Potential benefits of a ketogenic diet to improve response and recovery from physical exertion in people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A feasibility study

Background. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) affects approximately 250,000 people in the UK. The condition varies in severity causing long-term physical and cognitive fatigue which is not alleviated by rest. Whilst the pathology is not understood, recent evidence suggests metabolic abnormalities may be associated with the manifestation of symptoms, particularly involving the metabolism of glucose and energy production. The use of ketone bodies as an alternative energy substrate may be beneficial to people with ME/CFS, in order to by-pass the glycolytic pathway, enhance energy production and reduce fatiguing outcomes. Study Design and Methods. Using a pragmatic collective case study with repeated measures methodology we investigated the feasibility of following a ketogenic diet and potential effects of the high fat, low carbohydrate diet on response to physical activity in people with ME/CFS (n=3) and healthy controls (n=3) using a submaximal exercise stress test both with and without dietary intervention. Exercise tolerance (mins), rate of oxygen consumption (VO2) to workload (75W), respiratory exchange ratio (RER), rate of perceived effort (RPE) and lactate response were measured throughout and descriptive statistics performed.   Results. We found that the ketogenic diet was followed, with compliance higher in the pwME/CFS. Variations in response following the ketogenic diet was observed across individuals in minutes performed, VO2, HR, RER, and RPE post diet but the KD only limited exercise capacity in the control individuals. Individuals responded differently to the KD but group trends have been reported as means and standard deviation. The KD resulted in a decrease in RER at submax in the controls with a mean change of 0.07 from baseline (0.86 ± 0.1) to post intervention (0.79 ± 0.1) compared to a mean change of 0.02 in the ME/CFS from baseline (1.03 ± 0.1) to post intervention (1.01 ± 0.1). A decrease in VO2 (L/min) at submax showed a mean change of 0.06 (L/min) in the pwME/CFS at baseline (1.34 ± 0.1) to post intervention (1.27 ± 0.2) compared to a mean change of 0.07 (L/min) in the controls at baseline (1.40 ± 0.3) to post intervention (1.33 ± 0.2). HR (bpm) at submax decreased in all individuals, with a mean change of 4 (bpm), with pwME/CFS at baseline (139 ± 8.2) to post intervention (135 ± 14) and control individuals at baseline (107 ± 7.8) to intervention (103 ± 3.2). RPE at submax decreased in the pwME/CFS from baseline (6 ± 1.0) to post intervention (5 ± 2.1) whereas the controls increased from baseline (2 ± 1.0) to post intervention (3 ± 1.5).  Conclusion. Our observations suggest individualised but metabolic flexibility in healthy individuals is achievable via dietary manipulation showing the ability to switch from glucose to fats under controlled conditions. The different response in substrate utilisation in individuals with ME/CFS suggests that potential metabolic abnormalities may be present in ME/CFS.  Further investigation is now warranted in order to assess whether the KD is beneficial for people with ME/CFS

A cross-sectional pilot study assessing dietary intake in people with multiple sclerosis and the relationships with national diet guidelines

People with the Multiple Sclerosis (PwMS) modify their diet, however their knowledge of diet is unknown and dietary modifications may have long term health implications. We set out to assess the feasibility of a study to determine diet patterns compared to national nutritional guidelines in PwMS, and in those with and without fatigue. Methods: In this cross sectional study four MS support groups were attended throughout the Thames Valley area, with approximately 20 to 25 people attending each group at any one point in time. Measures of feasibility were sought. Descriptive statistics were used to determine inconsistencies in nutrient intake in PwMS with and without fatigue compared to the Scientific Advisory Committee on Nutrition guidelines. Results: 31 PwMS provided dietary data using a Food Frequency Questionnaire, alongside the Fatigue Severity Scale, Barthel Index activities of daily living and demographic data. One third of participants were on a modified diet. Compared to the UK nutrition guidelines, several nutrients were ±1 standard deviation in PwMS, and PwMS tended to miss targets for diet guidelines. Those who were fatigued showed further differences in nutrient intake compared to those who were non-fatigued, and women tended to have healthier diets than men. Missing data was low and response rate was high Conclusion: For the first time data is provided that shows PwMS may have altered dietary intake compared to national guidelines. Furthermore, those who were fatigued show further differences compared to non-fatigued PwMS. Considering the high incidence of modified diets in this group, more substantial investigation of diet is required

Prediction of discontinuation of structured exercise programme in chronic fatigue syndrome patients.

Purpose: The purpose of this study was to assess differences in the physiological profiles of completers vs. non-completers following a structured exercise programme (SEP) and the ability to predict non-completers, which is currently unknown in this group. Methods: Sixty-nine patients met the Fukuda criteria. Patients completed baseline measures assessing fatigue, autonomic nervous system (ANS), cognitive, and cardiovascular function. Thirty-four patients completed a home-based SEP consisting of 10–40 min per day at between 30 and 80% actual HR max. Exercise intensity and time was increased gradually across the 16 weeks and baseline measures were repeated following the SEP. Results: Thirty-five patients discontinued, while 34 completed SEP. For every increase in sympathetic drive for blood pressure control as measured by the taskforce, completion of SEP decreased by a multiple of 0.1. For a 1 millisecond increase in reaction time for the simple reaction time (SRT), the probability for completion of SEP also decreases by a multiple of 0.01. For a one beat HRmax increase, there is a 4% increase in the odds of completing SEP. Conclusion: The more sympathetic drive in the control of blood vessels, the longer the reaction time on simple visual stimuli and the lower the HRmax during physical exercise, then the lower the chance of SEP completion in ME/CFS

