What if one of the most prescribed life-saving medications on the planet came with a terrifying secret?
That this very medicine designed to protect your heart was silently damaging your mind?
Well, statins, also known as HMG CoH reductase inhibitors, are a cornerstone of modern medicine, right?
Celebrated for their proven powers to lower LDL and prevent life-threat cardiovascular disease.
But this success isn't without controversy.
Over the past few decades, there have been many who claim that statins can cause dementia.
This controversy is fueled by a compelling mix of patient report experiences of brain fog and memory loss.
And a plausible biological framework for how statins could affect the brain and a specific body of scientific literature that supports this harm hypothesis.
So, the goal of this episode is to dive deep into both sides of this debate.
We'll explore the origins of the controversy, dissect the scientific arguments from harm, and then we're going to weigh them against the highest quality evidence to reach a clear, evidence-based verdict.
Let's get started.
And welcome back, team, to the Building Lif Athletes Podcast.
Thanks so much for stopping by.
I really appreciate it.
We haven't had the chance to meet me yet.
My name is Jordan Ren, and I a dual board certified physician in family and sports medicine.
And the goal of this podcast is to keep you active and healthy for life.
Through actual evidence-inform medication.
And here we going to talk all about statins and dementia.
So let's dive into it.
All right, so let's talk about the origin of these things, right?
So the concern that statins could harm the brain didn't come from large clinical trials, right?
They didn't show up in a trial saying, oh, we're seeing this pattern.
It came from real-world experiences of people who are having symptoms like brain fog, confusion, and short-term memory impairments.
So, the big scientific document for the harm was suggested in this 2003 paper by Wag and colleagues, which examined. 60 case reports of memory loss submitted to the FDA's Med program.
And a Med program, essentially, after a medication comes out, you still have an opportunity to list if you've had symptoms, side effects, or anything like that.
So, you don just put a medication out and, Oh, that it, like, we're good.
No, it's continuous surveillance, and there are multiple cases reported saying, Hey, after this statin, my patient had this, or patients can say, I had this.
And so, that's kind of that thing there.
And this analysis identified a consistent clinical picture where symptoms were often emerged within two months of starting the therapy and were usually linked to lipophilic or fat-soluble medications, the ones like Sim and Tor.
So these are.
Lip, which means more fat-soluble, theoretically, probably getting into the brain easier.
That's what we're thinking, or at least the thinking was here.
And then only one case of the 60 were linked to hydrophilic or water-soluble pravostatin. obviously, this is going back a while.
Just as,, Ros is another one now that we have that is hydrophilic.
So that's another option we have.
And then additional data that was convincing was they had the D-challenge and re-challenge, right?
So they had four patients who Stopped the medication, right?
Completely stopped it.
And then they, Hey, let's just try it again.
And then when they retried it, they had the same symptoms.
So they're saying, Hey, there might be something to this.
When we re-challenge, they still have the same symptoms.
Maybe this person on this medication might not be a good foot.
That's what they were thinking.
And then a pivotal moment happened, though, in February 2012 when the U FDA mandated a label change for all statins to include information on potential cognitive side effects.
But one thing that's really important to mention is that this data and this notification was not based on any randomized controlled trials or really any trials, more just coming from adverse reports of side effects.
That's essentially what it's coming from.
And it collects voluntary, unverified reports of patients and clinicians.
And that's not to, like, oh, these are verified, there's nothing going on.
I will paint that picture that it's more nuanced than that.
But we do have to understand this wasn, hey, we're doing lots of studies on this and we're seeing people develop dementia left and right.
Like, that's not the case at all.
It was people saying, hey, I have these kinds of Symptoms, what's going on?
And just to mention, a lot of times we're talking about these short-term symptoms.
That's the big thing that's going on here: these short-term symptoms, not dementia, is what they're saying, but that gets turned into things.
We'll talk more about that later.
But that's kind of what we're looking at there.
And it was really carefully worded as well, right?
So they described as generally not serious and reversible cognitive side effects, and explicitly stating the cases did not appear to be associated with fixed or progressive dementia.
Once again, No long-term stuff.
And then upon discontinuation, the FDA noted that symptom resolution occurred for most people within three weeks.
So just a couple of weeks, you're back there, good to go.
