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1.
Food Funct ; 14(8): 3600-3612, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-36946764

ABSTRACT

The antioxidant properties of polyphenols, which are found in most plants, have been shown to be useful for maintaining health, including enhancing brain function and alleviating stress. We aimed to investigate the effect of a single intake of taxifolin-containing foods on cognitive task performance and whole blood gene expression in healthy young adults. This study was a randomized, placebo-controlled, double-blind, crossover trial in which healthy young adults were administered a single dose of either a placebo or food containing taxifolin. Cognitive tests (serial 3s, serial 7s, and rapid visual information processing) to examine brain activity and visual analog scale questionnaires to analyze mental fatigue were applied. The set of tests was repeated four times. The findings showed that taxifolin intake improved calculation abilities and reduced mental fatigue. An analysis of whole blood gene expression before and after the test revealed that the expression of foreign substance removal-related genes increased following the ingestion of taxifolin and that most differentially expressed genes were enriched in granulocytes. Taxifolin intake was shown to affect the brain activity of healthy young adults and demonstrated an antifatigue effect, thereby reducing subjective fatigue. A single intake of taxifolin may enhance the removal of foreign substances by strengthening the innate immune system and suppressing the occurrence of injury.


Subject(s)
Cognition , Transcriptome , Humans , Young Adult , Cross-Over Studies , Mental Fatigue/drug therapy , Mental Fatigue/psychology , Eating , Brain , Double-Blind Method
2.
J Transl Med ; 20(1): 295, 2022 06 28.
Article in English | MEDLINE | ID: mdl-35764955

ABSTRACT

BACKGROUND: There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and currently, it is estimated that up to 20 million Americans have significant symptoms after COVID, and the most common symptom is fatigue. Anhydrous Enol-Oxaloacetate, (AEO) a nutritional supplement, has been anecdotally reported to relieve physical and mental fatigue and is dimished in ME/CFS patients. Here, we examine the use of higher dosage AEO as a medical food to relieve pathological fatigue. METHODS: ME/CFS and Long-COVID patients were enrolled in an open label dose escalating "Proof of Concept" non-randomized controlled clinical trial with 500 mg AEO capsules. Control was provided by a historical ME/CFS fatigue trial and supporting meta-analysis study, which showed average improvement with oral placebo using the Chalder Scale of 5.9% improvement from baseline. At baseline, 73.7% of the ME/CFS patients were women, average age was 47 and length of ME/CFS from diagnosis was 8.9 years. The Long-COVID patients were a random group that responded to social media advertising (Face Book) with symptoms for at least 6 months. ME/CFS patients were given separate doses of 500 mg BID (N = 23), 1,000 mg BID (N = 29) and 1000 mg TID (N = 24) AEO for six weeks. Long COVID patients were given 500 mg AEO BID (N = 22) and 1000 mg AEO (N = 21), again over a six-week period. The main outcome measure was to compare baseline scoring with results at 6 weeks with the Chalder Fatigue Score (Likert Scoring) versus historical placebo. The hypothesis being tested was formulated prior to data collection. RESULTS: 76 ME/CFS patients (73.7% women, median age of 47) showed an average reduction in fatigue at 6 weeks as measured by the "Chalder Fatigue Questionnaire" of 22.5% to 27.9% from baseline (P < 0.005) (Likert scoring). Both physical and mental fatigue were significantly improved over baseline and historical placebo. Fatigue amelioration in ME/CFS patients increased in a dose dependent manner from 21.7% for 500 mg BID to 27.6% for 1000 mg Oxaloacetate BID to 33.3% for 1000 mg TID. Long COVID patients' fatigue was significantly reduced by up to 46.8% in 6-weeks. CONCLUSIONS: Significant reductions in physical and metal fatigue for ME/CFS and Long-COVID patients were seen after 6 weeks of treatment. As there has been little progress in providing fatigue relief for the millions of ME/CFS and Long COVID patients, anhydrous enol oxaloacetate may bridge this important medical need. Further study of oxaloacetate supplementation for the treatment of ME/CFS and Long COVID is warranted. Trial Registration https://clinicaltrials.gov/ct2/show/NCT04592354 Registered October 19, 2020. 1,000 mg BID Normalized Fatigue Data for Baseline, 2-weeks and 6-weeks evaluated by 3 Validated Fatigue Scoring Questionnaires.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Fatigue Syndrome, Chronic , Oxaloacetic Acid , COVID-19/complications , Fatigue Syndrome, Chronic/complications , Fatigue Syndrome, Chronic/drug therapy , Female , Humans , Male , Mental Fatigue/drug therapy , Mental Fatigue/virology , Middle Aged , Oxaloacetic Acid/therapeutic use , Post-Acute COVID-19 Syndrome
3.
Mult Scler Relat Disord ; 56: 103273, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34564057

