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Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study.
Pedersen, M, Asprusten, TT, Godang, K, Leegaard, TM, Osnes, LT, Skovlund, E, Tjade, T, Øie, MG, Wyller, VBB
Brain, behavior, and immunity. 2019;75:94-100
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Chronic fatigue is defined as substantial fatigue lasting for more than six months. The main aim of this study is to investigate predictors of chronic fatigue six months after an acute Epstein-Barr virus (EBV) infection. This study includes the prospective results from the first six months of the CEBA project (chronic fatigue following acute Epstein-Barr virus infection in adolescents), which encompasses a prospective, a cross-sectional and a randomized controlled design with a total follow-up time of 21 months. A total of 200 adolescents with EBV and 70 healthy controls were included. Results indicate that fatigue six months after acute EBV infection is significantly and independently predicted by baseline clinical symptoms, functional impairments, negative emotions, verbal memory, plasma c-reactive protein (CRP) and plasma vitamin B12. On average, baseline CRP levels were significantly lower in the acute EBV infection group as compared to healthy controls. Authors conclude that development of fatigue is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes.
Abstract
INTRODUCTION Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection. MATERIALS AND METHODS A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09-1.6]), pain severity (0.2[0.02-0.3]), functional impairment (1000 steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2-0.6]), verbal memory (correct word recognition) (1.7[0.1-3.3]), plasma C-reactive protein (2.8[1.1-4.4] for CRP values >0.86) and plasma Vitamin B12 (-0.005[-0.01 to -0.001]). CONCLUSIONS Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes. TRIAL REGISTRATION ClinicalTrials, ID: NCT02335437, https://clinicaltrials.gov/ct2/show/NCT02335437.
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Dietary Diversity Was Positively Associated with Psychological Resilience among Elders: A Population-Based Study.
Yin, Z, Brasher, MS, Kraus, VB, Lv, Y, Shi, X, Zeng, Y
Nutrients. 2019;11(3)
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There's a growing interest by researchers in the relationship between the diversity of people's diets and their health, including their psychological resilience. This study looked at the associations between dietary diversity (DD) and psychological resilience in 8571 elderly individuals in China. Frequency and variety of food groups was collected in order to produce an average (mean) DD score. The psychological resilience of participants was assessed using a validated research tool known as "simplified resilience score" (SRS). The statistical analysis of the data collected showed that those elders with the poorest psychological resilience scores were also eating the least diverse diets. Based on separate analyses by age group, the association of a low SRS with poor DD was more prominent in the younger elderly than the oldest old. Compared with younger participants with good DD, the risk of a low SRS was greater for younger participants with poor DD, the oldest old with good DD, and the oldest old with poor DD, with OR respectively. The greatest contribution to DD was from a high consumption of vegetables, fruits, and nuts. Our study suggested that poor DD was associated with a low psychological resilience among the Chinese elderly, especially the younger elderly. These findings suggest that eating a diet rich in a variety of vegetables, fruits, and nuts might promote psychological resilience.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dietary polyphenols abundant in fruits, vegetables and nuts have been associated with improved psychological resilience.
- Healthcare practitioners working on the dietary diversity of their clients should focus attention on these phenolic-rich foods in the interests of psychological resilience.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This is a population-based study involving 8571 community-based elderly individuals, where dietary diversity (DD) was assessed by means of food frequency questionnaires, and correlated with psychological resilience, assessed by a validated simplified resilience score (SRS). Low DD has been previously correlated with a high level of oxidative stress mediating oxidative damage to mitochondria and lipids in neuronal circuits, as seen in affective (anxiety, depression) and neurodegenerative conditions (Alzheimer's and Parkinson's Diseases). Conversely, dietary polyphenols, a group of phenolic compounds abundant in fruits, vegetables, and other plant sources, have been associated with improved psychological resilience.
Clinical practice applications:
The greatest contribution to dietary diversity from the totality of food groups was from a high consumption of vegetables, fruits, and nuts. This can help nutrition practitioners inform their clinical decisions when supporting individuals wanting to improve the diversity of their diet.
Considerations for future research:
Future work is necessary to further assess these findings in longitudinal studies and clinical trials, and to ascertain what the mechanisms of action are in this process. It would be particularly interesting to find out whether the gut microbiota and its communication with the brain via the gut-brain axis is part of the process.
