The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727)

Abstract

Background. Recent studies have confirmed the essential and paramount role of the L-Citrulline on the nitric oxide regulation and the endothelial function improvement.Materials and Methods. In this cross-over clinical trial, thirty patients, diagnosed with coronary artery disease (CAD) and flow mediated dilation to nitroglycerin dependent vasodilation (FMD/NMD) ratio less than 1, were included. The patients were randomly divided into two groups of 15 patients and underwent treatment by L-Citrulline or placebo for 15 days, in 2 step protocol. The indicators of assessment in the current study were the ratio of the FMD/NMD and FMD value.Results. In the current cross-over clinical trial, the mean of FMD to NMD ratio and mean FMD value of all patients before starting the protocol were 0.91 ± 0.08 and 4.04 ± 0.51 mm, respectively. The final results of study showed that following L-Citrulline administration, mean FMD to NMD ratio and mean FMD value were enhanced to: 1.03 ± 0.09 and 4.96 ± 0.72 mm, respectively, which were statistically significant (P<0.001 and P<0.001, respectively). However, following placebo administration, mean FMD to NMD ratio and mean FMD value were receded to: 0.92 ± 0.09 and 4.06 ± 0.22 mm, respectively, which were not statistically significant (P = 0.75 and P = 0.89, respectively). Moreover, the improvement of mean FMD to NMD ratio (0.12 ± 0.02) and mean FMD value (0.92 ± 0.16 mm), following L-Citrulline administration, were statistically significant in comparison with the change of mean FMD to NMD ratio (0.01 ± 0.002) and mean FMD value (0.02 ± 0.003), following placebo administration (P<0.001 and P<0.001, respectively).Conclusion. L-Citrulline treatment can lead to improvement of the endothelial function in patients diagnosed with CAD which are assessed via FMD to NMD ratio FMD value enhancements.

The Effects of L-Citrulline on Blood-Lactate Removal Kinetics Following Maximal-Effort Exercise

“…Based on the results of this study, it can be concluded that five days of supplementation with L-citrulline does not impact that rate at which lactate is cleared from the blood during active recovery. While prior research indicates that supplementation with L-citrulline augments vasodilatory responses in the body (Gonzales et al 2017;Safi et al 2017) and other research suggests that augmenting vasodilation facilitates greater lactate removal from the blood (Gladden 2000;2004), the results of the current investigation do not support this relationship. Research up to this point on the effects of L-citrulline supplementation and exercise-induced blood lactate are mixed.…”

“…Our study design and hypothesis were based upon the previously mentioned findings that both acute (Raghavan and Dikshit 2001;Sureda et al 2009;Mori et al 2015;Le Roux-Mallouf et al 2017) and prolonged supplementation (i.e. 7þ days) (Schwedhelm et al 2008;Alsop and Hauton 2016;Gonzales et al 2017;Safi et al 2017) with L-citrulline have been previously reported to enhance vasodilation by facilitating production of nitric oxide. Thus, while the measurement of NO x would have provided information as to the magnitude of the effect provided by L-citrulline, we are very confident that NO x levels were sufficiently elevated and we do not believe that the lack of this measurement undermines the validity of the study.…”

Effects of l-citrulline supplementation and watermelon consumption on longer-term and postprandial vascular function and cardiometabolic risk markers: a meta-analysis of randomised controlled trials in adults

“…1, seventeen studies involved L-citrulline supplementation. Six studies with eight relevant study arms investigated postprandial effects (24)(25)(26)(27)(28)(29) , while twelve studies with twelve relevant study arms investigated longer-term effects (27,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) . One trial investigated both postprandial and longer-term effects (27) .…”

“…Three studies did not receive any funding (30,36,40) , while one study did not report any information on funding or grants (27) . Ten studies mentioned that their supplements were provided by Pronat Laboratories, NOW Foods, Milne Fruits or Cobell Ltd, without receiving any direct funding (31,32,35,37,39,(45)(46)(47)(48)(49) , while two studies reported that they received funding from the National Watermelon Promotion Board (41,44) .…”

“…Ten studies mentioned that their supplements were provided by Pronat Laboratories, NOW Foods, Milne Fruits or Cobell Ltd, without receiving any direct funding (31,32,35,37,39,(45)(46)(47)(48)(49) , while two studies reported that they received funding from the National Watermelon Promotion Board (41,44) . Studies investigating longer-term effects of L-citrulline supplementation had a study duration between 1 week and 4 months (27,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) . In total, 311 participants were included ranging from fifteen to thirty-eight participants per study arm.…”