And yeah, that's what.
But despite these nuances, the official advisory legitimized patient concerns, right?
Fueling immediate amplification and has been cited as a significant factor in stat non-adherence, being people, hey, they hear this, they say, I don't want to be on these medications.
I'm worried about my brain, which is a very valid thing, right?
If you hear this and think it might cause dementia, like you should absolutely be worried.
Like, I would not tell you, like, hey, if you're worried about a medication that's going to cause dementia.
We should probably look into that.
So that's very, very valid.
But that's what it looks like.
But on top of that, there were also, to kind of fuel things as well, there were some case reports on top of this.
They're measuring objective things, so, like essentially, Mocha scores, which is for your mental status.
We do this typically for patients with Alzheimer's and dementia, we just kind of look at their mental status.
They saw people like improve their scores after stopping their statin.
And so that's what people are like, what is going on here?
If it's reversible, you know, that's what's going on.
Once again, not long-term.
This is not like they're showing any long-term dementia.
They, hey, these are reversible.
Very quantifiable things, right?
If a milk that's low and then you stop stat and you get better, you're thinking, hey, there actually may be something there.
But that's what we've seen.
That's kind of where this all starts from.
And so we've had reports.
What's the biological rationale between this, though?
How it could be harming the brain.
And the arguing for harm is built on a very plausible biological framework, right?
Starting the fact that the brain is uniquely cholesterol-rich.
It has lots of cholesterol in there.
We need cholesterol for everything for our entire body everywhere.
So that's like not a thing that just into the brain, but.
The brain only makes up 2% of the body's mass, but contains roughly 23% of the cholesterol.
So, very, very important.
And a critical feature here of the brain is the uh, it's not just it doesn't live on its own, but it's kind of isolated, right?
it has something called The blood barrier, which prevents cholesterol from the peripheral circulation from entering.
So, your brain typically can make all the cholesterol it needs.
So, the isolation means it synthesizes its own cholesterol, which is absolutely essential for neuronal health.
Including things like my sheath, which is important for synapses and brain chemicals being released, lots of all the very important stuff.
And yeah, the foundation for learning, memory, cognition, all those things require cholesterol and synapses.
And so that 's the big thing.
And this leads to the central pillar, though, of the harm argument, the lip hypothesis, which differentiates statins based on their ability to penetrate this blood-brain barrier.
That's kind of what we're all thinking about.
So, lipophilic, like I mentioned before, this means fat sab.
So, lip meaning fat, philic means loves, so fat soluble.
These statins are like a tor lipit or sim zoc, the big ones, and are hypothesized.
To more readily cross the blood-brain barrier and enter the brain tissue than the other forms.
That's where, whereas, in contrast, hydrophilic or water-soluble fattins like pravastatin, which we pravac, or ros crest, are largely excluded from the brain.
It's kind of looking through this.
Data is kind of not like the most robust thing in the world, but they've kind of done m studies.
They've cerebral sp fluid sampling and say that, hey, these lipophilic ones, you see a higher concentration of them than these hydrophilic ones.
That's kind of what they've gone through.
And the potential harm may not just be just from that, though, right?
So it may extend beyond cholesterol as statins inhibit entire Mevon pathway, which reduces synthesis of other downstream products.
Things like Co, so enzyme at CoQ.
It's a vital, important component for generating cellular ATP in mitochondria, and its depletion could potentially lead to energy deficit in the brain, leading to these possible brain fog or something like that.
Not only just the cholesterol synthesis, but also the potential CoQ.
And then also, they also block the synthesis of other molecules, right, which are essential.
So, we talk about isopren can be very important for other signaling pathways in the brain.
So, these are a couple of the mechanistic ideas of what's going on.
Will we know definitively?
Like, I mean, that's a whole discussion here, but there's definitely, I just want to step back, there's definitely mechanistic plausibility for why we'd be concerned, right?
Like, why potentially it could be causing these symptoms for some people.
And so, that's, I want to understand that and not just say, hey, oh, there's nothing.
But I wanted to move on to as, kind looking at the formal research for harm.
So that's just patient stories and anecdotes, and then a little bit of mechanism.
And I like going a little deeper than that, right?
Because a lot of times.