ABSTRACT

BACKGROUND: Fatigue is the most common symptom in multiple sclerosis (MS), previously attributed to dopamine imbalance. Evidence suggests that methylphenidate, a psychostimulant that increases striatal and prefrontal dopamine levels, is effective in reducing fatigue in various disorders. However, its effect on state vs. trait mental fatigue in MS is yet to be examined. METHODS: This pilot study investigates the efficacy of methylphenidate on decreasing self-reported mental fatigue in 12 individuals with MS in a double-blind, placebo-controlled, cross-over randomized clinical trial. RESULTS: Our results show that "state", but not "trait" MS-related fatigue, was reduced after 4 weeks of methylphenidate administration as compared to placebo.


Subject(s)
Methylphenidate , Multiple Sclerosis , Double-Blind Method , Humans , Mental Fatigue/drug therapy , Mental Fatigue/etiology , Methylphenidate/therapeutic use , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Pilot Projects
4.
Acta Neuropsychiatr ; 32(6): 303-312, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32418546

ABSTRACT

OBJECTIVE: The purpose of the present study was to evaluate the efficacy and safety of (-)-OSU6162 in doses up to 30 mg b.i.d. in patients suffering from mental fatigue following stroke or traumatic brain injury (TBI). METHODS: This 4 + 4 weeks double-blind randomised cross-over study included 30 patients afflicted with mental fatigue following a stroke or head trauma occurring at least 12 months earlier. Efficacy was assessed using the Mental Fatigue Scale (MFS), the Self-rating Scale for Affective Syndromes [Comprehensive Psychopathological Rating Scale (CPRS)], the Frenchay Activity Index (FAI), and a battery of neuropsychological tests. Safety was evaluated by recording spontaneously reported adverse events (AEs). RESULTS: There were significant differences on the patients' total FAI scores (p = 0.0097), the subscale FAI outdoor scores (p = 0.0243), and on the trail making test (TMT-B) (p = 0.0325) in favour of (-)-OSU6162 treatment. Principal component analysis showed a clear overall positive treatment effect in 10 of 28 patients; those who responded best to treatment had their greatest improvements on the MFS. Reported AEs were mild or moderate in severity and did not differ between the (-)-OSU6162 and the placebo period. CONCLUSION: The most obvious beneficial effects of (-)-OSU6162 were on the patients' activity level, illustrated by the improvement on the FAI scale. Moreover, a subgroup of patients showed substantial improvements on the MFS. Based on these observed therapeutic effects, in conjunction with the good tolerability of (-)-OSU6162, this compound may offer promise for treating at least part of the symptomatology in patients suffering from stroke- or TBI-induced mental fatigue.


Subject(s)
Brain Injuries, Traumatic/complications , Mental Fatigue/drug therapy , Mental Fatigue/etiology , Piperidines/therapeutic use , Receptors, Dopamine/drug effects , Stroke/complications , Adult , Aged , Case-Control Studies , Cross-Over Studies , Dopamine Agonists/adverse effects , Dopamine Agonists/blood , Dopamine Agonists/therapeutic use , Dopamine Antagonists/adverse effects , Dopamine Antagonists/blood , Dopamine Antagonists/therapeutic use , Double-Blind Method , Female , Humans , Male , Middle Aged , Neuropsychological Tests/standards , Piperidines/adverse effects , Piperidines/blood , Placebos/administration & dosage , Safety , Surveys and Questionnaires , Treatment Outcome
5.
Brain Inj ; 34(2): 229-235, 2020.
Article in English | MEDLINE | ID: mdl-31657646

