The acute effects of alpha-lactalbumin intake on tryptophan metabolites and mood in older adults with Mild Cognitive Impairment.

Objective: This study explores the relationship between Mild Cognitive Impairment (MCI), mood disturbances, and tryptophan (TRP) metabolites of the kynurenine and serotonin pathway in older adults, focusing on the acute effects of a TRP-rich protein meal.

Methods: 32 older adults (age 55 and up) with MCI (MoCA score 18-26) and 26 older adults without MCI matched for age, sex, and body mass index (BMI) were assessed for mood and TRP metabolites. A subset of these subjects then consumed an alpha-lactalbumin (ALAC) meal rich in TRP. Plasma TRP metabolite concentrations and mood (using the Profile of Mood States (POMS) scale) were assessed before and 3 h after intake.

Results: At baseline, MCI subjects had higher plasma anthranilic acid than non-MCI controls (p = 0.015). Intake of ALAC resulted in increases in plasma TRP, kynurenine, 3-hydroxykynurenine, kynurenic acid, picolinic acid (all p < 0.001), and anthranilic acid (p = <0.001) but not in serotonin (p = 0.065). Higher picolinic acid levels were found after ALAC intake in the MCI than in the non-MCI group (p = <0.001). The TRP/large neutral amino acid ratio increased by 89.9% in MCI subjects and 95.9% in controls. There were no acute changes in mood after ALAC intake.

Discussion: Older adults with MCI showed elevated baseline anthranilic acid, and TRP-rich protein intake acutely increases TRP availability and upregulates the kynurenine but not serotonin pathway without mood improvement. Post-ALAC increases in picolinic acid in MCI subjects warrants further investigation.Trial registration: ClinicalTrials.gov identifiers: NCT05395390, NCT02082418.