l-homoarginine (l-hArg) is an endogenous non-proteinogenic amino acid. Low l-hArg concentrations are associated with increased all-cause mortality, fatal strokes, and worse outcome after stroke. On the other hand, oral supplementation with l-hArg in mice improved neurological deficits and preserved cardiac function in experimental models of stroke and heart failure, respectively. Recently, oral supplementation with 125 mg daily l-hArg capsules in healthy volunteers demonstrated increased l-hArg plasma levels. Therefore, oral l-hArg supplementation could represent a potential treatment for patients with cerebrovascular disease. In addition to vascular physiology, animal studies have suggested that l-hArg might play a role in synapse function, neurotransmitter metabolism and cognitive training. However the direct influence of l-hArg on cognitive function has not been studied so far. In this study, cognitive performance in healthy humans was analyzed concerning memory, learning, and attention following supplementation with placebo or l-hArg for 4 weeks. Our results did not reveal any effects on cognition, neither impairment nor improvement, upon l-hArg supplementation. Therefore, potential l-hArg treatment is not expected to cause any acute neurocognitive or behavioral side effects.