What people on will do is they read a stud that has a mechanistic plausibility and say, that's it, we're good to go.
And then they extrapolate that to like human life.
That's not necessarily fantastic.
This is cool because we have some additional studies to talk about as well.
And so, beyond just the argument, there is definitely form research looking at these anecdotes and concerns for things.
There was a 2015 retrospective cohort study by a str and colleagues that analyzed over 480,000 people and found a potential signal for acute risk.
And the study reported that first time statin users had a more than four increased odds of being diagnosed with acute memory loss from the first 30 days of exposure to when compared to non-users.
So that 's pretty significant, right?
Four times more likely to have this ac onset with statin.
And while in association, this magnitude is definitely difficult to dismiss.
You don't want to be, oh, it's nothing.
The authors did note themselves that it could be influenced by a powerful detection bias where patients starting any new medication.
Right, could become more vigilant and worry about more new symptoms that they have, right?
So, you start a medication, you get a new symptom, you're saying, Oh, uh, that's actually much more concerning because you're on edge, and so that's that's something they mention, but that is definitely there.
There was also an interesting study that came from the 2021 Society of Nuclear Medicine and Molecular Imaging.
This was a meeting and presentation there.
It looked at PET scans to look at brain function.
And it focused on vulnerable populations, specifically those with.
Existing early mild cognitive impairment.
So, this is not your average healthy person.
They have early mild cognitive impairment.
So, this is not like a normal, normal brain necessarily, but And looked at it and it found that those ellipophilic statins showed a significant decline in glucose metabolism in the posterior cingle cortex, a key brain region affected in the earliest stages of Alzheimer.
So they saying, hey, in that area.
They weren getting what they needed when they were on label philic medications, and it was kind of interesting.
They didn't necessarily see that with those who had the hydrophilic ones, so interesting as well.
And then this biological change also had a direct clinical correlate.
So, over eight-year follow-up, these patients had more than double the risk of converting from early mild cognitive impairment to full dementia compared to non-users.
So, 24% to 10%, which is pretty significant.
But There's also always limitations, right?
It's critical to note that these findings were presented at a conference.
It's kind of where I found initially and seen the initial ones.
And so I have to get some more corroboration.
That's just one study, but it's there.
And then finally, there are some Mendelian randomization studies, which can be kind of interesting.
It might provide evidence of a potential causal link, right?
So we go back and say, hey, Mendelian randomization, what that is, is We get inherited traits, right?
That's random.
We think that random.
So essentially, we're using that randomization of genetic traits to discover if a trait means something.
So, a classic Mendelian randomization example.
Is for like a PCSK inhibitors.
Those medications, right, are inhibiting the PCSK.
Some people have that genetic mutation, and we followed them up for You know, their lifetime and they had decreased cardiovascular disease.
We're, oh, like maybe that's actually causal and prevents you from having cardiovascular disease.
This is the same thing here.
They're looking this Mendelian randomization, but for all types of reasons.
And a 2022 randomization study, so MR study.
Found that genetically proxied inhibition of the HMG-CoA reductase enzyme, which is the target of statins, right?
That's what they do, was causally associated with poor performance on tests of reaction time and reduced cortical surface area.
Not exactly a specific link to dementia, right?
That's the big thing.
They found some things, but once again, just potential mechanistic plausibility.
And with Mendelian randomization, we that's Very interesting because you can prove kind of causation through not exactly doing an RCT.
Like the best thing we have that's not an RCT to potential talk about causation.
There's definitely some data out there that's like, oh, okay, we might have some legitimate things to think about.
And so that's why I wanted to present those and say, hey, I don want to just poo-poo someone away saying, oh, that gets not real.
There's no data or anything like that.
I wanted to talk about that.
But I did want to talk about the counter ev as well and the scientific consensus of quote no harm, which we'll talk more about what that means.
While the harm hypothesis is definitely there and plausible, built on theories, suggestive data, and like actual scientific data, it has to be weighed against other data as well, right?
So we have this data, but there's also this other data on the other side.
So we have to think about it.
When we think about gold standards, usually we think about like randomized controlled trials.
They are usually the best for determining causality because they randomize participants, minimizing the potential for bias that can affect other outcomes.
And so that's what we like to do.
