The Grapefruit Juice Effect

Unlike grapefruit, St John’s Wort (pictured above), is commonly used to combat depressed mood, is known to have the opposite effect on CYP3A4, causing some interacting medications to have lower concentrations.


Grapefruit is one of the most notorious foods known to cause drug interactions, for good reason - there are over 85 medications that are known to interact with grapefruit. The compounds in grapefruit involved in this interaction are called furanocoumarins. Research has shown that plants use these furanocoumarins as a natural defense mechanism against predators such as insects, fungi and mammals - so it’s safe to say it’s a strong compound. In humans, certain furanocoumarins are responsible for the "grapefruit juice effect", in which these furanocoumarins affect certain P450 liver and gut enzymes, such as the inhibition of our CYP3A4 enzyme - which either activates or deactivates many drugs, thus leading to higher or lower levels in the bloodstream.

It is not just grapefruit that contain these drug-interacting furanocoumarins -related citrus fruits such as seville oranges, (often used in marmalades), limes and pomelos also produce the furanocoumarins and thus can cause the “grapefruit juice effect”. Kava-kava has also been found to cause the CYP3A4 interaction with its kavalactones.

Recent studies have shown that some other plant genus compounds such as aqueous extracts of Acacia catechu, Andrographis paniculata, Arctium lappa, Areca catechu, Bupleurum marginatum, Dysosma versipellis, and Spatholobus suberectus inhibited CYP3A4 by more than 85% (at a dose of 100 μg/mL). So keep an eye for these when combining medications.

On the other hand, prolonged use of Hypericum extracts (St. John’s Wort) are known to cause the opposite reaction - ramping up the CYP3A4 enzyme, which for certain medications can actually lower the amount in your system and cause the medication to not work.

As you can see herbal-drug interactions can be complex to say the least. We’re not trying to scare you - we just want you to be aware of the interactions so you can safely and effectively get the most out of your medicine - both plant and pharmaceutical. If you are on any medications or supplements and are thinking about incorporating herbal supplements, please feel free to reach out to one of our herbalists or pharmacists to make sure that you can avoid these interactions.


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Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290:1500–4.