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CYP3A4 is a phase I detoxification gene (and member of the CYP450 superfamily) involved in estrogen metabolism, particularly the production of 16aOH estrogen, which is thought to be harmful in the body. A large number of medications are metabolised through the CYP3A4 pathway such as codeine, acetaminophen (paracetamol), diazepam, the oral contraceptive pill (OCP) and statins. CYP3A4 also converts E2 to E3. Variants in this gene are associated with increased activity, undesirable for estrogen metabolism, and affecting drug metabolism.

The GG genotype in this gene is associated with a possible increased CYP3A4 activity. This is unfavourable since 16aOH estrogen has been associated with estrogen excess conditions. CYP3A4 enzyme activity can increase due to diet and lifestyle factors such as obesity, excess alcohol consumption, stress, certain medications, and toxic chemical exposure. Regular physical exercise, moderate alcohol consumption, and increased antioxidant intake would be beneficial. Grapefruit is a potent inhibitor of this pathway together with curcumin, I3C, resveratrol and sulporaphane. Consult your doctor if you are on medication since you may be affected.