ABSTRACT

Objective: Prolonged mental fatigue and cognitive impairments are common after a mild traumatic brain injury (TBI). This sets limits for rehabilitation and for regaining the capacity for work and participation in social life.Method: This follow-up study, over a period of approximately 5.5 years was designed to evaluate the effect and safety of methylphenidate treatment for mental fatigue after a mild TBI. A comparison was made between those who had continued, and those who had discontinued the treatment. The effect was also evaluated after a four-week treatment break.Results: Significant improvement in mental fatigue, depression, and anxiety for the group treated with methylphenidate (p < .001) was found, while no significant change was found for the group without methylphenidate. The methylphenidate treatment group also improved their processing speed (p = .008). Withdrawal produced a pronounced and significant deterioration in mental fatigue, depression, and anxiety and a slower processing speed. This indicates that the methylphenidate effect is reversible if discontinued and that continued methylphenidate treatment can be a prerequisite for long-term improvement. The effect was found to be stable and safe over the years.Conclusion: We suggest methylphenidate to be a possible treatment option for patients with post-TBI symptoms including mental fatigue and cognitive symptoms.


Subject(s)
Brain Concussion , Brain Injuries, Traumatic , Central Nervous System Stimulants , Methylphenidate , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Central Nervous System Stimulants/therapeutic use , Cognition , Follow-Up Studies , Humans , Mental Fatigue/drug therapy , Mental Fatigue/etiology , Methylphenidate/therapeutic use
6.
RMD Open ; 5(1): e000885, 2019.
Article in English | MEDLINE | ID: mdl-31168409

ABSTRACT

Objectives: To report on fatigue in patients from the United Kingdom primary Sjögren's syndrome (pSS) registry identifying factors associated with fatigue and robust to assignable causes such as comorbidities and medications associated with drowsiness. Methods: From our cohort (n = 608), we identified those with comorbidities associated with fatigue, and those taking medications associated with drowsiness. We constructed dummy variables, permitting the contribution of these potentially assignable causes of fatigue to be assessed. Using multiple regression analysis, we modelled the relationship between Profile of Fatigue and Discomfort physical and mental fatigue scores and potentially related variables. Results: Pain, depression and daytime sleepiness scores were closely associated with both physical and mental fatigue (all p ≤ 0.0001). In addition, dryness was strongly associated with physical fatigue (p ≤ 0.0001). These effects were observed even after adjustment for comorbidities associated with fatigue or medications associated with drowsiness. Conclusions: These findings support further research and clinical interventions targeting pain, dryness, depression and sleep to improve fatigue in patients with pSS.This finding is robust to both the effect of other comorbidities associated with fatigue and medications associated with drowsiness.


Subject(s)
Depression/epidemiology , Mental Fatigue/epidemiology , Pain/epidemiology , Sjogren's Syndrome/epidemiology , Adolescent , Child , Child, Preschool , Comorbidity , Depression/drug therapy , Depression/etiology , Female , Humans , Mental Fatigue/drug therapy , Mental Fatigue/etiology , Pain/drug therapy , Pain/etiology , Physical Examination , Registries , Severity of Illness Index , Sjogren's Syndrome/drug therapy , Sjogren's Syndrome/psychology , United Kingdom/epidemiology
7.
Physiol Behav ; 204: 41-48, 2019 05 15.
Article in English | MEDLINE | ID: mdl-30742838

ABSTRACT

PURPOSE: To verify whether caffeine (CAF) could increase the prefrontal cortex (PFC) activation and improve 20 km cycling time trial (TT20km) performance in mentally fatigued cyclists. METHODS: After preliminary TT20km, twelve recreational cyclists (VO2MAX of 58.9 ±â€¯6.2 mL kg min-1) performed a familiarization with a cognitive test to induce mental fatigue (MF) and psychological scales. Thereafter, they performed: 2) a baseline TT20km; 3) a mentally fatigued TT20km (MF); 4 and 5) a mentally fatigued TT20km after CAF (MF + CAF) or placebo (MF + PLA) ingestion, in a double-blind, counterbalanced design. Performance and psychological responses were obtained throughout the TT20km, while PFC electroencephalography (EEG) theta wave was obtained before and after the mental fatigue test. RESULTS: The mental fatigue-induced increase in EEG theta wave (↑ ~ 4.8%) was reverted with CAF (↓ 8.8%) and PLA ingestion (↓ 4.8%). CAF improved TT20km performance in mentally fatigued cyclists by reducing time (p = .00; ↓ ~ 1.7%) and increasing WMEAN (p = .00; ↑ ~ 3.6%), when compared to MF + PLA. The RPE-power output ratio was lower (p = .01), but affect (p = .018), motivation (p = .033) and emotional arousal (p = .001) were greater throughout the TT20km in MF + CAF than in MF + PLA. CONCLUSIONS: CAF ingestion improved TT20km performance and psychological responses in mentally fatigued cyclists, despite the unaltered PFC activation.


