A systematic review of nutraceutical interventions for mitochondrial dysfunctions in ME/CFS

Posted on 03/03/2021 by wames

A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome, by  in Journal of Translational Medicine vol 19, no.: 81 (2021)

 

Review 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.

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WAMES AGM 27th March 2021

Posted on 03/03/2021 by wames

Annual General Meeting of WAMES

 

The annual business meeting of the Welsh Association of ME & CFS Support will be held virtually to appoint officers, review past events and plan future activities. As Covid-19 continues to impact life at many levels we need to continue to adapt.

Please contact jan@wames.org.uk if you have anything to report to WAMES, or topics you wish us to discuss, or more importantly, if you would like to get involved with the running of WAMES or volunteer in any way.  WAMES is entirely run by volunteers and there is always more work than workers!

Could you be an Admin volunteer?

The secretary would welcome some assistance with the administration.

Please let Jan know if you wish to attend and you will be given a link to join the meeting nearer the time.

When:  Saturday 27th March 2020 at  11.30am

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Elin Williams: the mind/body split

Posted on 03/02/2021 by wames

Disability talk blog post: The mind/body split, by Elin Williams

 

As a chronically ill workaholic, I have a slight problem. My mind and my body don’t always cooperate.

One races through the to-do list,  whilst the other demands rest. One produces a new idea just as the other retaliates. One likes to think it’s invincible, whilst the other, well, the other has plenty of evidence in its arsenal to prove otherwise.

I give you The Mind/Body Split.

Ironically, I’m experiencing this conflict as we speak; interrupting what should deservedly be a restful afternoon with intermittent bouts of writing as my mind gravitates towards this idea and all it wants to say about it.

It’s a peculiar divide.

I’d like to think that I have this enduring loyalty to looking after my body, to listening to its cries when things get a little too much. But I have to hold my hands up and say that I’m not always committed to dedicating the care it needs and deserves.

It’s an almost constant battle; the split stretches into a chasm, leaving space for some peculiar emotions to swell. For years, the commitment between my mind and body to look out for each other has been puckered and bruised.

When I’m too weak to do anything, my mind feels guilty for not being productive. When I attempt a small task, my body quivers under the strain.

I’ve always placed unnecessary pressure on myself in terms of my work, my studies, my writing, and doing the best I can…

…Every day unfolds in different directions when it comes to The Mind/Body Split: Sometimes, a splash of common sense exists between them, making it easier to mould the shape of the day into something that will satisfy them both.

But some are harder than others. My ME/CFS symptoms fluctuate from one day to the next, sometimes gripping me from the moment I wake up, whilst, on others, they progress as the hours stretch on. Take the other day, for example: It was early afternoon when a thicker veil of weakness started to cascade over me, alerting me to the fact that it was time for a break, time to stop. But did I?

I did not.

Here is where I’d usually find myself typing carefully constructed explanations, but honestly? It was simply a matter of that newly accepted task being too tantalising to dismiss. It needed to be done, and I knew the worry of completing it would eat away at my energy whilst resting, just as an extra 20 minutes at my desk would.

So I stayed.

You’d think that I’d be quite the pro at navigating this whole ME/CFS experience, having lived with the symptoms in various forms for the best part of the last ten years, but consistent evidence proves that I am very much not. I barely touch intermediate.

It’s this hierarchy that gets me. The way in which both entities fight for superiority: The way I let the thought of productivity erode the precious concept of rest. Or the way in which the layering of symptoms makes it impossible to see a task or an activity through.

Because, my mind doesn’t always take the lead. Sometimes the thoughts are cast in the symptom of brain fog, or my arms are too heavy, too weak, to reach for the laptop.

I’ve become better at accepting these moments, better at submitting to resting when I need to.

But over-exertion is still a constant threat, and I know I need to make more of a conscious effort to diminish its presence…

Read the full article

Black tulip beauty: Elin Williams on life with vision impairment and CFS

Elin’s blog: My blurred world

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Mental health screening in adolescents with CFS/ME

Posted on 03/01/2021 by wames

Mental health screening in adolescents with CFS/ME, by Maria E Loades, Paul Stallard, David Kessler & Esther Crawley in European Child & Adolescent Psychiatry (2021) [doi.org/10.1007/s00787-021-01734-5]

 

Excerpts from Letter to the editor:

Psychiatric co-morbidity in adolescents is common, with the majority of those who have depression also having at least one anxiety disorder, and many meeting the diagnostic criteria for more than one anxiety disorder. In our recent paper published in this journal, we reported that approximately one in three adolescents with Chronic Fatigue Syndrome (CFS/ME) has either an anxiety disorder, or major depressive disorder, or both.

