J William M Tweedie
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Blockage of a key metabolic enzyme could explain the profound lack of energy and other symptoms experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), new research suggests.
The findings were published December 22, 2016, in the Journal of Clinical Investigation Insight by Øystein Fluge, MD, from the Department of Oncology and Medical Physics at Haukeland University Hospital, Bergen, Norway, and colleagues.
The study included 200 patients with ME/CFS, as defined by the 2003 Canadian Consensus Criteria, which requires the hallmark symptom of postexertional malaise, among others, to make the diagnosis of ME/CFS. The authors compared serum concentrations of 20 standard amino acids from the 200 patients with ME/CFS and 102 healthy control patients.
In the patients with ME/CFS, there was a specific reduction of amino acids that fuel oxidative metabolism, pointing to functional impairment of pyruvate dehydrogenase (PDH), a key enzyme for the conversion of carbohydrates to energy. Impairment of PDH could result in the cells switching to consumption of alternative fuels, causing a sudden shortage of energy in the muscles and a buildup of lactate, experienced by patients as a burning sensation in their muscles after even minor exertion.
"I think that at present our data are primarily telling us something about the ME/CFS disease. Our findings indicate an impaired function of the PDH enzyme complex, resulting in reduced flux of pyruvate to the [tricarboxylic acid (TCA)] cycle. Increased lactic acid accumulates upon limited exertion, and there is a compensatory use of alternative substrates to fuel the TCA cycle. So, the results indicate an impaired mitochondrial PDH complex function, we believe induced by the immune system," Dr Fluge told Medscape Medical News.
The model, if correct, has implications for prescribing exercise for patients with ME/CFS. "Based on the findings in the study, we can understand why patients need to stay at rest, minimizing the energy deficiency and reducing the symptoms caused by lactic acid accumulation.... The value of doing exercise should, however, not be underestimated, and the level of activity tolerated will depend on the severity of the disease," Dr Fluge said.
He added, "An ME/CFS patient's ability to handle exercise is very individual. Generally, I think the physicians should listen carefully to the patients, and find the optimal activity level through pacing, to avoid 'crashing' with the resulting major symptom increase that can last for weeks and months."
Asked to comment, Anthony L. Komaroff, MD, professor of medicine at Harvard University, Boston, Massachusetts, and editor-in-chief of the Harvard Health Letter, told Medscape Medical News, "This is the latest of many research studies that are pursuing a simple idea: That the human being who says 'I don't have enough energy' could have a problem with their cells producing enough energy.... It adds to a large literature indicating that cellular energy metabolism is abnormal in patients with ME/CFS."
However, he cautioned that the investigators inferred the abnormality in PDH, rather than directly measuring it, and that although "[t]heir argument seems plausible...I wouldn't be convinced until a second study by other investigators, studying other patients with ME/CFS, confirmed this." Continue Reading
Blockage of a key metabolic enzyme could explain the profound lack of energy and other symptoms experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), new research suggests.
The findings were published December 22, 2016, in the Journal of Clinical Investigation Insight by Øystein Fluge, MD, from the Department of Oncology and Medical Physics at Haukeland University Hospital, Bergen, Norway, and colleagues.
The study included 200 patients with ME/CFS, as defined by the 2003 Canadian Consensus Criteria, which requires the hallmark symptom of postexertional malaise, among others, to make the diagnosis of ME/CFS. The authors compared serum concentrations of 20 standard amino acids from the 200 patients with ME/CFS and 102 healthy control patients.
In the patients with ME/CFS, there was a specific reduction of amino acids that fuel oxidative metabolism, pointing to functional impairment of pyruvate dehydrogenase (PDH), a key enzyme for the conversion of carbohydrates to energy. Impairment of PDH could result in the cells switching to consumption of alternative fuels, causing a sudden shortage of energy in the muscles and a buildup of lactate, experienced by patients as a burning sensation in their muscles after even minor exertion.
"I think that at present our data are primarily telling us something about the ME/CFS disease. Our findings indicate an impaired function of the PDH enzyme complex, resulting in reduced flux of pyruvate to the [tricarboxylic acid (TCA)] cycle. Increased lactic acid accumulates upon limited exertion, and there is a compensatory use of alternative substrates to fuel the TCA cycle. So, the results indicate an impaired mitochondrial PDH complex function, we believe induced by the immune system," Dr Fluge told Medscape Medical News.
The model, if correct, has implications for prescribing exercise for patients with ME/CFS. "Based on the findings in the study, we can understand why patients need to stay at rest, minimizing the energy deficiency and reducing the symptoms caused by lactic acid accumulation.... The value of doing exercise should, however, not be underestimated, and the level of activity tolerated will depend on the severity of the disease," Dr Fluge said.
He added, "An ME/CFS patient's ability to handle exercise is very individual. Generally, I think the physicians should listen carefully to the patients, and find the optimal activity level through pacing, to avoid 'crashing' with the resulting major symptom increase that can last for weeks and months."
Asked to comment, Anthony L. Komaroff, MD, professor of medicine at Harvard University, Boston, Massachusetts, and editor-in-chief of the Harvard Health Letter, told Medscape Medical News, "This is the latest of many research studies that are pursuing a simple idea: That the human being who says 'I don't have enough energy' could have a problem with their cells producing enough energy.... It adds to a large literature indicating that cellular energy metabolism is abnormal in patients with ME/CFS."
However, he cautioned that the investigators inferred the abnormality in PDH, rather than directly measuring it, and that although "[t]heir argument seems plausible...I wouldn't be convinced until a second study by other investigators, studying other patients with ME/CFS, confirmed this." Continue Reading