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?
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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@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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I posted a link to a video a while ago in this subject.
Have you considered bezafibrate?
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.
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.
I think I’d like to try Bempedoic Acid before another statin. Ezetimibe is working fine as well.
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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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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.
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?
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
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.
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.
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.
Interesting. Thx for the perspective.
My end goal is better functioning cells. I think the reason people use Yamanka factors is the concept of resetting a program of aging (like rebooting a computer). I don’t think that’s how aging works.
My ApoB has been as low as 77mg/dl and normally bounces around the 90 mark. The last measurement was 92.
How much of aging do you think your approach will cover (or solve)? I think there must be more things than just a shortage of acetyl-CoA, if I am understanding it correctly. 90 is around 50th percentile, but ASCVD is normal thing happening to people in the 50th percentile.
I am working on two cellular functions. One relates to acetyl-CoA levels in the nucleus and is the issue of aberrant splicing and transcription failures. The other relates to mitochondrial efficiency and the provision of ATP to the Ribosome. In the former case the wrong mRNA is produced and in the latter case the proteins are not produced and sent off to Ribosome Qualty Control for recycling.
I think these are the major causes of the phenotypes of aging and also those cancers relating to aberrant splicing (I don’t know what proportion this is). I count metabolic syndrome as a phenotype of aging.
There are other stochastic elements and obviously there is some DNA damage that occurs that this does not fix.
Allocating any numbers to this is hard, however. My personal view is to fix this and then see what happens.
There was an experiment with citrate and drosophila
I think they got the mechanism wrong.
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John, how are you dosing the citrate?
Which type/ types?
Are you measuring systemically?