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

TY - JOUR

T1 - Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice

AU - O'Gallagher, Kevin

AU - Borg Cardona, Sarah

AU - Hill, Callum

AU - Al-Saedi, Ali

AU - Shahed, Fawzia

AU - Floyd, Christopher N

AU - McNeill, Karen

AU - Mills, Charlotte E

AU - Webb, Andrew J

N1 - Funding Information: There was no support from any external organization specifically for the submitted work. We acknowledge internal infrastructure financial support from King's College London British Heart Foundation Centre; National Institute for Health Research (NIHR), Clinical Research Facility at Guy's & St Thomas' NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society

PY - 2020/6/10

Y1 - 2020/6/10

N2 - 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+H 2O); 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+H 2O (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+H 2O (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+H 2O (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.

AB - 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+H 2O); 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+H 2O (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+H 2O (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+H 2O (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.

KW - blood pressure

KW - cytochrome p450

KW - nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=85087688555&partnerID=8YFLogxK

U2 - 10.1111/bcp.14420

DO - 10.1111/bcp.14420

M3 - Article

C2 - 32520418

SN - 0306-5251

VL - 87

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 2

ER -