Tag: Staines

A preliminary investigation of nutritional intake and supplement use in Australians with myalgic encephalomyelitis/chronic fatigue syndrome and the implications on health-related quality of life

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness without a currently recognized pharmacological treatment. Dietary supplementation and modification have been posited as potential management strategies; however, their efficacy is controversial.

Objective: This study aimed to assess the nutritional intake and supplement use of Australian ME/CFS patients and the perceived effect on health-related quality of life (HRQoL) for the first time in an Australian patient population.

Design: Between February 2019 and January 2020, ME/CFS patients across Australia volunteered in this cross-sectional study in response to online advertisements. Eligible respondents were invited to complete three online self-administered questionnaires investigating their supplement use, nutritional intake, and HRQoL. The study participants’ supplement use and nutritional intake were summarized and compared with the population data returned from the Australian Health Survey (2011-2012). Multiple linear regression analysis was also performed to determine the effect of participants’ supplement use and nutrient intake on HRQoL.

Results: Twenty-four eligible ME/CFS patients (54.2% meeting the International Consensus Criteria, 79.2% female, mean age = 43.4 ± 10.5 years) completed the online questionnaires. Supplement use was highly prevalent among the study sample (87.5%) and considerably more common when compared with population data (31.9%). Daily total fats and caffeine intakes were significantly higher among ME/CFS patients when compared with the Australian population (P = 0.009 and P = 0.033, respectively), whereas daily intakes of total carbohydrates and alcohol were significantly lower (both P < 0.001). No consistent trends between nutrition and supplement use with patients’ HRQoL could be identified.

Conclusions: The daily diet and supplement use of ME/CFS patients appear to vary considerably from those of the general Australian population. Although the role of nutritional intake and supplement use on ME/CFS patients’ HRQoL remains unclear, dietary changes and the use of supplements appear to be of value to ME/CFS patients.

Keywords: chronic fatigue syndrome (CFS); health-related quality of life (HRQoL); myalgic encephalomyelitis (ME); nutrition; nutritional intake; supplements.

Source: Weigel B, Eaton-Fitch N, Passmore R, Cabanas H, Staines D, Marshall-Gradisnik S. A preliminary investigation of nutritional intake and supplement use in Australians with myalgic encephalomyelitis/chronic fatigue syndrome and the implications on health-related quality of life. Food Nutr Res. 2021;65:10.29219/fnr.v65.5730. Published 2021 Jun 7. doi:10.29219/fnr.v65.5730 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254462/ (Full text)

Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-systemic chronic condition of unknown aetiology classified as an immune dysfunction syndrome and neurological disorder. The discovery of the widely expressed Transient Receptor Potential Melastatin 3 (TRPM3) as a nociceptor channel substantially targeted by certain opioid receptors, and its implication in calcium (Ca2+)-dependent Natural Killer (NK) cell immune functions has raised the possibility that TRPM3 may be pharmacologically targeted to treat characteristic symptoms of ME/CFS. Naltrexone hydrochloride (NTX) acts as an antagonist to the mu (μ)-opioid receptor thus negating its inhibitory function on TRPM3.

Based on the benefits reported by patients on their symptoms, low dose NTX (LDN, 3.0–5.0 mg/day) treatment seems to offer some potential benefit suggesting that its effect may be targeted towards the pathomechanism of ME/CFS. As there is no literature confirming the efficacy of LDN for ME/CFS patients in vitro, this study investigates the potential therapeutic effect of LDN in ME/CFS patients. TRPM3 ion channel activity was measured after modulation with Pregnenolone sulfate (PregS) and ononetin in NK cells on 9 ME/CFS patients taking LDN and 9 age- and sex-matched healthy controls using whole-cell patch-clamp technique.

We report that ME/CFS patients taking LDN have restored TRPM3-like ionic currents in NK cells. Small ionic currents with a typical TRPM3-like outward rectification were measured after application of PregS, a TRPM3-agonist, in NK cells from patients taking LDN. Additionally, PregS-evoked ionic currents through TRPM3 were significantly modulated by ononetin, a TRPM3-antagonist, in NK cells from ME/CFS patients taking LDN.

These data support the hypothesis that LDN may have potential as a treatment for ME/CFS by characterising the underlying regulatory mechanisms of LDN treatment involving TRPM3 and opioid receptors in NK cells. Finally, this study may serve for the repurpose of marketed drugs, as well as support the approval of prospective randomized clinical studies on the role and dose of NTX in treating ME/CFS patients.

