Clinical and Sociodemographic Factors Related to Amyotrophic Lateral Sclerosis in Spain: A Pilot Study.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknow etiology. Male sex is a well stablished risk factor, but other factors such as early and adult life expositions show contradictory evidence. Aim: to explore the link of clinical, sociodemographic, and occupational factors with ALS patients in Spain and the impact of these factors in functionality. Methods: A cross-sectional study was conducted with ALS patients and healthy controls. Registered variables were smoking, arterial hypertension, diabetes mellitus type 2, previous cancer to reproductive organs or breast, occupational exposure, and early life exposures. Functionality in ALS patients was compared according to each exposure. Results: The ALS group consisted of 59 participants and the control group of 90 participants. ALS patients showed a significant association with previous cancer (p = 0.011), occupational exposure (p < 0.001), and older siblings (p = 0.029). ALS patients presented significant differences in BMI according to hypertension and older-sibling factors. Moreover, respiratory function was affected in patients with previous cancer (p = 0.031). Conclusions: Occupational exposure and previous cancer to reproductive organs or breast could be linked to ALS patients. In addition, hypertension and previous cancer could affect their BMI and respiratory function. Other factors such as longer smoking periods and exposition to older siblings could also characterize ALS patients.

Relationship between Experiential Avoidance and Emotional Disturbances in Coping with Disease in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease that presents with both motor and non-motor symptoms, with anxiety and depression being prominent and potentially exacerbated by negative thoughts. Therefore, the experiential avoidance (EA) exhibited by patients post diagnosis is particularly relevant. This study aimed to measure the degree of EA in patients with MS and determine its relationship with emotional disturbances. A cross-sectional descriptive study was conducted using a sample of 64 patients diagnosed with MS. In October 2018, these patients underwent evaluations of functional and cognitive variables, such as anxiety, depression, and avoidant behaviors towards the disease, using the Expanded Disability Status Scale, Acceptance and Action Questionnaire-II, Self-Compassion Scale Short Form, Five Facet Mindfulness Questionnaire-15, prefrontal symptoms inventory, Beck Depression Inventory II, and State-Trait Anxiety Inventory to assess coping mechanisms in handling the disease. Higher levels of state anxiety (ß = 0.79; p < 0.001), trait anxiety (ß = 0.82; p < 0.001), and depression (ß = 0.62; p < 0.001) were observed in patients with MS as their EA and psychological inflexibility increased. Participants with high self-compassion/self-acceptance tended to have fewer negative thoughts and exhibited better coping with the disease, which may, in turn, affect patterns of psychological rigidity or inflexibility. Dimensions such as kindness and humility could act as positive factors in coping with the disease, whereas self-judgment and isolation are negative elements often associated with avoidant behaviors that hinder effective coping with the illness.

Predictive Model of Anxiety and Depression Perception in Multiple Sclerosis Patients: Possible Implications for Clinical Treatment.

Multiple Sclerosis (MS) is a neurodegenerative disease characterized by motor and non-motor symptoms, including emotional distress, anxiety, and depression. These emotional symptoms currently have a pharmacological treatment with limited effectiveness; therefore, it is necessary to delve into their relationship with other psychological, functional, or prefrontal alterations. Additionally, exploring non-pharmacological therapeutic alternatives that have shown benefits in addressing emotional distress in MS patients is essential. AIM: To establish a predictive model for the presence of anxiety and depression in MS patients, based on variables such as psychological well-being, functional activity, and prefrontal symptoms. Additionally, this study aimed to propose non-pharmacological therapeutic alternatives based on this model. MATERIALS AND METHODS: A descriptive, observational, and cross-sectional study was conducted with a sample of 64 diagnosed MS patients who underwent functional and cognitive assessments using the following questionnaires and scales: Functional Activities Questionnaire (FAQ), Acceptance and Action Questionnaire (AAQ-II), Experiences Questionnaire (EQ), Self-Compassion Scale Short Form (SCS-SF), Beck Depression Inventory II (BDI-II), State-Trait Anxiety Inventory (STAI), and Prefrontal Symptoms Inventory (PSI). RESULTS: The model showed an excellent fit to the data and indicated that psychological well-being was the most significant predictor of the criteria (ß = -0.83), followed by functional activity (ß = -0.18) and prefrontal symptoms (ß = 0.15). The latter two are negatively related to psychological well-being (ß = -0.16 and ß = -0.75, respectively). CONCLUSIONS: Low psychological well-being is the variable that most significantly predicts the presence of anxiety and depression in MS patients, followed by functional activity and prefrontal alterations. Interventions based on mindfulness and acceptance are recommended, along with nutritional interventions such as antioxidant-enriched ketogenic diets and moderate group physical exercise.

