It appears for many of us that rapamycin (especially after roughly 3 months of use) begins reducing visceral fat.
I’ve dropped approximately 10 lbs with no measurable muscle mass loss.
It seems that as one’s body metabolizes that fat, it would naturally affect (raise) measures of triglycerides and cholesterol.
Following the above hypothesis, once rapamycin use reduces visceral fat and resets one’s body weight “set point”, could we expect measures of triglycerides and cholesterol to reduce and perhaps improve over their levels before undertaking a rapamycin regime?
When converting dosage from mouse to human, you need to apply an interspecies dosage scaling factor. The most common equation used leads to dividing the mouse dose by 12.3. So with the 700 mg dose you calculated above: 700 ÷ 12.3 = 56.9 mg.
But I would hope that no one would self-experiment with very high dosages that have no precedent. The risk is too high.
I have to say that with 3 mg + GFJ + EVOO + Metformin on a 2-week cycle, I feel amazing. My body feels very healthy. The higher the dosage, the better it feels even though I have to deal with canker sores and acne/bacterial rashes. I know this is just a feeling, but I hope it continues. I think I will keep increasing the dosage by 1 mg per month until the trend reverses itself. I continue to lose about an lb. a week and am now 3 lbs. down.
Thanks so much for this thorough report, Agetron. I’ve been contemplating “where to go from here” now that I’m consistently at 5mg/once per week. Reports like yours give us such helpful food for thought.
Just a thought on the idea of routinely taking antibiotics to offset the adverse side effects of high Rapa doses and short intervals . . .
Much of what I personally am reading (or watching on YouTube) recently involves a growing understanding of the positive effects on longevity of the microbiome and increased metabolytes like Short Chain Fatty Acids, Urolithin A, Ergothionine . . . I’m sure others can added to the list here.
E.G. for Acarbose a proposed mechanism of actions is more “sugars” getting to the microbiome and creating some of the metabolytes mentioned above.
It’s pretty obvious where I’m going with this, but . . . If regular use of Antibiotics to treat bacterial infections cause by immune disregulation of high dose RAPA intermittently destroys our microbiome . . . how can that possibly be net positive on longevity?
Further, can we be 100% certain that none of the positive benefits of RAPA are related to the microbiome?
Well, the mouse studies (and all other organisms) show a positive increase in lifespan with rapamycin use, so either the microbiome impact is minimal, or greatly outweighed by the postive impacts in other areas.
Regarding your new goal protocol of 6 mg weekly, with Acarbose: Were you taking Acarbose previously along with Metformin? Or are you only now starting Acarbose perhaps as a somewhat substitute for Metformin? My doctor recommended Metformin along with the Acarbose and not “mess with” the grapefruit juice. Also, I am trying to decide whether a bit higher dose (more than 6 mg) every 2 weeks is better, trying to decide if both Metformin and Acarbose better., one over the other, none…decisions, decisions… Thank you for sharing your results and experience.
You asked are you…Starting Acarbose perhaps as a somewhat substitute for Metformin?
Originally my physician put me on Metformin for anti-aging benefits. Over a year ago. I never could adjust to the side effects… so went off of it… when I would do a 500 mg pill … I got diarrhea. He wanted me to do 4 a day. Impossible. Always weak, washed out and unsettled gut on Metformin. Again… that’s me.
A month a go I asked him to switch me to Acarbose… 3 pills…50mg a day… taken with meals. Now 3 weeks past on Acarbose… 3x’s a day… no gut issues…feeling amazing. My body seems to like Acarbose.
As to Rapamycin I am back on… one 2mg pill with GFJ… gives me a 12 mg dose (about 1/3 of previous amount for last 7 months)… doing 10 days washout between doses. Will try for 6 months and see how my biological age tests rate me. Trying to find my sweet spot.
Pretty sure those mice were not given intermittent regimens of antibiotics . . . my point wasn’t the impact of Rapa on the microbiome . . . but rather, the impact of antibiotics necessary at times to treat bacterial infections that are side effects of too high a dose – does that shorten life or undermine the positive effects Rapa might have on the microbiome?
Just trying to offer up that if one takes such a high effective dose that you need antibiotics (or anti-virals for that matter), you may in fact be reducing not extending your lifespan.
