There are currently no human studies which have identified interactions between hesperidin and medications. However, some animal studies suggest potential drug-supplement interactions, warranting caution.
Both hesperidin and hesperetin, albeit to different degrees, show inhibitory activity towards cytochrome P450 enzymes, notably CYP2C8 and CYP3A4, which play a role in the metabolism of various substances and medications. One study in rats indicated that orally administered hesperidin at 5-15 mg/kg (but not at 1 mg/kg) reduced the metabolism of the antiarrhythmic drug diltiazem, therefore increasing its overall and maximum plasma concentration. This suggests hesperidin’s potential to inhibit CYP3A4 or P-glycoprotein, which are responsible for expelling substances like toxins or drugs (such as diltiazem) and drug metabolites from cells.[1]
In another animal study, rats receiving orange juice or a hesperidin supplement for eight weeks exhibited increased exposure and peak concentration of the cholesterol-lowering drug pravastatin. This effect might be attributed to the inhibition of a transporter protein that facilitates pravastatin efflux into the intestine following absorption.[2]