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J Hum Hypertens. 2019 Jan;33(1):10-21. doi: 10.1038/s41371-018-0108-4. Epub 2018 Sep 11.

Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials.

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Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Faculty of Health and Social Care, Edge Hill University, Ormskirk, Lancashire, UK.
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.


The objective of this study was to systematically investigate the efficacy of oral L-citrulline supplementation on systolic and diastolic blood pressure. Studies were identified by a search of electronic databases from inception to April 2018, and combined and stratified analyses were used. Fifteen trials were identified, and data from 424 participants were included. Pooled analysis showed significant reductions in systolic blood pressure by -7.54 mmHg (95% confidence interval (CI): -9.44, -5.63; P < 0.001, I2 = 14%) and diastolic blood pressure by -3.77 mmHg (95% CI: -5.67, -1.86, P < 0.001, I2 = 42%) following oral supplementation of L-citrulline or a watermelon extract. No changes were detected in controls. Significant heterogeneity (I2 = 42%, P = 0.04) was found for diastolic blood pressure, and subgroup analysis showed significant improvements in systolic and diastolic blood pressure, particularly for study durations: ≥6 weeks, lower doses: ≤4 g/day, and in participants with higher baseline values: ≥130/85 mmHg. In conclusion, L-citrulline improves systolic and diastolic blood pressure and may be more efficacious in pre-hypertensive and hypertensive populations.


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