While it is true that rapamycin has been associated with increased lipids, the claim that rapamycin causes heart disease as a side effect is not supported by the available evidence.
In fact, studies have suggested that TORC1 inhibition may have cardioprotective effects by reducing inflammation and oxidative stress in the heart, which are key drivers of heart disease. For example, a study published in the journal Aging Cell in 2019 found that rapamycin treatment reduced cardiac fibrosis and improved cardiac function in aged mice.
Furthermore, the claim that the lipid number is all that matters when assessing the risk of heart disease is also not entirely accurate. While elevated lipids are a risk factor for heart disease, they are not the only factor. Other risk factors such as hypertension, smoking, and diabetes also play important roles in the development of heart disease. Therefore, simply controlling lipid levels may not completely nullify the risk of heart disease in individuals
I think both of those statements are are accurate… I don’t want to repeat the cardiovascular disease thread discussion here, just saying that higher APOB trends are something I’m going to watch/measure and work to reduce. Nobody knows yet how the beneficial effects of rapamycin on the heart balance out against any possible lipid increases, in humans.
Forgive me. I didn’t realize you were an MD. If yes then, of course, the studies would mean more to you than to me. If you were not a cardiologist, I would take the views of a pediatric endocrinologist over yours any day of the week.
Oh yeah, humans are WAY more vulnerable to cardiovascular disease than mice, which barely die of it.
ApoB is mostly bad when oxidized/glycated - thus reductions in inflammation/ROS [with BOTH rapamycin+metformin+taurine+carnosine] should reduce much of the risk associated with increased lipids.
Citation needed, and mechanistic speculations isn’t high quality evidence, it is actually next to the lowest on the evidence hierarchy. Until there is (1) genetic studies showing significance of inflammation/ROS (2) randomized controlled trial of a drug via the same mechanism, then it is too early to say.
And if that was the case, just take the drug proven in a randomized controlled trial.
To gamble on mitigating causal risk with increased lipoprotein concentration via other mechanisms, is just an unnecessary gamble imo. When there are safe drugs to lower said lipoprotein concentration.
A couple weeks ago I was doing research on Trametinib using ChatGPT and I asked it for academic references. I spent the next hour trying to find any of the references it quoted. I couldn’t, they were all made up.
According to Dr. Lustig and most of the other experts, avoiding sugar plays the most important role in prevention of atherosclerosis and heart disease. Insulin resistance affects development or worsening of hyperlipidemia. Low carb diet is probably the most reasonable.
Sugar only plays a role in as far as it reduces apoB, the vast majority of apoB is due to saturated fat, so for most people a low carb diet will have the opposite result.
apoB measures all atherogenic lipoproteins, including those with triglycerides.
But it’s possible to have a healthy low carb diet, replacing saturated fat for polyunsaturated or monounsaturated fat. And measuring apoB every now and then to make sure things are (or are going) in the right direction.
I have a friend who did keto and had sky-high apoB. Tbf it was meat-based keto, not MUFA-based keto
Jose Ricon also speculated that the increasing prevalence of keto may increase heart disease risks in people in the future
I tried plant-based keto for like a month and while my panels weren’t terrible, they were still elevated a bit. Even olives and nuts have SOME saturated fat in them, and the unsaturated fats don’t increase HDL that much (HDL seems more genetically determined)
Saturated fat increases apoB → apoB causes heart disease → keto often has a lot of saturated fat → heart disease will increase.
Yes, I’ve seen some people try high fat diets on reddit with a lot of nuts, etc, yet have high apoB. I think it might be because of the some amount of SFA in them. Or that the replacing SFA with PUFA/MUFA discovery breaks down with high dietary fat intakes¸ I’m not sure.
N=1
I am 82 and in very good health with no heart problems.
I have been on keto in the past and I still eat a lot of saturated fats in the form of milk, cream,
MCT oils and steaks. All of my cholesterol levels are currently in normal ranges. My apoB is good.
