biomarkers in their blood before and after one month of rapamycin, I don’t think the biomarker changes will give you the conclusion that it will extend their life. The short term negative changes in blood glucose and lipids might lead people to think it would shorten their lives. So why would people expect this to be different in humans? Blood test biomarkers measured at baseline and then several months or a few years later don’t tell you so much about the rate of aging or the effect of anti-aging interventions that have gradual effects. The things that predicted that rapamycin would extend life in mice are its mechanisms of action and the hypofunction theory proposed by Blagosklonny, not some short term biomarker changes.
Having said this. Of course I agree it’s important for you to take into account the effect rapamycin has on your glucose and lipids, and you have to weight those negatives against the potential positives and find some balance regarding your dose, but you can’t just take these results and assume they mean rapamycin is not working. The increased blood glucose and lipids are good examples of things that effect your health without you being able to measure it in the short term. We know that increased lipids will likely speed up atherosclerosis and we know that higher blood glucose will accelerate aging through increasing glycation. Yet this happens over decades. You wouldn’t detect increased damage from the mildly elevated lipids and blood glucose by some blood tests taken a year later. But you know from evidence on the mechanism of action that the glucose and lipids are still most certainly harming you slowly. You wouldn’t assume they don’t just because you can’t detect the slowly accumulating damage to your arteries a month or a year later. Same with rapamycin. On a related note, the increased glucose and lipids, although harmful for longevity per se, are ironically also signs that the rapamycin is inhibiting your mTOR, which is exactly what you want if you’re after the longevity benefits.
Btw I rely far more on evidence from literature research than I rely on biomarkers for myself when it comes to longevity. As an example, since 15 years ago I’ve been trying to regularly activate autophagy by things like skipping meals occasionally, even though I have never been able to measure if it’s working. Of course, for some things, blood test biomarkers are super useful though.
Btw have you tried reducing the dosing frequency to every other week instead of taking it weekly? That might help with the mTORC2 activation that is likely partly responsible for the side effects of increased lipids and glucose you’re experiencing. I think it would be a good experiment.
My next blood tests will determine my future dosing protocol. Based on my last tests I am leaning towards 1mg/daily for 1 week then 1 week off.
It’s very close to what I do: 1 mg/ day for 4 days. Then 7-10 off. All my bio markers are normal so far, besides lower WBC. Will remeasure all next week.
I think your plan might be better as it allows for a full 7-day plus for the rapamycin to clear.
“rinse and repeat”
@LaraPo your dosing schedule is intriguing. You may have stumbled upon an optimal strategy. 
What do you think are the pros and cons of your strategy?