Tag: lactate increase

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome

Abstract:

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate.

Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment.

We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.

Source: Ghali A, Lacout C, Ghali M, Gury A, Beucher AB, Lozac’h P, Lavigne C, Urbanski G. Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. Sci Rep. 2019 Dec 11;9(1):18817. doi: 10.1038/s41598-019-55473-4. ncbi.nlm.nih.gov/pubmed/31827223

Suggested pathology of systemic exertion intolerance disease: Impairment of the E3 subunit or crossover of swinging arms of the E2 subunit of the pyruvate dehydrogenase complex decreases regeneration of cofactor dihydrolipoic acid of the E2 subunit

Abstract:

Systemic Exertion Intolerance Disease (SEID) or myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) has an unknown aetiology, with no known treatment and a prevalence of approximately 22 million individuals (2%) in Western countries. Although strongly suspected, the role of lactate in pathology is unknown, nor has the nature of the two most central symptoms of the condition – post exertional malaise and fatigue. The proposed mechanism of action of pyruvate dehydrogenase complex (PDC) plays a central role in maintaining energy production with cofactors alpha-lipoic acid (LA) and its counterpart dihydrolipoic acid (DHLA), its regeneration suggested as the new rate limiting factor.

Decreased DHLA regeneration due to impairment of the E3 subunit or crossover of the swinging arms of the E2 subunit of PDC have been suggested as a cause of ME/CFS/SEID resulting in instantaneous fluctuations in lactate levels and instantaneous offset of the DHLA/LA ratio and defining the condition as an LA deficiency with chronic instantaneous hyperlactataemia with explicit stratification of symptoms. While instantaneous hyperlactataemia has been suggested to account for the PEM, the fatigue was explained by the downregulated throughput of pyruvate and consequently lower production of ATP with the residual enzymatic efficacy of the E3 subunit or crossover of the E2 as a proposed explanation of the fatigue severity. Functional diagnostics and visualization of instantaneous elevations of lactate and DHLA has been suggested.

Novel treatment strategies have been implicated to compensate for chronic PDC impairment and hyperlactataemia. This hypothesis potentially influences the current understanding and treatment methods for any type of hyperlactataemia, fatigue, ME/CFS/SEID, and conditions associated with PDC impairment.

Copyright © 2019. Published by Elsevier Ltd.

Source: Bohne VJB, Bohne Ø.Suggested pathology of systemic exertion intolerance disease: Impairment of the E3 subunit or crossover of swinging arms of the E2 subunit of the pyruvate dehydrogenase complex decreases regeneration of cofactor dihydrolipoic acid of the E2 subunit. Med Hypotheses. 2019 Sep;130:109260. doi: 10.1016/j.mehy.2019.109260. Epub 2019 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/31383326

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Post-exertional malaise and delayed recovery are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies on repeated cardiopulmonary exercise testing (CPET) show that previous exercise negatively affects oxygen uptake (VO2 ) and power output (PO) in ME/CFS. Whether this affects arterial lactate concentrations ([Laa ]) is unknown.

We studied 18 female patients (18-50 years) fulfilling the Canadian Consensus Criteria for ME/CFS and 15 healthy females (18-50 years) who underwent repeated CPETs 24 h apart (CPET1 and CPET2 ) with [Laa ] measured every 30th second. VO2 at peak exercise (VO2 peak) was lower in patients than in controls on CPET1 (P < 0.001) and decreased in patients on CPET2 (P < 0.001).

However, the difference in VO2peak between CPETs did not differ significantly between groups. [Laa ] per PO was higher in patients during both CPETs (Pinteraction < 0.001), but increased in patients and decreased in controls from CPET1 to CPET2 (Pinteraction < 0.001). Patients had lower VO2 (P = 0.02) and PO (P = 0.002) at the gas exchange threshold (GET, the point where CO2 production increases relative to VO2 ), but relative intensity (%VO2peak ) and [Laa ] at GET did not differ significantly from controls on CPET1 .