Subject(s)
Athletic Performance , Bicycling , Caffeine/pharmacology , Central Nervous System Stimulants/pharmacology , Mental Fatigue/drug therapy , Mental Fatigue/psychology , Prefrontal Cortex/drug effects , Adult , Arousal/drug effects , Cognition/drug effects , Double-Blind Method , Electroencephalography/drug effects , Humans , Male , Motivation/drug effects , Physical Endurance , Theta Rhythm/drug effects
8.
Nutrients ; 10(3)2018 Feb 28.
Article in English | MEDLINE | ID: mdl-29495607

ABSTRACT

Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS), strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively). Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH)) and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people.


Subject(s)
Antioxidants/administration & dosage , Dietary Supplements , Dioxoles/administration & dosage , Lignans/administration & dosage , Mental Fatigue/drug therapy , Oxidative Stress/drug effects , Adult , Antioxidants/adverse effects , Biomarkers/blood , Cross-Over Studies , Dietary Supplements/adverse effects , Dioxoles/adverse effects , Double-Blind Method , Female , Health Status , Humans , Japan , Lignans/adverse effects , Lipid Peroxidation/drug effects , Male , Mental Fatigue/diagnosis , Mental Fatigue/physiopathology , Mental Fatigue/psychology , Mental Health , Middle Aged , Neuropsychological Tests , Phosphatidylcholines/blood , Recovery of Function , Surveys and Questionnaires , Time Factors , Treatment Outcome , Xanthophylls/administration & dosage , Xanthophylls/adverse effects
10.
Acta Neuropsychiatr ; 30(3): 148-157, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29212562

ABSTRACT

OBJECTIVE: The monoaminergic stabiliser (-)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome. METHODS: A total of 62 patients were randomly assigned to placebo or (-)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks. RESULTS: MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (-)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1-0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (-)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment. CONCLUSION: (-)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (-)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.


Subject(s)
Antidepressive Agents/pharmacology , Depression/drug therapy , Dopamine Agents/pharmacology , Fatigue Syndrome, Chronic/drug therapy , Mental Fatigue/drug therapy , Outcome Assessment, Health Care/methods , Piperidines/pharmacology , Adult , Combined Modality Therapy , Depression/physiopathology , Dopamine Agents/administration & dosage , Dose-Response Relationship, Drug , Fatigue Syndrome, Chronic/physiopathology , Female , Follow-Up Studies , Humans , Male , Mental Fatigue/physiopathology , Middle Aged , Piperidines/administration & dosage
11.
Psychopharmacology (Berl) ; 235(4): 947-958, 2018 04.
Article in English | MEDLINE | ID: mdl-29247343

ABSTRACT

INTRODUCTION: Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity that has negative implications on many aspects in daily life. Caffeine and carbohydrate ingestion have been shown to be able to reduce these negative effects of mental fatigue. Intake of these substances might however be less desirable in some situations (e.g., restricted caloric intake, Ramadan). Rinsing caffeine or glucose within the mouth has already been shown to improve exercise performance. Therefore, we sought to evaluate the effect of frequent caffeine-maltodextrin (CAF-MALT) mouth rinsing on mental fatigue induced by a prolonged cognitive task. METHODS: Ten males (age 23 ± 2 years, physical activity 7.3 ± 4.3 h/week, low CAF users) performed two trials. Participants first completed a Flanker task (3 min), then performed a 90-min mentally fatiguing task (Stroop task), followed by another Flanker task. Before the start and after each 12.5% of the Stroop task (eight blocks), subjects received a CAF-MALT mouth rinse (MR: 0.3 g/25 ml CAF: 1.6g/25 ml MALT) or placebo (PLAC: 25 ml artificial saliva). RESULTS: Self-reported mental fatigue was lower in MR (p = 0.017) compared to PLAC. Normalized accuracy (accuracy first block = 100%) was higher in the last block of the Stroop in MR (p = 0.032) compared to PLAC. P2 amplitude in the dorsolateral prefrontal cortex (DLPFC) decreased over time only in PLAC (p = 0.017). CONCLUSION: Frequent mouth rinsing during a prolonged and demanding cognitive task reduces mental fatigue compared to mouth rinsing with artificial saliva.


