Investigation Of Metabolic Profiles Of Cancer Related Fatigue And Changes Following A Clinical Exercise Program

Cancer-related fatigue (CRF) is common in cancer survivors, yet underlying mechanisms remain unclear. Exercise is one of the best known CRF interventions, but the associated physiology is poorly understood. Recent analyses in other populations indicate metabolic impairments as a potential mechanism of fatigue and the exercise response, though this has not been explored in cancer survivors. PURPOSE: Investigate associations between metabolic markers and CRF in cancer survivors, and changes following a three-month clinical exercise program. METHODS: Adult participants were recruited from a clinical exercise oncology program (eligibility requiring current or recently completed cancer treatment). The program included Baseline and Final assessments and weekly exercise sessions. Whole dried blood samples were collected with a patient-centric device (Tasso M20) at both assessments. CRF was measured with the Functional Assessment of Chronic Illness Therapy -using the FACIT-Fatigue scale. Metabolomics data were acquired using liquid chromatography-mass spectrometry. Changes in FACIT-Fatigue were calculated (ΔFACIT-Fatigue) and statistically compared to zero (one-sample t-test). Pearson correlation coefficients were calculated between metabolites and FACIT-Fatigue. Metabolite changes following exercise were calculated and statistically assessed. RESULTS: Data was collected from 23 participants (Age ± sd = 55 ± 14 years, 74% women, BMI ± sd = 28.5 ± 6.1 kg/m2), with 15 completing the program. Most had breast cancer (48%) and were currently receiving treatment (70%). FACIT-Fatigue significantly improved (ΔFACIT-Fatigue±sd = 4.5 ± 7.7, p = 0.04). Markers of fat metabolism (L-carnitine and several polyunsaturated fatty acids) were among the top correlates with FACIT-Fatigue. Several free fatty acids decreased after the program (fold change<0.8, p < 0.05). CONCLUSIONS: This investigation provides preliminary evidence linking CRF and exercise-associated improvements to metabolic function. These findings have the potential to inform personalized exercise prescriptions for survivors, optimizing metabolic improvements and associated CRF reductions.