Effect of cranberry dietary supplements with different brands on human CYP3A4 enzyme

The use of dietary supplements has increased dramatically, making drug interactions with those supplements a major concern. Because dietary supplements are not subject to the same regulations as prescription drugs, we hypothesize that the content of their active ingredients may vary among manufacturers, potentially causing a large variation in therapeutic outcome. The current study aimed to test this hypothesis on commonly used cranberry dietary supplements. Activity of human CYP3A4 enzyme was used as a parameter to determine the effect of cranberry supplement from nine manufacturers. The content of a cranberry product, equivalent to one capsule, was extracted with methanol. Aliquots of the extract were tested for their ability to inhibit the metabolism of the human CYP3A4 substrate quinine, using an in vitro liver microsomal technique. Human liver microsomes and quinine were incubated with or without (i.e. as control) cranberry extract. Formation of quinine's metabolite 3-hydroxyquinine, generated by the CYP3A4-mediated reaction was measured by a HPLC method. Of nine cranberry products tested, eight products had little or no effect but only one brand (Nature's Herbs 600 mg) caused very strong inhibition (67.2 %) of CYP3A4. The reason for this inhibition is unknown. The effect of cranberry was varied and ranged from 4.4 % activation by Ride Aid 800 mg to 67.2 % inhibition by Nature's Herbs 600 mg. Lack of effect on human CYP3A4 activity suggests that use of cranberry dietary supplement is unlikely to cause significant interactions with drugs metabolized by CYP3A4.