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

Research output: Contribution to journalArticle

Kevin O'Gallagher, Sarah Borg Cardona, Callum Hill, Ali Al-Saedi, Fawzia Shahed, Christopher N Floyd, Karen McNeill, Charlotte E Mills, Andrew J Webb

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Publication statusE-pub ahead of print - 10 Jun 2020

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INTRODUCTION: 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 re-oxidation 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 70ml-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 versus Active Beet+H2 O (P=0.02), and pulse pressure, PP (P=0.0003). Peak mean differences in SBP and PP were seen at T=5 hours: -3.3mmHg (95% 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 versus Active Beet+H2 O (P=0.006), as was salivary nitrite production (P=0.002) 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=0.03).

CONCLUSIONS: 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.

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