Pomegranate Juice and Rosuvastatin…a Surprising Interaction!

Do you know which foods might react badly with your medications? As a graduate student in the Department of Pharmacology at the University of Michigan over 50 years ago I was intrigued by food and drug interactions. I had a chapter in the first edition of The People’s Pharmacy (St. Martin’s Press, 1976) titled: “DRUG INTERACTIONS: When 1+1 May Equal 3.” That chapter was one of the reasons the book became a # 1 Best Seller on the New York Times list. Today, though, I share with you a somewhat unusual reaction between pomegranate juice and rosuvastatin (Crestor). It’s not the kind of interaction you will find in the official prescribing information.

How often does your doctor or pharmacist warn you about food and drug interactions? I suspect it is relatively rare. These days everyone is in such a hurry that taking time to warn people about foods that could pose problems seems unnecessary. Nothing could be further from the truth. Drug interactions can be deadly.

Statins are among the most widely prescribed drugs in the United States. They tend to interact with food somewhat differently. When you look online, you can find conflicting information, especially with regard to beverages like cranberry, grapefruit or pomegranate juice. What’s the straight and skinny on how these drinks interact with the cholesterol-lowering drug rosuvastatin?

A Surprising Discovery About Pomegranate Juice and Rosuvastatin

If it wasn’t for our readers we would not know about this interaction between pomegranate juice and rosuvastatin:

Q. Because I like grapefruit, my doctor prescribed rosuvastatin (Crestor) instead of a different statin to lower cholesterol. Later I added 1/4 cup pomegranate juice to my regimen twice a day. Wow! Joint and muscle pain came on suddenly. It hurt.

I stopped Crestor immediately and gradually felt better. My neighbor’s doctor told him pomegranate juice interacts with statins like grapefruit juice does. Who knew?

A. Grapefruit raises blood levels of statin-type cholesterol-lowering medicines such as simvastatin or lovastatin. That could increase the risk for side effects.

Rosuvastatin is not supposed to interact with grapefruit, however. Just the same, there is a case reported in the medical literature of a 48-year-old man who developed a serious complication while taking rosuvastatin with pomegranate juice (American Journal of Cardiology, Sep. 1, 2006). So even though this interaction is not supposed to occur, other people besides you have experienced it.

Here is another reader who experienced an interaction between pomegranate juice and rosuvastatin:

Q. I took Crestor for three years. All was well until I started taking my daily meds with pomegranate juice.

Then I developed cramps and muscle pain. It was awful until I discovered pomegranate acts like grapefruit with a statin. I stopped the Crestor and slowly my aches reduced.

A. Rosuvastatin (Crestor) is a statin-type cholesterol-lowering medication. Other statins (atorvastatin and simvastatin) are metabolized by the CYP3A4 enzyme. Grapefruit juice inhibits this enzyme and can raise blood levels of these drugs (American Journal of Cardiovascular Drugs, vol. 4, no. 5, 2004). However, it should have had no effect on the blood level of rosuvastatin. That said, there does seem to be an interaction between pomegranate juice and rosuvastatin.

Grapefruit Juice Does Not Affect Crestor:

Rosuvastatin is metabolized by a different intestinal enzyme, CYP2C9. Although pomegranate juice inhibits 2C9 activity in the laboratory, it doesn’t seem to have much effect on blood levels of the drugs that have been studied (Journal of Clinical Psychiatry, April 2014; European Journal of Drug Metabolism and Pharmacokinetics, June 2017). So, in theory, pomegranate juice and rosuvastatin should not be a problem. But we believe you and the other reader who had a similar reaction. The article in the American Journal of Cardiology (Sept. 1, 2006) closed with this key sentence:

“In conclusion, because both grapefruit and pomegranate juice are known to inhibit intestinal cytochrome P450 3A4, this report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment, despite the fact that rosuvastatin is not known to be metabolized by hepatic P450 3A4.”

This interaction has not been well studied. You should let your doctor know about this experience. The patient described in the article above developed a potentially life-threatening complication (rhabdomyolysis).

What Should Others Do About Pomegranate Juice and Rosuvastatin?

If you’re taking rosuvastatin and consuming pomegranate juice, be alert for symptoms like muscle pain, cramps, or joint discomfort. Should these develop, contact your doctor promptly. You may need to continue with a different strategy to reduce your risk of heart disease.

We discuss statin drugs and other ways to lower blood lipids in our eGuide to Cholesterol Control and Heart Health. You may also be interested in our free eGuide to Drug & Food Interactions.