Metabolic features of chronic fatigue syndrome

Abstract

More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

“…These findings were consistent with a lower ATP and GTP turnover and with decreased amounts of branched amino acid metabolic intermediates. However, there were also indications of reduced mitochondrial fatty acid oxidation only in female ME/CFS patients (32). Adding to PDH inhibition, reduced mitochondrial fatty acid oxidation would expectedly compromise the supply of acetyl-CoA further and thereby increase the dependency of category II amino acids for alternative fueling of the TCA cycle, as shown in our study.…”

“…A recent study assessed 612 metabolites in 45 ME/CFS patients and 39 healthy controls and reported multiple abnormalities in several pathways involved in lipid metabolism and mitochondrial energy metabolism (32). The most prominent changes in ME/CFS patients were widespread decreases in sphingolipids, glycosphingolipids, and phospholipids.…”

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

“…Targeted, broad‐spectrum, plasma metabolomic analysis, covering 63 biochemical pathways, was performed by LC‐MS/MS as described previously44 with minor modifications. In all, 431 of 610 targeted metabolites were measureable in plasma.…”

Inflammation correlates with symptoms in chronic fatigue syndrome

“…Recent metabolomics studies have found deficits in the pathways that generate energy from simple sugars, fatty acids, and amino acids (6)(7)(8)(9). Indeed, one study of over 600 metabolites, published in PNAS, found that the levels of most were unusually low, as occurs in states of hibernation (6).…”