It will be interesting to see what the dose - side effect response curve for this is. And also the impact over time.
The curve may be non-linear:
“The Fremantle Diabetes Study,30 an observational study in Australia, found that low-intensity statins (n = 119) were not associated with any change in hemoglobin A1c, moderate-intensity statins (n = 195) were associated with a mean increase of 0.22% (P = .022), and high-intensity statins (n = 11) were associated with a mean increase of 1.05% (P = .023).”
Given that the dose - therapeutic response is non linear the “other way round” (i.e. diminishing returns from increasing dose because say 1mg of rosuvastatin is about 60% as effective as 10mg). This would encourage favouring a low dose.
I’d love to see some research on length of use impact as well. Because we may find that cycling statins with other apob interventions is the best way to go.
Yes, I like that idea too. Or maybe pulsed dosing like most do with rapamycin. I looked at some studies that archive good results with weekly dosing of really small dose rosuvastatin (5-10mg once weekly). If combined with “benign” drugs like ezetimibe results in lowering LDL-C are quite impressive for that small dose.
That seems physically impossible to me as the half-life of rosuvastatin is 19 h.
If you want to minimize diabetes risk you should take atorvastatin, not rosuvastatin.
I don’t see the problem if you can monitor A1C.
This paper says mitochondrial disfunction causes insulin resistance.
If high dose statins cause mitochondrial disfunction in some way, that could point to a path toward higher diabetes. Perhaps that is known.
On a related note, I have been working to push my apoB and HbA1c down at the same time. I had big success driving down apoB to very low levels (48) and modest success in reducing HbA1c (5.8 —> 5.5). But, I felt a muscular weakness that I attributed to Rapa, and then to metformin, but now I don’t know but suspect the statin (keep reading).
I started backing off my apoB meds (rosu and eze) to see if I could give back some of the apoB improvement while solving the “weakness” issue.
I halved my rosu (5mg EOD) and eze (5mg/day) dose. In my unscientific way, I also added Akkermansia (blood sugar) later GG (mitochondrial function) in the middle of my test period (before next blood test).
Results were:
LDL (no apoB this time): 35 —> 65 mg/dl
HbA1c: 5.5 —> 5.0
Muscle strength: weakness is no longer present
I’m now increasing my eze dose back to 10mg/day and significantly reducing egg consumption (4/day to 1/day) to see if I can keep everything good and get back to lower LDL / apoB.
Patients tolerating the once-a-week regimen experienced a 17% reduction in total cholesterol, 23% reduction in low-density lipoprotein cholesterol, 12% reduction in triglycerides, and a 5% increase in high-density lipoprotein cholesterol (all p <0.001).
Rosuvastatin twice weekly alone or added to other lipid-lowering medications decreased total cholesterol by 19%, low-density lipoprotein cholesterol by 26%, and triglycerides by 14% (p<0.01 for all).
I’m no longer using any statin because these are too strong, it drops my LDL very low (30mg/dL) but it drops my HDL too. The only stastin wich is not that bad to my HDL is pravastatin, but it increases my liver enzymes. So no thanks.
I’m just using ezetimibe now. Works great and no side effects.
Oh, what did happen in between? Suddenly you think this is not good enough proxy for ASCVD?
Add ezetimibe and you are looking at maybe 30% reduction and that is not that bad any more.
I believe cycling or pulsing drugs in this case statin lessens the side effects and risk with enough reduction in apoB that it makes worthwhile. If you want a more favorable lipid composition and some further reduction maybe some fibrates. Ad fibers, omega3, some exercise and you can go from medium risk to really low risk.
Very interesting, this also got me thinking about the impact of statins on apoB vs ldl-c
Essentially they reduce ldl-c by more than they reduce apoB - suggesting they reduce the average size of the ldl-c particles as well as the number. That would put the apoB reduction at about 19% for apoB from the weekly dosing. Compared to say -40% with a daily dose.
So a weekly dose provides half the impact of an equivalent daily dose. And the following doses are roughly equivalent in terms of impact…
1mg daily Rosuvastatin = 20mg weekly Rosuvastatin
Here’s the apoB vs Ldl-c papers:
"In untreated patients, the apoB target of <90 mg/dl was roughly equivalent to an LDL-C level <100 mg/dl and a non**–** HDL-C level <130 mg/dl, which is consistent with existing apoB and lipoprotein guidelines. However, during statin therapy, to reach an apoB target of <90 mg/dl it was necessary to reduce non–HDL-C to <100 mg/dl or to reduce LDL-C to <70 mg/dl (in high-triglyceride patients) or <80 mg/dl (in lower-triglyceride patients). The tight correlation seen for non–HDL-C with apoB while on statin therapy (R2 = 0.92) implies that non–HDL-C may be an acceptable surrogate for direct apoB measurement. https://www.sciencedirect.com/science/article/pii/S073510970801930X
I thought my apoB reduction was too low for statins, and I thought it was because I already had low apoB. But it seems like a totally normal apoB reduction. 5 mg rosuvastatin decreases apoB by around 30%, so maximum reduction from statins is around that.
I know, but we are discussing pulsed dosing/cycling. Once week dosing was tried on statin intolerant patients and it showed major reduction in myopathy (70-80% of previously intolerant patients could tolerate statin). You could cycle fibrates to avoid interaction. maybe 5 days a week. IDK if this dosing would be viable but I will research it some more. If one is not as ambitious about apoB reduction, 30% with once weekly statin and ezetimibe is a great combo with minimized risk of side effects. I believe also long term problems with statins like T2D or possible dementia or elevated parkinsons risk could be minimized this way. But it is only speculative.
An article I read suggested some kind of reduced schedule statins (EOD/E3D/E7D), daily or EOD ezetimibe combined with bempedoic acid. This kind of therapy if purchased out of pocket in Europe would cost you maybe 75-90 EUR/month.
I will try to link the article, but I lost it in all the articles I skim lately.
