Abstract
Purpose: To measure the urinary excretion of amino acids in a large number of patients with chronic fatigue/pain disorders to determine whether distinct subgroups can be defined on the basis of the urine excretion patterns. Design: Laboratory-based survey, with comparison to prior control, chronic orofacial muscle pain and rheumatoid arthritis datasets. Materials and Methods: Urine samples and symptom data were collected from 1993 referral patients, with varying forms of chronic fatigue and pain conditions (including CFS and fibromyalgia), as part of their normal clinical evaluation over a period from June 1997 to October 1998. Each urine sample was analyzed for amino and organic acid content by gas chromatography-mass spectrometry (GC-MS). The urine profile data were analyzed by K-means clustering techniques. Results: It was found that six subgroups of patients could be delineated on the basis of the distributions of 13 amino acids measured in the urine. These groups were extremely well resolved by discriminant function analysis ( p <0.00001), and the canonical plot showed clear separation of all six groups. The groups were primarily differentiated by their concentrations of glycine, serine, alanine and glutamine/glutamic acid, but variations in the other amino acids contributed to the profile differences. Assessment of control and patient data compiled from previous studies revealed that all six phenotypes of amino acid homeostasis were present in healthy individuals, chronic myofacial pain patients and rheumatoid arthritis patients. The differences between the healthy individuals of a particular homeostatic phenotype and their corresponding chronically ill phenotype included the extent of amino acid depletion or excess, as well as alterations in non-protein amino acids (e.g. g -alanine) and organic acids. Conclusions: Six major types of amino acid homeostasis occurred in the patient cohort, each with its own specific nutritional requirements for amino acids. The same types of urinary excretion profiles could be observed in control subjects. The differences between the control and chronically ill patients depended on the extent of amino acid depletion or excess and variations in organic acid excretion. External influences such as pathogenic exposure, diet, genetic and environmental factors would also influence the final health status of the patient.
