The Effects of Epigallocatechin-3-Gallate Nutritional Supplementation in the Management of Multiple Sclerosis: A Systematic Review of Clinical Trials.

Multiple sclerosis (MS) is a chronic, debilitating neurological condition for which current treatments often focus on managing symptoms without curing the underlying disease. Recent studies have suggested that dietary supplements could potentially modify disease progression and enhance quality of life. This systematic review aims to evaluate the efficacy and safety of epigallocatechin-3-gallate (EGCG) as a dietary supplement in patients with MS, with a specific focus on its impact on disease progression, symptom management, and overall quality of life. We conducted a comprehensive systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing an exhaustive search across the databases PubMed, Scopus, and Web of Science up to 23 February 2024. Eligible studies were randomized controlled trials. Nine clinical trials involving 318 participants were analyzed, with dosages ranging from 600 mg to 1200 mg of EGCG daily, although most studies had only a 4-month follow-up period. Results indicated that EGCG supplementation, particularly when combined with coconut oil, led to significant improvements in metabolic health markers and functional abilities such as gait speed and balance. One trial observed significant improvements in the Berg balance scale score from an average of 49 to 52 after four months of treatment with 800 mg of EGCG daily. Additionally, interleukin-6 levels significantly decreased, suggesting anti-inflammatory effects. Measures of quality of life such as the Beck Depression Inventory (BDI) scale showed significant improvements after EGCG supplementation. However, primary outcomes like disease progression measured by the Expanded Disability Status Scale (EDSS) and Magnetic Resonance Imaging (MRI) of lesion activities showed minimal or no significant changes across most studies. EGCG supplementation appears to provide certain symptomatic and functional benefits in MS patients, particularly in terms of metabolic health and physical functionality. However, it does not significantly impact the primary disease progression markers such as EDSS scores and MRI lesions. These findings underscore the potential of EGCG as a supportive treatment in MS management, though its role in altering disease progression remains unclear. Future research should focus on long-term effects and optimal dosing to further elucidate its therapeutic potential.

Feasibility of a co-designed online nutrition education program for people with multiple sclerosis.

OBJECTIVE: Diet quality is important for people with multiple sclerosis (MS), but conflicting online information causes them confusion. People with MS want evidence-based MS-specific information to help them make healthy dietary changes, and we co-designed an asynchronous, online nutrition education program (Eating Well with MS) with the MS community. Our aim was to determine the feasibility of Eating Well with MS. METHODS: We used a single-arm pre-post design. The feasibility trial was a nine-week intervention with adults with confirmed MS. Feasibility outcomes: 1) demand (recruitment); 2) practicality (completion); 3) acceptability (Intrinsic Motivation Inventory: interest/enjoyment and value/usefulness subscales); and 4) limited efficacy testing (Diet Habits Questionnaire (DHQ); Critical Nutrition Literacy Tool (CNLT); Food Literacy Behaviour Checklist (FLBC), using intention-to-treat analysis). RESULTS: Recruitment (n = 70) exceeded the target (n = 48) within six weeks. Of the 70 enrolled, 84 % completed at least one module and 54 % completed the full program (five modules). The median interest/enjoyment rating was 5 out of 7 and median value/usefulness rating was 6 out of 7 (where 7 = 'very true'). Compared to pre-intervention, DHQ, CNLT, and FLBC scores all statistically significantly improved post-intervention. CONCLUSION: Eating Well with MS was well received by the MS community and improved their dietary behaviours; demonstrating feasibility. Our findings support the use of co-design methods when developing resources to improve dietary behaviours.

Web scraping of user-simulated online nutrition information for people with multiple sclerosis.

