Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases
Abstract
:1. Introduction
2. Methods
2.1. Clinical Measures
2.2. Biochemistry Assessments
2.3. Data Analysis
3. Results
3.1. Demographics
3.2. Biochemistry
3.3. Purine Metabolism Changes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
BMP | Bone Morphogenic Protein |
HDAC | Histone Deacetylase |
ME/CFS | FS Myalgic encephalomyelitis/Chronic Fatigue Syndrome |
PEM | Post-Exertional Malaise |
SMAD | Transforming Growth Factor-Beta Signaling Proteins |
TGF-β | Transforming Growth Factor-Beta |
TCA | tricarboxylic acid cycle |
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Control | ME/CFS NoPEM | ME/CFS PEM | |
---|---|---|---|
Number | 25 | 11 | 35 |
Age | 33.6 ± 7.8 * | 30.9 ± 9.6 | 42.1 ± 16.3 |
%Females | 96% | 100% | 80% |
Duration (years) | - | 8.7 ± 5.4 | 12.1 ± 9.7 |
Age at Onset | - | 22.8 ± 6.8 | 30 ± 13.9 |
Systolic BP | - | 116 ± 12 | 129 ± 17 |
Diastolic BP | - | 79 ± 7 | 83 ± 9 |
Pulse rate | - | 78 ± 11 | 73 ± 13 |
BMI x ± SD | 23.1 ± 2.6 | 22.7 ± 3.6 | 24.9 ± 6.1 |
DASS Depression | 0 | 11.2 ± 10.7 | 11.1 ± 11.1 |
DASS Anxiety | 0.5 ± 0.6 | 13.3 ± 8.3 | 9.8 ± 7.8 |
DASS Stress | 3.5 ± 3.6 * | 20.7 ± 9.4 * | 12.9 ± 8.7 |
PEM 7D | 0.1 ± 0.4 ** | 1.3 ± 0.65 ** | 3.7 ± 0.5 **,‡ |
12F | 0.1 ± 0.4 ** | 2.8 ± 1.2 ** | 3.5 ± 0.6 **,† |
Fatigue 7D | 0.7 ± 0.8 ** | 3.2 ± 0.9 ** | 3.7 ± 0.6 ** |
12F | 1.1 ± 0.8 ** | 3.8 ± 0.6 ** | 3.8 ± 0.4 ** |
Sleep Disturbance 7D | 1.6 ± 2.6 ** | 10.9 ± 2.5 ** | 10.5 ± 3.2 ** |
12F | 2.6 ± 2.3 ** | 12.3 ± 2.7 ** | 11.1 ± 2.8 ** |
Cognition scores 7D | 2.3 ± 2.9 ** | 16.1 ± 5.8 ** | 17.3 ± 6.5 ** |
12F | 3.6 ± 3.7 ** | 18.8 ± 5.6 ** | 18.3 ± 5.9 ** |
Body Pain 7D | 1.3 ± 1.3 ** | 6.3 ± 2.1 ** | 6.3 ± 2.2 ** |
Distribution 12F | 2.6 ± 1.3 ** | 7.1 ± 1.5 ** | 6.9 ± 2.1 ** |
Serum | Control Mean (SD) | ME/CFS NoPEM Mean (SD) | ME/CFS PEM Mean (SD) |
---|---|---|---|
Hypoxanthine (μM) | 15.7 ± 12.2 ** | 3.6 ± 1.4 ** | 6.6 ± 8.2 ** |
Lactate (μM) | 637 ± 335 ** | 339 ± 68 * | 399 ± 240 ** |
Phenylalanine (μM) | 18.4 ± 3.1 ** | 15.5 ± 2.2 | 15.1 ± 3.5 ** |
Glucose (μM) | 971 ± 233 * | 1266 ± 249 * | 1189 ± 318 * |
Hypoxanthine % | 0.55 ± 0.39 ** | 0.14 ± 0.05 ** | 0.24 ± 0.25 ** |
Lactate % | 22.7 ± 10.5 ** | 12.9 ± 2.0 * | 14.7 ± 6.5 ** |
Phenylalanine % | 0.68 ± 0.09 ** | 0.60 ± 0.10 | 0.58 ± 0.10 ** |
Glucose % | 36.2 ± 9.5 ** | 48.1 ± 5.3 ** | 45.4 ± 7.5 ** |
Urine | |||
Acetate (μM) | 91.9 ± 60.3 ** | 37.0 ± 14.9 ** | 63.3 ± 31.8 † |
Formate (μM) | 81.1 ± 56.1 * | 27.1 ± 15.2 ** | 43.0 ± 30.3 * |
Urea (μM) | 7969 ± 3050 * | 4868 ± 2678 ** | 5821 ± 2425 |
Mannitol (μM) | 312 ± 198 * | 96 ± 57 ** | 258 ± 344 * |
Serine (μM) | 383 ± 198 * | 178 ± 108 ** | 313 ± 193 |
Pyruvate (μM) | 22.2 ± 10.7 * | 11.3 ± 6.4 ** | 18.4 ± 12.6 |
Hippurate (μM) | 632 ± 424 * | 297 ± 253 * | 666 ± 612 |
Methylhistidine (μM) | 278 ± 192 * | 230 ± 418 * | 358 ± 373 † |
Pyruvate % | 0.36 ± 0.08 ** | 0.26 ± 0.11 * | 0.27 ± 0.09 ** |
Urea % | 4.7 ± 3.4 ** | 3.8 ± 5.3 | 5.6 ± 5.1 ** |
Serine % | 6.1 ± 1.6 * | 4.2 ± 0.9 * | 4.8 ± 1.9 * |
Creatinine % | 19.7 ± 10.3 * | 33.4 ± 9.2 * | 25.7 ± 11.5 |
