Chronic Fatigue Syndrome and Energy Biochemistry

Chronic Fatigue Syndrome and Energy Biochemistry

A research team from the University of Otago is using a Seahorse Analyser to study mitochondrial function and energy delivery.

Chronic Fatigue Syndrome and Energy Biochemistry

Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a life-long disease that has a severe impact on those affected. The illness strikes more women than men, and, while common in children and teenagers, the age of onset is commonly between 20-40.

Ongoing fatigue is severe, and there is an inability to exercise without a significant deterioration of health, a feature not associated with other fatigue illnesses like multiple sclerosis. Poor health care for ME/CFS patients primarily results from there being no etiological explanation for the symptoms, no simple diagnostic blood test, and no effective therapy. A significant proportion of patients (~25%) stay in a severe acute phase, while the majority (~75%) move to a chronic but relatively poor state of health beset by frequent relapse/partial recovery cycles.

In the last year, significant research advances have highlighted that problems in energy delivery might be the key feature of ME/CFS that could account for the fatigue. In research at the University of Otago, Dunedin, New Zealand, the research group of Professor Warren Tate has shown that biochemical pathways associated with general metabolism and energy delivery are depressed.

These studies complement a large study from Stanford University in 2016 that inferred about 20 biochemical pathways are operating at a low level as though patients were in a state of ‘hibernation’, and a study from Norway that showed there are problems in the regulation of energy production in the ‘energy powerhouse’ of the cell – called the mitochondria.

Professor Tate’s group is now focusing on measuring mitochondrial function utilizing a new technology with a ‘Seahorse XF Analyzer’. It enables a new energy parameter, ‘The Bioenergetic Health Index’, to be measured in the cells of a fresh blood sample taken from a subject. The Seahorse analyzer measures properties of energy delivery that can show whether mitochondria are under ‘oxidative stress’.

It measures the oxygen consumption rate and extracellular acidification rate of live cells to interrogate key cellular functions such as mitochondrial respiration and glycolysis. One study of ME/CFS patients just published from the United Kingdom showed the mitochondria of blood cells were unable to produce as much energy compared with those from healthy control subjects.

This technology can give an early warning of an energy crisis in patients, and as well test therapeutic compounds that might reverse the ‘unhealthy state’ of their mitochondria. One promising candidate for a potential replacement therapy is the essential mitochondrial cofactor, Coenzyme Q10 (ubiquinol), an important antioxidant involved in energy production. This cofactor is low in ME/CFS patients with levels inversely correlated with the severity of their fatigue.

Supplementation of CoQ10 might improve fatigue-related symptoms. One form of Coenzyme Q10 readily available as a nutraceutical, MitoQ, has a targeting component that would direct the supplement directly to the mitochondria in the cells. MitoQ was designed originally in the late 1990s at the University of Otago, as an antioxidant by Professors Michael Murphy and Rob Smith.