AnUser
#21
I eat a very low SFA diet as well, but I’ve started with rosuvastatin three times a week, a very low dose of 1 mg/day can lower LDL by around 30% IIRC, low dose ezetimibe around 14% IIRC.
Rosuvastatin was associated with highly significant dose-dependent reductions in LDL cholesterol compared with placebo (p <0.001); decreases ranged from 34% (1 mg) to 65% (80 mg).
Rosuvastatin has a harder time crossing the BBB compared to other statins which might reduce possible long term speculative cognitive side effects. I started because I think it’s impossible to have a low enough LDL without it (below 5th percentile apoB, or nearing 30 mg/dl), especially with genetic variation (I am in the 94th percentile for LDL genetically).
I think low dose statin + ezetimibe probably will work well with rapa. Higher dose or PCSK9i required if LDL/apoB doesn’t decrease enough, obviously.
Any differentiation between ‘natural’ vs. unnatural medications/therapies has been sucked into a black hole for me personally. The ‘appeal to nature’ fallacy isn’t good, IMO.
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Is a PSCK9 inhibitor superior to statins? Anyone have a good comparison of the risk reward between the two?
This literally the only study people point to, and the “benefits” dont really even pass stat error…
Look i do beleive if you have a bunch of people who are focused on there health… The low ldl group is obv, mostly vegetarians… Then you have a control pop of meat eaters… That are most likely sad diet that break the general num one rule. If you eat a high fat diet, you cant eat carbs/spike glucose. Sat fat and carbs dont mix. The sad dieters im sure also had high tri and apob
So basically you have a control group of vegetarians who are health conscious and then a control group of sad eaters who most likely eat junk food, smoke and dont excercise… And the ‘difference’ and this is the statin studies also are really not stat significant…
Arnt statins like 1 percent lol…
If you took keto or carnivore eaters, who prob have high ldl over 150 but low tri and low apob… And compare them to the healthy eaters, i believe will be obvious that they will live longer fuller lives, with more muscle mass and less inflamation. Dont alot here believe it is now obvious that carbs become sugar, spike glucose and cause disfunction in endo cells.
Totally seperate topic, but isnt it amazing what ucsd is doing with these hydogels… Im more excited about this then anything…
I wish i could seed invest in ventrixbio
AnUser
#24
That is false, the study I am referencing had a p-value of 0.009 which means it was statistically significant, much more than the typical 0.05 threshold.
It was also done in people without pre-existing cardiovascular disease.
Risk ratio for a 0.5 mmol/l lower LDL cholesterol: 0.95 (0.92–0.99); p = 0.009
Blue is the statin studies.
If you have a high LDL, you probably will have a high apoB, so that doesn’t make sense. But sure, apoB is a better measurement, and if you can keep apoB below 5th percentile for a long time you’re good.
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The clinic that ran my lipid panel got in touch and asked me if I want to take either ezetimibe or rosuvastatin. Told them I would go away and think about which option I want to choose.
Led me down an interesting train of thought. What’s the best medication to attenuate hypercholesterolemia induced by Rapamycin. My way of thinking (guessing 
) would be that ezetimibe would probably be less potent since it works more on cholesterol absorption at the level of the intestine - where as rapa is upregulating the liberation of fatty acids - so more receptors (statin) would be more beneficial.
Any thoughts on this?
FWIW - I am getting the rosuvastatin (because I can) but not taking anything. I will test again in 1 month and get a new baseline after rapa washout before deciding the next steps. I prefer not to play polypharmacy honestly. Will probably just find a dose of rapa I can tolerate ultimately.
I keep hearing on doctor podcasts (while I am walking/working out, hence why I don’t have the basis research paper references — sorry about that) that while LDL levels have a correlation with CVD (and many might argue it is a lower order correlation, albeit highly studied) the “damaging” LDL is the many small LDL particles which is why LDLp (particle count) has a stronger and higher-order correlation to CVD than a basic LDL reading; the belief was that the larger LDL is “beneficial”, bringing energy and building LDL and cholesterol around the body. A low Triglyceride/LDL is supposedly correlated to lower LDLp, and suggests more “larger” LDL particles as a percentage which may not be the arterial-damaging LDL which we are worried about (and instead might be useful energy/building blocks LDL and cholesterol around the body), and why TG/LDL has a solid higher-order correlation to CVD (high TG yields more small LDL particles and thus higher LDLp). Lower TG/TC (or TG/LDL) seems to be correlated with lower inflammation in many cases. Again, just what I’ve been hearing consistently from doctor podcasts (if it’s critical I’ll try to find the references at some point).