BACKGROUND: People diagnosed with multiple sclerosis (MS) often seek to modify their diet guided by online advice, however this advice may not align with national dietary guidelines. The aim of this study was to simulate an online search for dietary advice conducted by a person with MS and evaluate the content. It was hypothesised that a variety of eating patterns are promoted for MS online and these dietary approaches can be contradictory. METHODS: An online search was simulated using Google Trends-informed search terms and Google and Bing search engines. URLs were extracted using R. Nutrition data were extracted including recommendations for diets, foods, supplements, and health professional consultation. Statistical analyses were conducted using R. RESULTS: 73 URLs from 49 websites were extracted, with only 14 results common to both search engines. Dietary recommendations included overall eating patterns (58 webpages, 79%), individual foods (55 webpages, 75%), and supplements (33 webpages, 45%). The most promoted eating pattern for MS was a balanced diet (33 recommendations, 48%), more likely by nonprofit organisations and health information websites (14 and 17 recommendations, 100% and 89%); lifestyle program websites were more likely to recommend restrictive diets (19 recommendations, 100%) (p<0.001). 52% pages advised consulting a health professional, most often a doctor or dietitian. CONCLUSION: A balanced diet is the most recommended eating pattern for MS online, though advice promoting restrictive diets persists.

Functional outcomes of diets in multiple sclerosis (FOOD for MS): Protocol for a parallel arm randomized feeding trial for low glycemic load and calorie restriction.

BACKGROUND: Pilot trials indicate that both a low glycemic load (GL) diet and calorie restriction (CR) can be implemented successfully in people with multiple sclerosis (pMS) and may improve MS symptoms and physical function, but large randomized clinical trials (RCTs) have not yet been conducted. The purpose of this study is to test these interventions alone and in combination to determine their efficacy for improving clinical and patient reported outcomes (PROs) in pMS. METHODS: This 32-week, two-arm, RCT at two centers will randomly assign 100 adults with relapsing-remitting or secondary progressive MS to a low GL diet (n = 50) or a standard GL diet (n = 50). Both diet groups will complete two study phases: a eucaloric phase (16 weeks) and a CR phase (16 weeks). Groceries for the study meal plans will be delivered to participants' homes weekly. The primary outcome is physical function, measured by timed 25-ft walk test. Secondary outcomes are pain, fatigue, mood, and anxiety. DISCUSSION: This will be the most rigorous intervention trial to date of a low GL diet and CR in adults with MS, and among the first to assess the impact of intentional weight loss on MS symptoms. Results will provide valuable insight for recommending dietary change, weight loss, or both to adults with MS. These non-drug interventions pose few risks and have potential to yield significant improvements in MS symptoms. TRIAL REGISTRATION ID: NCT05327322.

Dietary Modification Combined with Nutrition Education and Counseling for Metabolic Comorbidities in Multiple Sclerosis: Implications for Clinical Practice and Research.

PURPOSE OF REVIEW: Metabolic comorbidities such as obesity, diabetes, hypertension, and dyslipidemia are common to multiple sclerosis (MS) and are associated with negative outcomes of the disease. Dietary intervention has the potential to improve MS co-morbidities; thus, it is a high priority for people living with MS to self-manage their disease. The present review aimed to summarize the recent evidence on the impacts of combining dietary modification with nutrition education and counseling on managing metabolic comorbidity markers in MS. RECENT FINDINGS: Evidence suggests important roles for tailored dietary change strategies and nutrition education and counseling in managing metabolic comorbidities for MS. There is also indirect evidence suggesting a relationship between dietary fiber, the gut microbiome, and improved metabolic markers in MS, highlighting the need for more research in this area. For people living with MS, addressing both barriers and facilitators to dietary changes through behavior change techniques can help them achieve sustainable and tailored dietary behavior changes. This will support person-centered care, ultimately improving metabolic comorbidity outcomes. Metabolic comorbidities in MS are considered modifiable diseases that can be prevented and managed by changes in dietary behavior. However, the impact of targeted dietary interventions on mitigating MS-related metabolic comorbidities remains inadequately explored. Therefore, this review has provided insights into recommendations to inform future best practices in MS. Further well-designed studies based on tailored dietary strategies applying behavior change theories are needed to address the underlying determinants of dietary practice in this population.

Diet and omega-3 and vitamin D supplement use predict five-year fatigue and disability trajectories in people with multiple sclerosis.

