ABSTRACT
PURPOSE: To monitor changes in mood, cognitive function, brain electrical activity, and circulating kynurenine pathway metabolites in response to a three-week severe physical activity restriction, followed by three weeks of resumed activity adding resistance and high-intensity interval exercise training. METHODS: Twenty healthy participants (14 males, six females; 25.4 ± 5.2 years) underwent three weeks of limited physical activity using forearm crutches with one leg suspended (INACT) and then three weeks of resumed activity plus supervised resistance and high-intensity interval training sessions (ACT, three to six sessions per week). At baseline, after INACT, and then after ACT, venous blood was sampled for analysis of major kynurenine pathway metabolites, a short version of the International Physical Activity Questionnaire (IPAQ-SF), Hospital Anxiety and Depression Scale (HADS) and Profile of Mood States (POMS) questionnaires were completed, and cognitive tests with EEG were performed. RESULTS: During INACT, the depression score on the HADS scale tended to increase (3.5 to 6.8; p = 0.065), while it was reduced with ACT compared with after INACT (2.8; p = 0.022). On the POMS scale, depression, fatigue, and confusion increased within INACT (p < 0.05). Notably, subjects exhibited considerable variability, and those experiencing depression symptoms recorded by the HADS scale (n = 4) displayed distinct mood disturbances on POMS. All HADS and POMS scores were fully restored to baseline with ACT. Neither INACT nor ACT induced significant changes in cognition, brain electrical activity, or kynurenine pathway metabolites (p > 0.05). CONCLUSIONS: While young healthy individuals with three weeks of severely restricted physical activity do not undergo changes in circulating kynurenine pathway metabolites, cognitive performance, and brain electrical activity, their mood response is quite variable, and depression develops in some. Three weeks of resuming mobility plus exercise training reversed the mood profile.
ABSTRACT
BACKGROUND/OBJECTIVES: Prolonged fasting triggers a stress response within the human body. Our objective was to investigate the impact of prolonged fasting, in conjunction with stress, on kynurenine pathway metabolites. SUBJECTS/METHODS: Healthy males were divided into fasting group (zero-calorie-restriction) for 6 days (FAST, n = 14), and control group (CON, n = 10). Blood and saliva samples were collected at baseline, Day 2, Day 4, Day 6 during fasting period, and 1 week after resuming regular diet. Plasma levels of kynurenine pathway metabolites were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Plasma and salivary samples were analyzed for stress markers. RESULTS: A pronounced activation of the kynurenine pathway in individuals on FAST trial was revealed. Concentrations of picolinic acid (PIC), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were significantly increased, with peak levels observed on Day 6 (P < 0.0001). Conversely, concentrations of tryptophan (TRP) and quinolinic acid (QUIN) decreased (P < 0.0001), while kynurenine (KYN) and nicotinamide (NAM) levels remained stable. Cortisol and noradrenaline concentrations remained unchanged. However, adrenaline levels significantly increased on Day 4 within FAST compared to CON (P = 0.005). Notably, all deviations in kynurenine pathway metabolite levels returned to baseline values upon resuming regular diet following the 6-day fasting regimen, even when weight and BMI parameters were not restored. CONCLUSIONS: Extended fasting over 6 days induces the kynurenine pathway and has minimal effects on stress markers. Restoration of metabolite concentrations upon regular feeding implies rapid adaptation of the kynurenine pathway synthetic enzymes to maintain homeostasis when faced with perturbations.