So my questions are:
-
Does this make sense?
-
Assuming #1 is true if Rapamycin can raise LDL levels and lower inflammation, is it lowering TG levels as well, and thus could be thought of as improving metabolic function with a larger percentage of “healthy” lower-risk LDL? If so, should we be worked up about LDL?
And 3) Again assuming #1 is true, do statins lower LDL indiscriminately (i.e. the “beneficial” larger LDL with the “dangerous” smaller LDL) or just the smaller “inflammatory”LDL? Or is this known/measured?
Thanks for the understanding.
J0hn
#27
Has anyone else used lithium supplement to cancel Rapamycin’s effects on lipid metabolism ?
Proc Natl Acad Sci U S A. 2019 Oct 15; 116(42): 20817–20819.
https://www.pnas.org/doi/full/10.1073/pnas.1913212116
A triple drug combination targeting components of the nutrient-sensing network maximizes longevity
ABSTRACT
Increasing life expectancy is causing the prevalence of age-related diseases to rise, and there is an urgent need for new strategies to improve health at older ages. Reduced activity of insulin/insulin-like growth factor signaling (IIS) and mechanistic target of rapamycin (mTOR) nutrient-sensing signaling network can extend lifespan and improve health during aging in diverse organisms. However, the extensive feedback in this network and adverse side effects of inhibition imply that simultaneous targeting of specific effectors in the network may most effectively combat the effects of aging. We show that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, the mTOR complex 1 (mTORC1) inhibitor rapamycin, and the glycogen synthase kinase-3 (GSK-3) inhibitor lithium act additively to increase longevity in Drosophila. Remarkably, the triple drug combination increased lifespan by 48%.
Furthermore, the combination of lithium with rapamycin cancelled the latter’s effects on lipid metabolism.
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health.
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JuanDaw
#28
That was discussed in the two threads below:
Take note of the post of Livin, quoted below:
Do not take trametinib for longevity purposes. I worked on synthetic lethal chemo combinations in cancer at a startup for years. We tested this compound and it is not a good idea. The Erk pathway is very important for most epithelial cells. Stick to low risk acarbose and rapamycin combinations and do not consider trametinib. If you have melanoma or another type of solid tumor type then you could consider trametinib. Just trying to prevent you from causing long term damage.
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I’m having a non-HDL test in 2 days - and interested to see the results since I’ve been on a 4mg weekly dose for rapa for the last 3 months. Last time I got a high non-HDL while on rapa - but at that time I was also getting side effects, likely because the dosage was too high. Will report back with the results in 1 week.
But with this test upcoming, it got me thinking about reopening the discussion of raised lipids on rapa and the risk vs reward trade off. It’s still unclear in my mind, and I’m open to more viewpoints from anyone who hasn’t chimed in on this subject already? Is there any quality more-recent literature? It’s something I think about a lot and never feel definitive either way.
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AnUser
#30
It’s dose dependent and apoB is more accurate causal marker of risk.
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Ok….
In the UK NHS they test non-HDL as standard of care - which is almost as good as testing ApoB - so I’ll be getting my free non-HDL test as opposed to paying out of pocket to test ApoB. But this is not the question that was asked anyway…
In regards to your response, I’ve been a paid member of Peter Attia’s for multiple years - so the view of ‘it’s dose dependent’ is not exactly a ground breaking sentence for me to hear. Clearly I’m looking for a more nuanced discussion around Rapa and it’s impacts on lipid metabolism rather than an off-handed line parroting back Tom Dayspring’s thesis
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Rapamycin increases lifespan in mice while also raising blood sugar. Using rapamycin with any anti-diabetic medication increases lifespan in mice even more than when rapamycin is used on its own. This implies that the rapamycin-fed mice live longer in spite of the negative side effect that is raised blood sugar.
Similarly, higher lipids in humans is a negative side effect from rapamycin which needs to be addressed with appropiate medication.
I agree with this. I’ve had higher LDL anyway so was treating it anyway, but I’m working on lowering it further now, and the 20% or so bump I get in lipids when I’m on higher doses of rapamycin is also something I’m concerned about and so I’m working to address it with ezetimibe and / or bempadoic acid.
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Absolutely agree - one needs to monitor insulin sensitivity and ApoB and optimize these - typically with agents that have the best evidence of addition of longevity. It’s not necessarily a bad thing to have these elevate a bit, so long as it is measured, tracked and optimized.
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Actually my father is now taking Bempedoic Acid, Ezetemibe and Atorvastatin to reduce LDL and ApoB further after he got his 352 CAC score. Here’s hoping he gets them into the 40s.
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