Abstract
The association between dietary diversity (DD) and psychological resilience among older people is an underdeveloped area of research. This cross-sectional study explored the associations of DD with psychological resilience among 8571 community-based elderly individuals. The intake frequencies of food groups were collected, and dietary diversity was assessed based on the mean DD score. Psychological resilience was assessed using a simplified resilience score (SRS). Data were analyzed using multiple linear regression and logistic regression models. Poor DD was significantly associated with psychological resilience, with a β (95% CI) of -0.94 (-1.07, -0.81) for the SRS (p < 0.01) and an odds ratio (95% CI) of 1.83 (1.66, 2.01) for low SRS status. The interaction effects of age with DD were observed for the SRS (p < 0.001) and low SRS status (p < 0.001). Based on separate analyses by age group, the association of a low SRS with poor DD was more prominent in the younger elderly than the oldest old, with OR (95% CI) 2.32 (1.96, 2.74) and 1.61 (1.43, 1.82), respectively. Compared with younger participants with good DD, the risk of a low SRS was greater for younger participants with poor DD, the oldest old with good DD, and the oldest old with poor DD, with OR (95% CI) 2.39 (2.02, 2.81), 1.28 (1.09, 1.51), and 2.03 (1.72, 2.39), respectively. The greatest contribution to DD was from a high consumption of vegetables, fruits, and nuts. Our study suggested that poor DD was associated with a low psychological resilience among the Chinese elderly, especially the younger elderly. These findings suggest that augmentation of DD might promote psychological resilience.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
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Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial.
de Oliveira, IJ, de Souza, VV, Motta, V, Da-Silva, SL
Pakistan journal of biological sciences : PJBS. 2015;18(1):11-8
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Vitamin C (ascorbic acid) is a well known anti-oxidant that has been studied in relation to anxious behaviour triggered by stressful situations. This study set out to examine the effects of vitamin C (50mg per day) or placebo on 42 high school students in a double-blind, randomised, placebo controlled trial. Levels of anxiety were measured before and after a 14 day supplementation of vitamin C or placebo using the Beck Anxiety Inventory. Plasma levels of vitamin C, heart rate and blood pressure were also measured. The results showed vitamin C supplementation reduced anxiety levels and increased plasma vitamin C levels. There was also a significant decrease in heart rate. There was no significant difference in blood pressure. The study concluded that vitamin C has a therapeutic affect on reducing anxiety levels. It was recommend high schools implement nutritional programs high in antioxidants such as vitamin C to reduce anxiety and improve academic performance.
Abstract
Vitamin C ascorbic acid) is a well-known antioxidant that is involved in anxiety, stress, depression, fatigue and mood state in humans. Studies have suggested that oxidative stress may trigger neuropsychological disorders. Antioxidants may play an important therapeutic role in combating the damage caused by oxidative stress in individuals that suffer from anxiety. In this context, it was hypothesized that oral vitamin C supplementation would reduce anxiety. However, few up to date studies have evaluated the consequences of oral vitamin C supplementation on anxiety in humans. The present study examined the effects of oral vitamin C supplements in 42 high school students, in a randomized, double-blind, placebo-controlled trial. The students were given either vitamin C (500 mg day(-1)) or placebo. Plasma concentrations of vitamin C and blood pressure were measured before the intervention and then one day after the intervention. Anxiety levels were evaluated for each student before and after 14 days following supplementation with the Beck Anxiety Inventory. Results showed that vitamin C reduced anxiety levels and led to higher plasma vitamin C concentration compared to the placebo. The mean heart rates were also significantly different between vitamin C group and placebo control group. Present study results not only provide evidence that vitamin C plays an important therapeutic role for anxiety but also point a possible use for antioxidants in the prevention or reduction of anxiety. This suggests that a diet rich in vitamin C may be an effective adjunct to medical and psychological treatment of anxiety and improve academic performance.
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Reversal of cognitive decline: a novel therapeutic program.
Bredesen, DE
Aging. 2014;6(9):707-17
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Alzheimer’s Disease (AD) is estimated to affect 30 million individuals globally, with projections as high as 150 million by 2050 if no effective treatment is found. This report describes a personalised, multi-modal, therapeutic programme used with 10 individuals with various degrees of cognitive decline. The goal was to optimise metabolic parameters and lifestyle factors and was personalised based on laboratory test results. 9 out of 10 of the case study patients experienced improvement in cognitive abilities, beginning within 3-6 months of starting the programme. These effects were sustained at 2.5 year follow up. The 1 patient who did not benefit had advanced AD, in comparison to the other patients with subjective or mild cognitive decline. The authors call for a more extensive trial of the therapeutic programme.
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.