Decided to just give ezetimibe a go for giggles, assuming I’d need to throw on a couple other agents immediately. 10mg daily dropped my LDL to 100 and had maintained that.
That's amazing. I tried ezetimibe monotherapy for a while and had mediocre results.
I’m taking 10mg/10mg of Rosuvastatin/Ezetimibe. I’m getting labs Wednesday. I have at least 12 months worth of bempedoic acid 180mg. If my lipids justify it would you add 180 or can you split them?
I dug into the literature a bit on this. There's sparse information, but I did find one study from 2018 that showed a trial of 40mg, 80mg, and 120mg. 120mg daily reduced LDL-C by >20%. 180mg daily is generally around 25-28%. There should still be some benefit in terms of reducing LDL-C, but the 180mg dose was settled upon pretty early on and is the subject of the CLEAR outcomes trial. If you're at risk for the progression of plaque burden, which I presume because of your existing pharmaceutical interventions, then I would wager, you'd benefit from smashing ApoB to as low a number as possible.
I think this boils down to the flush vs flush free products. I've only taken Niacin w/ flushing, have had no liver or insulin sensitivity issues;
Not really.
Findings about a metabolite of niacin, or vitamin B3, raise concerns about the health effects of too much niacin and suggest new measures to help prevent or treat cardiovascular disease
www.nih.gov
Study outlines genetic links between 4PY and vascular inflammation, indicates need for future research.
www.lerner.ccf.org
Cleveland Clinic researchers have identified a new pathway that contributes to cardiovascular disease associated with high levels of niacin, a common B vitamin previously recommended to lower cholesterol. The team, led by Stanley Hazen, M.D., Ph.D., discovered a link between 4PY, a breakdown...
newsroom.clevelandclinic.org
Seems that any dietary niacin taken in excess could be a problem.
Then why is ezetimibe superior (it seems so from most replies on here)? Do you mind explaining? I'm not at all educated when it comes to cholesterol medications.
It's cheap and relatively benign in terms of side effects. Further, I think it was popularized several years ago by one of the YT dudes (now dead) "Leo and Longevity".
+1 on the importance of fibers.
Psyllium husk in particular will sequester bile acid in the gut triggering the liver to take up cholesterol to synthesize more bile acids. Bound bile acids and cholesterol are excreted. It and other forms of fiber is fermented by gut bacteria creating short chain fatty acids like propionate which inhibits cholesterol synthesis in the liver.
Rosuvastatin: lowers cholesterol synthesis throughout the body
Ezetemibe: lowers absorption of cholesterol in the gut
Bempedoic Acid: lowers cholesterol synthesis specifically in the liver
Rosuvastatin is a hydrophilic statin meaning that it doesn't cross the blood brain barrier and is though to have a better side effect profile as a result.
All statins inhibit HMG-CoA reductase which is an enzyme needed to create mevalonate, a precursor in the biosynthesis of cholesterol. As a result of this, LDL synthesis is reduced.
As a result of this inhibited synthesis, the liver increases the expression of LDL receptors which remove more LDL from the blood stream.
Ezetimibe inhibits the absorption of cholesterol absorbed in the small intestine which in turn reduces cholesterol delivered to the liver. This again causes the liver to upregulate LDL receptors removing more LDL from the bloodstream.
Bempedoic acid is a prodrug, that is activated only the liver by a particular liver enzyme (ACSVL1) which is thought to reduce the potential for muscular side effects that statins may have. Once activated it inhibits ATP citrate lyase (ACL) which is an enzyme required for cholesterol biosynthesis and so the synthesis of cholesterol is reduced.
...and (tell me if you've heard this before) as a result of diminished cholesterol synthesis, the liver yet again upregulates LDL receptors removing even more LDL from the bloodstream.
PCSK9 inhibitors (Repatha, Inclisiran or LEQVIO) work by inhibiting the protein PCSK9 which degrades the LDL receptors resulting in an increase number of LDL receptors in the liver and we know what happens next.