Source: Helene Cabanas, Katsuhiko Muraki, Natalie Eaton-Fitch, Donald Ross Staines and Sonya Marshall-Gradisnik. Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment. Front. Immunol. | https://doi.org/10.3389/fimmu.2021.687806 https://www.frontiersin.org/articles/10.3389/fimmu.2021.687806/full (Full text)

A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination with a range of other disabling symptoms. There is no diagnostic test nor targeted treatment available for this illness. The pathomechanism also remains unclear. Mitochondrial dysfunctions have been considered a possible underlying pathology based on reported differences including structural and functional changes in ME/CFS patients compared to healthy controls. Due to the potential role that mitochondria may play in ME/CFS, mitochondrial-targeting nutraceutical interventions have been used to potentially assist in improving patient outcomes such as fatigue. The aim of this systematic review is to appraise literature assessing these nutraceuticals as a possible intervention for treating ME/CFS.

Methods: A systematic search of Pubmed, Embase, Medline (EBSCO host) and Web of Science (via Clarivate Analytics) for journal articles published between January 1995 and 10th November 2020 was conducted. Articles assessing nutraceutical interventions and ME/CFS patient outcomes were retrieved. Using specific inclusion and exclusion criteria, the list of articles was further refined. Quality was measured using the Rosendal scale.

Results: Nine intervention studies were included in this review. The studies investigated patient symptom severity changes such as altered fatigue levels in response to mitochondrial-targeting nutraceuticals. Improvements in fatigue levels were observed in six of the nine studies. Secondary outcomes assessed include biochemical, psychological, and quality of life parameters.

Conclusion: There is insufficient evidence on the effectiveness of mitochondria- targeting nutraceuticals in ME/CFS patients. Future well-designed studies are required to elucidate both the involvement of mitochondria in the pathomechanism of ME/CFS and the effect of mitochondrial-modifying agents on illness severity.

Source: Maksoud R, Balinas C, Holden S, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2021 Feb 17;19(1):81. doi: 10.1186/s12967-021-02742-4. PMID: 33596913; PMCID: PMC7890871. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02742-4  (Full text)

The Economic Impacts of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in an Australian Cohort

Abstract:

Objectives: This study aims to estimate direct and indirect health economic costs associated with government and out-of-pocket (OOP) expenditure based on health care service utilization and lost income of participants and carers, as reported by Australian Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patient survey participants.

Design: A cost of illness study was conducted to estimate Australian cost data for individuals with a ME/CFS diagnosis as determined by the Canadian Consensus Criteria (CCC), International Consensus Criteria (ICC), and the 1994 CDC Criteria (Fukuda).

Setting and participants: Survey participants identified from a research registry database provided self-report of expenditure associated with ME/CFS related healthcare across a 1-month timeframe between 2017 and 2019.

Main outcome measures: ME/CFS related direct annual government health care costs, OOP health expenditure costs, indirect costs associated with lost income and health care service use patterns.

Results: The mean annual cost of health care related expenditure and associated income loss among survey participants meeting diagnostic criteria for ME/CFS was estimated at $14.5 billion. For direct OOP and Government health care expenditure, high average costs were related to medical practitioner attendance, diagnostics, natural medicines, and device expenditure, with an average attendance of 10.6 referred attendances per annum and 12.1 GP visits per annum related specifically to managing ME/CFS.

Conclusions: The economic impacts of ME/CFS in Australia are significant. Improved understanding of the illness pathology, diagnosis, and management, may reduce costs, improve patient prognosis and decrease the burden of ME/CFS in Australia.

Source: Close S, Marshall-Gradisnik S, Byrnes J, Smith P, Nghiem S, Staines D. The Economic Impacts of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in an Australian Cohort. Front Public Health. 2020 Aug 21;8:420. doi: 10.3389/fpubh.2020.00420. PMID: 32974259; PMCID: PMC7472917. https://www.frontiersin.org/articles/10.3389/fpubh.2020.00420/full (Full text)

Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans

Abstract:

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) subjects suffer from a variety of cognitive complaints indicating that the central nervous system plays a role in its pathophysiology. Recently, the ratio T1w/T2w has been used to study changes in tissue myelin and/or iron levels in neurodegenerative diseases such as multiple sclerosis and schizophrenia. In this study, we applied the T1w/T2w method to detect changes in tissue microstructure in ME/CFS patients relative to healthy controls.

We mapped the T1w/T2w signal intensity values in the whole brain for forty-five ME/CFS patients who met Fukuda criteria and twenty-seven healthy controls and applied both region- and voxel-based quantification. We also performed interaction-with-group regressions with clinical measures to test for T1w/T2w relationships that are abnormal in ME/CFS at the population level.

