Toward a neuroprotective shift: Eight weeks of high intensity interval training reduces the neurotoxic kynurenine activity concurrently to impulsivity in emotionally impulsive humans - A randomized controlled trial

Abstract

Background: Previous findings suggest that impulsivity is related to chronic low-grade inflammation. Inflammation is known to trigger the kynurenine pathway to a pathological level in various impulsivity-related disorders. Nonetheless, murine models and recent human studies have shown that physical exercise, in particular High Intensity Interval Training (HIIT), could counterbalance the negative effects of inflammation on the kynurenine pathway.

Aim: This study evaluates the effects of eight weeks of HIIT versus an active control group on impulsivity levels and accompanying alterations of inflammatory-mediated changes of the kynurenine pathway in a sample of emotionally impulsive humans.

Methods: Participants were randomly allocated to either HIIT or stretching conditions (three trainings per week for eight weeks). Fitness level was evaluated via VO₂peak values at the beginning at end of the intervention. Kynurenine metabolites, pro-inflammatory cytokines, and impulsivity levels were evaluated at T0, T4, and T8 weeks. Statistical analyses were performed using mixed models.

Results: Fifty-three participants were included in the modified Intention To Treat analysis (45 finished the intervention). The HIIT group (n = 28) largely increased the aerobic fitness of its participants and produced physiological changes while the stretching group (n = 25) did not. HIIT reduced interleukin 6 levels (small to moderate interaction) and reduced the activity of the neurotoxic branch of the kynurenine pathway (small to moderate interaction for KYNA/QA and KYN/QA) after eight weeks of training while the active control did not change. Both interventions were effective to decrease emotion-related impulsivity, however only the HIIT group decreased participants' emotion-unrelated levels. Changes in emotion-related and -unrelated impulsivity were moderately correlated to changes in KYNA/KYN.

Conclusion: This study demonstrated that HIIT was able to switch the kynurenine pathway from its neurotoxic branch to its neuroprotective one. This shift was associated with a decrease in impulsivity. Based on these findings, future work may consider investigating more intensively the effect of HIIT on impulsivity-related disorders.

Keywords: Emotion; Exercise; Impulsivity; Inflammation; Interleukin 6; Kynurenine; Kynurenine 3-monooxygenase; Neuroprotective; Neurotoxic; Tryptophan.