And there was a pretty important one, a recent study in 2021, which was the As trial published in the Journal of American Cardioc.
And followed over 18,000 older adults for nearly five years with comprehensive cognitive testing, right?
And the results from this were pretty straightforward: that statin use was not associated with incident dementia or mild cognitive depirment. or declines in memory language or processing speed.
So this is actually a prospective study, looked at it for 18,000 people and didn't see those outcomes.
So that's pretty strong evidence there.
And on top of that, though, it did deliver a blow to the lipophilicity hypothesis, right?
So they found no significant difference in cognitive outcomes between patients taking lipophilic versus hydrophilic statins.
You know, the idea before is that, hey, we mentioned that, hey, it lipophilic versus hydrophilic.
Lipophilic, maybe there's more problems than hydrophilic.
They didn't see that signal necessarily.
Just wanted to mention that as well.
And these studies are consistent with earlier other trials.
So, landmark trials like the heart protection study and the Pros trial, which also found no significant difference in cognitive decline between statin and placebo groups.
Wh individual trials are good and powerful, meta-analyses also provide power at scale by combining data from many studies, including sometimes millions of patients.
There are some meta-analyses that have shown statin use are not associated with harm, but actually potentially a modest protective effect against dementia.
So that's the opposite, right?
People are saying causes dementia.
This is, well, actually, it may protect from it.
In 2025, here there was a meta-analysis looking at over 7 million patients that found statin use was associated with a 14% reduced risk of all-cause dementia and an 18% reduced risk for Alzheimer's disease.
And another 2022 meta-analysis looked at a million people.
They reported a 20% lower risk of dementia and 32% lower risk of Alzheimer disease for statin users.
And then there was a Coch review in 2016 as well, which is kind of like the most authoritative.
Health organization that kind of looks at all the data and puts it together, do a great job.
And they said that statins don't necessarily prevent cognitive decline or dementia, but it didn't also cause ag.
So it's kind of neutrality, right?
That 's the big thing.
And AHA said there's no credible evidence that statins increase the risk of developing Alzheimer.
And so this is not to say these studies are perfect.
No study is ever perfect.
There's just multiple other You know, bigger studies that are saying, Hey, we don't quite see this signal.
And of a dementia cause, it doesn't seem to be there.
They say, Hey, overall, it doesn't seem that statin cause dementia.
Or could they actually improve it?
That's not necessarily seen in the RCTs, but the population-based studies, they saw that.
So there might be other confounding factors there, but that's kind of what we're seeing.
I do want to talk about though next is like, how do we make this all fit, right?
So we have the narrative of this causes harm.
Other people say this does nothing, and there's lots of confusion, right?
Because one side's saying one thing, one side saying the other.
How do we make sense of this?
So The single greatest reason this myth persists, though, is probably the misinterpretation or weaponization of the side effects.
So, like, people have Very real side effects.
Like that is very, very real.
Like having brain fog, having confusion, all that after starting medication clearly is documented and clearly can happen.
But that is very different from saying Saturn's caused dementia, right?
Which doesn't seem to necessarily be supported by the evidence.
And so those two different things are kind of Juxtap against each other.
And so some people might say, well, any sort of brain thing I'm worried about later causing dement.
So that why I'm worried about it.
And that, you know, that's a reasonable argument to make, but it just seems like overall the data doesn't show like the leap to dement is quite there.
But That's what I want to mention here.
And as I mentioned before, that 2012 FDA warning kind of opened the gates, right, to say, hey, like, this is legit, and this is something I should be very worried about.
Um, but it was a little bit just misinterpreted potentially.
That being said, though, it's something you should absolutely be looking for.
We shouldn just be, oh, like, it's nothing.
Like, no, we should absolutely be aware of this, and we should always, you know, if there's a signal somewhere, we should investigate it to make sure it's safe.
But that's kind of where it came from.
So, these short temporary symptoms, very, very different from dementia, which is a progressive neurogen that does not get reversed.
It's irreversible, right?
And so.
The studies don't seem to show that dementia is linked to statin use, potentially.
And yeah, what's actually kind of interesting, though, is that Potentially, we may have some benefit, but a lot of times that's going to be some biases and they can't prove causation, right?
And the most significant bias here is saying, hey, why would we see improvement?
