Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.

Abstract

Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of  malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of  biomarkers hampers development of diagnostic tests and successful therapy. Recent  studies on the changes of amino acid levels and other metabolites in patients  with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to  possible central defects in energy metabolism. Here we report a comprehensive  analysis of serum concentrations of amino acids, including metabolites of  tryptophan, the kynurenine pathway and vitamin B6 in a well characterized  national Norwegian cohort of lymphoma survivors after high-dose therapy and  autologous stem cell transplantation. Among the 20 standard amino acids in  humans, only tryptophan levels were significantly lower in both males and females  with CF compared to non-fatigued survivors, a strikingly different pattern than  seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway  (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic  acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with  or without CF and correlated with known markers of immune activation and  inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among  personal traits and clinical findings assessed simultaneously in participating  survivors, higher neuroticism score, obesity and higher PAr index were  significantly associated with increased risk of CF. Collectively, these data  point to low grade immune activation and inflammation as a basis for CF in  lymphoma survivors.