BACKGROUND: Fatigue and disability are indicators of disease progression experienced by many people with multiple sclerosis (pwMS). Understanding trajectories of these outcomes, and their predictors, may provide insight to potential interventions for MS management. METHODS: Survey data from 839 pwMS from the Health Outcomes and Lifestyle in pwMS study were analysed. Fatigue was defined as mean Fatigue Severity Scale >5, and severe disability as Patient Determined Disease Steps >5. Group-based trajectory modelling was used to identify fatigue and disability trajectories over five-years. Dietary predictors associated with outcome trajectory group membership were assessed using log-binomial regression. Demographic and clinical characteristics were considered in multivariable models. RESULTS: Distinct trajectories for fatigue and disability were identified. For fatigue, 58 % of pwMS were assigned to low-, and 42 % to high-, fatigue trajectory groups. For disability, 85 % of pwMS were assigned to low-, and 15 % to high-, disability groups. Baseline high-quality diet, and omega-3 and vitamin D supplement use, were associated with reduced risk of being in high-fatigue and high-disability trajectories, while meat and dairy consumption were associated with increased risk. CONCLUSIONS: A high-quality diet, avoiding meat and dairy, and omega-3 and vitamin D supplement use, individually predict better fatigue and disability trajectories. Dietary modifications should be considered in MS management.

Associations between diet and disease progression and symptomatology in multiple sclerosis: A systematic review of observational studies.

BACKGROUND: Although many people with MS (pwMS) modify their diet after diagnosis, there is still no consensus on dietary recommendations for pwMS. A number of observational studies have explored associations of diet and MS progression, but no studies have systematically reviewed the evidence. This systematic review aimed to provide an objective synthesis of the evidence for associations between diet and MS progression, including symptoms and clinical outcomes from observational studies. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic database searches were performed for studies completed up to 26 July 2023 using PubMed (Medline), Web of Science, CINAHL, Embase (Ovid), and Scopus, followed by citation and reference list checking. We included studies using diet quality scores or dietary indices. Studies assessing individual foods, nutrients, or dietary supplements were excluded. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies. RESULTS: Thirty-two studies met the inclusion criteria. Of these, 20 were cross-sectional and 12 prospective. The most frequent outcomes assessed were disability (n = 19), quality of life (n = 12), fatigue (n = 12), depression (n = 9), relapse (n = 8), anxiety (n = 3), and magnetic resonance imaging (MRI) outcomes (n = 4). Based on prospective studies, this review suggests that diet might be associated with quality of life and disability. There were also potential effects of higher diet quality scores on improved fatigue, disability, depression, anxiety, and MRI outcomes but more evidence is needed from prospective studies. CONCLUSIONS: Observational studies show some evidence for an association between diet and MS symptoms, particularly quality of life and disability. However, the impact of diet on other MS outcomes remains inconclusive. Ultimately, our findings suggest more evidence is needed from prospective studies and well-designed tailored intervention studies to confirm associations.

The effect of dietary interventions on inflammatory biomarkers among people with multiple sclerosis: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system, characterized by demyelination and neurodegeneration, which has a profound impact on the quality of life. Dysregulated inflammatory processes are a major driver of MS progression, with many areas of research being dedicated to modulating inflammation in people with MS. Several dietary patterns have been associated with improvements in inflammatory biomarkers; although, the findings have been inconsistent. Thus, this study aims to evaluate the effects of dietary interventions on inflammatory markers in adults with MS. METHODS: Electronic databases, including PubMed/MEDLINE, Web of Science, Scopus, and Cochrane/Central, will be searched. Screening, selection, and extraction of data, along with quality assessment of included studies, will be done by two separate reviewers, and any potential conflicts will be settled through discussion. Two reviewers will independently assess the risk of bias in included studies using the Cochrane Risk of Bias Tool. If plausible, the results will be synthesized and pooled for meta-analysis. The overall quality of evidence of each study will be evaluated using the NutriGRADE tool, which is a modification to the Grading Recommendations Assessment, Development, and Evaluation (GRADE) developed specifically for nutrition research. DISCUSSION: Studies have demonstrated conflicting results regarding the effects of dietary interventions on serum levels of inflammatory biomarkers among people with MS. Thus, it is expected that the planned systematic review and meta-analysis will yield robust evidence on the effects of diet on inflammatory profile in the setting of MS.