A novel criticality analysis method for assessing obesity treatment efficacy

Human gait is a significant indicator of overall health and well-being due to its dependence on metabolic requirements. Abnormalities in gait can indicate the presence of metabolic dysfunction, such as diabetes or obesity. However, detecting these can be challenging using classical methods, which often involve subjective clinical assessments or invasive procedures. In this work, a novel methodology known as Criticality Analysis (CA) was applied to the monitoring of the gait of teenagers with varying amounts of metabolic stress who are taking part in an clinical intervention to increase their activity and reduce overall weight. The CA approach analysed gait using inertial measurement units (IMU) by mapping the dynamic gait pattern into a nonlinear representation space. The resulting dynamic paths were then classified using a Support Vector Machine (SVM) algorithm, which is well-suited for this task due to its ability to handle nonlinear and dynamic data. The combination of the CA approach and the SVM algorithm demonstrated high accuracy and non-invasive detection of metabolic stress. It resulted in an average accuracy within the range of 78.2% to 90%. Additionally, at the group level, it was observed to improve fitness and health during the period of the intervention. Therefore, this methodology showed a great potential to be a valuable tool for healthcare professionals in detecting and monitoring metabolic stress, as well as other associated disorders

Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients

Background: The therapeutic effects of exercise from structured activity programmes have recently been questioned; as a result, this study examines the impact of an Individualised Activity Program (IAP) on the relationship with cardiovascular, mitochondrial and fatigue parameters. Methods: Chronic fatigue syndrome (CFS) patients were assessed using Chalder Fatigue Questionnaire (CFQ), Fatigue Severity Score (FSS) and the Fatigue Impact Scale (FIS). VO(2)peak, VO(2)submax and heart rate (HR) were assessed using cardiopulmonary exercise testing. Mfn1 and Mfn2 levels in plasma were assessed. A Task Force Monitor was used to assess ANS functioning in supine rest and in response to the Head-Up Tilt Test (HUTT). Results: Thirty-four patients completed 16 weeks of the IAP. The CFQ, FSS and FIS scores decreased significantly along with a significant increase in Mfn1 and Mfn2 levels (p = 0.002 and p = 0.00005, respectively). The relationships between VO2 peak and Mfn1 increase in response to IAP (p = 0.03) and between VO2 at anaerobic threshold and ANS response to the HUTT (p = 0.03) were noted. Conclusions: It is concluded that IAP reduces fatigue and improves functional performance along with changes in autonomic and mitochondrial function. However, caution must be applied as exercise was not well tolerated by 51% of patients

The effect of breaking sitting time with physical activity breaks on cognitive performance in young people with cerebral palsy : an exposure response cross-over feasibility design

Objectives. To assess the feasibility of methods and estimate the potential effect of interrupting sedentary behaviour, with intermittent or continuous physical activity breaks, on cognitive performance in young people with Cerebral Palsy. Methods. A randomised three-arm exposure response cross-over design with process evaluation. Participants were recruited throughout the Thames Valley, UK between 01/11/2018 to 31/03/2020. The three 2 h activity exposure visits included: (i) sitting only (controls), (ii) sitting plus 20 min of moderate-to-vigorous activity burst, or (iii) 4×5 min of moderate-to-vigorous activity bursts, during a 2.5 h sedentary session. Measures of feasibility were sought. Cognitive performance outcomes (using the Eriksen Flanker task and Forward and Backward Digit Span) were delivered before and after the 2 h testing period. Results. 36 participants were randomised (age 13.2±2.7, Gross-Motor Functional Classification System 1–3). Study retention was 83 % across all three interventions and overall missing data for measures was 4 %. A small intervention effect was found in reaction time in the 4×5 min physical activity exposure session compared to the sedentary control condition (0.42; 95 % CI 0.40 to 0.79). There were two research-related minor adverse effects, an allergic reaction to the FreeStyle Libre and feeling faint and vomiting after consumption of glucose solution. Both events were resolved and participants continued with the study. Conclusions. The study design and intervention implementing short bursts of physical activity was feasible and indicated a potential effect on reaction time as a measure of cognitive performance in young people with cerebral palsy

A feasibility study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue and fatigability in people with Parkinson’s (pwP)

Flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue and fatigability. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with Parkinson's (pwP) have been performed. Objectives. To determine the feasibility and estimate potential effect of flavonoid-rich cocoa on fatigue and fatigability in pwP. Methods. This was a randomised (1:1) double-blind placebo controlled feasibility study in which 30 pwP were recruited from the European Parkinson Therapy Centre, Italy (trial registration: NCT03288155). During a six day intervention participants consumed a high (10.79 mg/g) or low flavonoid cocoa (1.02 mg/g) beverage (18 g Cocoa with 200 ml Rice milk) once daily. Potential effect on fatigue and fatigability was measured (baseline to day 6). Feasibility and fidelity were assessed through recruitment and retention, adherence and a process evaluation. Results. From July 2017 to May 2018, 30 pwP were recruited and randomised and allocated to high (n = 15) or low (n = 15) flavonoid groups and included in analysis. Missing data was less than 5% and adherence to intervention of all allocated individuals was 97%. There was a small effect on fatigability (6 min walk test: ES 0.11 (95%CI = −0.11-0.26); Z = 0.81). There were two adverse events (one in the control and one in the intervention group). Conclusion. The consumption of cocoa is feasible and well received in pwP, and further investigation on the effect on fatigability is warranted