CITRULLINE AND ITS EFFECTS ON MOOD AND COGNITVE FUNCTION

Abstract

Background: Oral citrulline supplementation is more effective at increasing circulating arginine levels than arginine itself. Upon stimulation, about 80% of citrulline is recycled to arginine by endothelial cells to produce nitric oxide. As little as 0.18 grams of L-citrulline has been reported to double plasma arginine levels. Arginine is a precursor for nitric oxide synthase (NOS) which is an enzyme that converts arginine into nitric oxide in the vascular endothelial cells with the presence of NADPH and oxygen as a co-substrate. Nitric oxide is produced through the conversion of arginine into citrulline and this is done with the presence of one of the three isoforms of NOS. Nitric oxide production is largely dependent on extracellular arginine availability. Nitric oxide is also known as an endothelial-derived relaxation factor that causes vasodilation. Arginine directly creates nitric oxide and citrulline inside the cell and citrulline is then recycled back into arginine, producing more nitric oxide. Citrulline supplementation should have a positive effect on both mood and cognitive function due to the enhanced production of nitric oxide from citrulline and due to this mechanism, an increase in vasodilation resulting from an increase in nitric oxide. Vasodilation is the increase of blood flow and an increased flow of blood to the brain, will reduce cognitive impairment and enhance cognitive function. Nitric oxide is also involved in the formation of several types of long-term memory and preferentially affects memory acquisition. Nitric oxide signalling is a candidate mechanism in the assembly of neocortial circuits underlying language and higher cognitive functions. Objective: The objective of the study was to examine the effect of citrulline supplementation on mood and cognitive function. Two intervention groups were selected, a younger group aged between 18 - 35 and an older group aged 50+. It was anticipated that a widened demographic scope would therefore, lead to different outcomes. Design: This was a single blinded, placebo-controlled parallel group study. A total number of 16 participants were recruited, 8 for the younger population group (18-35) and 8 for the older (50+) population. Participants were randomly allocated to either the intervention or placebo group. In each group, 4 participants were assigned to citrulline supplementation (1.5 grams daily for 4 weeks) and 4 participants to placebo (100mg vitamin C). Equal numbers were chosen to make the study an equal parallel group study. Tests were carried out at baseline and after completing the 4-week trial to obtain the final results. Results: Significant results were seen for pulse wave velocity in both groups; young (p-value = 0.032) and older (p-value = 0.030) before and after citrulline supplementation. This was the same for nitric oxide levels (p - value = 0.018) in the younger population after the 4 weeks of citrulline supplementation (p-value = 0.004). There was a significant reduction in the depressive mood state and in total mood disturbance in both younger and older groups taking citrulline supplementation. When the citrulline supplemented group was compared to the placebo group, no statistical significance was observed in any of the changes for the populations.