How do statins work?

H

helli

Well-Known Member
Relationship to Diabetes
Type 1
After a decade of declining the kind offer of statins, and my cholesterol creeping very very very slowly up, I decided to give them a go. My idea is to try them for 3 months and then decide whether I have any side effects and whether the benefit outweighs them.

All I was told was "they will reduce your cholesterol and chance of having a heart attack". But I was given no information about how they work. For example, do they reduce the damage already done? Does it matter if I forget to take them one day? Is there a best time of day to take them?

Google has helped me a little bit but I still want to know more without scouring through turgid academic papers (apologies to academics who love their papers).
I now know that statins reduce the amount of cholesterol our livers produce which they do more at night (so better to take statins in the evening) and they stop existing fatty deposits from breaking off and causing blood clots but do not undo any harm already done.

I still do not know if the effect is cumulative - does the amount of cholesterol produced by our livers reduce over weeks or months of statins or does it each pill reduce cholesterol production by the same amount? I do not know the affect if I go away for a week and forget to take them with me - am I starting from scratch when I get home or does some of the "good" linger?

Does anyone have the equivalent of the IT industries Guides "... For dummies" about statins?
 
You might find this article by Zoe Harcombe interesting as to how they work. The important part comes as you scroll down and is labelled 1) How statin drugs really lower cholesterol. It's a bit scary!
 
They help with clearing LDL cholesterol and reducing production of it. This is good because the rate at which you can develop and progress atherosclerosis (plaque in your arteries) is governed to a large extent by how many LDL-containing particles you have in your bloodstream, for how long. (Approximately: there are other bits & pieces of particles which can contribute but it's mainly LDL-containing particles. And BP, insulin resistance and inflammation also play a role).

Statins can help regress existing arterial plaque to some extent by keeping LDL levels very low. But their main benefit in terms of existing plaque is to help stabilise it, promoting development of fibrous coverings and calcification which prevent plaque from rupturing. It is this rupturing which causes heart attacks and stroke: gunk and clots breaking away and suddenly blocking a coronary or carotid artery.

They also have an anti-inflammatory effect, which to some extent is a product of their action in slowing down plaque development (which causes inflammation) and to some extent is an independent action which in turn reduces susceptibility of the artery to plaque development.

I think it shouldn't matter much what time of day you take them. This is true for rosuvastatin, the statin I take, which has a relatively long half-life in the blood. Maybe different atorvastatin?

Their LDL-lowering effect is pretty fast acting: a handful of days at most to see the full impact, I think. If you don't take them for a week I'd expect LDL to go back to what it was before, but then to come down again quickly once you start taking them again.

The bad effect of LDL is a matter of level x time, like pack-years with smoking. Probably not a huge deal if it's raised sharply for a week; a bigger deal if it's raised moderately for a year.

An important point is that (despite the Internet and maybe also your GP) there is no downside to having low LDL. People with genetic variants and taking powerful non-statin drugs routinely see LDL levels <0.5 mmol/l, with no ill effects from it, and reduced risks. You won't go that low on a statin, but there would be no risk from doing so,
 
Last edited:
How statins work - they slightly inhibit the production of cholesterol in the entire body. Every cell in the body can and does produce its own cholesterol. The biggest effect of inhibiting cholesterol production a bit occurs in the liver.

The liver needs a lot of cholesterol, primarily to produce bile acids. Contrary to popular belief the liver takes in more cholesterol from the blood, which is coming in from other cells in the body via HDL particles, than it puts out into the blood. By making cholesterol a more 'scare resource' it will 'upregulate the expression of LDL receptors' - what this means is it will start scooping up more LDL particles from the blood to scavenge and recycle the cholesterol those particles contain. Interestingly, the body may also respond by increasing the amount of cholesterol that is taken in from the intestine (food) with another bit of upregulation, to address the scarcity. For this and other reasons a specific statin dose can be more effective in one person than another. The level of 'upregulation' varies from person to person.

The full effect of that inhibition occurs in about a week, however it can take a month or more to see the full effect on blood LDL levels. Changes to the expression of LDL receptors may take time to 'settle.' When put on a statin a doctor will generally ask for a blood lipid test 1 to 3 months after starting a statin. Testing earlier may not give the full picture. The effect on inhibition will go away after a week of stopping a statin, but again the full effect on LDL levels may take a month or more to settle to a new level. It doesn't matter much if you skip a dose and time of day doesn't matter very much (at least with Atorvastatin, which I'm on) though like most medications being consistent with time of day taking the pill is probably a good idea.

