Thirteen years ago, Cara Tomas was rendered bedbound with chronic fatigue syndrome. It came on suddenly, she says, without warning signs. Even now she has good days and bad days due to the lingering effects of the disease. “A lot of people dismiss it as a psychological disease, which is a big frustration,” she says.
Tomas knows more about CFS than most. A PhD student at Newcastle University in the UK, she has just published a paper demonstrating that white blood cells in people with the disease are as listless as the people themselves often feel. She says:
“Now we’ve shown there’s a physiological difference, it could explain the whole-body fatigue shown by patients”
The finding adds to mounting evidence that the disorder has a biological explanation, and raises the prospects for new treatments and diagnostic tests.
For many years, arguments have raged over whether CFS — also known as myalgic encephalomyelitis, or ME — has a physiological or psychological basis. But the latest research comparing samples of peripheral blood mononuclear cells (PBMCs) from 52 people with the condition and 35 without has reinforced the case for a biological explanation.
Less mighty mitochondria
Across almost all measures of energy capacity, the cells from people with CFS were weaker compared with their healthy counterparts. If other cells are equally compromised, it could explain why people with the condition are often bed- or wheelchair-bound for months, and struggle with even modest physical exertion.
“The CFS cells couldn’t produce as much energy as the control cells … At baseline, they didn’t perform as well, but the maximum they could reach under any conditions was so much lower than the controls.”
Tomas and her colleagues measured the efficiency of mitochondria, the energy-generating powerhouses in cells. The mitochondria are the dominant source of energy for all of our cells. The team found that mitochondria in CFS cells can’t produce energy properly.
“We’ve shown definitively that it’s a fault in mitochondria … it points directly to a physiological, not psychological disorder.”
Tomas measured the oxygen consumption of cells in comfortable and stressed conditions, to see how well they could raise their game with glucose in short supply, a situation forcing the cells to consume more oxygen to compensate. Even at baseline, control cells consumed twice as much oxygen as the CFS cells. The disparity widened dramatically when the cells were stressed.
In another test that artificially pushed cells to their maximum capacity starting from baseline, CFS cells could only increase their mitochondrial output by 47 per cent, roughly half the 98 per cent increase achieved by control cells.
The implication is that cells from CFS patients can’t raise their output to meet the energy demands of routine physical tasks.
“These exciting results confirm what others have postulated but not been able to prove, namely that cells of patients with CFS are easily metabolically exhausted when put under any form of stress,” says Stephen Holgate of Southampton General Hospital. “In many ways, this is how patients describe their whole-body experience with CFS.”
“This is a major step forwards, supporting previous studies, which demonstrated that mitochondrial function can be impaired in this illness,” says Karl Morten of the University of Oxford. “A major question now is whether the situation in these white blood cells reflects whole-body mitochondrial dysfunction in patients,” he says.
To that end, Tomas is currently taking samples of muscle cells and testing them in the same way as the blood cells. “It would be good if we could get this repeated in muscle cells,” she says. “It’s important the patient population know we are looking into this. Patients sometimes think no one cares, but we do have interest, and want to find out what’s going on.”
This article appeared in the New Scientist on November 3rd, 2017, and was written by Andy Coghlan.
It provides a summary for the recent research from Cara Thomas, who worked alongside Professor Julia Newton and colleagues in Newcastle, and it relates to mitochondria and energy metabolism.
The research, Cellular bioenergetics is impaired in patients with chronic fatigue syndrome, is in open access and we hope to have a summary review available soon.
Funding for this study came from the Medical Research Council, the ME Association, ME Research UK, Action for M.E., and the Newcastle Molecular Pathology Node (jointly sponsored by the Medical Research Council and the Engineering and Physical Sciences Research Council).