Region-based analysis showed significantly elevated T1w/T2w values (increased myelin and/or iron) in ME/CFS in both white matter (WM) and subcortical grey matter. The voxel-based group comparison with sub-millimetre resolution voxels detected very significant clusters with increased T1w/T2w in ME/CFS, mostly in subcortical grey matter, but also in brainstem and projection WM tracts. No areas with decreased T1w/T2w were found in either analysis. ME/CFS T1w/T2w regressions with heart-rate variability, cognitive performance, respiration rate and physical well-being were abnormal in both gray and white matter foci. Our study demonstrates that the T1w/T2w approach is very sensitive and shows increases in myelin and/or iron in WM and basal ganglia in ME/CFS.

Source: Thapaliya K, Marshall-Gradisnik S, Staines D, Barnden L. Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans [published online ahead of print, 2020 Jul 31]. Neuroimage Clin. 2020;28:102366. doi:10.1016/j.nicl.2020.102366 https://pubmed.ncbi.nlm.nih.gov/32777701/

A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease

Abstract:

Background: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls.

Methods: Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.

Results: Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes.

Conclusion: Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.

Source: Holden S, Maksoud R, Eaton-Fitch N, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease. J Transl Med. 2020;18(1):290. Published 2020 Jul 29. doi:10.1186/s12967-020-02452-3 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02452-3 (Full text)

A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease

Abstract:

BACKGROUND: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been proposed that metabolomics may contribute to the illness pathogenesis of CFS/ME/SEID. In metabolomics, the systematic identification of measurable changes in small molecule metabolite products have been identified in cases of both monogenic and heterogenic diseases. Therefore, the aim of this systematic review was to evaluate if there is any evidence of metabolomics contributing to the pathogenesis of CFS/ME/SEID.

METHODS: PubMed, Scopus, EBSCOHost (Medline) and EMBASE were searched using medical subject headings terms for Chronic Fatigue Syndrome, metabolomics and metabolome to source papers published from 1994 to 2020. Inclusion and exclusion criteria were used to identify studies reporting on metabolites measured in blood and urine samples from CFS/ME/SEID patients compared with healthy controls. The Joanna Briggs Institute Checklist was used to complete a quality assessment for all the studies included in this review.

RESULTS: 11 observational case control studies met the inclusion criteria for this review. The primary outcome of metabolite measurement in blood samples of CFS/ME/SEID patients was reported in ten studies. The secondary outcome of urine metabolites was measured in three of the included studies. No studies were excluded from this review based on a low-quality assessment score, however there was inconsistency in the scientific research design of the included studies. Metabolites associated with the amino acid pathway were the most commonly impaired with significant results in seven out of the 10 studies. However, no specific metabolite was consistently impaired across all of the studies. Urine metabolite results were also inconsistent.

CONCLUSION: The findings of this systematic review reports that a lack of consistency with scientific research design provides little evidence for metabolomics to be clearly defined as a contributing factor to the pathogenesis of CFS/ME/SEID. Further research using the same CFS/ME/SEID diagnostic criteria, metabolite analysis method and control of the confounding factors that influence metabolite levels are required.

Source: Huth TK, Eaton-Fitch N, Staines D, Marshall-Gradisnik S. A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID). J Transl Med. 2020 May 13;18(1):198. doi: 10.1186/s12967-020-02356-2. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02356-2 (Full text)

A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques

Abstract:

BACKGROUND: Myalgic encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterised by a diverse range of debilitating symptoms including autonomic and cognitive dysfunction. The pathomechanism remains elusive, however, neurological and cognitive aberrations are consistently described. This systematic review is the first to collect and appraise the literature related to the structural and functional neurological changes in ME/CFS patients as measured by neuroimaging techniques and to investigate how these changes may influence onset, symptom presentation and severity of the illness.

METHODS: A systematic search of databases Pubmed, Embase, MEDLINE (via EBSCOhost) and Web of Science (via Clarivate Analytics) was performed for articles dating between December 1994 and August 2019. Included publications report on neurological differences in ME/CFS patients compared with healthy controls identified using neuroimaging techniques such as magnetic resonance imaging, positron emission tomography and electroencephalography. Article selection was further refined based on specific inclusion and exclusion criteria. A quality assessment of included publications was completed using the Joanna Briggs Institute checklist.

RESULTS: A total of 55 studies were included in this review. All papers assessed neurological or cognitive differences in adult ME/CFS patients compared with healthy controls using neuroimaging techniques. The outcomes from the articles include changes in gray and white matter volumes, cerebral blood flow, brain structure, sleep, EEG activity, functional connectivity and cognitive function. Secondary measures including symptom severity were also reported in most studies.

CONCLUSIONS: The results suggest widespread disruption of the autonomic nervous system network including morphological changes, white matter abnormalities and aberrations in functional connectivity. However, these findings are not consistent across studies and the origins of these anomalies remain unknown. Future studies are required confirm the potential neurological contribution to the pathology of ME/CFS.

