Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice

Aims Dietary nitrate from sources such as beetroot juice lowers blood pressure (BP) via the nitrate-nitrite-nitric oxide (NO) pathway. However, NO and nitrite are inactivated via reoxidation to nitrate, potentially limiting their activity. Cytochrome P450-3A4 inhibition with troleandomycin prevents nitrite re-oxidation to nitrate in rodent liver. Grapefruit juice contains the CYP3A4 inhibitor furanocoumarin. We therefore hypothesized that grapefruit juice would enhance BP-lowering with beetroot juice by maintaining circulating [nitrite]. Methods We performed a randomized, placebo-controlled, 7-hour crossover study in 11 healthy volunteers, attending on 3 occasions, receiving: a 70-mL shot of active beetroot juice (Beet-It) and either (i) 250 mL grapefruit juice (Active Beet+GFJ), or (ii) 250 mL water (Buxton, Active Beet+H2O); or (iii) Placebo Beet+GFJ. Results The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJvsActive Beet+H2O (P =.02), and pulse pressure, PP (P =.0003). Peak mean differences in SBP and PP were seen atT= 5 hours: -3.3 mmHg (95% confidence interval [CI] -6.43 to -0.15) and atT= 2.5 hours: -4.2 mmHg (95% CI -0.3 to -8.2), respectively. Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJvsActive Beet+H2O (P =.006), as was salivary nitrite production (P =.002) and saliva volume (-0.34 mL/min [95% CI -0.05 to -0.68]). The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2O (P =.03). Conclusion Grapefruit juice enhanced beetroot juice's effect on lowering SBP and PP despite decreasing plasma [nitrite]. Besides suggesting more complex mechanisms, there is potential for maximising the clinical benefit of dietary nitrate and targeting isolated systolic hypertension.