Effects of nutrition education given to persons with multiple sclerosis and their families on diet quality and anthropometric and biochemical measurements / Efeito da educação nutricional dada a pessoas com esclerose múltipla e suas famílias em relação a qualidade da dieta, medidas antropométricas e bioquímicas

ABSTRACT Objective: In this study, it was aimed to investigate the effects of nutrition education given to persons with multiple sclerosis and their families on anthropometric and biochemical measurements and diet quality. Methods: Data from 51 persons with multiple sclerosis were analysed in this intervention study. The study was conducted with 3 groups. The education group consisted of only persons with multiple sclerosis, the family education group consisted of persons with multiple sclerosis and a family member living with them, and the control group consisted of persons with multiple sclerosis who had not received an education. Anthropometric and biochemical measurements and dietary quality assessments were made before (T1) and immediately after education (T2) and also 3 months after education (follow-up, T3). Results: The distribution of family education group diet quality scores showed a significant increase from "poor" to "needs improvement" at T3 compared to T1. The upper middle arm circumference measurements of the female control group were decreased at T2 and T3 [from 29.0 (23-34) cm to 28.0 (22-31) cm and to 27.5 (22-31) cm]. Women in family education group, levels of serum haemoglobin and haematocrit were higher than in control group at T2 and T3. Also, men in family education group, levels of alanine aminotransferase were lower than those in education group at follow up. Levels of total cholesterol and low-density lipoprotein cholesterol in education group were higher than those control group at T1, T2, and T3. Conclusion: This study indicates that nutrition education affects some biochemical and anthropometric measurements in persons with multiple sclerosis. Diet quality improved when receiving education together with families.

RESUMO Objetivo: Objetivou-se investigar os efeitos da educação nutricional dada a pessoas com esclerose múltipla e seus familiares, avaliação de medidas antropométricas, bioquímicas e da qualidade da dieta. Métodos: Dados de 51 participantes com esclerose múltipla foram analisados neste estudo de intervenção. O estudo foi dividido em 3 grupos, sendo o primeiro composto por indivíduos que obtiveram educação nutricional, o segundo, composto por indivíduos mais um membro da família que morava com eles e obtiveram educação nutricional, e o terceiro, grupo controle, composto por indivíduos que não obtiveram educação nutricional. Medidas antropométricas, bioquímicas e avaliações da qualidade da dieta foram feitas antes (T1) imediatamente após a educação nutricional (T2) e também 3 meses após a educação nutricional (T3). Resultados: A distribuição dos escores de qualidade da dieta do grupo de educação familiar mostrou um aumento significativo de "ruim" para "precisa melhorar" no T3 em comparação ao T1. As medidas da circunferência do braço médio do grupo controle feminino foram menores em T2 e T3 [de 29,0 (23-34) cm para 28,0 (22-31) cm e para 27,5 (22-31) cm]. Nas mulheres do grupo família, os níveis séricos de hemoglobina e hematocrito foram maiores do que no grupo controle em T2 e T3. Também nos homens do grupo família, os níveis de alanina aminotransferasa foram mais baixos do que os do grupo educação no seguimento. Os níveis de CT e LDL-C no grupo educação foram superiores aos do grupo controle em T1, T2 e T3. Conclusão: Este estudo observou que a educação nutricional afeta algumas medidas bioquímicas antropométricas em pessoas com esclerose múltipla. A qualidade da dieta melhorou quando recebeu educação junto com as famílias.

Intermittent Fasting and the Possible Benefits in Obesity, Diabetes, and Multiple Sclerosis: A Systematic Review of Randomized Clinical Trials.

