I have a container of powdered HMB. Unfortunately, I should have bought the capsules. It ruins the flavor of everything I put it in, so I have not really taken very much of it.
3 Likes
medaura
#103
Yeah I’d been warned so I got capsules but only take them once in a while. Need to put them in pill organizers so I actually take them.
1 Like
adssx
#104
Random Chinese university and journal but bad news: Mendelian randomization analysis of lipids traits and lipid-lowering drug-targets in relation to cognitive status 2025
Mendelian randomization reveals no causal link between lipid traits and cognition;
NPC1L1 inhibition genetically linked to higher cognitive impairment risk;
Ezetimibe’s cognitive effects may be independent of lipid-lowering action;
Findings highlight caution when prescribing ezetimibe to cognitively impaired patients.
1 Like
A_User
#105
That looks like p-hacking to me if they used 9 drug targets + lipids, and on top of that multiple different outcomes and six different datasets (and found a genetic correlation in three):
2 Likes
I wonder how much care we need to put into interpreting Mendelian randomization studies due to linkage disequilibrium types of effects. The rarer is any given mutation that drives the result, the more likely it would tend to be packaged with some other mutations that impact things we care about. If mutation A that causes lower LDL-C comes along with mutation B that causes X, should we conclude that lowering LDL-C also lowers X? We should not unless there is a sensible mechanistic story and observational evidence showing some relationship between LDL-C and X independent of the MR study.
2 Likes
adssx
#107
It’s possible. Might explain why it’s published by the “Department of Anesthesiology” (lol) of a university in the random “Journal of Affective Disorders”. If it was of higher quality it would be published in Brain by a Stanford team. I’m sure other teams looked at ezetimibe MR and dementia and found nothing and didn’t publish anything.
3 Likes
Null results are still valuable results. They should be published. If they have them, but didn’t publish, that’s a pity. I am not aware of it either way.
3 Likes
adssx
#109
Actually I was wrong, some good researchers published this null result in a good journal: Lipid lowering and Alzheimer disease risk: A mendelian randomization study 2019
University College London + Cambridge + Karolinska + Utrecht so Tier 1. In Annals of Neurology, Tier 1 as well.
Results:
NPC1L1 (encoding the target for ezetimibe)
Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23–1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.
6 Likes
That’s fantastic, and very encouraging. Great harm is done when null findings are suppressed, as it distorts what we know and obstructs hypothesis generation. Unfortunately publishing incentives don’t always align.
Concerning about PCSK9i and AD though.
4 Likes
Beth
#111
Huge sigh 
I have one apoe4 and I take repatha
Oh well, I guess my chances of an MI are greater than AD, so….
1 Like
On first pass, I was disappointed that the genetic deficiency of NPC1L1 does not protect against Alzheimer’s disease. The NPC1L1 protein in question is central to cholesterol absorption in the bowel and that function is blocked by the drug ezetimibe. So the implication is, in Mendelian Randomization, if that protein is absent due to an allele being disrupted/absent, then that should somehow represent taking ezetimibe in terms of lowering Alzheimer’s risk. My earlier hope was based on prior research that showed ezetimibe lowers the risk of Alzheimer’s and related dementias by > sevenfold. So Mendelian Randomization suggests that is not so, but we are in fact talking about two different mechanisms of action. I really comes down to this: not producing enough NPC1L1 does not increase Alzheimer’s risk, but taking ezetimibe has a different (non-cholesterol) mechanism of action in the brain by presumably lowering the binding of hexokinase-1::14-3-3G protein. That is, ezetimibe has a stronger affinity for that binding site and replacing hexokinase-1 with ezetimibe at that site lowers the risk of AD. My hope in ezetimibe is restored for now.
6 Likes
Where do you get prescriptions for ezetimibe in the USA these days? Or which pharmacies do you order from?
I’ve just used the sources we have listed on this page: How to Get Rapamycin, Where to get a Prescription
But if you’re looking for India-based resellers, there is this whole issue which is a quickly evolving situation (we’re hearing some people may be getting orders through)… Disturbing news regarding Medications Ordering from India, Price Increases, Parcels Stopped
2 Likes
Just ask your family doc for an rx. I printed out the study and handed it to my family doc. And who does not benefit by lowering cholesterol? It costs $45 for a 90 day supply here in the USA, but cheaper in India when I could get it there.
1 Like
Beth
#116
To add to your post…
PRO TIP:
Always check goodrx (cost plus is also an option). And ALWAYS put in custom amounts
For example, cash pay on good rx for:
90 pills is $38
180 pills is $41
365 pills is $45
4 Likes
Very good point - Thanks! Definitely worth it to ask your doctor if he/she will prescribe it for us. I’ll do that now, as I was just thinking of ordering more. Though I do like the combo Ezetimibe/Bempadoic Acid pill that is available from India (that I don’t think we have here in the US).
1 Like
Beth
#118
FWIW, incase you have not seen US sourced ezetimibe, it’s a tiny pill.
I loved the idea of a combo pill, so I bought that from India, too, but then I saw they were fairly large.
My next order from India was only for BA, and I will get EZ from a US pharmacy (the volume of the two pills won’t be larger than the one BZ/EZ pill). My thought was after seeing the poor quality incident with Sun Pharma, I figured there would be slightly less risk in quality with buying US drugs. If the combo pill was actually smaller, then I would throw risk out the window 
PS, not all BA is smaller, I specified brand after some great people here showed me their various sizes
Ah - the combo pill is available in the US, just probably expensive unless covered by insurance:
https://www.goodrx.com/nexlizet/what-is#cost
1 Like
adssx
#120
Cholesterol-lowering drug targets reduce risk of dementia: Mendelian randomization and meta-analyses of 1 million individuals 2025
Ezetimibe (NPC1L1) wins:
Meta-analysis of one-sample Mendelian randomization odds ratios per 1 mmol/L (39 mg/dL) lower non-HDL-C was 0.24 (0.18–0.31) for HMGCR, 0.18 (0.12–0.25) for NPC1L1, 0.97 (0.70–1.35) for PCSK9, 1.66 (0.52–5.36) for ANGPTL4, 1.41 (0.63–3.16) for LPL, and 0.30 (0.26–0.34) for CETP. Cox regression and two-sample Mendelian randomization results were mostly directionally consistent.
Several months ago (before tariffs) I asked my PCP and he gladly prescribed Nexlizet (bempo+ezet) but insurance wouldn’t cover. I read the guidelines for coverage (i.e. failure to adequately respond to statins) and I could have “staged” blood tests to get the numbers they wanted by eating before the blood draw or stopping rosuvastatin and forgetting to mention it during the blood draw, but instead I stocked up on the overseas version, and now have 1200 tabs in a special fridge.
1 Like
