drug metabolism, orange juice, grapefruit juice

Grapefruit juice has become notorious since the 1991 discovery that drinking grapefruit juice can change the blood levels of certain medications (The Lancet, Feb. 2, 1991). It turns out, however, that grapefruit juice and its effects on drug metabolism are just the tip of the iceberg. This topic is far more complicated than most of us imagine. It is no wonder this couple has become embroiled in a disagreement.

The Citrus Juice Quarrel:

Q. I have understood that grapefruit juice generally should not be used to take medicine. My wife believes that orange juice is also dangerous. She is urging me not to take my pills with orange juice.

Isn’t Grapefruit Juice Different from Orange Juice?

I understand that grapefruit juice contains an ingredient that orange juice does not and that is what interacts adversely with medicine. This is now becoming a major issue for us; can you resolve it?

A. As with most marital disputes, the answer to your question is complicated.

The Grapefruit Effect:

Scientists have known for 25 years that grapefruit juice has a special ability to increase blood levels of certain medications, including the hypertension drug felodipine, cholesterol-lowering meds such as atorvastatin and simvastatin and the anti-anxiety agent buspirone. It does this by inhibiting the intestinal enzyme CYP3A4 that metabolizes many medicines. The increased blood levels can make side effects more severe.

The only other fruits that act like grapefruit are Seville (sour) oranges and pomelos.

What About Orange Juice?

Ordinary orange juice and apple juice can affect other medications in a completely different way (Journal of Clinical Pharmacology, online June 10, 2015).  Instead of inhibiting CYP3A, these fruit juices inhibit the compounds that help move certain medications into tissues and cells.

Which Drugs Are Affected by Apple or Orange Juice?

The affected drugs include aliskiren (Tekturna), fexofenadine (Allegra) and atenolol (Tenormin), most notably. The impact is to lower tissue levels and effectiveness.

The grapefruit effect can last for a few days, while orange juice activity disappears within a few hours. Whether or not you need to avoid taking your medication with grapefruit or orange juice depends which drug you are taking. We hope this helps resolve the disagreement between the two of you.

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  1. Loretta
    Williamsburg. VA.

    I eat a small orange every morning and I take Tenormin usually shortly before or after I eat the orange. Will that have the same effect as orange juice?

  2. Virginia

    What’s wrong with water? It just seems too easy so why make things difficult?

  3. Carla

    Like to add, this info:

    Orange juice/oranges, contain salicylates, which makes Kids hyper. Specially on am empty stomac.
    grape fruit, is OK to take.

    Please. tell all your MD’s about it.

    What a great website we have. Thanks again, Joe and Terry

  4. Jane

    I have read in a health magazine that lime also causes problems like grapefruit does with statins. Is this true? If Seville oranges are a problem, what about blood oranges? Are they dangerous to eat if a person takes statins?

  5. Mary

    I love fresh orange juice and rarely drink it because of the blood sugar response I get.

    I will sometimes eat an orange or half a grapefruit. I am not taking any drug grapefruit might interact with.

  6. Joseph

    I am taking Doxycycline for Rosacea. The instructions say to avoid all citrus juices from 1 hour before, and until at least 2-3 hours after taking the drug. I drink orange juice nearly everyday. Is this directive the correct advise?

  7. Alex

    If you are on a low dose aspirin regimen, do not take your aspirin with orange juice. My father did that an burned a hole in his stomach!

  8. Mike

    This article included an offer for a free download of your Health Guide on Grapefruit Interactions, which is very nice, but I already had downloaded it in 2014. I had no way to know whether this was a new version w/o ordering and opening it. (It appears to be the same.) I would encourage you to include the date with each item you offer, so your readers/fans will know when there is something new.


  9. rick

    Rather than blame the orange juice and/or grapefruit juice maybe one should look in to the amount of enzymes that are required to detoxify a toxic substrate like pharmaceuticals and/or alcohol. Alcohol inhibits the ability of CYP450 to detoxify many substrates including itself probably due to the fact it causes CNS depression!

    • Terry Graedon

      Alcohol does inhibit CYP450-related metabolism of the beta blocker metoprolol. [http://www.ncbi.nlm.nih.gov/pubmed/26664053]
      It can also affect blood pressure. [http://www.ncbi.nlm.nih.gov/pubmed/24096258]

  10. Lola

    I take my vitamins and supplements with milk so I don’t have a problem with orange juice.

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