What Eddy says is all correct. Comparing cholesterol to 'pack years' for cigarettes is a good analogy. Smoking 20 a day for a year will likely do much less harm than 20 a day for 20 years. As diabetics, everyone on this forum is more susceptible to the effects of blood cholesterol levels than the average person. We're all 'smokers' to one degree or another. You mentioned that you're not keen on reading scientific papers though the summary text for this one, a clinical trial where they gave 10mg of Atorvastatin to Type 2 diabetics with at least one additional risk factor, is interesting - Link - Full text behind a paywall unfortunately, but the summary says it all. They ended the trial two years early because people in the placebo group, those not taking the statin, were having heart attacks, strokes and were dying so much more frequently than those on the statin that continuing the trial and thus denying those taking the placebo access to a statin would have been unethical.

There's no 'Statins for Dummies' that I know of (but there should be!) though I've found this series of video interviews with the lipidologist Dr. Thomas Dayspring, a true cholesterol expert. Much of what he says is hard to follow in the beginning, lots of technical details, but the videos are full of cutting-edge knowledge on the subject - Page of links to interview videos - He does not often refer to LDL, he talks about ApoB, which is a blood test that is very hard to access in the UK/Ireland but is the best test available to measure what is effectively the same thing - how many 'bad' particles there are in the blood. If you have the time, if you can get to the end of the third video and digest it all, you'll very probably know more than the average GP on the subject of cholesterol targets. I've fact-checked much of what Dayspring says which contradicts typical cholesterol advice that comes from GPs, by reading research papers and the whole deal, and I've found Dayspring to be on solid ground every time. It's not that the average GP is wrong (Total cholesterol to HDL ratio!) they're just giving outdated advice.

Listen to the likes of Zoe Harcombe on the subject of cholesterol and statins, as a diabetic, take her word over that of a doctor, and there's a strong possibility that her advice will shorten your life. It's that clear-cut - filter out all the BS there is out there on the subject of cholesterol and statins if you want to live longer.
 
Eddy Edson said:
She's a charlatan.
Click to expand...
Shes not a medical doctor and doesn't seem to have any research experience beyond a phd...pretty low level stuff.
 
Tdm said:
Shes not a medical doctor and doesn't seem to have any research experience beyond a phd...pretty low level stuff.
Click to expand...
A quick scan of her twitter history is informative for her positions on climate science, vaccines, Great White Replacement conspiracies etc etc etc as well as cholesterol denialism.

https://x.com/zoeharcombe
 
Eddy Edson said:
A quick scan of her twitter history is informative for her positions on climate science, vaccines, Great White Replacement conspiracies etc etc etc as well as cholesterol denialism.

https://x.com/zoeharcombe
Click to expand...
Unfortunately, an anti-vaxxer will see that and be like 'Oh yes!! This person is wise indeed! I will listen to her expert views on cholesterol and statins, for she is wise and knows 'The Truth'. There's a reason she spouts conspiracy theories and such - it actually gives her a perverse kind of credibility in certain circles.
 
Thanks guys.
I should have said that I am not interested in the conspiracy theories and learning about all the potential side effects of statins - I have read enough about this and made the decision to try them to see how they affect me.
My question was to learn how and when best to take them and what to do if I forget. But with knowledge on how they work rather than being told "take one tablet with your evening meal".
 
Last edited:
I did find an article yesterday with a link to a 20 year follow up on various factors and heart problems.
It had type 2 way out in front, so (logically, and raising one eyebrow) my advice would be to make every effort to control blood glucose levels and hope for 20 more years in which to enjoy heart health.
I have asked my GPs and other HCPs for information about the benefits of taking statins, the actual numbers, and none has been forthcoming, which seems a bit strange if they work.
 