In clinical practice, screening questionnaires which ask about depression and anxiety symptoms, such as the Revised Children’s Anxiety and Depression Scale, RCADS, and the Hospital Anxiety and Depression Scale, HADS, are often used as part of the assessment process. However, in our paper, we reported our findings of variable discriminative validity of these questionnaires for detecting anxiety and depression separately. Whilst we found sufficiently accurate threshold scores for classifying those with anxiety disorders on both the 47-item and 25-item parent and child versions of the RCADS, we could not identify a sufficiently accurate threshold score for classifying those with depression. We also could not identify sufficiently accurate threshold scores on the HADS for either anxiety or depression.

Clinicians treating children with health disorders need a simple screening mechanism to identify those with co-morbid mental health problems that will require further assessment. Using one threshold score is therefore arguably more useful than calculating two separate scores (for depression and anxiety). Given the high co-morbidity between depression and anxiety in this population, we sought to identify the threshold score for mental health problems on two commonly used screening questionnaires, the RCADS-total and the HADS-total…

A total of 164 participants, mean age 15, mostly female (70%) completed the HADS and a subsample of 89 (54%) completed the RCADS. The subsample did not differ significantly on fatigue, physical functioning, HADS total, or age (data not shown)…

For identifying co-morbid mental health problems (anxiety and/or depression), we found that both the full 47-item version and the brief 25-item version of the RCADS were sufficiently accurate and could identify threshold scores deemed to be suitably sensitive and specific to be useful for screening in a clinical setting…

Participants were recruited from specialist services, so findings may not generalise to other settings, nor to those who were too severely affected to participate. The diagnostic interview was also assumed to be completely accurate, and whilst we made every attempt to ensure that it was robustly conducted, diagnostic judgements may mean that errors were made. Nonetheless, our findings suggest that a total cut-off score of ≥ 27 on the 25-item RCADS offers a simple way of identifying children with CFS/ME with co-morbid anxiety and depression.

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Dysregulated provision of oxidisable substrates to the mitochondria in ME/CFS lymphoblasts

Posted on 02/24/2021 by wames

Dysregulated provision of oxidisable substrates to the mitochondria in ME/CFS lymphoblasts, by Daniel Missailidis, Oana Sanislav, Claire Y Allan, Paige K. Smith, Sarah J Annesley, and Paul R Fisher in Int. J. Mol. Sci. 2021, 22(4), 2046; 19 February 2021 [doi.org/10.3390/ijms22042046]  (This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

 

Research abstract:

Although understanding of the biomedical basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is growing, the underlying pathological mechanisms remain uncertain.

We recently reported a reduction in the proportion of basal oxygen consumption due to ATP synthesis by Complex V in ME/CFS patient-derived lymphoblast cell lines, suggesting mitochondrial respiratory inefficiency. This was accompanied by elevated respiratory capacity, elevated mammalian target of rapamycin complex 1 (mTORC1) signaling activity and elevated expression of enzymes involved in the TCA cycle, fatty acid β-oxidation and mitochondrial transport.  These and other observations led us to hypothesise the dysregulation of pathways providing the mitochondria with oxidisable substrates.

In our current study, we aimed to revisit this hypothesis by applying a combination of whole-cell transcriptomics, proteomics and energy stress signaling activity measures using subsets of up to 34 ME/CFS and 31 healthy control lymphoblast cell lines from our growing library.

While levels of glycolytic enzymes were unchanged in accordance with our previous observations of unaltered glycolytic rates, the whole-cell proteomes of ME/CFS lymphoblasts contained elevated levels of enzymes involved in the TCA cycle (p = 1.03 × 10−4), the pentose phosphate pathway (p = 0.034, G6PD p = 5.5 × 10−4), mitochondrial fatty acid β-oxidation (p = 9.2 × 10−3), and degradation of amino acids including glutamine/glutamate (GLS p = 0.034, GLUD1 p = 0.048, GOT2 p = 0.026), branched-chain amino acids (BCKDHA p = 0.028, BCKDHB p = 0.031) and essential amino acids (FAH p = 0.036, GCDH p = 0.006). The activity of the major cellular energy stress sensor, AMPK, was elevated but the increase did not reach statistical significance.

The results suggest that ME/CFS metabolism is dysregulated such that alternatives to glycolysis are more heavily utilised than in controls to provide the mitochondria with oxidisable substrates.