Acetate % | 1.53 ± 0.67 * | 0.94 ± 0.26 * | 1.08 ± 0.61 * |
Allantoin % | 0.53 ± 0.28 * | 0.96 ± 0.33 * | 0.78 ± 0.53 |
Tryptophan % | 0.49 ± 0.16 * | 0.49 ± 0.35 | 0.36 ± 0.10 * |
Fecal | |||
Butyrate % | 9.8 ± 3.5 * | 15.2 ± 4.5 * | 11.3 ± 4.4 † |
Ratios | |||
Serum Glucose: Lactate | 2.2 ± 1.4 ** | 3.8 ± 0.7 ** | 3.6 ± 1.4 ** |
Urine Glucose: Lactate | 5.2 ± 2.3 * | 7.8 ± 4.7 * | 6.2 ± 1.8 |
Serum Glucose: Acetate | 96.4 ± 53.6 ** | 150.6 ± 45.8 * | 155.2 ± 72.0 ** |
Urine Glucose: Acetate | 1.37 ± 0.61 * | 1.91 ± 0.52 * | 1.78 ± 0.70 |
Serum Acetate: Urine Acetate | 0.16 ± 0.09 * | 0.30 ± 0.18 * | 0.18 ± 0.09 † |
Serum | 7-Day PEM All Subjects | 7-Day PEM ME/CFS Subjects | 12-Month PEM All Subjects | 12-Month PEM ME/CFS Subjects |
---|---|---|---|---|
Phenylalanine | −0.40 ** | −0.11 | −0.42 ** | −0.08 |
Hypoxanthine | −0.35 * | +0.25 | −0.43 ** | +0.21 |
Lactate | −0.33 * | +0.13 | −0.37 * | +0.18 |
Threonine | −0.31 * | −0.13 | −0.25 | +0.07 |
Glucose | +0.31 * | −0.09 | +0.38 ** | +0.02 |
Urine | ||||
Total Metabolite | +0.10 | +0.38 * | −0.02 | +0.18 |
Mannitol | −0.01 | +0.43 * | −0.15 | +0.20 |
Serine | −0.07 | +0.42 * | −0.22 | +0.17 |
Acetate | −0.18 | +0.41 * | −0.32 * | +0.21 |
p-Methylhistidine | +0.08 | +0.40 * | −0.14 | −0.02 |
Glucose | +0.02 | +0.37 * | −0.09 | +0.23 |
Urine % | ||||
Urea% | −0.42 ** | −0.24 | −0.37 ** | −0.04 |
Pyruvate% | −0.35 * | +0.06 | −0.37 ** | 0.13 |
Tryptophan% | −0.32 * | −0.28 | −0.20 | 0.06 |
Malonate% | −0.32 * | −0.37 * | −0.18 | 0.05 |
Acetate% | −0.30 * | +0.06 | −0.35 * | −0.01 |
Fecal % | ||||
Uracil | +0.04 | +0.46 ** | −0.09 | 0.27 |
Metabolite | Control | NoPEM | PEM |
---|---|---|---|
Serum Hypoxanthine | 15.7 ± 12.2 ** | 3.6 ± 1.4 ** | 6.6 ± 8.2 ** |
% Serum Hypoxanthine | 0.55 ± 0.39% ** | 0.14 ± 0.05% ** | 0.24 ± 0.25% ** |
Urine Hypoxanthine | 14.9 ± 6.7 * | 7.6 ± 4.0* | 14.3 ± 11.3 |
%Urine Hypoxanthine | 0.26 ± 0.13% * | 0.17 ± 0.04% | 0.21 ± 0.10% |
Urine Allantoin | 32.8 ± 19.0 | 36.0 ± 13.5 | 43.7 ± 25.1 |
% Urine Allantoin | 0.53 ± 0.28% * | 0.96 ± 0.33% * | 0.78 ± 0.53% |
Serum Urate | 0.28 ± 0.03 | 0.28 ± 0.06 | 0.29 ± 0.09 |
Serum Purine Ring Precursors | 138.6 ± 32.8 | 117.9 ± 23.9 | 130.2 ± 29.8 |
Ratios | |||
Serum Hypoxanthine: Urine Hypoxanthine | 1.3 ± 1.6 | 0.7 ± 0.6 | 0.9 ± 1.4 |
Serum Hypoxanthine: Urate | 74.2 ± 65.3 ** | 13.6 ± 6.2 ** | 21.6 ± 26.3 ** |
Serum Hypoxanthine: Urine Allantoin | 0.75 ± 1.26 | 0.11 ± 0.05 | 0.34 ± 0.09 |
Urine Allantoin: Serum Urate | 135.5 ± 71.7 | 134.2 ± 57.1 | 162.5 ± 96.2 |
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McGregor, N.R.; Armstrong, C.W.; Lewis, D.P.; Gooley, P.R. Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases. Diagnostics 2019, 9, 70. https://doi.org/10.3390/diagnostics9030070
McGregor NR, Armstrong CW, Lewis DP, Gooley PR. Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases. Diagnostics. 2019; 9(3):70. https://doi.org/10.3390/diagnostics9030070
Chicago/Turabian StyleMcGregor, Neil R., Christopher W. Armstrong, Donald P. Lewis, and Paul R. Gooley. 2019. "Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases" Diagnostics 9, no. 3: 70. https://doi.org/10.3390/diagnostics9030070