Purple Peril? Grape Juice Interaction Differs from Grapefruit Juice

Have you ever been warned about a grape juice interaction with the heartburn medicine omeprazole (Prilosec)? I didn’t think so. If you were to poll most pharmacists and physicians and ask them about such a drug interaction you would likely get a blank stare. We did not realize such a combination could be problematic until we stumbled across an article in the journal Frontiers in Pharmacology (Dec. 4, 2024). Here is the title of this intriguing research: “Impact of fresh grape juice on the pharmacokinetics of omeprazole: results of a food–drug interaction study.” More about the significance of this study momentarily.

Our Fascination with Food and Drug Interactions Goes Way Back!

When my first book, The People’s Pharmacy, was published in 1976 (St. Martin’s Press), chapter 6 started this way:

“Drug interactions are the Achilles heel of the medical profession. The laws of nature no longer hold true. This is a crazy world where one plus one equals three, where down may very well be up and surely pigs have wings. In fact, mixing medicines is very much like playing Russian roulette. You never know when a particular combination will produce a lethal outcome.”

Sometimes, a drug interaction can lead to an exaggerated reaction because blood levels go up. That is often what happens when you combine grapefruit or grapefruit juice with certain medications. Other times, though, an interaction leads to reduced effectiveness. That is apparently what happens when you take the acid-suppressor Prilosec with grapefruit juice. Details to follow!

The Great Grapefruit Drug Interaction Mystery!

I will never forget when Terry came charging downstairs to announce to me a study she discovered about grapefruit and its ability to elevate levels of a blood pressure medication called felodipine (Plendil). A Canadian researcher, Dr. David Bailey, and his colleagues published in the journal Lancet (Feb. 2, 1991). We wrote about it in our syndicated newspaper column and interviewed Dr. Bailey on our People’s Pharmacy radio show.

Many health care professionals were skeptical. A reader reported to us that when she mentioned the interaction to her pharmacist the response was something along the lines of “there go the Graedons again…scaring people unnecessarily. Don’t worry about it.”

Since those early days, most prescribers and pharmacists have come to accept that grapefruit, along with limes, pomelos and Seville oranges, can indeed interact with certain medications. Even the FDA alerts health professionals to grapefruit-drug interactions. But the new grape juice interaction story is just starting to unfold, so most health professionals have not heard about it yet.

The Grape Juice Interaction with Omeprazole:

We stumbled across the grape juice interaction with the acid-suppressing drug omeprazole (Prilosec) entirely by accident. Here is the reader question that alerted us:

Q. I have Barrett’s esophagus, so my doctor prescribed Dexilant. Before that, the reflux was so bad it was going into my Eustachian tubes like a volcano and setting my ears on fire. I thought I was exploding. At that point, I was taking Prilosec twice a day with no relief.

When my symptoms first began, I tried drinking water and not eating to avoid the horrible reflux. That didn’t work, so I turned to grape juice and was disappointed again.

Dexilant saved me. My doctor said it would reduce the risk of Barrett’s esophagus turning into cancer. Recently the reflux has returned somewhat, and I would welcome any suggestions on managing it.

Finding the Grape Juice Interaction with Omeprazole:

In trying to answer the implicit question about omeprazole ineffectiveness posed by this reader, we started digging through the National Library of Medicine. This online resource is available to everyone. It is an absolute treasure. PubMed is a collection of around 30,000 of the world’s most important medical research publications. Let’s pray that it never gets cut back.

We wondered why a highly effective acid-suppressing drug like omeprazole did not work to control acid reflux. That’s when Terry once again discovered a fascinating problem: the grape juice interaction.

Here is our answer to this reader about the grape juice interaction with omeprazole:

A. Barrett’s esophagus is a condition in which the cells lining the swallowing tube (esophagus) change to more closely resemble cells in the intestines. There is an increased risk for esophageal cancer if these cells continue to be exposed to stomach acid splashing up into the esophagus. However, the increased risk is modest.

Taking Prilosec (omeprazole) with grape juice is not ideal, because grape juice reduces the amount of omeprazole that can get into the blood stream (Frontiers in Pharmacology, Dec. 4, 2024). The authors of this study warn that when people have conditions that require treatment with omeprazole, they should avoid drinking a glass of grape juice every day.

We do not know if grape juice might interact with Dexilant (dexlansoprazole). However, the intestines employ some of the same enzymes to metabolize these drugs, so we can’t rule that possibility out.

You will find many lifestyle measures for managing heartburn in our eGuide to Overcoming Digestive Disorders. This online resource is located under the Health eGuide tab at www.PeoplesPharmacy.com.

Confusion About Grapefruit and Drug Interactions:

What do you know about the story on grapefruit juice and drug interactions? Some people have heard that it is risky to combine juice but not fruit with certain medications; others insist that the interaction holds for the fruit as well as the juice. Pharmacists may dispense wildly different advice regarding potential reactions with specific medications.

Will Grapefruit Interact with Blood Pressure Pills?

Q. My pharmacist told me that it was OK for my mother to eat grapefruit with her blood pressure meds but that she must NOT drink grapefruit juice. He said that pressing the grapefruit for juice releases some chemical from the skin that is the culprit in the drug interaction.

