Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials

BACKGROUND: Experimental evidence indicates that oral L-citrulline (L-Cit) may reduce resting blood pressure (BP) as well as BP responses to exercise and cold exposure (non-resting). However, results from human intervention trials are inconsistent. This study aims to summarize the clinical evidence regarding the effects of L-Cit supplementation on brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), in addition to aortic SBP and aortic DBP at rest and non-resting conditions. METHODS: Multiple databases including PubMed, Embase, Cochrane library, Web of Science, and Clinical Trials were searched systematically. Randomized controlled trials of human participants were quantitatively meta-analyzed. RESULTS: Fourteen trials contained in eight studies were available for quantitative syntheses for brachial BP. Results showed that L-Cit supplementation significantly reduced both brachial SBP (− 4.490 mmHg, 95% CI: − 7.332 to − 1.648, P = 0.002) and brachial DBP (− 3.629 mmHg, 95% CI: − 5.825 to − 1.434, P = 0.001). Nine of the trials were meta-analyzed for aortic BP which showed that L-Cit intervention significantly reduced aortic SBP (− 6.763 mmHg, 95% CI: − 10.991 to − 2.534, P = 0.002), but not aortic DBP (− 3.396 mmHg, 95% CI: − 7.418 to 0.627, P = 0.098). The observed reducing effects of L-Cit appeared stronger for non-resting than for resting brachial SBP (P for difference = 0.044). CONCLUSION: L-Cit supplementation significantly decreased non-resting brachial and aortic SBP. Brachial DBP was significantly lowered by L-Cit regardless of resting status. Given the relatively small number of available trials in the stratified analyses and the potential limitations of these trials, the present findings should be interpreted cautiously and need to be confirmed in future well-designed trials with a larger sample size.