Anti-fibrotic effects of ezetimibe

#1

A welcome side effect for those taking ezetimibe: Ezetimibe Use and Reduced Mortality in Patients With Idiopathic Pulmonary Fibrosis 2024

Our previous studies on ezetimibe, an FDA-approved anti-cholesterol drug, demonstrated its anti-fibrotic effects in both in vitro and in vivo pulmonary fibrosis models, as well as in a retrospective chart review of patients with idiopathic pulmonary fibrosis (IPF).
A total of 8,768 IPF patients were included in this study. Median survival years from all-cause mortality was 8.8 for pirfenidone plus ezetimibe users, 8.9 for ezetimibe users, 5.9 for pirfenidone users, and 4.7 for those who did not use these medications. Ezetimibe users exhibited improved survival rates compared to their counterparts regardless of pirfenidone use (Log-rank test P<.0001). No difference in survival rates was observed between combined pirfenidone and ezetimibe users versus sole ezetimibe users. After stratifying by pirfenidone use and PSM, ezetimibe use resulted in superior survival rates in all-cause death, IPF-caused death, and transplant-free survival against non-users in both unadjusted and adjusted analyses, with hazard ratios ranging from 0.38 to 0.58.
Ezetimibe may serve as an alternative therapeutic option to pirfenidone for treating IPF. Further clinical trials are essential to validate this beneficial effect.

I donā€™t know how common pulmonary fibrosis, but I would assume that as we age, due to pollution and viral infections, our lungs necessarily become scarred over time (even though not enough to be diagnosed with pulmonary fibrosis).

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#2

Interesting outcome. It is always nice to see a medication have untargeted benefits. I have just started taking Ezetimibe and have experienced no apparent side effects. To me, itā€™s a no brainer for moderate cholesterol improvement.

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#3

Iā€™m the same. I just started ezetimibe 10 mg: my ApoB went from around 100 mg/dL to 66 mg/dL in two weeks (most of the effect is achieved after 2 weeks, but Iā€™ll check later if decreases further).

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#4

Thanks for sharing your experience. Those results are impressive. My LDL was 85 mg/dl about a month ago and I have been taking Ezetimibe for a couple weeks. Hoping to bring my levels below 70, at least.

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#5

Please be aware that Ezetemibe may interfere with fat soluble vitamin absorption such as K and with the blood thinner warfarin. I was going to have my mother try it, but this fact stopped us.

For me and my father, Ezetemibe and Bempedoic Acid have cut our cholesterol and inflammation in half. I think itā€™s got to add years onto our lifespan. Also itā€™s nice to know our chances of a heart attack or stroke or greatly reduced.

It helps me sleep well at night knowing that the number one killer of mankind is held at bay.

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#6

This means Vitamin D also? Do you have a playbook/protocol dealing with that, eg is it enough to separate when in the day ones takes Vit K and Vit D vs Eze?

@adssx do you take Vit D and/or Vit K?

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#7

Ezetemibe stays in your system 24 hours a day so I donā€™t think you can time this. I take my vitamins D3 and K daily as well. Iā€™ll be getting a vitamin D test this summer and I may have to up the dosage again. I am currently taking 10,000 IUs daily and still barely out of deficiency. I have added more magnesium to see if that helps as well.

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#8

I donā€™t. I didnā€™t see any difference in my vitamin D levels after 2 weeks of ezetimibe 10 mg, but good to have in mind, Iā€™ll report here if thereā€™s any change in my next test.

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#9

Strange that ezetimibe has been around for so long, yet there seems to be very little study or concern about inhibition of fat-soluble vitamins.

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#10
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#11

Ezitimibe appears to be low risk but perhaps not zero risk. An October 2021 study suggested it may decrease Alzheimers but also that "ā€¦ there was some evidence that ezitimibe was associated with an increased risk of vascular (HR2.33, 95%CI 1.11-4.89) and other dementias (HR 1.88,95% CI 1.01-3.5).
So, I take 5 mg instead of 10 as 5 has been shown to be nearly as effective. And I take breaks. And I use a little bit of stanols, (not sterols) which also block absorption of cholesterol in the gut, but by a different mechanism.

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#12

I assume youā€™re talking about this preprint: Association of lipid-regulating drugs with dementia and related conditions: an observational study of data from the Clinical Practice Research Datalink 2021

It looks like it hasnā€™t been published in a peer-reviewed journal since then, so itā€™s probably garbage.

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#13

Poster presentation from 2001. Itā€™s the only thing I can find so far that directly addresses this issue in humans, but it would be nice to have something better.