My mother lived to be 94, eating her daily grapefruit. I guess he was right.

A. There is ongoing confusion about the grapefruit-drug interaction issue. The FDA disagrees with your pharmacist. So does the world’s leading expert on this interaction, Dr. David Bailey. When he first wrote about grapefruit juice interacting with medications, many health professionals were skeptical. Now, some tell patients not to eat grapefruit at all when they are taking certain prescription drugs.

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Dr. David Bailey and his colleagues note that

“…all forms of the fruit (freshly squeezed juice, frozen concentrate and whole fruit) have the potential to reduce the activity of CYP3A4” (CMAJ, March 5, 2013).

This enzyme (CYP3A4) helps break down many commonly prescribed medications within the digestive tract. If it is less active because of grapefruit, some drugs become more potent and more risky.

Not all blood pressure medicines are affected, though. People taking calcium channel blockers such as felodipine, nifedipine and verapamil should probably avoid grapefruit (Prescrire International, Dec. 2012). Most other BP drugs are not impacted by grapefruit. Perhaps your mother was taking an antihypertensive medication that was not altered by grapefruit.

Can You Safely Eat Grapefruit While Taking Simvastatin?

Q. I love grapefruit, the whole fruit. Years ago, I used to eat grapefruit often, but I have given it up. That is because I take simvastatin to lower my cholesterol.

I discussed my cravings with my heart doctor and we reached a happy medium. He says I can have half a grapefruit in the morning every five or six days. I take my pill in the evening, and he figures 12 hours or so is a safe time spread between medication and fruit.

Is Breakfast to Bedtime Enough Time?

A. Your doctor has it partially correct. Grapefruit contains compounds (furanocoumarins) that inhibit a crucial enzyme in the digestive tract that breaks down many medications, including simvastatin. This means more medicine circulates in the body, increasing the risk for side effects. The enzyme, called CYP3A4, is responsible for the metabolism of numerous medications in addition to simvastatin.

When grapefruit and simvastatin are taken together, blood levels of the drug increase by 260 percent (Lee, Morris & Wald, American Journal of Medicine, Jan. 2016). When taken 12 hours apart, as your doctor recommends, blood levels go up by 90 percent. Dr. Bailey suggests that it might be better to avoid grapefruit with certain statins such as simvastatin (American Journal of Medicine, Nov. 2016).

Enjoying grapefruit once or twice a week probably won’t have a lasting effect. Daily grapefruit, however, could cause trouble since the grapefruit effect lasts at least 24 hours. Just to complicate the situation, some people react far more strongly when they eat grapefruit than others do. We don’t yet have good ways to tell ahead of time who will get a very noticeable boost in blood levels from this interaction.

Do Other Fruit Juices Share the Story of Grapefruit Juice?

People often wonder if other fruit juices, especially citrus juices, have a similar effect to grapefruit juice. Researchers have found that both clementine juice and to a lesser extent mandarin juice also inhibit CYP3A4 and could potentially interact with certain medications (European Journal of Pharmaceutical Sciences, Jan. 15, 2017). Seville orange juice and pomelo juice might also interact in a similar way, while orange juice does not (Journal of Food and Drug Analysis, April 2018).

Lessons to be Learned from the Grape Juice Interaction Challenge:

The authors of the study in Frontiers in Pharmacology (Dec. 4, 2024) offer some intriguing insights:

“To date, not much work has been done on the effects of grape juice on drugs, although it contains resveratrol, which has been found to have various pharmacological benefits and is being extensively used worldwide…These results show that a constant intake of grape juice for 4 days reduced the bioavailability of omeprazole, which may lead to therapeutic failure or dose adjustment, as the pharmacokinetics of omeprazole after co-administration with grape juice taken once a day continuously for 1 week were observed.

“In conclusion, consistent grape juice consumption modifies the pharmacokinetics of omeprazole and dramatically reduces its bioavailability. These results can be further assessed by performing in-vitro examinations of enzyme induction or inhibition investigations. Given the current research and findings, it is advised that people using omeprazole for peptic ulcers should avoid drinking grape juice on a daily basis or that the dosage should be changed to maintain efficacy.”

They go on to mention that other drugs may also be affected by grape juice interaction. One in particular got our attention. It is cyclosporine, a drug that is prescribed to prevent organ rejection after a transplant. That means the dose is critical and grape juice could pose a significant problem.

Learn More:

To learn more about the interactions of grapefruit and other foods with medicines, you may wish to download our free Guides to Drug and Food Interactions and Grapefruit Interactions. If you have family or friends who are taking medications, you might want to encourage them to think about the grape juice interaction issue by suggesting that they read this article. Better yet, why not suggest the value of our free newsletter so that they can stay up-to-date on this kind of health information? Here is a link.

Why do we care about the grape juice interaction? Who drinks grape juice anyway? Many readers of The People’s Pharmacy have read that one of our favorite remedies, Certo and Grape Juice, can ease joint pain for many people. Here is a link to our eGuide to Alternatives for Arthritis. It contains the Certo and Grape Juice formula along with many other non-drug approaches against inflammation. With so many folks drinking grape juice, some are likely to experience a drug interaction.