Subject(s)
Caffeine/administration & dosage , Mental Fatigue/drug therapy , Mouthwashes/administration & dosage , Polysaccharides/administration & dosage , Prefrontal Cortex/drug effects , Stroop Test , Adult , Central Nervous System Stimulants/administration & dosage , Double-Blind Method , Electroencephalography/drug effects , Electroencephalography/methods , Follow-Up Studies , Humans , Male , Mental Fatigue/diagnosis , Mental Fatigue/psychology , Prefrontal Cortex/physiology , Reaction Time/drug effects , Reaction Time/physiology , Young Adult
12.
Magy Onkol ; 61(3): 276-283, 2017 Sep 20.
Article in Hungarian | MEDLINE | ID: mdl-28931101

ABSTRACT

Unfortunately there have been no positive changes in the main indicators of cancer incidence in Hungarian population since the turn of the millennium. The main goal of psycho-oncologic treatment is to provide the highest possible quality of life to the patient. The prevalence of mental disorders in cancer patients is high and it is accompanied by a rather small number of qualified staff. Thus, the remedy might be the identification of high-risk patients, i.e. the systematic psycho-oncologic screening. Hungary is still lacking a unified screening method that involves all oncologic treatment-providing units. Compiling the Hungarian standards for the Distress Thermometer and the Problem List is the first step of a complex program for creating a general psycho-oncologic screening. Such a comprehensive program might improve oncologic patient-care and, eventually, the quality and prospect of the lives of patients.


Subject(s)
Early Diagnosis , Mental Disorders/drug therapy , Mental Fatigue/drug therapy , Neoplasms/psychology , Psycho-Oncology/organization & administration , Stress, Psychological/drug therapy , Antidepressive Agents/therapeutic use , Humans , Hungary , Mental Disorders/diagnosis , Mental Disorders/etiology , Mental Fatigue/etiology , Mental Health Services/statistics & numerical data , Neoplasms/diagnosis , Neoplasms/therapy , Program Evaluation , Psychotherapy/organization & administration , Risk Assessment , Severity of Illness Index , Stress, Psychological/etiology , Treatment Outcome
13.
Medicine (Baltimore) ; 96(25): e6960, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28640076

ABSTRACT

BACKGROUND: This study aimed to evaluate the effect of methylphenidate for treating mental sequelae after traumatic brain injury (TBI). METHODS: Thirty-six patients with TBI were randomly divided into the intervention group and placebo group. The participants in the intervention group received methylphenidate, while subjects in the placebo group were administered a placebo. This study was conducted from January 2014 to December 2016. The outcome measurements included Mental Fatigue Scale, Choice Reaction Time, Compensatory Tracking Task, Mental Arithmetic Test, Digit Symbol Substitution Test, Mini-Mental State Examination (MMSE), Beck Depression Inventory (BDI), and Hamilton Rating Scale for Depression. In addition, safety was also recorded and assessed. RESULTS: A total of 33 subjects completed the study. Methylphenidate showed greater efficacy than placebo, with decreased scores on the Mental Fatigue Scale, Choice Reaction Time, and Compensatory Tracking Task in the intervention group compared to the placebo group (P < .01, respectively). Furthermore, increased scores on the Mental Arithmetic Test, Digit Symbol Substitution Test, and MMSE in the intervention group, compared to those in the placebo group (P < .01 respectively), were observed. In addition, a significant difference in the scores on the BDI (P = .04) and Hamilton Rating Scale for Depression (P = .005) was observed between the 2 groups. The safety at the end of the 30 week-treatment was similar between the 2 groups (P > .05). CONCLUSION: The results of this study demonstrated that methylphenidate could effectively improve mental fatigue and cognitive functions in patients with TBI.


