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My Experience With Zetia

PCSK9 drugs

Ezetimibe, or “Zetia” for short is an important heart drug which helps people who hyper-absorb cholesterol (and plant sterol) from taking on more of these fats than their body can handle.

In the IMPROVE-IT trials, Zetia lowered cardiovascular events and LDL-C in patients already on statin therapy. Zetia is standard of care for those who have sitosterolemia, a genetic condition marked by elevated levels of plant sterols in the blood. 1

However, according to the Mayo Clinic, Zetia does have known side effects, one of which is dysphagia or trouble swallowing. Dysphagia and stomach upset were the two main side effects I experienced with Zetia, at both 5mg and 10mg doses.

My experience with Zetia

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.

Zetia is usually well tolerated

I want to emphasize that my reaction to Zetia may not be your reaction. If I could comfortably take Zetia I would. 

If this is a medicine your doctor recommends, presumably because you are hyper absorbing cholesterol and 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. I also experienced joint pain. 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 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. 2

So, for some, Zetia could make you healthier overall and may even extend your life. 3

My intention here is not to scare people away from taking Zetia.

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).

Zetia 5 mg vs 10 mg dose

This study, which appeared in the American Journal of Managed Care, found that 5 mg doses of Zetia performed on par with 10 mg doses in lowering LDL-C. As such, some people may find that they tolerate Zetia at 5 mg and not at 10 mg. This is a conversation worth having with your doctor if you experience side effects at 10 mg doses.

Why I tried Zetia

Simple. I was consistently seeing elevated levels of sitosterol (sometimes as high as 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. An excess of sitsosterol (or any sterol) in the blood is linked to increased risk for heart disease

Under normal circumstances, sitosterol helps stop cholesterol absorption because it competes to get into the blood stream with cholesterol. 4

Whereas, the dietary cholesterol we absorb (which often isn’t much) makes its way into the blood stream and eventually back to the liver, under normal circumstances 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.

However, if you’re someone like me with some loss of function 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 further weaponized when phytosterols bind to it’s unique structure of proteins. 5

I have had moderately elevated levels of Lp(a) as well as elevated sitosterol. This appears to be a bad combination in the 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, it simply blocks absorption.

Zetia side effects

Again, 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 larger list:

  • 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

Key Takeaway

Zetia is a proven drug that has the potential to benefit people that tend to hyper-absorb cholesterol and plant sterol. However, as with any pharmaceutical drug, side effects are a real possibility.

Lab tests that measure for plant sterols in the blood are hard to come by, but the Cholesterol Absorption Panel offered by Boston Heart Diagnostics does measure for all three absorption markers:

  1. Sitosterol
  2. Camposterol
  3. Cholestanol

It is possible to call Boston Heart and ask for a physician in your area that administers the tests.

John O'Connor

John O'Connor is the founder of Gene Food, a nutrigenomic startup helping people all over the world personalize nutrition. John is the 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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