Maybe I didn’t understand right, but he says no change in the dosing protocol, but he did change brand? That you could be right that you had a decrease from BA which was masked by something different about the Rapa dosing.
Either way, the most surprising thing is that Rapamycin increased your LDL by 60 points?! That’s insane. From what I recall of human studies, that’s an outlier for sure. For me, Rapa (only at 2mg/week) has had no effect on my lipids that I can tell.
Agreed!
That’s awesome. 60mg/dl is a great target when you already have a strong baseline. I had, for some reason, thought you were much younger based on your writing style!. (Take that as a compliment, haha!)
Haha, biology is a big old mess! Probably why I find it so fun and interesting. Measure the same thing multiple times, different times of day, different days, different machines etc and you’ll get different results. Part biological, part analytical.
It’s funny if you really look at research data where you’d expect a pretty consistent response. For example, if you lift weights you’ll gain muscle and get stronger, right? That should be a universally conserved response. However, in actual trials, some people gained no muscle or strength, while others pile on crazy amounts of both. Or you’d think that aerobic training would reliably increase VO2max. Nope - it does on average, but some participants actually reduced VO2max.
Now imagine the number of influences on our circulating cholesterol levels, adding medications etc!
I’m curious - lots of very well researched people here on CVD and cholesterol why the focus on single measure rather than ratios - as my understanding is that ratios are better at predicting CVD or MACE than single measures like LDL-C
You echo my thoughts entirely. I’d love to see more mendelian randomization studies on both psk9 and HMGCR (Statin). The UK biobank data should allow a very clear insight into both ACM and specific diseases.
The research i have seen is inadequate in many ways but does throw up worrying signals for Parkinson’s (Psk9) and cognition (HMGCR).
Here’s a recent (April 2025) publication of interest to those of us who have Coronary Artery Calcification and want to prevent it from worsening. The background for me is that I had elevated lipids, low HDL and still have relatively high Lp(a) - 160nmol/L ish. Both parents deceased at age 60 via MIs. I’m now 74yo and fortunately still asymptomatic. My lipid numbers are much improved (70) on max dose Rosuvastatin (which I fortunately tollerate well) + Ezitimibe. I’ve had a series of 3 CAC scans at 2 year intervals with numbers in the sub 300 area reasonably stable since starting PM melatonin 6 years ago. Initially 5mg qhs but i’ve increased that to 120mg qhs for its anticancer and anti-inflammatory properties. My hsCRP is < 1. Maybe it’s the melatonin, maybe it’s the Rosuvastatin. Anyway… for your consideration.
Yes, I do take Rapamycin 5mg qwk with rest periods at intervals. Other medications include Metformin 500mg tid x 2 years ( HbAic is 5.7, same as before starting Metformin) , Doxycyline 5omg qd, Tadalafil 5mg qd (BPH), ASA 81 mg qd x many years, as well as Vitamin C 6 gm/d and Lysine 3gm/d in addition to tocotrienols, Vitamin D 5000iU and a host of other supplements. The above are of course motivated by M Blagosklonny, Linus Pauling, Dr Green and others. So as you speculate I can’t be sure my CAC stability is because of the melatonin, but the article suggests that it may be helping. Just for completeness, I exercise (aerobic + strength), sleep 8 hours per night, and eat a near Vegan diet. I could do with a little more social interaction, but there’s always something to be improved on.
“Kashan University of Medical Sciences, Kashan, Iran” + Mechanistic paper => Might go to the trash (that being said I take melatonin, but not sure this paper is convincing)
If you don’t mind, how much are you taking, and how long have you been taking. Also are there any effects you can report? I ask, because I’m thinking about it, but I have RLS, so I am worried about supplementing with melatonin. Also, off the top of your head, if you supplement, what happens with endogenous melatonin production, does it stop? If it stops, can it resume, or ist it like TRT? Thanks!
I’ve just started testing melatonin. 5 mg IR 1h before bed. 5 mg if I wake up during the night. Better sleep. Unexpectedly stronger morning érections I don’t think trials found an impact on endogenous MLT production. But we don’t have long-term data. When I stop it I’m fine.
About my sleep: when I was taking melatonin, 3 - 5 mg my sleep was ok (7-8 h), when I stopped it’s still ok but the deep sleep stage increased. Coincidence?
Interesting study comparing BAM15 to atorvastatin.
"In summary, the in vivo experiments demonstrated that oral administration of BAM15 significantly reduced the increased plaque area and the increased necrotic core area of plaque induced by WD feeding in ApoE(−/−) mice. In in vitro experiments, cell biological assays confirmed that BAM15 inhibited RAW264.7 macrophages invasive ability and reduced PA-induced lipid accumulation. By combining RNA-seq techniques, molecular docking, and experimental validation, we found that IL-1α, SRC, and CSF3 are key anti-AS molecules of BAM15.
This study reveals that BAM15 may be a promising drug against AS, providing scientific evidence to reveal the pharmacological mechanism of BAM15 in the treatment of AS, and facilitating future clinical translational research."
The practical question is what’s causing what. Clinical trials and mendelian randomization studies that separately investigate a change in either apoB or apoA-1 levels tells us whether it’s higher apoB or lower apoA-1 that’s increasing the risk, or vice versa lower apoB or higher apoA-1 that is decreasing the risk, if that makes sense.
So correct me if I’m wrong if you believe that the ratio is a better predictor than apoB you would need to know whether apoA-1 independently changes risk of apoB levels, as that would tell you whether a lower ratio from higher apoA-1 levels would decrease risk.
Atherosclerotic blood vessel cells grow similar to tumors, study reveals
"Researchers from the University of Southern Denmark and Odense University Hospital have studied tissue from patients with atherosclerosis. They found that many of the cells in the diseased tissue carried the same genetic alteration and appeared to originate from a single ancestral cell that had divided repeatedly—a pattern otherwise associated with tumor biology.
In several patients, a large proportion of the cells were derived from one single mutated cell that had undergone many rounds of cell division.
“It’s striking how many cells in the tissue share the exact same genetic change. In several samples, more than 10% of the cells—hundreds of thousands cells—carried the same alteration. It’s difficult to interpret this as anything other than all these cells originating from a shared ancestral cell that, at some point during disease development, acquired the mutation,” says Lasse Bach Steffensen, Associate Professor at the Department of Molecular Medicine at the University of Southern Denmark.
In a tumor, the disease often begins when a single cell acquires a genetic alteration that causes it to divide more than it should. As the daughter cells inherit the same alteration and continue to divide, a progressively larger mass of cells forms—what we call a tumor.
This finding offers a new perspective on atherosclerosis—a disease primarily associated with cholesterol, inflammation and lifestyle factors."
I don’t think trials found an impact on endogenous MLT production. But we don’t have long-term data. When I stop it I’m fine.