Abstract
Chronic fatigue, in its various manifestations, frequently co-occur with pain, sleep disturbances and depression and is a non-communicable condition which is rapidly becoming endemic worldwide. However, it is handicapped by a lack of objective definitions and diagnostic measures. This has prompted the World Health Organization to develop an international instrument whose intended purpose is to improve quality of life (QOL), with energy and fatigue as one domain of focus. To complement this objective, the interface between detoxification, the exposome, and xenobiotic-sensing by nuclear receptors that mediate induction of biotransformation-linked genes, is stimulating renewed attention to a rational development of strategies to identify the metabolic profiles in complex multifactorial conditions like fatigue. Here we present results from a seven-year study of a cohort of 576 female patients suffering from low to high levels of chronic fatigue, in which phase I and phase II biotransformation was assessed. The biotransformation profiles used were based on hepatic detoxification challenge tests through oral caffeine, acetaminophen and acetylsalicylic acid ingestion coupled with oxidative stress analyses. The interventions indicated normal phase I but increased phase II glucuronidation and glycination conjugation. Complementarity was indicated between a fatigue scale, medical symptoms and associated energy-related parameters by application of Chi-square Automatic Interaction Detector (CHAID) analysis. The presented study provides a cluster of data from which we propose that multidisciplinary inputs from the combination of a fatigue scale, medical symptoms and biotransformation profiles provide the rationale for the development of a comprehensive laboratory instrument for improved diagnostics and personalized interventions in patients with chronic fatigue with a view to improving their QOL.
Highlights
The analysis of the Piper Fatigue Scale (PFS) of the mild, energy only and mental only fatigue categories were 196, 107 (18.6%) and 26 (4.5%), respectively. These results clearly indicate that a physical experience of energy depletion, rather than a psychological mood of mental fatigue, dominates in the experimental group
The revised PFS that we used [36] was designed as a measure of fatigue in women with breast cancer, the scale was previously reported to be successfully used for different population groups [41][42] [43] and the results presented here indicate that the revised PFS provide a measure of fatigue
This provides evidence that the four subscales of the PFS may represent distinct aspects of the fatigue experience as reported by patients with the condition, supported by the different trends in the biotransformation profiles observed for the Mainly Energy Fatigue and the Mainly Mental Fatigue groups (Table 1)
Summary
Chronic fatigue is a condition commonly reported by patients in primary care practice, whose medical practitioners use diverse definitions and diagnostic labels to describe their symptoms. The need for further basic research remains on the role of receptors, transcription factors and signalling cascades in the coordinated regulation of phase I and phase II metabolism, in addition to phase III transport of endogenous as well as of exogenous agents, for modelling of diseases and toxicities induced by xenobiotics These developments call for renewed attention to a rational basis for alternative strategies to identify the metabolic differences that contribute to health and disease in complex multifactorial conditions like fatigue. Against this background, this paper addresses chronic fatigue with the focus on the role of biotransformation as an essential metabolic process for maintaining energy homeostasis in patients suffering from the condition. In combination with the multidisciplinary contributions from the clinicians, we propose that a novel combination of the three assessment instruments (a fatigue scale, medical symptoms, and biotransformation profiles) provides foundational knowledge for further development of a comprehensive laboratory instrument for directed personal interventions that we believe can lead to improved QOL in patients across a spectrum of chronic fatigue manifestations
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