I am very late to this conversation, and I have not (yet) read the entire 1,500 post thread (I’m only up to July 2022 number 375) and am having tremendous difficulty not replying to many of this discussion before I’ve read everything up-to-date. However going through the paper that @MAC cited (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061792/pdf/BCP-82-1267.pdf) something immediately jumped out at me from the table, but not from the circled column:
It was difficult (for me) to tell from the discussion in the table (in the paper) if all these groups were on Rapamycin AND statins, or just Rapamycin (which was specified on the table itself and is suggested from the referenced papers). However the thing I noticed immediately was whichever course of treatment they used, plaques were reduced significantly regardless of TC, LDL, and TG trends — isn’t this a huge positive that the risk of Atherosclerosis can be mitigated regardless by Rapamycin? (Below; “Table 1” is the table that @MAC attached with the circled column regarding TC, LDL, and TG impacts). The references cited (listed below) suggest that the treatments were simply Rapamycin or rapalogs and no statins — even better, in my opinion.
I am going through this discussion/thread because I have been keto for almost two years with phenomenal results but have not yet pulled the trigger on Rapamycin (I’m 52 and definitely want to start this year) but since January have been “carnivore” (combined with heavy weights workouts) to build real muscle — real muscle additions is something I am betting will improve both healthspan AND lifespan — but my LDL shot up to 172 (all my other labs were outstanding). I know keto and carnivore aren’t popular here, and I’m not suggesting anyone else try it, although to me it seems to solve many of the metabolic issues others are taking supplements and drugs to solve. I probably need to either stop carnivore (what my doctor and anyone you ask outside of Joe Rogan and Shawn Baker would love to see), or at least do a full lipid apoA/B oxLDL work up to see if there is any real damage instead of just metabolizing fat as energy (planning this now) and maybe CAC scan and or Cardiac IMT scan (probably good for a baseline) before adding Rapamycin. I’m only taking GlyNAC now but haven’t yet found it useful or noticeable positive (lower dose than the Baylor study: I’m taking 3g daily of glycine and 50mg of NACET which should be equivalent to 500mg to 1g of NAC. Oh, by the way: I discovered cancer four years ago (kidney tumor stage iii removed, all clear thus far) so I’m likely to keep at least healthy keto for the rest of my life — one of the reasons I started, aside from weight management, generally feeling fantastic, and straight-up vanity. I’d rather not take a statin but will if it meaningfully will improve my health/longevity.
I apologize if I am repeating someone else’s post or if I am simply an ignorant but well-meaning buffoon who missed the point. A Masters in Chemistry and three years working in a biochem/oncology lab (on DNA polymerases) back in the Bronze Age hasn’t apparently made me any smarter.
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Different studies in ApoE-/- and low-density lipoprotein receptor-deficient (LDLR-/-) mice [67–72] as well as in rabbits [73, 74], have shown that systemic administration of rapamycin and everolimus is effective in reducing plaque size and com- plexity (Table 1). “
67 Pakala R, Stabile E, Jang GJ, Clavijo L, Waksman R. Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice: inhibitory effect on monocyte chemotaxis. J Cardiovasc Pharmacol 2005; 46: 481–6.
68 Castro C, Campistol JM, Sancho D, Sánchez-Madrid F, Casals E, Andrés V. Rapamycin attenuates atherosclerosis induced by dietary cholesterol in apolipoprotein-deficient mice through a p27Kip1-independent pathway. Atherosclerosis 2004; 172: 31–8.
69 Gadioli ALN, Nogueira BV, Arruda RMP, Pereira RB, Meyrelles SS, Arruda JA, Vasquez EC. Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice. Braz J Med Biol Res 2009; 42: 1191–5.
70 Zhao L, Ding T, Cyrus T, Cheng Y, Tian H, Ma M, Falotico R, Praticò D. Low-dose oral sirolimus reduces atherogenesis, vascular inflammation and modulates plaque composition in mice lacking the LDL receptor. Br J Pharmacol 2009; 156: 774–85.
71 Mueller MA, Beutner F, Teupser D, Ceglarek U, Thiery J. Prevention of atherosclerosis by the mTOR inhibitor
everolimus in LDLR-/- mice despite severe hypercholesterolemia. Atherosclerosis 2008; 198: 39–48.
72 Elloso MM, Azrolan N, Sehgal SN, Hsu P-L, Phiel KL, Kopec CA, Basso MD, Adelman SJ. Protective effect of the immunosuppressant sirolimus against aortic atherosclerosis in apo E-deficient mice. Am J Transplant 2003; 3: 562–9.
73 Baetta R, Granata A, Canavesi M, Ferri N, Arnaboldi L, Bellosta S, Pfister P, Corsini A. Everolimus inhibits monocyte/macrophage migration in vitro and their accumulation in carotid lesions of cholesterol-fed rabbits. J Pharmacol Exp Ther 2009; 328: 419–25.
74 Chen WQ, Zhong L, Zhang L, Ji XP, Zhang M, Zhao YX, Zhang C, Zhang Y. Oral rapamycin attenuates inflammation and enhances stability of atherosclerotic plaques in rabbits independent of serum lipid levels. Br J Pharmacol 2009; 156: 941–51.