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Sex-based differences in plasma autoantibodies to CNS proteins in Gulf War veterans versus healthy & symptomatic controls

Posted on 02/22/2021 by wames

Sex-based differences in plasma autoantibodies to Central Nervous System proteins in Gulf War veterans versus healthy and symptomatic controls, by Mohamed B Abou-Donia, Maxine H Krengel, Elizabeth S Lapadula, Clara G Zundel, Jessica LeClair, Joseph Massaro, Emily Quinn, Lisa A Conboy, Efi Kokkotou, Daniel D Nguyen, Maria Abreu, Nancy G Klimas, Kimberly Sullivan in Brain Sci. 2021 Jan 23;11(2):148 [doi: 10.3390/brainsci11020148] (This article belongs to the Special Issue Advancing the Role of Neuroimmunity and Genetic Susceptibility in Gulf War Illness)

 

Research abstract

Veterans from the 1991 Gulf War (GW) have suffered from Gulf War illness (GWI) for nearly 30 years. This illness encompasses multiple body systems, including the central nervous system (CNS). Diagnosis and treatment of GWI is difficult because there has not been an objective diagnostic biomarker. Recently, we reported on a newly developed blood biomarker that discriminates GWI from GW healthy controls, and symptomatic controls with irritable bowel syndrome (IBS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

The present study was designed to compare levels of these biomarkers between men and women with GWI, as well as sex-specific effects in comparison to healthy GW veterans and symptomatic controls (IBS, ME/CFS). The results showed that men and women with GWI differ in 2 of 10 plasma autoantibodies, with men showing significantly elevated levels. Men and women with GWI showed significantly different levels of autoantibodies in 8 of 10 biomarkers to neuronal and glial proteins in plasma relative to controls.

In summary, the present study addressed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among both men and women veterans with GWI and other healthy and symptomatic control groups.

Excerpt

Our next analyses compared male veterans with GWI to all male controls from our prior study (healthy GW veterans, non-veterans with IBS or ME/CFS) [19]. We then performed the same analyses comparing women veterans with GWI to the combined all women control group (non-veterans with IBS and ME/CFS). The results showed that men with GWI had significantly higher levels of autoantibodies for 9 out of the 10 autoantibodies when compared with male healthy GW veterans or with the combined male control group. Women with GWI showed significantly higher values for 2 out of the 10 autoantibodies when compared with women healthy GW veterans and with 8 out of 10 autoantibodies when compared with their respective combined women control group (nonveterans with IBS and ME/CFS).

These results suggest that women with GWI appear to be showing more neuronal cytoskeletal and neuroinflammatory changes when compared to healthy GW controls or women with IBS or ME/CFS

This suggests that male GWI veterans may be showing more chronic glial activation, neuronal damage, and neuroinflammation than their male control healthy and symptomatic counterparts with IBS and ME/CFS because S100B is a marker of current BBB disruption and GFAP is a marker of current neuroinflammation [39,40]. This is because GFAP is secreted by activated astrocytes, which leads to neuroinflammation [41,42,43].

A major strength of our study is that it represents both healthy and symptomatic GW veteran groups as well as symptomatic non-veteran controls with ME/CFS or IBS. This suggests that both men and women veterans with GWI differ not only from their healthy GW veteran controls but also have more CNS differences than other groups of men and women with chronic multi-symptom illnesses. In addition, the CNS autoantibody analyses were performed with the laboratory staff blinded to the case status of all participants.

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Sick of the sick role: narratives of what ‘recovery’ means to people with CFS/ME

Posted on 02/21/2021 by wames

Sick of the sick role: narratives of what “Recovery” means to people with CFS/ME, by Anna Cheshire, Damien Ridge, Lucy V Clark, Peter D White in Qualitative Health Research Vol 31, Issue 2, 2021 [doi.org/10.1177/1049732320969395]

 

Research abstract:

Little is known about what recovery means to those with chronic fatigue syndrome/ myalgic encephalomyelitis, a poorly understood, disabling chronic health condition.

To explore this issue, semi-structured interviews were conducted with patients reporting improvement (n = 9) and deterioration (n = 10) after a guided self-help intervention, and analyzed via “constant comparison.”

The meaning of recovery differed between participants—expectations for improvement and deployment of the sick role (and associated stigma) were key influences. While some saw recovery as complete freedom from symptoms, many defined it as freedom from the “sick role,” with functionality prioritized. Others redefined recovery, reluctant to return to the lifestyle that may have contributed to their illness, or rejected the concept as unhelpful.

