Kynurenine Metabolism as a Mechanism to Improve Fatigue and Physical Function in Postmenopausal Breast Cancer Survivors Following Resistance Training

Abstract

This pilot examines whether resistance training (RT) can induce changes in kynurenine (KYN) metabolism, which may contribute to improved physical function in breast cancer survivors (BCSs). Thirty-six BCSs (63.2 ± 1.1 years) underwent assessments of physical function and visual analog scale (100 cm) fatigue and quality of life before and after 12 weeks of RT (N = 22) or non-exercise control (CBCT©: Cognitively Based Compassion Training, N = 10). Blood was collected before and after interventions for assessment of KYN, kynurenic acid (KYNA), and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). At baseline, the women were moderately fatigued (mean score: 46 cm) and at risk of poor functional mobility. A group*time interaction was observed for all measures of strength with improvements (~25–35%) following RT (p’s < 0.01), but not CBCT. Time effects were observed for fatigue (−36%) and quality of life (5%) (p’s < 0.01), where both groups improved in a similar manner. A group*time interaction was observed for KYN (p = 0.02) and PGC-1α (p < 0.05), with KYN decreasing and PGC-1α increasing following RT and the opposite following CBCT. These changes resulted in KYN/KYNA decreasing 34% post-RT, but increasing 21% following CBCT. These data support RT as a therapeutic intervention to counteract the long-term side effect of fatigue and physical dysfunction in BCSs. Additionally, the results suggest that this effect may be mediated through the activation of PGC-1α leading to alterations in KYN metabolism.

Quinolinic acid links kidney injury to brain toxicity

“…Our data are consistent with several reports that showed correlation of QA with fatigue in patients with chronic fatigue syndrome, fibromyalgia, and systemic lupus erythematosus (52, 53). Reducing KYN in postmenopausal breast cancer survivors has demonstrated to correlate with reduced fatigue (54). Our research holds particular relevance for neurologic dysfunction associated with progressive CKD and acute kidney injury (55).…”

Effect of exercise therapy on cancer-related fatigue in patients with breast cancer: A systematic review and network meta-analysis

“…There were fewer studies on resistance exercise than on combined and aerobic exercise. Recent studies have indicated that the onset of inflammation and fatigue is related to elevated levels of the tryptophan metabolite, kynurenine, and that resistance exercise may modulate the neural mechanisms of inflammation onset by improving kynurenine metabolism and further alleviating fatigue 107,108 . However, another study revealed that resistance exercises may not be suitable for patients with breast cancer with severe fatigue 109 .…”

“…Recent studies have indicated that the onset of inflammation and fatigue is related to elevated levels of the tryptophan metabolite, kynurenine, and that resistance exercise may modulate the neural mechanisms of inflammation onset by improving kynurenine metabolism and further alleviating fatigue. 107,108 However, another study revealed that resistance exercises may not be suitable for patients with breast cancer with severe fatigue. 109 Excessive resistance training or inadequate recovery can lead to a decline in physical and mental performance, and even cause a subjective sense of fatigue.…”