Citing reference above: " We also are learning that other drugs are affecting the microbiome in ways that were not anticipated. For example, metformin, widely used in the treatment of type 2 diabetes, has important effects on microbial populations. It may be that metformin’s antimicrobial actions, which in turn affect short-chain fatty acid metabolism, determine the efficacy of the drug, rather than its direct effects on tissues (13)."
“Even later in life, antibiotic exposures may have consequences in terms of risks for metabolic (14) and neoplastic diseases and for acquisition of resistant organisms.”
From my own labcorp blood levels of sirolimus testing post several scenarios I found I had to take ALOT of rapa And GFJ to get over 20(??) blood levels. But I’m grinding pills in a blender allowing longer stomach acid (etc) to degrade the rapa. I can’t swallow pills. Just mentioning, for folks not seeing benefits especially at the lower doses, you may not actually be absorbing a useful amount into your blood… ;(
IMHO and personal experience you have to blood test 2hr post taking the rapa which is 2 hr post GFJ (and other CYP3A4 suppressors for me). From another thread here on dose / absorbtion; I add to the GFJ: 1g ALA, 1g berberine, 50mg or so peperine. Then at 2 hrs take 20mg+ rapa. I bearly break 20(?? units) blood levels…
I suspect I may be a low absorber plus I grind my rapa… I suggest everyone spendnig this kind of $$ should blood test till you know for sure your dose and protocol.
Just out of curiosity did you ever try time release Metformin. My wife ( a doctor) tells me that most diabetes patients in the UK end up switching to time release to avoid the (mainly gastric) side effects
Hi Agetron and other “age” test takers. No science URLs being shared, just asking a question(s):
My looking at the age tests what they measure, I ask; can OTHER life style practices negate or push the underlying test measures to be better or worse?
If one becomes overly confident that rapa negates bad life style choices and over indulges can one blame rapa for not reducing age tests?
I’m not suggesting anything, just that us citizen scientists need to be rigorous in our self experiements. Keep good diaries on what we eat, drink, nutricals, bad vs good foods, etc along with our rapa dosing.
What if I took rapa for a year, but I found I really really had a love of good Scotch and upped my consumption? Just a nutty example of why high rapa may not be the root cause showing ever dropping age on these (possibly simplistic) age tests.
Repeating what I heard on a youtube by a researcher on a list of the anti-aging compounds; acarbose produces more gas on a wheat diet vs low carb vs rice. One might have varying experiences on acarbose depending on what else is in your diet.
Best to all, curt
Jason, many thanks for sharing your Rapamycin observations, the more info we can gather, the better. Was surprised to see how responsive you were to GFJ. Personally found that 16 oz of fresh squeezed GFJ only doubled the absorption rate (pasteurized GFJ, and piperine, for that matter, were completely ineffective)…interesting how everybody is different.
Wanted to ask a few questions since jumping in late here:
Seems like you were maintaining a regimen, at ~ 36ng/ml per week, approaching that prescribed for kidney transplant patients (who try to maintain an ~ 8 ng/ml trough minimum?). Was wondering what your half-life measurements were with and without GFJ (fyi, my half-life measurement, w/o GFJ, is an unusually short 41 hours)? Since you’re particularly sensitive to GFJ, it may be that it extends your half-life values even further (affecting not only first-pass, but second-pass metabolism)?
For future use, here’s a Google sheets link to a Rapamycin half-life chart (modified the original from a related forum here) where you can enter some variables to arrive at peak dose (e.g. if taken the night before) and half-life. (Rapamycins Half Life Graphs 1-2-23.xlsx - Google Sheets) You’ll have to download it first to enter your own data.
If you haven’t already, once you find your half-life measurements, you might want to try the same dose, but with a much longer/lower trough. Besides even more beneficial mTORC1 suppression, apparently another reason for higher peak Rapamycin blood levels (per Blagosklonny) is to better penetrate the blood-brain barrier and confer more benefit to our neurons (and overall brain function including all-important hypothalamic function).
Second question was, if you had considered Berberine as a substitute for Metformin—both of which reduce glucose production in the liver (and nearly identical in effect in every other metric except stomach discomfort)? It might help compliment the Acarbose which directly inhibits complex carbohydrate metabolism directly from a meal (post-prandial). Having control of both blood-glucose pathways might be of most benefit. Both Metformin, and more clearly, Acarbose have shown to have an additive effect with Rapamycin in previous ITP studies…something (per Dr. Miller) that is rare to find.