Oral Citrulline supplementation in pregnancies with preeclampsia: a multicentre, randomized, double blind clinical trial

• Published in: The American journal of clinical nutrition 2024-12
• Main Authors: Winer, Norbert, Misbert, Emilie, Masson, Damien, Girault, Aude, Alexandre -Gouabau, Marie-Cecile, Ducarme, Guillaume, Dochez, Vincent, Thubert, Thibault, Boivin, Marion, Ferchaud-Roucher, Véronique, Péré, Morgane, Darmaun, Dominique
• Format: Article
• Language: English
• Subjects: Citrulline; Life Sciences; NO Donor; placental dysfunction; Preeclampsia; sflt1/PLGF ratio
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1016/j.ajcnut.2024.12.001

Preeclampsia contributes to maternal and fetal mortality and morbidity. Supplementation with L-arginine, precursor of Nitric Oxide (NO), has not proven effective, possibly due to extensive arginine catabolism in splanchnic bed. Citrulline is converted by the kidney to L-arginine. Citrulline therefore, could be a more effective NO donor in the treatment of preeclampsia. The aim of the study was to determine whether oral L-citrulline supplementation would prolong the delay between diagnosis and delivery in preeclamptic women. A total of 115 women with mono-fetal preeclamptic pregnancy were enrolled before 36 weeks of gestation in a multicenter randomized double-blind, trial: 58 received oral L-citrulline supplementation, and 57 received placebo. Duration of pregnancy, neonatal and maternal outcome, and, soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PLGF ratio), an index of placental dysfunction, were monitored. Gestational age at inclusion was similar in both groups. The duration of pregnancy between inclusion and delivery was unaltered (HR 0.90, 95% CI [0.62 ; 1.31]). Neither neonatal weight nor pregnancy outcome differed between groups. Liver enzymes were higher on the day of delivery in the treated, compared to placebo group ( 65.1 vs 33.2 UI and 70.4 vs 33.7 UI for ALAT and ASAT, respectively, (estimate 5.92, 95%CI [1.09 ; 10.74]) . Systolic blood pressure was higher at delivery in citrulline group versus control group (p = 0.015) whereas the diastolic blood pressure showed no difference. We did not find any difference on neonatal outcomes nor sFlt-1/ PlGF ratio. The current trial found no benefit of oral L-citrulline supplementation to women with preeclampsia regarding either the duration of pregnancy, fetal growth, or maternal and neonatal outcome. Systolic blood pressure and liver enzymes at delivery were increased in the treated group. L-citrulline oral supplementation does not seem to be a promising candidate as a therapeutic intervention in pregnancies with preeclampsia. Clinical Trial Registration (Registration. CITRUPE) NCT02801695