AHMF: 98 Conference: Niblett

Alterations in Urinary Amino and Organic Acid Excretion in Patients with CFS

Suzanne H. Niblett [1], Leigh A. Hoskin [4], R. Hugh Dunstan [1], Phillip Clifton-Bligh [5], Neil R. McGregor [2], Timothy K. Roberts [1], Greg R. Fulcher [5], Henry L. Butt [3], Katrina E. King [1], Julie Dunsmore [4], M. L. Neary [5], Tracey L. Harrison [1], Warren G Taylor [1].

1 Collaborative Pain Research Group
Department of Biological Sciences
The University of Newcastle
Callaghan, NSW 2308, Australia.
2 Neurobiology Research Unit
Centre for Oral Health Research
University of Sydney
Westmead Hospital
Westmead, NSW 2084, Australia.
3 Division of Microbiology and Infectious Diseases
Hunter Area Pathology Services (HAPS)
John Hunter Hospital
Newcastle, NSW 2308, Australia.
4 Department of Health Promotion and Education
Royal North Shore Hospital
St Leonards, NSW 2065, Australia.
5 Department of Endocrinology
Royal North Shore Hospital
St Leonards, NSW 2065, Australia.

Abstract
100 CDC-defined Chronic Fatigue Syndrome (CFS) patients (27 males; 73 females) and 83 healthy control patients (23males; 60 females) were recruited for a large collaborative study designed to 1) assess alterations in metabolism and homeostasis associated with CFS 2) relate these changes to physical and neuropsychological symptom expression and changes in nose and throat microbiota and 3) evaluate the homogeneity of a CDC-defined CFS group. All subjects were clinically reviewed and asked to complete questionnaires addressing subject demographics, medical history, presentation of signs, symptoms and sensitivities, psychological status and cognitive function. Over-night fasted blood and urine samples and nose and throat swabs were collected from each subject.

Prelimary statistical analyses revealed significant differences in urinary metabolite excretion profiles in CFS patients compared with healthy controls implicating that changes in metabolism and homeostasis were associated with CFS. The urinary profiles of CFS subjects (percentage composition and excretion rate) had increases in tyrosine, 3-methylhistidine, reductions in succinic acid, asparagine, phenylalanine, and hippuric acid and changes in several compounds which are yet to be identified. Reductions in the excretion rate of alanine, valine, leucine, proline and S-methylcysteine were also associated with CFS. These data are suggestive of alterations in protein and energy metabolism and imply changes in gut bacteria.

Male and female CFS and control subjects could be separated into four groups on the basis of their urinary metabolite profiles suggesting that the profiles were distinctive. The data suggest that gender specific anomalies occur in CFS patients compared with controls. Age was also significantly correlated with changes in the multivariate urinary metabolite excretion profiles in this study. When the groups were further stratified into under 25 and over 25 year old age groups the CFS-control group differences were again distinct. These findings suggest that the pathophysiology of CFS is different in females compared with males and that these differences are themselves influenced by subject age.

It was concluded that alterations in urine metabolite excretion by CFS patients were indicative of changes in metabolism and homeostasis in CFS patients. Preliminary evaluation of the CDC-defined CFS group homogeneity found that sex and age contributed to heterogeneity in the CFS group and suggested that these factors should be considered in future studies of CFS patients. Subsequent analysis of the data from the present study will examine the relationship of CFS-related changes in urinary excretion to clinical and psychological symptom expression and to changes in the other parameters measured. CFS group heterogeneity will be further assessed using cluster analysis and multivariate techniques which will involve sub-grouping patients on the basis of changes to objectively measured parameters such as urine excretion.