Intermittent fasting has become popular in recent years and is controversially presented as a possible therapeutic adjunct. A bibliographic review of the literature on intermittent fasting and obesity, diabetes, and multiple sclerosis was carried out. The scientific quality of the methodology and the results obtained were evaluated in pairs. Intermittent fasting has beneficial effects on the lipid profile, and it is associated with weight loss and a modification of the distribution of abdominal fat in people with obesity and type 2 diabetes as well as an improvement in the control of glycemic levels. In patients with multiple sclerosis, the data available are too scarce to draw any firm conclusions, but it does appear that intermittent fasting may be a safe and feasible intervention. However, it is necessary to continue investigating its long-term effects since so far, the studies carried out are small and of short duration.

"I need personal experiences or some sort of documentation": a qualitative study on where people with multiple sclerosis seek information on dietary and herbal supplements.

BACKGROUND: The use of dietary and herbal supplements (DIHES) is widespread among people with multiple sclerosis (PwMS). PwMS are a highly informed patient group, and they use several types of sources to seek information on subjects related to their disease. However, it is still unknown where PwMS seek information about DIHES. It is important that PwMS make decisions about DIHES based on accurate, useful and accessible information. Therefore, the aim of this study was to explore where PwMS seek information on DIHES and how they experience and engage with this information. METHODS: Semi-structured interviews were conducted with eighteen PwMS using DIHES. Participants were selected from a cross-sectional survey. Diversity sampling was used, based on relevant characteristics such as gender and number of DIHES used during the past 12 months. The interviews were conducted face-to-face or over the telephone and lasted between 30 min and 1 hour. The interviews were recorded, transcribed verbatim, and analyzed using thematic network analysis in NVivo 12 Pro software. RESULTS: Three main themes emerged in the analysis: i) engaging with healthcare professionals (HCPs) regarding DIHES, ii) social networks as a source of information regarding DIHES, and iii) reliance on bodily sensations. Most participants navigated all three types of sources. All participants had at some point discussed DIHES with an HCP. Information from HCPs was considered reliable and valuable, but HCPs were viewed as uncommitted to the dialogue about DIHES. Recommendations from others were often the driver of decisions regarding use of DIHES. However, the information from PwMS' networks could be overwhelming and difficult to navigate. Finally, PwMS relied on their own experiences regarding DIHES and let their bodily sensations guide their use of DIHES. CONCLUSIONS: Participants often rely on all three types of information sources to create a nuanced and comprehensive information base. However, PwMS may feel overwhelmed or confused with all the information they have gathered. These findings indicate the need for better guidance for PwMS concerning DIHES and an openness among HCPs to engage in dialogue.

Vitamin D and Blood Parameters.

BACKGROUND: Vitamin D has a steroid- and an anabolic-resembling chemical structure. Vitamin D is essential for many processes in the human body after hydroxylation. AIMS OF THE STUDY: To investigate the impact of 25-hydroxy-vitamin D plasma concentrations on the blood parameters number of erythrocytes, hematocrit, mean corpuscular hemoglobin and mean corpuscular volume. METHODS: Serial assessments were done in 290 patients with multiple sclerosis and repeated after a mean interval of 245 days. A recommendation for vitamin D supplementation was given in case of a concentration lower than 20 ng/mL combined with a prescription of a formulation containing vitamin D but not vitamin K. RESULTS: There was a fall of vitamin D in 119 subjects and a rise in 164, while no change appeared in 7 participants. When vitamin D values went down between both assessments moments, the computed increase of mean corpuscular haemoglobin was significantly lower compared with the rise of mean corpuscular haemoglobin associated with a vitamin D elevation. When vitamin D declined, the computed fall of mean corpuscular volume fall was significantly lower compared with the decrease of mean corpuscular volume, when vitamin D rose. Positive correlations were found between differences of vitamin D and mean corpuscular haemoglobin, respectively mean corpuscular volume. Inverse relations appeared between disparities of vitamin D and erythrocytes, respectively haematocrit. CONCLUSIONS: The elevation of vitamin D plasma levels provides enhanced preconditions for a better tissue oxygenation on a cellular level.

