I have written about grapefruit essential oil and drug interactions before, but after my presentation on Slique last week, I was inundated with question about whether grapefruit essential oil and grapefruit essential oil-infused products can be used while on medications. Let’s review the evidence again.
Grapefruit juice is well known to be contraindicated in patients taking medicines that are CYP3A4 substrates. As a reminder, CYPs are the cytochrome enzymes that metabolize foreign substances such as medications, and 3A4 is the name of a specific enzyme. CYP3A4 is responsible for the metabolism of a wide variety of medicine, including: cholesterol lowering medicines (‘statins”), and select medicines for blood pressure, HIV, infection, anxiety and pain.
What is a drug interaction?
There are two primary types of drug interactions: inhibition and induction. Inhibition happens when a drug causes a CYP enzyme to slow down, and drug levels in the body stay high for longer. Induction is when a drug causes an enzyme to speed up, and drug levels fall faster than expected.
How do interactions between grapefruit and medicines happen?
Grapefruit juice is very high in a constituent called 6,7-dihydryoxybergamottin (or 6,7-DHB for those who don’t like tongue twisters), and 6,7-DHB is a furanocoumarin primarily responsible for enzyme inhibition. Enzyme inhibition is a risk factor for adverse drug effects because if we inhibit an enzyme, metabolism of medications and other substances goes down, and therefore medication levels in the blood remain high instead of falling as expected. Grapefruit flavonoids also contribute to the enzyme inhibition of grapefruit juice, but not to the same extent as 6,7-DHB. There are less potent inhibitors of CYP3A4 found in grapefruit essential oil such as bergamottin and bergapten, but the action is weaker and not a source of major, clinically–significant drug interactions. Importantly, while 6,7-DHB and grapefruit flavonoids are found in high concentrations in grapefruit juice, they are not found in high concentrations in grapefruit essential oil, and are therefore less likely to cause clinically important drug interactions.
What about enzymes other than 3A4?
If we examine the effect of grapefruit essential oil on other enzymes, there is some evidence that in rabbit liver microsomes grapefruit oil can inhibit CYP2E1, however it is not the strongest inhibitor. Fewer medications are metabolized by CYP2E1 than by CYP3A4, so it is less likely to encounter a reaction.
However, a very common medication, acetaminophen (paracetamol, Tylenol®) is toxified to a more reactive substance by CYP2E1. So, the metabolite of acetaminophen and CYP2E1 produces N-acetyl-p-benzoquinoneimine is more likely to use glutathione to detoxify or react with healthy cells. Ethanol (the common alcohol in beer, wine, and spirits), induces CYP2E1, and, theoretically, grapefruit and other citrus oils may compete with the induction. With these two drugs, it may be prudent to exercise additional caution.
Consideration of the benefits as well as the potential risks allows you to be an empowered patient who listens to your own body. In my opinion, I do not think that the combined use of grapefruit essential oil and medicines are banned for all people. If you want to use grapefruit essential oil while on medicine, start low and go slow with a small amount of grapefruit oil in a diffuser or supplement.