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.

Automated summary

This study found that grapefruit juice enhanced the effect of beetroot juice on lowering systolic blood pressure and pulse pressure, despite decreasing plasma nitrite levels. This suggests more complex mechanisms at play and potential for maximizing the clinical benefits of dietary nitrate in targeting isolated systolic hypertension.