#2410

Why? Is this because of mechanistic speculations?

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#2411

Evolutionary considerations really. It has evolved to work as it does. There may be a benefit in one aspect in inhibiting it, but there is likely to be a negative. For me it was harm to memory.

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#2412

mTOR has also evolved to work as it does.
NutritionMadeSimple once theorized that higher LDL levels were beneficial during phases of starvation. Nowadays we have an abundance of food so that pathway is no longer useful for us.

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#2413

I am not a fan of permanently inhibiting mTOR. i am one for relatively infrequent Rapa dosing.

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#2414

It was those high, daily rapamycin doses that extended the lifespan of mice by up to 30%. We don’t know yet whether infrequent doses and/or low doses work to extend lifespan in dogs or humans.

#2415

Joan Mannick has presented evidence that intermittent dosing every 5 days improves lifespan in mice.

image

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#2416

That’s the equivalent of roughly taking rapamycin once every 1-2 months in humans. What was the dose used?

#2417

Also:

One possible strategy to decrease the side effects of chronic rapamycin treatment is to allow for frequent drug holidays, and indeed rapamycin administration for 2 weeks out of every 4 also extends life span in mice (15,16).

2 mg/kg

4 Likes
#2418

Would love to read up a bit more on this (although my desmosterol was high the last time I tested), do you have any source I could look at?

Btw - what statin and what those did you settle on?

And what sore of Ez?

#2419

Not sure that is the right way to think of time translation in this context? That would eg not factor in that they were on rapa 20% of the days/the time (perhaps with mechanism of actions a higher % of the time)

#2420

Search for Peter Attia statins Alzheimer’s disease, he brings up the desmosterol connection. I think I read about BBB in a recent scientific study looking at dementia and statins link, I could try and find it if you can’t. It was in the ESC I think.

Rosuvastatin 5 mg, and Ezetimibe 10 mg, a day I will try.

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#2421

You should probably follow Dr. Attias advice and go for bempedoic acid and Ezetimibe. Unless cost is an issue.

#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.

3 Likes
#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.

1 Like