Lipid Profile in Multiple Sclerosis: Functional Capacity and Therapeutic Potential of Its Regulation after Intervention with Epigallocatechin Gallate and Coconut Oil.

BACKGROUND: Multiple sclerosis (MS) patients present dyslipidemia and functional disability. Epigallocatechin gallate (EGCG) and coconut oil have been shown to be effective against dyslipidemia. OBJECTIVE: To analyze the relationship between lipid profiles, fat consumption, and functional disability in patients with MS after administering EGCG and coconut oil. METHODS: A four-month pilot study was conducted on 45 MS patients, divided into an intervention group (IG) and a control group (CG). The IG received 800 mg of EGCG and 60 mL of coconut oil. Lipid profiles were measured before and after the intervention, along with other data such as dietary habits, inflammatory markers, and functional capacity. RESULTS: Dyslipidemia did not correlate with the patients' fat consumption. After the intervention, triglycerides (TG) levels were lower in IG compared to CG. This decrease was positively correlated with an improvement in functional disability (determined by the Expanded Disability Status Scale (EDSS)) and negatively with high-density cholesterol (HDL) and apolipoprotein A1. Significant and positive correlations were observed between EDSS and C-reactive protein (CRP) in the IG. These changes in the IG could be related to body fat decrease, whose percentage shows a positive correlation with CRP and TG levels, and a negative correlation with HDL levels. CONCLUSIONS: Patients with MS present a certain type of dyslipemia not associated with their nutritional habits. The administration of EGCG and coconut oil seems to decrease blood TG levels, which could explain the functional improvements.

Exploring the impact of ketogenic diet on multiple sclerosis: obesity, anxiety, depression, and the glutamate system.

Background: Multiple sclerosis (MS) is a neurodegenerative disorder. Individuals with MS frequently present symptoms such as functional disability, obesity, and anxiety and depression. Axonal demyelination can be observed and implies alterations in mitochondrial activity and increased inflammation associated with disruptions in glutamate neurotransmitter activity. In this context, the ketogenic diet (KD), which promotes the production of ketone bodies in the blood [mainly ß-hydroxybutyrate (ßHB)], is a non-pharmacological therapeutic alternative that has shown promising results in peripheral obesity reduction and central inflammation reduction. However, the association of this type of diet with emotional symptoms through the modulation of glutamate activity in MS individuals remains unknown. Aim: To provide an update on the topic and discuss the potential impact of KD on anxiety and depression through the modulation of glutamate activity in subjects with MS. Discussion: The main findings suggest that the KD, as a source of ketone bodies in the blood, improves glutamate activity by reducing obesity, which is associated with insulin resistance and dyslipidemia, promoting central inflammation (particularly through an increase in interleukins IL-1ß, IL-6, and IL-17). This improvement would imply a decrease in extrasynaptic glutamate activity, which has been linked to functional disability and the presence of emotional disorders such as anxiety and depression.

Improvements in gait and balance in patients with multiple sclerosis after treatment with coconut oil and epigallocatechin gallate. A pilot study.

