AHMF: Conf 2001: P Clifton Bligh

Deregulation of Succinate Metabolism in A Cohort of Patients with Defined Chronic Fatigue Syndrome

Clifton Bligh P [1], McGregor NR [3,4], Fulcher G [1], Dunstan RH [3], King K [3], Niblett S [3], Hoskin L [1], Roberts TK [3], Butt HL [3], Dunsmore J [2], Klineberg IJ [4].

1: Royal North Shore Hospital CFS Research Unit
Department of Endocrinology,
Royal North Shore Hospital,
St Leonards,
NSW 2065,
Australia.

2: Department of Health Promotion and Education,
Royal North Shore Hospital,
St Leonards,
NSW 2065,
Australia.

3: Collaborative Pain Research Unit.
Bioanalytical Research Group,
Department of Biological Sciences,
University of Newcastle,
Callaghan,
NSW 2308,
Australia.

4. Neurobiology Research Unit,
Centre for Oral Health Research,
University of Sydney,
Westmead Hospital,
Westmead,
NSW 2084,
Australia.

To assess if variation in excretion of succinate was associated with variations in chemistry and symptoms in CFS patients.

Methods: 88 CFS patients and age and sex matched controls were assessed. Subjects completed questionnaires were examined and had serum amino acids, serum chemistry and urinary amino and organic acids assessed.

CFS patients had reductions in urinary succinic acid and several amino acids that supply the citric acid cycle at or following the entry of succinate, as well as increases in the amino acid suggestive of increase protein turnover, tyrosine and 3-methylhistidine. Reductions in succinic acid and leucine were associated with fatigue whilst reductions in succinic acid and increases in tyrosine were associated with increases in muscle soreness. Succinic acid was negatively correlated with the markers of proteolysis (tyrosine, 3-methylhistidine) as well as the urea cycle-related metabolites (lysine, ornithine) suggesting a nitric oxide mediated event. Succinic acid was positively correlated with serum glucose, creatine and creatine kinase levels. These events suggest that the a cytokine-mediated nitric oxide mediated change which causes an increase in protein turnover, an increase in glucose dependence and a fall in oxidative phosphorylation is occurring and is related to the expression of fatigue.

Thus the fall in urinary succinic acid in CFS patients was associated with deregulation of energy availability, protein synthesis: proteolysis and amino acids oxidized in the succinate-oxaloacetate portion of the citric acid cycle suggestive of a cytokine mediated change in chemistry.