Patients had a reduction in VO2 (P = 0.02) and PO (P = 0.01) at GET on CPET2 , but no significant differences in %VO2peak and [Laa ] at GET between CPETs. Controls had no significant differences in VO2 , PO or %VO2peak at GET between CPETs, but [Laa ] at GET was reduced on CPET2 (P = 0.008).

In conclusion, previous exercise deteriorates physical performance and increases [Laa ] during exercise in patients with ME/CFS while it lowers [Laa ] in healthy subjects.

© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Source: Lien K, Johansen B, Veierød MB, Haslestad AS, Bøhn SK, Melsom MN, Kardel KR, Iversen PO. Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome. Physiol Rep. 2019 Jun;7(11):e14138. doi: 10.14814/phy2.14138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546966/ (Full article)

Antioxidant and immunomodulatory properties of Spilanthes oleracea with potential effect in chronic fatigue syndrome infirmity

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) holds a mystery for researchers due to its multifactorial nature; hence, its diagnosis is still based on symptoms and aetiology remains obscured. Number of scientific evidences regarding the role of oxidative stress, immune dysfunction in CFS and alleviation of symptoms with the help of nutritional supplements guided us to study effect of ethanolic extract of Spilanthes oleracea (SPE) in CFS.

OBJECTIVES: Present study was designed to evaluate antioxidant, immunomodulatory properties of S. oleracea flower to ameliorate CFS infirmity in mice.

MATERIALS AND METHOD: In order to induce fatigue, experimental animals were stressed by chronic water – immersion stress model. Meanwhile, parameters like immobility period and tail withdrawal latency were assessed. On the 21st day, mice blood was collected and they were immediately sacrificed for biochemical estimations.

RESULTS: Biochemical analysis results revealed that CFS elevates lipid peroxidation, nitrite level and diminishes the endogenous antioxidant enzyme like catalase level in stressed animal’s brain homogenate. Stressful condition developed muscle fatigue leading in alteration of lactate dehydrogenase level (LDH), Blood urea nitrogen (BUN) and Triglycerides (TG) levels. Concurrent and chronic treatment of SPE for 21 days restored all these behavioural despairs and associated biochemical adaptation in mice in dose-dependent manner.

CONCLUSION: The outcome of this study indicates ability of SPE in amelioration of CFS by mitigating the oxidative stress and thus provide a powerful combat against CFS which may be due to its antioxidant and immunomodulatory properties.

Source: Nipate SS, Tiwari AH. Antioxidant and immunomodulatory properties of Spilanthes oleracea with potential effect in chronic fatigue syndrome infirmity. J Ayurveda Integr Med. 2018 Nov 16. pii: S0975-9476(17)30116-X. doi: 10.1016/j.jaim.2017.08.008. [Epub ahead of print] https://www.sciencedirect.com/science/article/pii/S097594761730116X?via%3Dihub (Full article)

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

Abstract:

Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor.

We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients.

The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients.

These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

 

Source: Fluge Ø, Mella O, Bruland O, Risa K, Dyrstad SE, Alme K, Rekeland IG, Sapkota D, Røsland GV, Fosså A, Ktoridou-Valen I, Lunde S, Sørland K, Lien K, Herder I, Thürmer H, Gotaas ME, Baranowska KA, Bohnen LM, Schäfer C, McCann A, Sommerfelt K, Helgeland L, Ueland PM, Dahl O, Tronstad KJ. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016 Dec 22;1(21):e89376. doi: 10.1172/jci.insight.89376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/ (Full article)

 

Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

Abstract:

Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level.

Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis.

Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction.

Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

 

Source: Rutherford G, Manning P, Newton JL. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome. J Aging Res. 2016;2016:2497348. doi: 10.1155/2016/2497348. Epub 2016 Feb 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779819/ (Full article)

 

In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Post-exertional malaise is commonly observed in patients with myalgic encephalomyelitis/chronic fatigue syndrome, but its mechanism is not yet well understood. A reduced capacity for mitochondrial ATP synthesis is associated with the pathogenesis of CFS and is suspected to be a major contribution to exercise intolerance in CFS patients.

