Effect of L‐Citrulline Intake on Blood Pressure in Cold Environments: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

TL;DR

This study finds that L-citrulline supplementation can lower blood pressure increases caused by cold environments, suggesting it may help protect cardiovascular health.

Contribution

This is the first systematic review and meta-analysis to evaluate L-citrulline's effect on cold-induced blood pressure changes.

Findings

L-citrulline intake significantly reduced cold-induced systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Subgroup analysis showed significant reductions in brachial and aortic SBP and aortic DBP.

Brachial DBP reduction was not statistically significant but showed a decreasing trend.

Abstract

The primary objective of this systematic review and meta‐analysis is to investigate whether L‐citrulline supplementation can counteract the adverse effects of cold environments on individual blood pressure (BP), providing scientific evidence for the clinical development and application of L‐citrulline as a cardiovascular protective nutritional supplement. A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Embase, and Web of Science. The search period was limited from database inception to May 28, 2025. The Cochrane Risk of Bias tool and JADAD scoring scale were used to assess risk of bias and literature quality of the included randomized controlled trials (RCTs). Statistical analysis of BP data was performed using RevMan 5.4.1 software, employing both random‐effects and fixed‐effects models for data analysis, and forest plots were generated. The overall intervention effect was evaluated using the weighted mean difference (WMD) and its 95% confidence interval (CI). A total of 6 RCTs investigating the effects of L‐citrulline intake on BP in cold environments were included, involving 162 participants (intervention group: 87; control group: 75). Results indicate that L‐citrulline intake significantly reduced cold‐induced SBP (−9.28 mmHg [95% CI: −10.66 to −7.90], p < 0.001) and DBP (−5.33 mmHg [95% CI: −9.38 to −1.27], p = 0.01). Subgroup analysis revealed significant reductions in brachial SBP (−8.74 mmHg [95% CI: −10.61 to −6.88], p < 0.001), aortic SBP (−9.93 mmHg [95% CI: −11.98 to −7.88], p < 0.001), and aortic DBP (−5.60 mmHg [95% CI: −9.56 to −1.64], p < 0.001). However, brachial DBP reduction did not reach statistical significance but showed a trend toward decrease (−5.10 mmHg [95% CI: −11.71 to 1.52], p = 0.13). Meta‐analysis results indicate that L‐citrulline supplementation can significantly improve cold exposure‐induced BP elevation, providing scientific evidence for the clinical development and application of cardiovascular protective nutritional supplements.

This study investigated the effect of L‐citrulline supplementation on BP under cold exposure and found that it significantly reduced both SBP and DBP, thereby alleviating cold‐induced hypertension, thus providing a scientific basis for cardiovascular protection. Future studies should further investigate its optimal dosage.

Figures