Source: Maksoud R, du Preez S, Eaton-Fitch N, Thapaliya K, Barnden L, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques. PLoS One. 2020 Apr 30;15(4):e0232475. doi: 10.1371/journal.pone.0232475. eCollection 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232475

Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is hallmarked by a significant reduction in natural killer (NK) cell cytotoxicity, a mechanism tightly regulated by calcium (Ca2+). Interestingly, interleukin-2 (IL-2) increases NK cell cytotoxicity. Transient receptor potential melastatin 2 (TRPM2) ion channels are fundamental for Ca2+ signalling in NK cells. This pilot investigation aimed to characterise TRPM2 and CD38 surface expression in vitro on NK cells in ME/CFS patients. This investigation furthermore examined the pharmaceutical effect of 8-bromoadenosine phosphoribose (8-Br-ADPR) and N6-Benzoyladenosine-3′,5′-cyclic monophosphate (N6-Bnz-cAMP) on TRPM2 and CD38 surface expression and NK cell cytotoxicity between ME/CFS and healthy control (HC) participants.

METHODS: Ten ME/CFS patients (43.45 ± 12.36) and 10 HCs (43 ± 12.27) were age and sex-matched. Isolated NK cells were labelled with fluorescent antibodies to determine baseline and drug-treated TRPM2 and CD38 surface expression on NK cell subsets. Following IL-2 stimulation, NK cell cytotoxicity was measured following 8-Br-ADPR and N6-Bnz-cAMP drug treatments by flow cytometry.

RESULTS: Baseline TRPM2 and CD38 surface expression was significantly higher on NK cell subsets in ME/CFS patients compared with HCs. Post IL-2 stimulation, TRPM2 and CD38 surface expression solely decreased on the CD56DimCD16+ subset. 8-Br-ADPR treatment significantly reduced TRPM2 surface expression on the CD56BrightCD16Dim/- subset within the ME/CFS group. Baseline cell cytotoxicity was significantly reduced in ME/CFS patients, however no changes were observed post drug treatment in either group.

CONCLUSION: Overexpression of TRPM2 on NK cells may function as a compensatory mechanism to alert a dysregulation in Ca2+ homeostasis to enhance NK cell function in ME/CFS, such as NK cell cytotoxicity. As no improvement in NK cell cytotoxicity was observed within the ME/CFS group, an impairment in the TRPM2 ion channel may be present in ME/CFS patients, resulting in alterations in [Ca2+]i mobilisation and influx, which is fundamental in driving NK cell cytotoxicity. Differential expression of TRPM2 between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in ME/CFS.

Source: Balinas C, Cabanas H, Staines D, Marshall-Gradisnik S. Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients. J Transl Med. 2019 Dec 3;17(1):401. doi: 10.1186/s12967-019-02155-4. https://www.ncbi.nlm.nih.gov/pubmed/31796045

A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

BACKGROUND: Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other outcomes evaluated in NK cells of ME/CFS patients, however, remain equivocal. The aim of this study was to conduct a systematic review of the literature regarding NK cell phenotype, receptor expression, cytokine production and cytotoxicity in ME/CFS patients and determine the appropriateness as a model for ME/CFS.

METHODS: Medline (EBSCOHost), Scopus, EMBASE and PubMed databases were systematically searched to source relevant papers published between 1994 and March 2018. This review included studies examining NK cells’ features in ME/CFS patients compared with HC following administration of specific inclusion and exclusion criteria. Secondary outcomes included genetic analysis in isolated NK cells or quality of life assessment. Quality assessment was completed using the Downs and Black checklist in addition to The Joanna Briggs Institute checklist.

RESULTS: Seventeen eligible publications were included in this review. All studies were observational case control studies. Of these, 11 investigated NK cell cytotoxicity, 14 investigated NK cell phenotype and receptor profiles, three examined NK cell cytokine production, six investigated NK cell lytic protein levels and four investigated NK cell degranulation. Impaired NK cell cytotoxicity remained the most consistent immunological report across all publications. Other outcomes investigated differed between studies.

CONCLUSION: A consistent finding among all papers included in this review was impaired NK cell cytotoxicity, suggesting that it is a reliable and appropriate cellular model for continued research in ME/CFS patients. Aberrations in NK cell lytic protein levels were also reported. Although additional research is recommended, current research provides a foundation for subsequent investigations. It is possible that NK cell abnormalities can be used to characterise a subset of ME/CFS due to the heterogeneity of both the illness itself and findings between studies investigating specific features of NK function.

Source: Eaton-Fitch N, du Preez S, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome. Syst Rev. 2019 Nov 14;8(1):279. doi: 10.1186/s13643-019-1202-6. https://www.ncbi.nlm.nih.gov/pubmed/31727160