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Why I Tried Ezetimibe (Zetia) and Why I Stopped Almost Immediately

Zetia side effects

NOTE: I wrote this post to ease the mind of someone sitting at home with a similar experience who is concerned they may be dealing with a serious medical condition that is really just a nasty side effect of a common heart drug. My experience is not typical and if your doctor believes you should try this drug (presumably because you tested for elevated sitosterol) please follow your doctor’s advice. Zetia is a great drug for a subset of the population why hyper absorb sterol and who tolerate it well. 

Imagine walking to a friend’s dinner party. You’ve been looking forward to attending and the date’s been circled on your calendar as a night of cocktails and good conversation.

Your friend is an amazing cook and the first hint of fall is in the air.

It’s good to be alive.

There’s just one problem.

Due to a prescription drug you’ve been taking called Zetia, it’s possible you might not be able to actually swallow the food your friend is serving. That’s right, every so often the food you’re doing your best to eat will lodge for a moment in your throat and you have to try with all your might to get it down. Even then, it’s not a slam dunk. Eating, something you normally enjoy, has now become a source of stress and the last thing you want is to risk sitting and eating with friends and people you’ve only just met, because who knows what will happen?

Nightmare scenario, right?


It’s actually mortifying.

I know because I’ve been there.

Welcome to a “bio-hacking gone very wrong” edition of the Gene Food blog.

Zetia can be effective, but…

Before I begin describing my sub optimal experience with a drug called ezitimibe (also known as Zetia), I want to emphasize that my reaction to Zetia may not be your reaction. If this is a medicine your doctor recommends, presumably because you are hyper absorbing plant sterol, his or her advice trumps my N=1 experience. I could tell instantly that taking Zetia didn’t agree with my body, but pushed through with additional doses to be sure. This was a mistake, but it could be good news for those considering Zetia – if your reaction is anything like mine, you might know right away that you don’t tolerate the drug. For me, the first symptom was stomach upset – it felt like a bomb had gone off in my stomach. However, you might not get an immediate reaction, so it’s important to keep an eye on things to see how they progress if you decide to take Zetia.

In clinical trials, Zetia has been fairly well tolerated, so this could be a good drug for you. In the IMPROVE-IT trial, 10mg of ezetimibe added to 40 mg of simvastatin reduced further heart attacks, but not many deaths, compared to simvastatin alone in patients sick with heart disease who already had their LDL-C lowered to less than 125 mg/dl. 1

Note: we will get to this in a minute – but as it relates to Zetia, I am much more interested in data we don’t have than data we do. What I would like to know is not whether Zetia helps very ill patients in some small way once their disease has progressed for an entire lifetime and has now reached an advanced stage. Instead, I would like to know what would happen had these ill patients received small doses of Zetia 20 or 30 years before becoming ill and immediately after they were diagnosed as “hyper absorbers” of cholesterol or plant sterol. We have no way of knowing that, but my money would be on major improvements in mortality and heart risk if the right patient population was selected.

So, for some, Zetia could make you healthier overall and may even extend your life. 2

My intention here is not to scare people away from taking Zetia. Having said that, I’ve heard cardiologists I trust and respect theorize that “putting Zetia in the drinking water” could be a helpful intervention for society at large.

If that ever happened, I’d die of thirst, because Zetia was not a good option for me.

I am sharing my experience because I believe it may help someone out there wondering if their reaction to this drug is “normal,” or worrying that they’e come down with some terrible illness when in fact they just reacted to a drug with known side effects (like all drugs).

There is a place for drugs

My first thought when sitting down to write this post was – “whoa, I am not touching a pharmaceutical drug for a long while.” And I hadn’t, up until very recently with this Zetia bio-hacking idea. Before I get to the “why” of my short lived Zetia journey, I will say that, at least in my view, the anti-pharmaceutical movement in the integrative health world has gone a bit too far.

Yes, drugs are not the answer to most chronic health conditions. And yes, they are over prescribed, but conversely, there are some people who probably should be on a statin (Zetia is not a statin, but they are often prescribed together).

Although it’s a very supplement focused world (after all, most “bio-hackers” sell supplements) you still see members of the bio-hacking community having success with drugs, testosterone replacement therapy being a big one. Many of the influencers you know and love use some kind of testosterone replacement. Smart drugs, like modafinil are another popular “bio-hack.”

David Sinclair, a well known anti-aging researcher at Harvard, has been public about his long term use of a statin to keep high cholesterol under raps.

The lesson: there is a time and a place for pharmaceuticals, even among the health conscious.

It is against that backdrop that I gave Zetia a try.

Why I tried Zetia

Simple. I was consistently seeing elevated levels of sitosterol (sometimes around 5.5 mg/dl) in my blood. Depending on what I was eating, my LDL-C was sometimes moderately elevated at around 110 mg/dl (it ranges from 90 – 115).

Cholesterol is a type of fat only found in animals. Sitosterol is a “phytosterol” fat found in plants. The best heart labs measure for sitosterol for two reasons:

  1. Sitosterol levels are thought to be a proxy for cholesterol absorption
  2. You don’t want a lot of sitsosterol (or any sterol) in the blood

Under normal circumstances, sitosterol helps stop cholesterol absorption because it competes to get into the blood stream with cholesterol. 3 Whereas, the cholesterol we absorb (which often isn’t much) makes its way into the blood stream and eventually back to the liver, sitosterol and other phytosterols are only temporarily absorbed. When they get past the wall of the gut a process driven by two genes ABCG5 and ABCG8 kicks these sterols out of the gut wall where they are then excreted in stool. That is the normal scenario. But, if you’re someone like me with a few mutations in the ABCG5/8 genes, you may be hyper absorbing both plant sterols and cholesterol. When absorbed at high enough quantities, these phytosterols can be damaging to heart health. Of particular interest to me is this New England Journal of Medicine study which found that oxidized sterols bind preferentially to Lp(a), a particularly dangerous type of LDL particle, that apparently becomes “extra bad” when phytosterols bind to it’s unique structure of proteins. 4

I have had moderately elevated levels of Lp(a) as well as elevated sitosterol. This is a bad combo long term. Two cardiologists told me to consider Zetia which seemed logical as a preventative measure. After all, Zetia is not a statin, it does not stop the body from making its own cholesterol.

