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Double-blind controlled dietary cross-over intervention with differentially fertilised intact lettuce leaves shows acute reduction in blood pressure in young adults, associated with faster uptake of nitrate than of phenolics

Lookup NU author(s): Dr Othman Qadir, Emeritus Professor Chris SealORCiD, Ammar Ashor, Dr Mario Siervo, Dr Kirsten BrandtORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022, The Author(s). Purpose: To compare acute effects on blood pressure (BP) of ingestion of visually similar lettuce with controlled high and low content of either nitrate or phenolic compounds. Methods: In a randomised cross-over design, 19 healthy participants (22–31 years) received 50 g of lettuce containing either 530 mg (8.4 mmol) nitrate + 11 mg (0.03 mmol) phenolic compounds (HNLP); or 3 mg nitrate (0.05 mmol) + 77 mg (0.2 mmol) phenolic compounds (LNHP), obtained by differential fertilisation. Ambulatory BP was recorded along with plasma, salivary and urinary nitrate and nitrite and plasma concentrations of cyclic guanosine monophosphate (cGMP), phenolic metabolites, Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). Results: Compared with LNHP, 3 h post ingestion of HNLP, plasma nitrate increased 0.31 ± (95%CI) 0.12 mM (+ 240%), and salivary nitrate 5.5 ± 1.4 mM (+ 910%); accumulated urinary nitrate excretion increased 188 ± 72 mg (+ 296%) (all P < 0.001). Systolic BP was reduced 4.9 ± 4.2 mmHg (P = 0.031) between 3 and 6 h after ingestion of HNLP compared with LNHP; systolic BP differences were negatively correlated (P = 0.004) with differences in saliva nitrate concentrations. LNHP increased plasma phenolics at 6 h, predominantly 3ʹ-methoxycinnamic acid-4ʹ-glucuronide (ferulic acid-4ʹ-glucuronide), 116%, 204 ± 138 nM more than HNLP (P = 0.001); increased cGMP 14% (P = 0.019); and reduced FRAP 3.1% (P = 0.009). Conclusion: The acute BP difference within 6 h of consumption matched the plasma/saliva nitrate peak, not the slower changes of plasma phenolics. This is the first double-blind controlled dietary intervention demonstrating differential effects on human physiology by consumption of an intact plant food, where compositional differences were obtained by controlling growing conditions, indicating potential opportunities for health claims relating to precision/vertical farming. Clinical trial registration: The trial was retrospectively registered on, with identifier NCT02701959, on March 8, 2016.

Publication metadata

Author(s): Qadir OK, Seal CJ, Ashor AW, Tassotti M, Mena P, Del Rio D, Siervo M, Brandt K

Publication type: Article

Publication status: Published

Journal: European Journal of Nutrition

Year: 2022

Volume: 61

Issue: 8

Pages: 4191-4203

Online publication date: 23/07/2022

Acceptance date: 08/07/2022

Date deposited: 12/08/2022

ISSN (print): 1436-6207

ISSN (electronic): 1436-6215

Publisher: Springer Nature


DOI: 10.1007/s00394-022-02961-5

PubMed id: 35871120


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Funder referenceFunder name
Higher Committee for Education Development (HCED) in Iraq
MR/N007921/1Medical Research Council (MRC)