To demonstrate the connection between a reduced mitochondrial capacity and exercise intolerance, we present a model which simulates metabolite dynamics in skeletal muscles during exercise and recovery. CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected. To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress. Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations.

Copyright © 2015 Elsevier B.V. All rights reserved.

 

Source: Lengert N, Drossel B. In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Biophys Chem. 2015 Jul;202:21-31. doi: 10.1016/j.bpc.2015.03.009. Epub 2015 Apr 4. https://www.ncbi.nlm.nih.gov/pubmed/25899994

 

Exercise responses and psychiatric disorder in chronic fatigue syndrome

Comment in: Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data. [BMJ. 1995]

 

Fatigue, exercise intolerance, and myalgia are cardinal symptoms of the chronic fatigue syndrome, but whether they reflect neuromuscular dysfunction or are a manifestation of depression or other psychiatric or psychological disorders diagnosed in a high proportion of fatigued patients in the community is unclear.’ In previous studies patients with the chronic fatigue syndrome showed exercise intolerance in incremental exercise tests, which seemed to be related to an increased perception of effort; also, blood lactate concentrations in some patients tended to increase more rapidly than normal at low work rates, implying inefficient aerobic muscle metabolism.2 We examined venous blood lactate responses to exercise at a work rate below the anaerobic threshold in relation to psychiatric disorder.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550606/pdf/bmj00607-0028.pdf

 

Source: Lane RJ, Burgess AP, Flint J, Riccio M, Archard LC. Exercise responses and psychiatric disorder in chronic fatigue syndrome. BMJ. 1995 Aug 26;311(7004):544-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550606/pdf/bmj00607-0028.pdf

 

Lactate responses to exercise in chronic fatigue syndrome

Comment on: Exercise performance and fatiguability in patients with chronic fatigue syndrome. [J Neurol Neurosurg Psychiatry. 1993]

 

We were interested to read the recent account of exercise characteristics in patients with chronic fatigue syndrome by Gibson et al,’ which concluded that there was no abnormality of neuromuscular function in this condition. Patients reached the limits of exercise tolerance at lower heart rates than controls during incremental exercise to exhaustion but their peak work rates and duration of exercise did not differ significantly from the control group, although the total work done (the product of these variables) would appear to have been less; the authors had previously reported that patients with this condition showed a reduction in maximal work rate achieved in such tests.2 Despite this, plasma lactate levels at the end of exercise were as high in the patients as the controls.

In an earlier study using incremental exercise on a treadmill, Riley et a13 had found higher heart rates and increased lactate levels compared with normal controls at submaximal work rates but similarly noted no differences at peak exercise.

We have found that a proportion of patients with chronic fatigue syndrome exhibit abnormally raised lactate levels following steady state exercise at work rates below the anerobic threshold, corresponding to roughly half the peak work rates achieved in the incremental test paradigm.4 It is thus possible that lactate levels in some patients increase more rapidly than normal at lower work rates.

The cause of this apparent ‘left shift’ of the anaerobic threshold is unclear. Neither we nor Gibson et al 2 found evidence of “deconditioning” in terms of cardiac responses to exercise in our patients, and phosphorus spectroscopy of muscle in the syndrome has shown no consistent disturbance of muscle energy metabolism.5 The phenomenon may be of significance in the pathogenesis of “fatigue” in some patients, and it may be premature to conclude that neuromuscular function in all patients is normal, or that the “fatigue” is exclusively “central” in origin. Indeed, it may be presumptuous to consider chronic fatigue syndrome as a unitary entity.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1072952/pdf/jnnpsyc00035-0134b.pdf

 

Source: Lane RJ, Woodrow D, Archard LC. Lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1994 May;57(5):662-3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1072952/