#1421

Just did my Apob test after about 6 months of weekly rapa. I’m at 91, which is missing “optimal” by 2 points.

Now Peter Attia says everyone should be under 60, which is definitely more extreme, but I understand the point. There’s no benefit to high atherogenic particles. Not sure if it’s worth a low dose statin or not. I’m pretty good about exercise and diet already.

3 Likes
#1422

Definitely worth it if you don’t get any side effects.
On the topic, age reveral will have zero effect on ASCVD if it doesn’t affect apoB concentration. Or if it can’t reverse ASCVD. The latter would be curing ASCVD, not longevity per say.
So ‘1000 year’ longevity like Aubrey says will actually result in 90 year longevity due to ASCVD.

People don’t seem to see the significance in this. If ASCVD is the bottleneck it doesn’t matter how many organs are rejuvenated.

3 Likes
#1423

There’s a recent study using statins in premature infants.

These infants have poor lung development leading to the use of high dose steroids. This is extremely beneficial, but unfortunately it leads to premature cardiac aging. In this study, statins reversed the cardiac aging when given along with the steroids.

Was this benefit due to LDL lowering? Obviously not.

Statins are dirty drugs , so they act through a myriad of mechanisms, so the benefits are hard ,to impossible, to sort out. And like all dirty drugs, the potential for side effects is high. Clozapine is a great example.

So, in the healthy rapamycin user where LDL is somewhat elevated, does the benefit/ risk work? No, since the absolute reduction in total mortality is very low in that instance - assuming primary prevention.

If you believe that statins are cardiac protective due to their myriad functions, and not necessarily LDL related, then it may make sense to add them to rapamycin as a synergy, though this has yet to be proven.

#1424

Did you really compare clozapine with statins? Check the receptor binding on clozapine and compare it with statins mechanism of action. Statins inhibit HMG-CoA reductase. That is not a dirty drug and 90% having no side effects. If that is, then it is a meaningless word.

Statins is the poster child for drug specificity.

#1425

It’s absurd to say that statins only have one mechanism of action.

At least half of patients stop taking statins due to side effects. For the same reason, clinicians hesitate to use them.

#1426

That is the mechanism of action.
It is actually 10% that stop because of side effects:

In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase.

https://www.ahajournals.org/doi/10.1161/ATV.0000000000000073

Statins clearly help to lower the risk for future ASCVD events in patients at risk. In general, statins are very well tolerated and about 85-90% of patients report no side effects.

None of the longevity gurus would take statins where side effects are in 50% of patients.
None of us would take rapamycin if that was the case as well.

1 Like
#1427

If your apoB is zero, you would most likely die. So much for “no benefit”

2 Likes
#1428

jakexbd did say high atherogenic particles.

2 Likes
#1429

My bad, I misread - thank you for catching it

4 Likes
#1430

If one eliminates known nocebo effects, maybe if one uses pharmacogenetics, hydrophilic statins, lower dose, and modified intermittent dosing - it is plausible to drastically reduce a lot of potential side effects often which are dose dependent. The main issue is it’s still not quite certain what an “optimal” level is and under what circumstances if we assume the LDL hypothesis is true (there is a compelling case). It could be right around LDL 75 with pattern A for all we know - which can be done through lifestyle and specific dietary changes alone.

2 Likes
#1431

Realistically patients are not going to have an LDL at 75 or apoB around the same from diet and lifestyle. Especially when genetic variance with respect to LDL cholesterol is taken into account, if I am speculating. It seems impossible for many people. Like the top 30th percentile when it comes to LDL, can they really get to the 75 with diet and lifestyle?

2 Likes
#1432

I suggest you look at soluble fiber/psyllium husk, cacao nibs, and plenty of vegetables with no highly processed foods, avoidance of overweight/obesity, EPA/DHA from fatty fish, certain strains of bacteria in fermented foods, the addition of nuts (walnuts well studied), and minimization of certain types of saturated fats. Perhaps even certain citrus peels if processed correctly.

The traditional Mediterranean diet is around 25% LDL reduction alone.

5 Likes
#1433

If someone did that, and LDL goes below 75 (inevitable with genetic variation), do you see a reason to increase it?

1 Like
#1434

There are relative accuracy issues with testing LDL. I’ve taken two samples on the same day using different testing at the same hour partly because one was free. Pretty different values. To be clear I mean very roughly 75. It’s not a magic number.

1 Like
#1435

My main argument is with those who think it’s somehow an established fact that getting LDL close to zero would eliminate CVD and total mortality. We don’t know that.
Using statins as an example also isn’t clear since they work in multiple ways, not just LDL.
Also, saying that the side effects are minor contradicts what most of us hear from actual patients on a daily basis. Sometimes it takes some probing. They deny cognitive issues , but admit to having poor word retrieval upon further questioning.
We saw this with Paxil. All of the studies showed no weight gains, but patients were constantly complaining of it after 6-12 months of usage.

2 Likes
#1436

Did you find a patient with any negative cognitive impairments (that we would expect from statins) using say low-dose rosuvastatin and target LDL around 75 at a frequency beyond what would be expected from nocebo? It shouldn’t cross the BBB as opposed to say simvastatin or atorvastatin.

#1437

Well if the test is actually accurate and repeated below 75?

That’s okay if the downside is low, it’s called making good bets (atherogenicity of 70 vs 20 LDL, linear)

It’s through the HMG-CoA reductase inhibition. A drug can have multiple benefits through the same mechanism.

90% do not have side effects. If 50% of your patients have side effects yet 90% do not have it in the literature, maybe you are doing something wrong? Priming?

1 Like
#1438

That’s fine, but the value itself can fluctuate. Let’s say it’s slightly below - I wouldn’t be really all that concerned at 70. I suppose I shouldn’t have used a specific number but use a range instead even though it’s somewhat arbitrary, partly based on mortality curves adjusted for LDL-lowering treatment.

I’d say outside of a medical condition - it’s unlikely to be <40 from lifestyle alone. I’d pull back a bit on any dietary additions that likely lower LDL if I went down to say 25. Hope that helps get an idea what I mean

1 Like
#1439

Ultimately, what is the theoretical absolute risk reduction involved with addition of a statin for LDL 75 vs 40? That’s the main issue - potential benefits vs potential risks.

1 Like
#1440

That’s interesting, you wouldn’t be completely opposed to LDL’s in the low 30’s then? I think that’s around where there stops being a benefit of lowering further as we do not have clinical trials from levels that low.

I don’t think there is any risks, so there is only potential benefits IMO. Those assosciation studies are not convincing at all. The PCSK9 genetic and inhibitor trials, also statin trials, lowering from already low is very convincing.

1 Like