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.
