What foods, besides grapefruit, can inhibit CYP2C9 (cytochrome P450 2C9) enzyme activity?

Foods That Inhibit CYP2C9 Enzyme Activity

Several foods besides grapefruit can inhibit CYP2C9 enzyme activity, with turmeric being one of the most potent inhibitors, reducing CYP2C9 activity by 25-75% 1.

Major Food Inhibitors of CYP2C9

Strong Inhibitors

• Turmeric/Curcumin: Significantly inhibits CYP2C9 activity by 25-75% 1
• St. John's Wort: While primarily known as an inducer of CYP enzymes, it can initially inhibit CYP2C9 before induction occurs 2

Moderate Inhibitors

• Grapefruit juice and components: Contains furocoumarins that inhibit CYP2C9
  • Bergamottin - stronger inhibitory effect on CYP2C9 than on CYP3A4 1
  • 6',7'-dihydroxybergamottin (DHB) - potent CYP2C9 inhibitor with IC50 of 1.58 μM 3

Other Potential Inhibitors

• Cranberry juice: Contains flavonoids that may inhibit CYP2C9 2
• Pomegranate juice: May have similar effects to grapefruit juice 4
• Red wine: Contains flavonoids that may inhibit CYP enzymes 2

Clinical Significance

The inhibition of CYP2C9 is particularly important for medications with narrow therapeutic indices that are metabolized by this enzyme, including:

• Warfarin: CYP2C9 inhibition can increase warfarin concentration, potentially increasing INR by 25% with propafenone 2
• NSAIDs: Many are metabolized by CYP2C9
• Phenytoin: Reduced metabolism can lead to toxicity
• Sulfonylureas: May cause hypoglycemia with reduced metabolism

Mechanism of Inhibition

CYP2C9 inhibition by food components typically occurs through:

1. Competitive inhibition: Food components compete with drugs for the enzyme binding site
2. Mechanism-based inhibition: Some components (like furocoumarins) can irreversibly inactivate the enzyme 5

Recommendations for Patients on CYP2C9 Substrates

For patients taking medications metabolized by CYP2C9:

• Monitor closely when consuming foods known to inhibit CYP2C9, especially with narrow therapeutic index drugs
• Consider avoiding turmeric supplements, which have concentrated amounts of curcumin
• Be cautious with grapefruit juice, pomegranate juice, and cranberry juice
• Pay attention to herbal supplements like St. John's Wort that can affect CYP2C9 activity

Special Considerations

• The effect of food inhibitors varies between individuals due to genetic polymorphisms in CYP2C9
• The inhibitory effect may last 24+ hours after consumption 4
• Even small amounts of these foods can potentially cause clinically significant interactions 4
• Separating the timing of medication and consumption of these foods may not prevent interaction 4

For patients already consuming these foods while on CYP2C9 substrate medications, monitor for signs of increased drug effect and consider dose adjustments if necessary.