In dementia on statins is confounding by indication, meaning lots of people who are prescribed a statin might have other risk factors, and improving their other risk factors because we're doing that may show benefits.
So it's like Not necessarily putting someone on a statin, it might be like all the other things we're doing for them as well.
You know, we're trying to control the blood pressure and blood sugar and all these things, and all those things may show a signal.
And so it's going be hard to tease those out.
Either way, that's generally where we're at.
And Other RCTs, though, as I mentioned before, have showed overall it's pretty good.
But at the end of the day, there might be this kind of dual mechanism hypothesis, which posits that statins have two opposing effects on the brain, allowing all the data to kind of simultaneously be true, right?
So we have.
One side saying, there's something going on here.
Another side saying, dude, look at the data, there's nothing going on.
But can we like meld this together?
How do we do it?
This is kind of a theory.
I've kind of.
When reading through, going through this, may kind of think about it.
So, we may have a protective pathway that's indirect and long term, meaning statins are proven to improve vascular health.
And prevent strokes.
So they're a major contributor to vascular dementia and Alzheimer.
And so, why do we see protection potentially?
Well, because we are probably Decreasing the amount of mini-strokes we're having, therefore, decreasing the amount of damage to the brain.
So, maybe that's what's doing it.
Whereas we may have that harmful pathway as well, we're in a small subset of people who are susceptible to this.
These statins may cross the blood-brain barrier, cause some transient neurologic dysfunction, and have reversible brain fog.
That being said, if you're on them forever, that's probably not good for you.
So, it could be lasting if someone just stayed on the statin forever and had minor brain fog, could it last forever?
Maybe if you're on the medication forever.
But once again, very real to think: like, hey, people who have had symptoms, how do we reconcile that with?
Other data showing that actually may be beneficial for like long-term brain health.
And so that's kind of the unifying theory that I think about there.
You know, this is not a generally accepted thing, like, oh, this is for sure about, that's kind of the way I think about it.
But for the vast majority of patients, the powerful and indirect protective vascular benefits of satins will probably outweigh any subtle, transient, or non-existent harmful effects.
Which in net the population is probably neutral or beneficial for people on a big scale.
And so, just based on like long-term what we've seen in the RCTs and meta-analys, it seems like it's probably net neutral for you.
If you are a person who is susceptible to it and you have these symptoms, then it may not be the right move for you, right?
And I think a lot of times in the medical community, we get caught up in evidence-based medicine, right?
Saying, hey, in general, like Look, it's safe, it's fine.
You should be fine.
Okay, evidence-based medicine is wonderful and it helps understand a big population-wide understanding of things.
But when it comes down to you and what you're doing with your doctor, like that might be different.
You might say, hey, I've tried this and it didn't work.
Or hey, I'm really, really worried about this thing.
I can't accept any risk there.
Well, that's a discussion we can have.
I just want people to have, once again, information so they can make decisions.
I don't care what you make.
You're an autonomous adult.
You can make your own decision.
I just want everyone to have solid information so they can make that decision in an informed fashion.
Let's kind of move on to here the final verdict and clinical guidance.
After reviewing all this stuff, it looks like the claim that statins cause or accelerate dement.
Isn't supported by the high quality scientific evidence that I've seen in looking at there.
But the controversy does stem from the perfect storm of The FDA warnings, maybe misinterpreting it to say, hey, brain fog will lead to dementia, and maybe it's conflated a little bit.
So that's kind of what it is.
But the narrative did also gain.
Some, I wouldn say unwarrant, maybe unwarranted legitimacy, meaning, hey, like the claim about dementia is unwarranted.
I think the claim about the side effects is very valid.
But the claim saying, hey, this causes dementia came from those 20-12 kind of FDA warnings saying, hey, may cause some cognitive things.
But once again, the highest levels of evidence, including large RCTs like As and system Cochrane views, don't show a causal link between statin use and development of dementia or long-term cognitive decline.
And I think the most likely overall effect of statin therapy might be modest, small improvements, but most likely it's probably net neutral is what it looks down to.
Yeah, for anybody listening, the fear of dementia shouldn't be a barrier for using these medications if they're indicated for you, right?
Like if you have high risk factors and would benefit from it.