Influence of a High-Impact Multidimensional Rehabilitation Program on the Gut Microbiota of Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative inflammatory condition mediated by autoreactive immune processes. Due to its potential to influence host immunity and gut-brain communication, the gut microbiota has been suggested to be involved in the onset and progression of MS. To date, there is no definitive cure for MS, and rehabilitation programs are of the utmost importance, especially in the later stages. However, only a few people generally participate due to poor support, knowledge, and motivation, and no information is available on gut microbiota changes. Herein we evaluated the potential of a brief high-impact multidimensional rehabilitation program (B-HIPE) in a leisure environment to affect the gut microbiota, mitigate MS symptoms and improve quality of life. B-HIPE resulted in modulation of the MS-typical dysbiosis, with reduced levels of pathobionts and the replenishment of beneficial short-chain fatty acid producers. This partial recovery of a eubiotic profile could help counteract the inflammatory tone typically observed in MS, as supported by reduced circulating lipopolysaccharide levels and decreased populations of pro-inflammatory lymphocytes. Improved physical performance and fatigue relief were also found. Our findings pave the way for integrating clinical practice with holistic approaches to mitigate MS symptoms and improve patients' quality of life.

Feasibility, Acceptability, and Preliminary Validity of Self-Report Dietary Assessment in Adults with Multiple Sclerosis: Comparison with Doubly Labeled Water Measured Total Energy Expenditure.

BACKGROUND: Diet is a modifiable behavior of interest in multiple sclerosis (MS); however, measures of diet in persons with MS have not been vetted for feasibility, acceptability, and validity. METHODS: This cross-sectional study examined the Automated Self-Administered 24-H (ASA24) Dietary Assessment Tool in 30 persons with MS and 15 healthy control (HC) participants. Participants were prompted to complete six ASA24 recalls and undergo a standard doubly labeled water (DLW) protocol. Acceptability of ASA24 was assessed using an online questionnaire. Total energy expenditure (TEE) from DLW was compared with ASA24-reported energy intake for assessing validity. RESULTS: All participants completed four or more ASA24 recalls, indicating feasibility of ASA24. Regarding acceptability, the hardest part of completing the ASA24 was remembering everything eaten the previous day. Pearson correlation coefficients between DLW TEE and ASA24 kcal/day were not significant among HC (r = 0.40; p = 0.14) or MS (r = 0.26; p = 0.16) participants. The absolute mean error between DLW TEE and ASA24 among HC participants was 694.96 ± 506.25 mean kcal/day and among MS participants was 585.37 ± 529.02 mean kcal/day; this represents a mean difference of 30 and 25%, respectively. CONCLUSION: This study established the feasibility and acceptability of ASA24 in persons with MS and provides a foundation regarding the need for further validation research examining appropriate outcomes for supporting dietary interventions.

Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials.

Preliminary evidence shows the potential role of probiotics in ameliorating multiple sclerosis (MS); however, the effects of probiotics on MS remain unclear. Therefore, the aim of this study was to evaluate the efficacy of probiotics on multiple sclerosis by systematically reviewing the preclinical trials (animal trials) and performing meta-analysis of randomized controlled trials. PubMed, Web of Science, Cochrane central of randomized clinical trials, EMBASE, Clinical Trials, and a search engine Google Scholar were systematically searched and manually screened updated to November 2020, resulting in eligible 3 randomized controlled trials (RCTs) and 22 preclinical studies. Meta-analysis of RCTs enrolling 173 patients with MS receiving probiotics revealed significant beneficial effects of probiotic supplementation on mental health (expanded disability status scale scores: standardized mean difference [SMD] = -1.22; I2 = 92%; 95% CI, -2.40 to -0.03, P = 0.04; Beck depression inventory total scores: SMD = -1.58; I2 = 94%; 95% CI, -3.03 to -0.12; P = 0.03; general health questionnaire scores: SMD = -0.71; I2 = 0%; 95% CI, -1.02 to -0.40; P < 0.00001; depression anxiety and stress scale scores: SMD = -0.72; I2 = 0%; 95% CI, -1.12 to -0.33; P = 0.0003), with very low certainty of evidence. In addition, probiotic intake markedly improved insulin resistance and inflammatory and oxidative stress markers. Preclinical studies have shown that probiotic consumption reduces the incidence and severity of MS, delays MS progression (15 studies), and improves motor impairment (3 studies) with favorable alterations of immune and inflammatory markers (20 studies) and intestinal microbiome compositions (4 studies) in MS. These results indicated that probiotics may have beneficial effects on the prevention and treatment of multiple sclerosis.