Subject(s)
Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/psychology , Cognition Disorders/drug therapy , Mental Fatigue/drug therapy , Methylphenidate/therapeutic use , Psychotropic Drugs/therapeutic use , Adult , Brain Injuries, Traumatic/complications , Cognition Disorders/etiology , Depression/drug therapy , Depression/etiology , Double-Blind Method , Female , Humans , Male , Mathematical Concepts , Mental Fatigue/etiology , Mental Status Schedule , Neuropsychological Tests , Psychiatric Status Rating Scales , Treatment Outcome
14.
Contemp Clin Trials ; 58: 47-57, 2017 07.
Article in English | MEDLINE | ID: mdl-28479217

ABSTRACT

BACKGROUND: The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation. METHODS: Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg-1∙d-1; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state. DISCUSSION: The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding. TRIAL REGISTRATION: NCT02734238.


Subject(s)
Androgens/pharmacology , Energy Metabolism/drug effects , Mental Fatigue/drug therapy , Military Personnel , Muscle, Skeletal/drug effects , Testosterone/analogs & derivatives , Adolescent , Adult , Appetite , Biomarkers , Body Mass Index , Body Weights and Measures , Cognition/drug effects , Exercise , Gastrointestinal Microbiome/physiology , Humans , Male , Muscle, Skeletal/physiology , Personality Assessment , Research Design , Sleep/drug effects , Testosterone/pharmacology , Young Adult
15.
Dev Neuropsychol ; 42(2): 93-103, 2017.
Article in English | MEDLINE | ID: mdl-28452602

ABSTRACT

This study examined the feasibility of Enzogenol® as a potential treatment modality for concussed individuals with residual symptoms in the chronic phase. Forty-two student-athletes with history of sport-related concussion were enrolled, comparing Enzogenol® versus placebo. Testing was conducted using virtual reality (VR) and electroencephalography (EEG), with neuropsychological (NP) tasks primarily used to induce cognitive challenges. After six weeks, the Enzogenol® group showed enhanced frontal-midline theta, and decreased parietal theta power, indicating reduced mental fatigue. Subjects enrolled in the Enzogenol® group also self-reported reduced mental fatigue and sleep problems. This suggests that Enzogenol® has the potential to improve brain functioning in the chronic phase of concussion.


Subject(s)
Athletic Injuries/drug therapy , Brain Concussion/drug therapy , Cognition/drug effects , Executive Function/drug effects , Flavonoids/therapeutic use , Postural Balance/drug effects , Quercetin/analogs & derivatives , Adolescent , Athletes , Athletic Injuries/diagnosis , Athletic Injuries/psychology , Brain Concussion/diagnosis , Brain Concussion/psychology , Electroencephalography , Female , Flavonoids/pharmacology , Humans , Male , Mental Fatigue/drug therapy , Mental Fatigue/psychology , Neuropsychological Tests , Quercetin/pharmacology , Quercetin/therapeutic use , Sleep/drug effects , Young Adult
16.
Mult Scler Relat Disord ; 11: 4-9, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28104253

