Rapamycin and risk of cardiovascular disease

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#2422

It is not approved in EU so not possible.

#2423

Very strong - and bad - words that in my view should hardly ever be used

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#2424

Well it’d probably be difficult for me to get.
Regardless, I also am a bit wary about the mechanism of action as it decreases acetyl-CoA in the liver which might be important as @John_Hemming says. Statins have a long history of use and low dose might not suppress desmosterol all that much.

The two best drugs seems to be PCSK9 inhibitor and ezetimibe.

#2425

Thx @AnUser I’ve been working with repatha and if I doesn’t dial in the Apo B effects I want (I have non optimal L(a) levels) I may add ezemb.

If that still is not enough what would you consider then if you were me?
(I live in the US where eg bemp is approved)

#2426

If I didn’t have an Apoe4 allele I would use rosuvastatin 5 mg (Crestor) for sure, even if I did have one I would use it but check my desmosterol levels in the USA to see if my desmosterol levels became overly suppressed:

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#2427

Thx. Luckily no Apoe4 on my end and at least last I checked my demost was on the high end.

Is Rosuv because that is better from a brain perspective than others?

#2428

No they all pass the BBB, but it’s a good and potent drug regardless, 5 mg should reduce LDL by around 40% IIRC. It is also the first statin to show it decreased heart attacks, strokes and all cause mortality in primary prevention in the JUPITER trial, which is probably why both President Trump and President Biden takes it.

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#2429

@DeStrider if you don’t have any large reservations regarding all statins crossing the BBB, I don’t know if you have an apoe4 allele and can’t test desmosterol, but you can always try other statins to see if one doesn’t give you muscle pains.

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#2430

I posted a link to a video a while ago in this subject.

#2431

Have you considered bezafibrate?

#2432

Why that one specifically? Gemfibrozil seems the best, but interacts with Ezetimibe it seems:

I think it mostly decreases triglycerides and doesn’t affect LDL by much. If I used it would for be for possible small increase in apoa1 for a possible decrease risk in alz by taking over apoe4 allele, but then I wouldn’t be able to use ezetimibe. I will look into increasing apoa1 when my apob is around where I want it.

#2433

How common exactly is the alzheimer gene in the general population? If it was larger than say 1-2%, we would expect the statin studies to detect an uptick in alzheimer rates which we don’t.

#2434

I think I’d like to try Bempedoic Acid before another statin. Ezetimibe is working fine as well.

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#2435

It’s complicated because I think statins will decrease rates of Alzheimer’s, including those with ApoE4 which about 25% of the population because of a reduction in atherosclerosis and possibly because of inflammation. The only exception might be where desmosterol levels are decreased and it doesn’t happen often.

Low desmosterol, a biomarker related to cholesterol synthesis & low levels predict AD. When using statins at any dose in patients with AD risk (apoE4, family history) I reduce statin dose when absolute concentrations of desmosterol hits or is < 20th %tile cut point. This is not a common occurrence but bears watching. If needed lower apoB by adding other Rx - No other lipid lowering Rx inhibits brain cholesterol synthesis. This is outside of the box thinking.

https://twitter.com/Drlipid/status/1670796947337236482

5 mg rosuvastatin might not decrease desmosterol enough anyway…

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#2436

One potential positive of HMG-CoA Reductase Inhibitors is reducing the usage of acetyl-CoA in the creation of cholesterol and as a consequence more being available for other purposes.

#2437

Statins are longevity drugs, and in fact probably the only proven one. That does help your theory.
I used GPT4 to look at your patent a bit and it’s an interesting one but I don’t know what role other things play in cell differentiation, if I understand that to be the gist of it.

Is it related to what the people are trying to do with yamanaka factors, making stem cells etc?

#2438

Thanks!

@AnUser saw you said this earlier in the summer on the thread above, have you changed your mind on whether hydrophilic statins are better/less worse?

That to me suggest hydrophilic statins as they don’t cross the BBB as easily

#2439

Its not really anything to do with the Yamanka factors. One of the Yamanaka factors SOX2 encourages autophagy, but my citrate patent is not about autophagy although Becln1 is a long gene which needs expressing for autophagy.

I would think the reason statins have a broader longevity effect is the change to acetyl-CoA metabolism. As I do that directly through a combination of citrate and acetate I don’t see a reason to take statins beyond if I wished to reduce cholesterol production.

My ApoB is in good territory even when LDL-C goes haywire for a week.

#2440

I did not look in depth, just stuck in my mind. Seems that it works not just by reducing the LDL-C but changes particle size and thus disproportionally reduces ApoB. It is beneficial in reducing risk of insulin resistance and type B diabetes. And it is available and cheap.

#2441

I meant is your end goal with increasing acetyl-CoA the same as the people who use yamanaka factors? New cells and better functioning ones?
What is your ApoB?

Yes, no difference at least when it comes to crossing the BBB.