#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
#1441

No, the lower it goes, the more potential for risk. Especially if we have multiple repeated testing.

There are flaws with relying on Mendelian randomization. We have no idea what myriad of potential effects are involved with loss of function PCSK9 individuals as opposed to using statins to get to the same levels. Not only that, statins increase PCSK9.

1 Like
#1442

I don’t think we have to argue about this, 70 is good, below 60 is good too. It’s a magnitude of difference from the wackos who say that, 150, 200, 400 is just fine. Statins have shown benefits from reducing below 70. There isn’t genetic studies using the statin mechanism, sure. But the benefit from PCSK9 is obviously from LDL lowering, so statins would have the same one. I personally am targeting 30 apoB, but if I need a very high dose of statins, maybe i’ll be happy about having below 60. Genetic studies suggest low risk, some risks with certain types of LDL lowering.

2 Likes
#1443

The potential benefits in people who are indicated for it. They are making a tradeoff for benefit vs risk. Not the same as healthy individuals.

There is for HMGCR with negative cognitive effects.

1 Like
#1444

I suggest you do more digging with PCSK9. It’s not just some isolated protein that affects LDL.

1 Like
#1445

Yes, that was HMCGR inhibition in the brain and the effect was miniscule, just like every other gene on cognition (about 10 000 genes determine variation in cognition):

The effect in context:
In the general population (18-65) reaction time increases by 2.8 ms a year.

And the study found an increase of 0.067 milliseconds per 1 SD decrease (38.7 mg/dL) in LDL-C in total. So if you have 2 SD lower LDL-c you have 0.14 ms increase in reaction time. And HMCGR inhibition showed improved memory performance:

0.14 ms slower reaction time from two standard deviations lower LDL. But improved memory performance.

Just use rosuvastatin and it will be ok.

1 Like
#1446

It’s not miniscule. It’s small but it’s moderate negative effects when you account for positive cerebrovascular effects masking the total net effects. That’s only one issue.

As an example of many, new onset diabetes is a risk factor for statins that only have known HMGCoA as a specific target.

You’re looking at things in a very isolated manner.

1 Like
#1447

0.14 ms slower reaction time in total, when reaction time increases by 2.8 ms a year is a miniscule effect. And you already know you can mitigate some of the risk from using statins that have a harder time crossing the BBB.

Statins aren’t risk free. There are trade offs with everything. The risk is low though and most do not get side effects.

Diabetes risk can be mitigated by using a CGM every now and then.

1 Like
#1448

The risk is low in what time frame?

What is the proposed benefit in absolute risk reduction as opposed to LDL 75 and pattern A?

1 Like
#1449

The reaction time increase is a lifetime total increase of 0.14 ms. That is very low.

By low risk I mean 90% do not get side effects.

#1450

Not just reaction time. Look at the other potential cognitive factors and dementia in those “lifetime” risks.

Then look at net cognitive effects in statins. Still real. Note that using statins are not equivalent to Mendelian randomization.

#1451

I know that’s why it’s better to use a statin that does not as easily cross the BBB. I have an APOE ε4 allele, so I care about cognition risk. If I could do a Desmosterol test I would do that.