ABSTRACT

BACKGROUND: Cognitive fatigue (CF) is a common complaint in persons with MS (PwMS). Fampridine-SR improves ambulation, fatigue and endurance, due to enhancing action potential formation by blocking potassium channels in demyelinated axons. Thus, through this same mechanism, it is hypothesized that Fampridine-SR could improve CF. OBJECTIVE: To determine if Fampridine-SR objectively improves CF in PwMS. METHODS: Sixty PwMS of any type with CF, defined as 3 or less correct responses when comparing the last third to the first third on the Paced Auditory Serial Addition Test (PASAT), were recruited from a tertiary care MS clinic in London (ON) Canada. Subjects also had to be between 18 and 64 years of age, inclusive, not had a relapse in the last 60 days or corticosteroids in the last 30 days, EDSS 0.0-7.0, and no other diagnosis that could cause cognitive impairment. A randomized double blind crossover design was used: subjects were randomized to either placebo or Fampridine-SR for 4 weeks, then after at least a one week washout, received the opposite treatment. Subjects were assessed before and after each treatment block. The primary outcome was the PASAT CF score after treatment with Fampridine-SR compared to placebo. T-tests and chi-square were used to compare demographics between the two groups (placebo-Fampridine-SR vs. Fampridine SR-placebo). Treatment effects were assessed using factorial ANOVA, with treatment (Fampridine-SR vs. placebo) and time (before and after treatment) as within-subject variables. RESULTS: Of the 60 subjects randomized, 48 completed the study; three were removed due to an adverse event while in the treatment arm (one due to relapse while on placebo, one due to urinary retention and one due to dizziness and headache while on Fampridine-SR). The subjects had a mean age of 46.5±10.0 years, education of 13.6±1.9 years, and were diagnosed with MS 10.6±9.6 years ago. The majority were female (46, 76.7%), had relapsing remitting MS (41, 68.3%) with median EDSS of 3.5 (range 1.0-7.0). There were no significant demographic differences between the two groups. The treatment x time interaction within the factorial ANOVA on PASAT CF scores was statistically significant, F(1, 45)=8.28, p=0.006, suggesting there is a difference between the treatments (placebo vs. Fampridine-SR), over the course of the study. An evaluation of the mean scores suggests, however, that subjects saw a greater improvement when they were given the placebo, than when they were given the active medication. Similarly, individuals showed a greater increase in their information processing speed (as measured by the PASAT) over the course of treatment when they were given the placebo, as compared with the active medication F(1,45)=4.17, p=0.047. CONCLUSION: Although this small pilot study does not suggest that Fampridine-SR results in a statistically significant improvement of CF in MS patients, as compared to placebo, individuals demonstrated an improvement in both information processing speed and CF, suggesting further studies are warranted.


Subject(s)
4-Aminopyridine/therapeutic use , Mental Fatigue/drug therapy , Multiple Sclerosis/drug therapy , Multiple Sclerosis/psychology , Potassium Channel Blockers/therapeutic use , Adolescent , Adult , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Mental Fatigue/complications , Middle Aged , Multiple Sclerosis/complications , Treatment Outcome , Young Adult
17.
Acta Neurol Scand ; 135(1): 100-107, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26991608

ABSTRACT

OBJECTIVES: Traumatic brain injury (TBI) may cause long-lasting post-concussive symptoms, such as mental fatigue and concentration difficulties, and this may become the main hindrance for returning to work and studies. There is currently no effective treatment for long-lasting mental fatigue. In this hypothesis generating study, the long-term effects of methylphenidate on mental fatigue, cognitive function, and safety were assessed. MATERIALS & METHODS: Thirty participants who suffered from long-term post-concussion symptoms after a mild TBI or moderate TBI and who had reported positive effects with methylphenidate during an initial phase of this follow-up study were treated with methylphenidate for a further six months. RESULTS: After six-month follow-up, effects on Mental Fatigue Scale (MFS), depression, anxiety, and cognitive function (processing speed, attention, working memory) were significantly improved compared to baseline data (P < 0.001, respectively). Heart rate was significantly increased (P = 0.01), while blood pressure was not changed. CONCLUSIONS: Individuals suffering from prolonged symptoms after TBI reported reduced mental fatigue and improved cognitive functions with long-term methylphenidate treatment. It is suggested that methylphenidate can be a treatment option for long-term mental fatigue and cognitive impairment after a TBI, but further randomized control research is warranted.


Subject(s)
Brain Injuries, Traumatic/drug therapy , Central Nervous System Stimulants/therapeutic use , Mental Fatigue/drug therapy , Methylphenidate/therapeutic use , Post-Concussion Syndrome/drug therapy , Adult , Attention , Brain Injuries, Traumatic/complications , Central Nervous System Stimulants/adverse effects , Cognition , Female , Humans , Male , Memory, Short-Term , Mental Fatigue/etiology , Methylphenidate/adverse effects , Middle Aged , Post-Concussion Syndrome/etiology
18.
Int J Food Sci Nutr ; 67(2): 203-6, 2016.
Article in English | MEDLINE | ID: mdl-26888417

ABSTRACT

Spirulina may increase people's ability to resist mental and physical fatigue. This study tested that hypothesis in a randomized, double blinded, placebo controlled study in men. After 1 week, a 3 g/day dose of spirulina produced a small, but statistically significant increase in exercise output (Kcals consumed in 30 min exercise on a cross trainer machine). A mathematical based mental fatigue test showed improved performance 4 h after the first time of supplementation as well as 8 weeks later. Similarly, a subjective survey for a sense of physical and mental fatigue showed improvement within 4 h of the first supplementation as well as 8 weeks later. These results show that spirulina intake can affect fatigue in men.


