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

  • 2020-07-09
  • British journal of clinical pharmacology 87(2)
    • Kevin O'Gallagher
    • Sarah Borg Cardona
    • Callum Hill
    • Ali Al-Saedi
    • Fawzia Shahed
    • Christopher N Floyd
    • Karen McNeill
    • Charlotte E Mills
    • Andrew J Webb

Study Design

Type
Randomized Controlled Trial (RCT)
Population
11 healthy volunteers
Methods
randomized, placebo-controlled, 7-hour crossover study
Duration
7-hour

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+H2 O); or (iii) Placebo Beet+GFJ.

Results

The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ vs Active Beet+H2 O (P = .02), and pulse pressure, PP (P = .0003). Peak mean differences in SBP and PP were seen at T = 5 hours: -3.3 mmHg (95% confidence interval [CI] -6.43 to -0.15) and at T = 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+GFJ vs Active Beet+H2 O (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+H2 O (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.

Research Insights

  • Grapefruit→Improved Taste Score

    The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2O (P = .03)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    250 mL
  • Grapefruit→Reduced Nitrite Level

    Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJ vs Active Beet+H2O (P = .006)

    Effect
    Harmful
    Effect size
    Small
    Dose
    250 mL
  • Grapefruit→Reduced Pulse Pressure

    and pulse pressure, PP (P = .0003). Peak mean differences in SBP and PP were seen at T = 5 hours: -3.3 mmHg ... and at T = 2.5 hours: -4.2 mmHg

    Effect
    Beneficial
    Effect size
    Small
    Dose
    250 mL
  • Grapefruit→Reduced Saliva Volume

    saliva volume (-0.34 mL/min [95% CI -0.05 to -0.68])

    Effect
    Harmful
    Effect size
    Small
    Dose
    250 mL
  • Grapefruit→Reduced Salivary Nitrite Level

    as was salivary nitrite production (P = .002) and saliva volume (-0.34 mL/min [95% CI -0.05 to -0.68])

    Effect
    Harmful
    Effect size
    Small
    Dose
    250 mL
  • Grapefruit→Reduced Systolic Blood Pressure

    The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ vs Active Beet+H2O (P = .02)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    250 mL
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