Knopp, R. H., Bays, H., Manion, C. V., Lipka, L. J., Melani, L., LeBeaut, A. P., ā€¦ Veltri, E. P. (2001). Atherosclerosis Supplements, 2(2), 90.* doi:10.1016/s1567-5688(01)80226-9

EFFECT OF EZETIMIBE ON SERUM CONCENTRATIONS
OF LIPID-SOLUBLE VITAMINS
R.H. Knoppā€™ , H. Bays*, C.V Manion3, L.J. Lipka4, L. Melani4,
AI? LeBeaut4, R Suresh4, E.P. Veltri4. The Ezetimibe Study Group;
ā€˜Northwest Lipid Research Clinic, Seattle, WA; 2L-MARC Research Center,
Louisville, KX 30klahoma Medical Research Foundation, Oklahoma City,
OK; 4Schering-Plough Research Institute, Kenilwotih, NJ, USA
Purpose: To determine the effect of the novel selective cholesterol absorption inhibitor ezetimibe (EZE) on serum concentrations of lipid-soluble
vitamins.
Methods: In a randomized, double-blind, placebo-controlled study to
evaluate the safety and efficacy of EZE, serum concentrations of vitamins
A, D (25-hydroxy vitamin D and 1,25-dihydroxy vitamin D), the two major
components of vitamin E (a- and y-tocopherol), and the a- and S-carotenoids
were measured at baseline and after 12 weeks of once-daily therapy with
either EZE 10 mg (n = 85) or placebo (PBO; n = 28) at a subset of the
study centers. Prothrombin time (PT), an indicator of vitamin K, was also
assessed.
Results: For all subjects, levels of vitamin A, a-tocopherol, and 1,25-
dihydroxy vitamin D were 3 normal levels at baseline and remained 2
normal after 12 weeks of therapy. All PBO subjects had normal a- and
p-carotene levels at baseline and at 12 weeks. a- and p-carotene levels
were normal at baseline and at 12 weeks for 82 (97%) and 78 (92%) EZE
subjects, respectively; 2 and 4 EZE subjects, respectively, had < normal
levels at baseline with 2 and 1, respectively, normalizing at 12 weeks; 1
and 3, respectively, had normal levels at baseline and < normal at 12 weeks.
Twenty-three (82%) PBO subjects had normal y-tocopherol levels at baseline
and at 12 weeks, 3 had < normal at baseline normalizing at 12 weeks, and 2
had normal levels at baseline and < normal at 12 weeks. Seventy-two (85%)
EZE subjects had normal y-tocopherol levels at baseline and at 12 weeks,
10 had < normal levels at baseline with 5 normalizing at 12 weeks, and 3
had normal levels at baseline and < normal at 12 weeks. One PBO and 1
EZE subject had 25-hydroxy vitamin D levels c normal at baseline. Both
had normal levels at 12 weeks. PT was unatfected by EZE treatment.
Conclusions: EZE does not alter lipid-soluble vitamin status.

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#14

Skeptic that I am, I ignore any individual study. I have to see several papers backing up a premise before I start to believe it

Though there is no way of knowing for sure, I agree with this statement:

ā€œAccording to a 2016 PLOS Medicine article, most clinical research papers are not useful, and an estimated 85% of medical research spending is wasted. However, a 2023 Reddit post claims that 90% of peer-reviewed, level 4-5 research is ā€œbullshitā€.ā€

ā€œmost published research is falseā€

I may have posted this before, if so, I apologize.

Why Most Clinical Research Is Not Useful.

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#15

Seems like a smart approach. Do you use a pill splitter or do you have access to 5 mg?

#16

https://pubmed.ncbi.nlm.nih.gov/28531469/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216277/

I started taking daily Ezetimibe 10mg about a year ago and it did indeed further reduce my LDL in conjunction with Atorvastatin. However, after doing a bit of research upon seeing a comment somewhere here about possible issues with Omega 3 absorption I have decided to cut it for now. I may go back to it, perhaps even on a month on / month off cycle. My change of heart was caused by having my Lp(a) tested and the result came back as 177. One of the only ways I can find to potentially reduce my Lp(a) is high doses (4g per day) of Omega 3. So the last thing I want to do is jeopardise that by taking Ezetimibe. Maybe I shall experiment if I can get the Lp(a) down to anything safe.

Just something to be aware of for anyone with CV issues who would benefit from high levels of certain EFAs.

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#17

Does it really affect ALA absorption levels (ALA seems healthy)? What if you ate more ALA?

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#18
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#19

According to those papers I linked it does inhibit ALA unfortunately. I do eat a lot of chia and flax seeds anyway.

#20

Thank you for linking that study. That was the one that initially put me onto Omega 3 to help reduce my triglycerides which it did splendidly. However that was before I introduced the Ezetimibe.