Subject(s)
Dietary Supplements , Fatigue/drug therapy , Mental Fatigue/drug therapy , Spirulina , Adult , Double-Blind Method , Exercise , Humans , Male
19.
Physiol Behav ; 151: 629-37, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-26320858

ABSTRACT

During education and early career, young adults often face examinations and assessment centers. Coffee and energy drinks are convenient and commonly used to enhance or maintain performance in these situations. Whether these macronutrients improve performance in a demanding and drawn-out multi-task situation is not clear. Using double-blind, placebo-controlled studies, we set out to examine the effects of caffeine and glucose in an assessment center-like situation, under natural consumption conditions, in a group of young adults who were heterogeneous with respect to consumption patterns. We measured multi-task performance including logical thinking, processing speed, numeric and verbal memory, attention and the ability to concentrate, and mood over a two-hour period. Caffeine and glucose were administered in common beverages with appropriate placebo controls allowing the assessment of psychological effects of expectancy. Importantly, and in contrast to most previous studies, participants retained their habitual caffeine and sugar intake (studies 1 and 2) as this represents common behavior. Based on the bulk of literature, we hypothesized that (i) caffeine enhances attentional performance and mood, while performance in more complex tasks will remain unchanged, and that (ii) glucose enhances performance on memory tasks accompanied with negative mood. Our results provide evidence that neither caffeine nor glucose significantly influence cognitive performance when compared with placebo, water, or no treatment controls in a multi-task setting. Yet, caffeine and, by trend, placebo improve dispositions such that participants perceive preserved mental energy throughout the test procedure. These subjective effects were stronger after 24 h caffeine abstinence (study 3). Future studies will have to address whether these mood changes actually result in increased motivation during a challenging task.


Subject(s)
Affect/drug effects , Caffeine/administration & dosage , Glucose/administration & dosage , Mental Processes/drug effects , Self Concept , Adult , Affect/physiology , Double-Blind Method , Drinking Water/administration & dosage , Feeding Behavior , Humans , Male , Mental Fatigue/drug therapy , Mental Fatigue/metabolism , Mental Processes/physiology , Psychological Tests , Smoking , Young Adult
20.
Brain Inj ; 29(6): 758-65, 2015.
Article in English | MEDLINE | ID: mdl-25794299

ABSTRACT

OBJECTIVE: Post-traumatic brain injury symptoms, such as mental fatigue, have considerable negative impacts on quality-of-life. In the present study the effects of methylphenidate in two different dosages were assessed with regard to mental fatigue, pain and cognitive functions in persons who had suffered a traumatic brain injury. METHODS: Fifty-one subjects were included and 44 completed the study. The treatment continued for 12 weeks, including three treatment periods with no medication for 4 weeks, administration of low dose methylphenidate (up to 5 mg × 3) for 4 weeks and normal dose methylphenidate (up to 20 mg × 3) for a further 4 weeks. The patients were randomized into three groups where all groups were given all treatments. RESULTS: Significantly reduced mental fatigue, assessed with the Mental Fatigue Scale (MFS) and increased information processing speed (coding, WAIS-III), were detected. The SF-36 vitality and social functioning scales were also improved significantly. Pain was not reduced by methylphenidate. The positive effects of treatment were dose-dependent, with the most prominent effects being at 60 mg methylphenidate/day spread over three doses. Observed side-effects were increased blood pressure and increased heart rate. CONCLUSIONS: Methylphenidate was generally well-tolerated and it improved long-lasting mental fatigue and processing speed after traumatic brain injury.


Subject(s)
Brain Injuries/drug therapy , Mental Fatigue/drug therapy , Methylphenidate/therapeutic use , Adult , Brain Injuries/psychology , Cognition/drug effects , Dose-Response Relationship, Drug , Female , Humans , Male , Mental Fatigue/psychology , Middle Aged , Pain/drug therapy , Treatment Outcome
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