Not new to rapamycin, but new to rapamycin.news. This seems as good a place as any to post an introduction.
Me: Longevity enthusiast. I started down this path [sigh] when I listened to the Sam Harris podcast interview with Peter Attia. I really started down this path when I crossed the diabetes line (A1c 6.5) – lost 60 pounds, and left DM2 in the dust, thank you very much.
I am a clinician, a soon to be credentialed clinical lipid specialist. The Lp(a) thing is my calling. I’m already finding those highly elevated, and navigating expanded access to olpasiran for patients (the only drug “available” to lower Lp(a) [siRNA] with pelacarsen [ASO] coming soon)*.
Making raw rapamycin powder bioavailable: SQ route in MCT oil, oral route using 2:1 inclusion complex formation with HPβCD + emulsifier. (Both actually ridiculously simple processes anyone can do)
Just today: Q) what is the significance of 20ppm heavy metal content in 30 years of 6mg/wk rapamycin? A) If the heavy metal was entirely mercury, then same as about 3 servings of salmon. Whew
Calculated the log-linear dose-response relationship for rosuvastatin: Side effects are dose dependent, not potency/intensity dependent, and so compared to 40mg, the dose, dose-response, side effect risk be like:
1mg 50% 2.5%
4mg 86% 10%
(In other words, 1mg lowers LDL 50% as much as 40mg with 2.5% the side effects (e.g. myalgia)).
Hello world!
~fbol
* I can’t promise to be here frequently, but please feel free to have anyone frantic about their highly elevated Lp(a) pm me. There is a path…
A very interesting medicine indeed. There is a great thread about it here if you are interested in reading or contributing to: Telmisartan -- 40 or 80 mg
I’ve never heard of this, it sounds interesting. Have you looked into GLP1 agonists for Lp(a), in particular tirzepatide?
I have been taking telmisartan for more than a year and experience these off-design benefits. I wish for a modified telmisartan that could be taken by people whose BP is already low normal. My unmedicated BP was only mid- to high-normal so it worked out well for me.
This dose response claim for rosuvastatin is slightly misinterpreted. The 1 mg/day dose does not lower LDL-C by 50% but it does produce 50% of the maximum dose benefit.
Here is a reasonably accurate relationship based on fairly large trials.
That’s the bombshell for me. Pretty much everyone should be on at least 1mg from childhood on, IMHO.
I haven’t found much on the Lp(a} lowering effect of Tirz. Top PCSK9I’s lower about 20-25%. Olpasiran nearly eliminates Lp(a) entirely - like 98%. It’s incredible stuff. Now, we still wait for outcome data. Could it be a red herring like Niacin was? TBD, but I doubt it.
Oh yeah, and some of the telmisarran good stuff is at really high doses. I don’t remember numbers, but for e.g. seizure disorders, or Chron’s benefits (see 2nd link), the dosage is in the 1000s of milligrams (iirc). The BP effect is pretty much flat after 80mg, but the other effects continue.
The following comment could use a better home but for the portion addressing rosuvastatin and LDL-C, it is useful to keep in mind that the destructive particle is not LDL-C, but Apo(b). The relationship is complex and the discordance is significant and mostly bi-modal (relatively high concordance for most, low for some) which is why the correlation coefficient is only slightly above 0.70 (~half of the variance accounted for). The cholesterol content per ApoB particle can change, and statins can lower LDL-C partly by depleting cholesterol per particle in addition to reducing particle number. Typical cases of discordance might be insulin resistance, hypertriglyceridemia, and/or smaller LDL phenotypes where rosuvastatin will deliver a comfortable LDL-C result with high ApoB because each particle is carrying less cholesterol.
I this paragraph and you have me interested in learning more… here is what I could get on the topic from a simple Gemini Pro query, I’m sure you’ve done more research, so please add any of your own experiences when you have time…
Scientific Audit
Statement: “Making raw rapamycin powder bioavailable: SQ route in MCT oil, oral route using 2:1 inclusion complex formation with HPβCD + emulsifier.”
Verification Report
Original Claim
Verification Status
Evidence/Source
Correction
SQ route in MCT oil makes Rapamycin bioavailable
Imprecise / Experimental
Evidence: Search results confirm MCT oil is a valid oral vehicle and dietary supplement (e.g., PMC12812557), but no peer-reviewed clinical data validates simple SQ injection of Rapamycin in MCT oil as a standard bioavailable protocol.
Context: Validated SQ protocols utilize nanocarriers (e.g., polymersomes, liposomes) to ensure biodistribution and avoid depot entrapment (PMC8934301).
Correction: SQ administration typically requires nanocarrier/liposomal formulation for confirmed bioavailability; simple MCT oil suspension is an unverified (anecdotal/biohacker) protocol lacking pharmacokinetic validation.
Oral route using HPβCD inclusion complex
Verified
Evidence: “Complexes of rapamycin with… hydroxypropyl-β-cyclodextrin were prepared… rapamycin water solubility was highly enhanced” (ResearchGate).
N/A
2:1 Inclusion Complex Ratio
Imprecise
Evidence: Cyclodextrin inclusion complexes typically form at a 1:1 stoichiometric ratio according to Job’s plots and phase solubility diagrams for similar lipophilic drugs (PMC9100073). While specific optimizations exist (e.g., 1:2 or 2:1 for other compounds like Tosufloxacin, SciELO), “2:1” is not the universal standard for Rapamycin.
Correction: The stoichiometric standard is typically 1:1; specific 2:1 ratios are formulation-dependent and not a universal constant.
Addition of Emulsifier
Verified
Evidence: The addition of surfactants (e.g., Sodium Lauryl Sulfate or Tween) to HPβCD complexes is a verified strategy to further enhance permeation and dissolution of lipophilic drugs (PMC8463492).
N/A
Auditor’s Note
The statement mixes verified pharmaceutical science (Cyclodextrin complexation) with experimental/anecdotal protocols (SQ MCT injection). While chemically plausible due to Rapamycin’s lipophilicity (LogP > 5), the SQ MCT route lacks the pharmacokinetic data required to claim “bioavailability” equivalent to established clinical methods.
Next Step: Would you like me to generate a specific laboratory protocol for the Oral HPβCD + Emulsifier preparation based on the 1:1 stoichiometric standard?
Whew
Hello world!
Imprecise / Experimental
Verified