CHronic hypERtension and L-citRulline studY (CHERRY): an Early-Phase Randomised Controlled Trial in Pregnancy.


Ormesher, Laura, Worton, Stephanie A, Best, Ashley, Dodd, Susanna R ORCID: 0000-0003-2851-3337, Dempsey, Alice, Cottrell, Elizabeth C, Glossop, Heather, Chmiel, Catherine, Wu, Hoi Yee, Hardwick, Ben et al (show 3 more authors) (2023) CHronic hypERtension and L-citRulline studY (CHERRY): an Early-Phase Randomised Controlled Trial in Pregnancy. Reproductive sciences (Thousand Oaks, Calif.), 31 (2). pp. 560-568.

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Abstract

Oral supplementation with L-citrulline, which is sequentially converted to L-arginine then nitric oxide, improves vascular biomarkers and reduces blood pressure in non-pregnant, hypertensive human cohorts and pregnant mice with a pre-eclampsia-like syndrome. This early-phase randomised feasibility trial assessed the acceptability of L-citrulline supplementation to pregnant women with chronic hypertension and its effects on maternal BP and other vascular outcomes. Pregnant women with chronic hypertension were randomised at 12-16 weeks to receive 3-g L-citrulline twice daily (n = 24) or placebo (n = 12) for 8 weeks. Pregnant women reported high acceptability of oral L-citrulline. Treatment increased maternal plasma levels of citrulline, arginine and the arginine:asymmetric dimethylarginine ratio, particularly in women reporting good compliance. L-citrulline had no effect on diastolic BP (L-citrulline: - 1.82 95% CI (- 5.86, 2.22) vs placebo: - 5.00 95% CI (- 12.76, 2.76)), uterine artery Doppler or angiogenic biomarkers. Although there was no effect on BP, retrospectively, this study was underpowered to detect BP changes < 9 mmHg, limiting the conclusions about biological effects. The increase in arginine:asymmetric dimethylarginine ratio was less than in non-pregnant populations, which likely reflects altered pharmacokinetics of pregnancy, and further pharmacokinetic assessment of L-citrulline in pregnancy is advised.Trial Registration EudraCT 2015-005792-25 (2017-12-22) and ISRCTN12695929 (2018-09-20) In pregnant women with chronic hypertension, L-citrulline is an acceptable intervention which increased plasma L-citrulline bioavailability but did not affect BP, potentially due to altered pharmacokinetics of pregnancy.

Item Type: Article
Uncontrolled Keywords: Humans, Hypertension, Nitric Oxide, Arginine, Citrulline, Retrospective Studies, Pregnancy, Dietary Supplements, Female, Biomarkers
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 16 Oct 2023 08:29
Last Modified: 16 Feb 2024 14:31
DOI: 10.1007/s43032-023-01335-4
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3173724
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