Discussion on statins, Insulin resistance and sugar in our diet

 
Last edited by a moderator:
helli said:
Thanks guys.
I should have said that I am not interested in the conspiracy theories and learning about all the potential side effects of statins - I have read enough about this and made the decision to try them to see how they affect me.
My question was to learn how and when best to take them and what to do if I forget. But with knowledge on how they work rather than being told "take one table with your evening meal".
Click to expand...
Indeed. The answer to how best to take them is: because statins work 'indirectly' to an extent, with the desired effect on how many LDL particles are being scooped out of the blood changing quite some time after a change in the statin dose, it probably doesn't matter. If you skip a pill, the liver might take up a tiny fraction fewer LDL particles some time later. As far as I know, there is no best time of day to take them. As long as you are consistent with time and dose you can judge the effects based on the next blood test result. Inconsistency makes it trickier to judge whether a dose is too much or too little. I have read of people taking the pill every second day though I wouldn't recommend it - as there is basically no such thing as pushing cholesterol levels 'too low' to unhealthy levels artificially, might as well take the full dose prescribed and take it consistently so that the observed effect on blood test results months later is quite definitive.

EDIT - By the way I take my statin last thing at night. I do that as it makes it less likely that I'll forget to take it - part of my bedtime routine. I very rarely forget to take it, whereas I regularly forget to take my meds that I'm supposed to take with two of my three meals a day - the habit isn't as ingrained. The 10mg Atorvastatin dose I'm taking has been very effective, so it certainly seems that bedtime isn't a bad time to take it.
 
Last edited:
helli said:
(I also don't learn by watching videos.)
Click to expand...
Especially not from Dr Aseem Malholtra who's always had a fringe view of statins, dietary fats, and has since expanded his fringe views to Covid vaccines. (Not sure whether he's gone fully anti-vax yet.)
 
Eddy Edson said:
A quick scan of her twitter history is informative for her positions on climate science, vaccines, Great White Replacement conspiracies etc etc etc as well as cholesterol denialism.

https://x.com/zoeharcombe
Click to expand...
lol, I just looked at that link .. this post ... she should realise that viruses change and mutate :confused:
1722272268674.png
 
Following this thread with interest as I have also been resisting. Following a brief chat with my menopause doctor about statins and me whinging about how good my diet is now, yet my cholesterol continues to creep up, she did say diet plays a very small part. Genetics and age are the main contributory factors to high cholesterol and advised me to take them.
 
For some reason I stopped taking statins while I was losing weight a year or so ago to get rid of my fatty liver and T2.
I recently asked my (new) GP whether I should start taking them again.
Another blood test ensued, result cholesterol levels back to normal.
GP's note, no further action required.
Was he wrong?
Should I be worried about ApoB?
 
JITR said:
For some reason I stopped taking statins while I was losing weight a year or so ago to get rid of my fatty liver and T2.
I recently asked my (new) GP whether I should start taking them again.
Another blood test ensued, result cholesterol levels back to normal.
GP's note, no further action required.
Was he wrong?
Should I be worried about ApoB?
Click to expand...
I won't argue with your doctor. All I'll say on this is that the judgement call on the part of your doctor will take your age into account. For me, at 46 years of age, male, was obese for quite a while, ex-smoker of 20 years, with metabolic syndrome and a T2 diagnosis I may be quite some way along the path to heart disease already, and I have a long way to go before I reach your age. That's a lot of years where lower cholesterol levels might help me avoid a heart attack at some point down the line. On the day I was diagnosed the QRisk3 calculator put my odds of having a heart attack or stroke at higher than 50% in the next 10 years. That's extremely high for a 46 year old, as you can imagine. My GP advised a statin, and my diabetologist was keen that I aim for a very low cholesterol target (though I argued back at the time, because I didn't understand why). For me, with much damage done and far to go, a statin is an extremely good idea. If your cholesterol levels are now normal, and you've brought your HbA1c down, your doctor may not believe a statin is necessary to curb your heart disease risk for the remainder of your journey. Statins have their greatest effect over a span of decades.
 
Evening I finally decided to take them 3 months ago and have my first blood test next week so will report back.
My cholesterol has mainly been average to slightly higher but have always resisted as my general cardiac health has always been good so never saw a particular risk.
However my diabetes diagnosis has increased my risk score hence my decision to follow the GPs advice.
I remember a long time ago when I worked for Merck and they introduced a Statin and it got a lot of attention.
What I can say is they have proved very successful in reducing the risk of heart disease and as such am happy to take them to try and mitigate against the higher risk as a result of the diabetes
 
You must log in or register to reply here.
Back
Top