How Zetia works

Instead Ezetimibe blocks the absorption of both sterols and cholesterol from being absorbed through the gut wall. 5

Of course, this isn’t a drug for everyone because not everyone absorbs much of the sterol and cholesterol they eat. But for some of us, Zetia has the potential to lower LDL-C by blocking cholesterol absorption, but also to lower sterol count by blocking sterol absorption at the gut wall. In the hyper absorber group, both of these benefits can then cause a reduction in LDL-P.

It is important to note that there are a range of views on how dangerous elevated phytosterols are for heart health. Not everyone agrees that sitosterol, in normal ranges, is dangerous.

However, even the papers finding that elevated sterols are not usually a metric of concern for cardiovascular disease readily concede two important points:

  1. LDL-C is a metric of concern 6
  2. If sterols are high enough, as they are with sitosterolemia, there is definite cause for concern 6

Sitosterolemia, a condition I have discussed previous on the blog and on the podcast, is marked by huge absorption of plant sterols into the blood. No one disputes this level of absorption is dangerous. So, how then do we draw the line for those that fall short of sitosterolemia?

It’s not an easy thing to do, but my sense is seeing sitosterol in the red on a Boston Heart Panel is probably something that should catch your eye.

Taking ezitimibe, assuming you can tolerate side effects, can be a method for targeting LDL-C and dangerous levels of plant sterols in hyper absorbers.

Zetia side effects

According to the Mayo Clinic, these are the “more common” Zetia side effects:

  • Fever
  • headache
  • muscle pain
  • runny nose
  • sore throat

However, when you scan down the list of “less common” side effects, you get a pretty daunting roster of terribles, such as:

  • Back pain
  • body aches or pain
  • chest pain
  • chills
  • cold or flu-like symptoms
  • congestion
  • coughing
  • diarrhea
  • difficulty in moving
  • dizziness
  • dryness or soreness of throat
  • hoarseness
  • muscle pain or stiffness
  • pain in joints
  • pain or tenderness around eyes and cheekbones
  • shortness of breath or troubled breathing
  • stomach pain
  • stuffy nose
  • tender, swollen glands in neck
  • tightness of chest or wheezing
  • trouble in swallowing
  • unusual tiredness or weakness
  • voice changes

My Zetia side effects

Now comes the fun part.

My total dose was probably no more than 60 mg over the course of about two weeks (I cut the dose to 5 mg every other day after seeing research 7 arguing that a 10mg dose may be overkill), but I still experienced what you would call a grand buffet of side effects when taking Zetia.

I got to order off the regular menu, but was also served some special dishes that only the VIPs know about.

Sore throat? Check.

Runny nose? Check.

Dizziness? Check.

Depressed mood and tiredness? Check and check.

Stomach pain? By stomach pain, do you mean the feeling that a bomb has gone off in your stomach and you can’t quite fathom how uncomfortable it is? Check, although oddly this came and went such that I thought it could have been the combo of scotch and Zetia that was causing the issues, making me resolve not to combine Zetia and booze (now I know not to combine Zetia with my life).

Pain in joints? Yes! Big check. I noticed that when I’d do dips at the gym, my hands hurt as I applied pressure to the bars.

And here comes the big one, the most terrifying side effect I have ever had from any drug or supplement ever – trouble swallowing, otherwise known as dysphagia. Holy crap. You do not want to have this. As I polish up this blog and get ready to publish, I am happy to say that my throat has gotten better every day since I took my last dose of Zetia about 9 days ago, and that I can now eat normally again. However, as the medicine built up in my system and my throat grew more irritated, on a few occasions towards the end of meals I had a sensation like I couldn’t swallow after taking a bite of food. It wasn’t every meal and it was only a handful of times, but I only took a small amount of Zetia.

Dysphagia is a lesser reported side effect with Zetia, but man, it’s a doozy.

What will I do now?

The issue for me seems to be cholesterol and sterol absorption. I want to get a handle on this now, while I am still young, to get on a regimen that will be heart healthy for me.

In my case, this means ignoring people who tell you that eggs and avocado are “good for you.” I am more liberal with eggs since my LDL-C never goes crazy high (had some at brunch yesterday), but overall I eat very few.

Next, with the exception of some almond butter here and there, I stay away from plant fats. This means cutting out high sterol foods like avocado, walnuts, vegetable oil, etc.

When I do this 90% of the time, I can get my sitosterol in the yellow range on a Boston Heart Panel. This will have to be good enough as Zetia is a no fly zone for me. Some have sitosterolemia and can’t handle any sterol. Others, and I seem to fall into this camp, appear to be able move my phytosterol number from potentially dangerous to likely safe 6 by simple dietary interventions.

If you’re interested in playing along at home but don’t have access to a Boston Heart panel, we report on the sterol absorption genes in our custom nutrition plan product.

John O'Connor

John O'Connor is the founder of Gene Food, host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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