Recovery is not always about eliminating all symptoms. Rather, it is a nexus between the reality of limited opportunities for full recovery, yet a strong desire to leave the illness behind and regain a sense of “normality.”

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Plasma proteomics publication shows disrupted cell-to-cell signaling in ME/CFS

Posted on 02/18/2021 by wames

Cornell University news post from the Center for Enervating NeuroImmune Disease: Plasma proteomics publication shows disrupted cell-to-cell signaling

 

We are proud to announce our latest plasma proteomics publication is available as open access in Proteomes.

In-depth analysis of the plasma proteome in ME/CFS exposes disrupted Ephrin-Eph and immune system signaling by Arnaud Germain, Susan M Levine and Maureen R Hanson in Proteomes 2021, 9(1), 6; [doi.org/10.3390/proteomes9010006]

This manuscript takes a look at 4,790 circulating plasma proteins from 20 ME/CFS women compared to 20 healthy women, over an unprecedented range, for ME/CFS, of 9 orders of magnitude.

Pathway analysis uncovered disrupted cell-to-cell communication, specifically in the ephrin-Eph signaling pathway. This pathway is crucial for many aspects of our body’s homeostasis, including development, physiology, and disease regulation.

Additionally, the paper outlines promising results for the development of a diagnostic test using protein ratios.

First author, Arnaud Germain, PhD, outlines these findings in a video abstract below (4 mins).

A transcript for the video: English        German

 

 

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Open‐label study with the monoamine stabilizer (‐)‐OSU6162 [drug] in ME/CFS

Posted on 02/18/2021 by wames

Open‐label study with the monoamine stabilizer (‐)‐OSU6162 in myalgic encephalomyelitis/ chronic fatigue syndrome, by Sara Haghighi, Sara Forsmark, Olof Zachrisson, Arvid Carlsson, Marie K L Nilsson, Maria L Carlsson, Robert C Schuit, Carl‐Gerhard Gottfries in Brain and Behavior, 02 February 2021 [doi.org/10.1002/brb3.2040]

 

Research abstract:

Objectives

The purpose of the present study was to investigate the safety and tolerability of the monoaminergic stabilizer (‐)‐OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In addition, a potential therapeutic effect of (‐)‐OSU6162 in ME/CFS was evaluated by means of observer‐rated scales and self‐assessment rating scales.

Materials and Methods

In the current study using an open‐label single‐arm design ME/CFS patient received treatment with (‐)‐OSU6162 during 12 weeks. The patients received the following doses of (‐)‐OSU6162: 15 mg b.i.d. during the first 4‐week period, up to 30 mg b.i.d. during the second 4‐week period and up to 45 mg b.i.d. during the third 4‐week period, with follow‐up visits after 16 and 20 weeks.

Results

Out of 33 included patients, 28 completed the 12 weeks treatment period. (‐)‐OSU6162 was well tolerated; only one patient discontinued due to an adverse event. Vital signs and physical examinations showed no abnormal changes. Blood analyses showed an increase in serum prolactin. Therapeutically, improvements were seen on the Clinical Global Impression of Change scale, the FibroFatigue scale, the Mental Fatigue Scale, the Fatigue Severity Scale, Beck Depression Inventory, and the Short Form 36 Health Survey Questionnaire.

Conclusions

(‐)‐OSU6162 is well tolerated in ME/CFS patients and shows promise as a novel treatment to mitigate fatigue and improve mood and health‐related quality of life in ME/CFS. Obviously, the present results need to be confirmed in future placebo‐controlled double‐blind trials.

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Diagnostic & pharmacological potency of Creatine in Post-Viral Fatigue Syndrome

Posted on 02/18/2021 by wames

Diagnostic and pharmacological potency of creatine in Post-Viral Fatigue Syndrome
by  Sergej M. Ostojic in Nutrients 2021, 13(2), 503; [doi.org/10.3390/nu13020503] (This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)

 

Review abstract

Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure.

Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue.

This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.

Conclusions

Currently, there is not enough evidence to unequivocally endorse supplemental creatine for PVFS. However, the findings from initial trials on the metabolic substrate of PVFS, along with promising results from interventional studies, emphasize the need to explore creatine and similar compounds in this ever-prevalent yet baffling disorder.

The need for an effective, low-risk, and affordable dietary intervention to tackle post-COVID-19 fatigue, which is going to remain an issue for years to come, perhaps provides a unique research opportunity to explore creatine in PVFS using expedited yet diligent approaches.

 

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