Impact of 5-Hydroxytryptophan Supplementa-tion on Cognitive Function in Singapore Older Adults: A Randomized Controlled Trial

and specific metabolic perturbations of brain-related amino acids.Methods: In total 127 subjects (age >60) were stratified into 3 groups based on Fried frailty phenotype (FP): 18 nonfrail (13m/5f), 76 prefrail (39m/37f), and 33 frail (10m/23f) participants.Cognition assessment: Stroop Color Word Test (SCWT), Trail Making Test (TMT), and word fluency.Motor control: dualtask gait test.Mood: Hospital Anxiety and Depression Scale (HADS) and Profile of Mood States (POMS).Postabsorptive whole body amino acid kinetics: a pulse administration of stable isotope tracers of amino acids.Plasma enrichments of amino acids: LC-MS/MS to calculate whole-body production (WBP) rates.Statistics: GLM with covariate sex, age, (lean mass for metabolic data), and Charlson comorbidity index and Pearson correlation coefficient.Results: We observed in the frail poor cognitive performance (higher TMT, lower word fluency), motor control (dual-task time (carrying water)), and mood disturbances as compared to the non-and prefrail groups (p< 0.05).Also, higher SCWT times and interference, anxiety, and anger were observed in frailty vs prefrailty (p< 0.05).In frailty, TMT interference and dual-task time (naming animals) were higher as compared to the nonfrail (p< 0.05) while single-task time was higher in prefrail and frail vs nonfrail (p< 0.02).Moreover, we found lower WBP of glutamine, glycine, taurine, and tryptophan in prefrailty vs nonfrailty (p< 0.04).A negative association was found between dual gait task times and WBP of glycine, glutamate, glutamine, taurine, and net protein breakdown (r: [-0.31, -0.22], p< 0.02).Conclusions: Although more severe in frailty, prefrail older adults are characterized by early signs of poor motor control and cognitive dysfunction.Our data indicate metabolism of brainrelated amino acids is already impaired in the prefrail.To what extent restoring metabolic perturbations via nutritional approaches may reduce the frailty-associated decline in brain health in the early phase of frailty warrants further investigation.