Intermittent caloric restriction with a modified fasting-mimicking diet ameliorates autoimmunity and promotes recovery in a mouse model of multiple sclerosis.

Dietary interventions such as fasting have been proved to be effective in the prevention of metabolic and autoimmune diseases as well as aging-related conditions. The complicated interaction between nutrition and immunity has drawn wide attention in recent years. In this study, we investigated the therapeutic effect of intermittent caloric restriction on autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, in mice. EAE was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 peptide. After the EAE symptoms became obvious at the 4th week post-immunization, the mice were administered with a modified fasting-mimicking diet (FMD) at 1/3 cal of control for 3 days, followed by ad libitum with normal chow for 4 days. A total of two cycles of FMD was applied. Compared with the mice without receiving caloric restriction, the mice using FMD had significant decreases in EAE severity, immune cell infiltration in spinal cord and CNS demyelination. FMD administration also reversed EAE-mediated CNS accumulation of total CD4+ T cells and in particular, IFN-γ-producing CD4+ T cells. Moreover, FMD application elevated the cell proliferation rate in CNS and enhanced expression of brain-derived neurotrophic factor (BDNF) and remyelination markers. In conclusion, our results indicate that intermittent caloric restriction using the modified FMD was effective in the treatment of EAE through ameliorating inflammatory response and promoting recovery of the damaged tissue.

Effect of omega-3 fatty acids and fish oil supplementation on multiple sclerosis: a systematic review.

Background: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, resulting in the degradation of the myelin sheath. Diet especially fish oils and omega-3 has been found to play an important role in MS. This work aimed to review the literature systematically for evidence on the effect of omega-3 fatty acids (EPA, DPA and DHA) on MS progression in adults.Methods: The literature search was conducted in PubMed, Oxford, Cochrane, Embase, International pharmaceutical abstract, PsychINFO, and clinical trials government. The inclusions were studies performed on humans both male and female, aged 18 years at minimum, diagnosed with MS according to McDonald 2010 criteria. Otherwise, all studies were excluded.Results: A total of 5554 studies were screened and seven were thoroughly focused on as they typically met the inclusion criteria. These studies showed the beneficial roles of fish oil supplementation and omega-3 fatty acids in improving the quality of life of MS patients. These roles were attributed to their beneficial effects on inflammatory markers, glutathione reductase, reducing the relapsing rate, and achieving balanced omega-6 to omega-3 ratios.Conclusion: Omega-3 and fish oils supplementations have beneficial effects on reducing the relapsing rate, inflammatory markers, and improving the quality of life for MS patients.

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review.

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

Remote testing of vitamin D levels across the UK MS population-A case control study.

OBJECTIVE: The association between vitamin D deficiency and multiple sclerosis (MS) is well described. We set out to use remote sampling to ascertain vitamin D status and vitamin D supplementation in a cross-sectional study of people with MS across the UK. METHODS: People with MS and matched controls were recruited from across the UK. 1768 people with MS enrolled in the study; remote sampling kits were distributed to a subgroup. Dried blood spots (DBS) were used to assess serum 25(OH)D in people with MS and controls. RESULTS: 1768 MS participants completed the questionnaire; 388 MS participants and 309 controls provided biological samples. Serum 25(OH)D was higher in MS than controls (median 71nmol/L vs 49nmol/L). A higher proportion of MS participants than controls supplemented (72% vs 26%, p<0.001); people with MS supplemented at higher vD doses than controls (median 1600 vs 600 IU/day, p<0.001). People with MS who did not supplement had lower serum 25(OH)D levels than non-supplementing controls (median 38 nmol/L vs 44 nmol/L). Participants engaged well with remote sampling. CONCLUSIONS: The UK MS population have higher serum 25(OH)D than controls, mainly as a result of vitamin D supplementation. Remote sampling is a feasible way of carrying out large studies.