The fever dement wouldn't be one that I'd necessarily worry about specifically.
And if you experience symptoms or are concerned about that, talk with your doctor, right?
I'm not your doctor.
I just some dude on the internet talking things.
So that's why, you know, why do you believe me?
You shouldn't probably either.
You should probably do your, you know, some research from multiple sides of things and trying to find.
Unbiased views, but if you're having symptoms, then talk with your doctor.
I'm not saying continue to take a medication because that's crazy.
But it'd just be worthwhile to consider.
I think if you're a very high-risk patient, Completely ignoring these things and saying, I've never tried a statin or I would never do that because of things you read online without fully understanding it may also be risky for you.
That's the thing.
It may be risky.
People will think, like, You know, these medications are gonna kill you or do whatever.
And for some people, they might have some side effects.
That's like for sure.
I always tell people on the internet.
They say, Oh, this medication has no side effects.
I, Well, that medication won't work then.
Because if there's no side effects, like there's no medication that has absolutely no side effects, we're not quite there yet.
We have biologics that are getting closer and closer.
And you, CRISPR therapy, but we not there yet.
If you take a medication, an oral medication, it's going to have some other side effects.
Like that just means it has powerful enough effect to enact change in your body, which we want.
And so, side effects may happen, but talk with your doctor about that.
But yeah, your doctor should also be able to validate kind of your, your, should validate your symptoms, right?
So if you go up to there and, I have these things, and your doctor says, like, Too bad you're fine.
Like that, that's not ideal as well.
And so I want to be here, hopefully, to say, hey, this is valid.
And I hear these things from multiple sides, just understanding both sides of things.
But if you are worried, right?
If you want to say, hey, I.
I'm worried about my cholesterol, and I have a strong family history of something, or this or that.
And like, I want to be on those vacations, but I'm really worried about.
Dement risk, what do I do?
Well, then maybe we talk about you know the lipophilic versus hydrophilic ones, right?
Maybe starting on something like ros, which is hydrophilic, might be a better idea than starting on something like Lip, which is more lipophilic.
Is that rock solid evidence?
Like, no, it's not.
We obviously seen in trials sometimes that signal didn't show, but like mechanistically, that may be the case.
Also, it may have other benefits as well.
I don't know what's going to happen in your physiology, right?
Studies show this, but like you're not a study, you're just a single person.
So, something I want to just talk about and consider as well.
But yeah.
Other things we always have to think about as well is that before attributing symptoms to a statin, we have to also make sure other stuff's not going on.
So, other stuff could be going on.
If it's very temporal, meaning, like, hey, you start medication, then you have symptoms, like, okay, probably, probably, that's what's going on.
But we have to consider other things as well.
So, just a couple of things I want to think about overall.
Hopefully, this has not been crazy.
Hopefully, you're not super lost in this, but I just want to say.
Both sides have some merit.
And that's the thing.
I think what I'm, what drives me crazy is I live in this world like in between where I know evidence-based medicine is wonderful and it's progressed us like to a phenomenal level of medicine today, which you know, we haven't had.
I know people complain, it like, oh, like.
You know, we just push pills and big pharma and whatnot.
Okay, but at the end of the day, like our standard of living is like so exponentially better, and people aren just like dying everywhere of disease.
Like, that's wonderful.
But when we do that, sometimes we go too far in that pendulum, saying, Oh, because the data doesn't show quote unquote this, you can't be having that.
And then that leaves us this whole group of people who are like, well, I have these symptoms, or I've experienced these things, like, how do I fit in?
And then it just leads to distrust in the medical establishment.
So, I'm just trying to bridge the gap a little bit here.
Just once again, I'm one beggar to another beggar telling you where to find food.
This is just what I've seen.
This is what I've researched.
If you hate my opinions, that's cool too.
That's fine.
But hopefully, I'm just helping someone here.
But that's going to be it for today.
Thank you so much for stopping by.
I really appreciate it.
If you liked this, I would really mean the world to me if you shared this with a friend or you liked it on YouTube or subscribe or do something to kind of promote it.
That'd be helpful to get the word out.
But.
That's it for today.
Thanks so much.
Now, get off your phone and get outside.
Have a great rest of your day.
We'll see you next time.