Multiple sclerosis (MS) is a neurodegenerative disease that progressively decreases the muscular and functional capacity. Thus, there is an alteration in the ability to walk that affects balance, speed and resistance. Since MS pathology involves neuroinflammation, cellular oxidation and mitochondrial alterations, the objective of the study was to assess the impact of a nutritional intervention with coconut oil and epigallocatechin gallate (EGCG) on gait and balance. In order to do this, 51 patients with MS were enrolled and randomly distributed into an intervention group and a control group, which received either a daily dose of 800 mg of EGCG and 60 ml of coconut oil, or a placebo, all during a period of 4 months and which followed a Mediterranean isocaloric diet. Initial and final assessments consisted of the evaluation of quantitative balance (Berg scale), perceived balance (ABC scale), gait speed (10MWT) and resistance (2MWT). Besides, muscle strength was measured using a dynamometer and levels of ß-hydroxybutyrate (BHB) were measured in serum samples. In the intervention group, there was a significant improvement in the gait speed, quantitative balance and muscle strength of the right quadriceps; an improvement in gait resistance was observed in both groups. There were also significant and positive correlations between balance and gait scales. In conclusion, the administration of EGCG and coconut oil seems to improve gait speed and balance in MS patients, although the latter was not perceived by them. Furthermore, these variables appear to be related and contribute to functionality.

Relationship of Motor Impairment with Cognitive and Emotional Alterations in Patients with Multiple Sclerosis.

Introduction. Multiple sclerosis (MS) is a neurodegenerative disease that, despite mainly affecting women, is more severe in men and causes motor, cognitive and emotional alterations. The objective of this study was to determine the possible relationship between motor, cognitive and emotional alterations. Materials and Methods. This is a descriptive, observational and cross-sectional study, with 67 patients with MS (20 men and 47 women), who were given the following questionnaires: Expanded Disability Status Scale (EDSS), Two-Minute Walk Test (2MWT), Berg Balance Scale, Beck's Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI) and Prefrontal Symptoms Inventory (PSI) to analyze their cognitive level, body mass index (BMI) and percentage of muscle mass. In addition, regression analysis was conducted to study the relationship among variables. Results. No significant differences were found between men and women in any of the variables. Regarding the relationship between parameters, the regression analysis was statistically significant, showing an effect of age on the walking and balance performance (ß â‰… −0.4, p < 0.05); in addition, there was a relationship between 2MWT and STAI A/S, indicating that both older age and a high anxiety state could impact walking performance. On the other hand, prefrontal symptoms showed moderate relationships with both anxiety and depression (ß â‰… 0.6, p < 0.05); thus, high levels of anxiety and depression could increase prefrontal alterations. Conclusions. There is a relationship between motor and emotional variables. Specifically, state anxiety is related to walking resistance. No relationship was found between depression and cognitive alteration and balance or walking ability. Only age has an effect in these relationships.

The Impact of Epigallocatechin Gallate and Coconut Oil Treatment on Cortisol Activity and Depression in Multiple Sclerosis Patients.

(1) Background: Multiple sclerosis (MS) is pathogenically characterized by high oxidative stress and symptomatically by progressive muscle loss and increased body fat associated with the presence of depression. Epigallocatechin gallate (EGCG) (particularly present in green tea) and ketone bodies (in particular beta-hydroxybutyrate (BHB)), whose main source is coconut oil, have shown emotional benefits and body fat loss. The aim of this study was to assess the impact of EGCG and coconut oil on cortisol activity related to fat loss and depression in MS patients. (2) Methods: The study involved 51 MS patients who were randomly divided into an intervention group or a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, which were included in their daily diet for four months. The control group received placebo and all patients followed an isocaloric diet. A blood sample was collected before and after the four-month period, and levels of cortisol, albumin and BHB were measured in serum. In addition, immediately before and after the intervention, anthropometric variables were measured: waist-to-hip ratio (WHR), body fat mass percentage, fat weight, total weight, and muscle mass percentage. Depression was assessed with the Beck Depression Inventory II (BDI-II). (3) Results: No significant changes were obtained in cortisol levels in any of the groups, and there was a significant increase in albumin in the blood of the intervention group only that could lead to a decrease in serum free cortisol. In addition, it was observed a significant decrease in levels of depression and abdominal fat. (4) Conclusions: EGCG combined with coconut oil increase the concentration of albumin in blood and produce less depression in MS patients.

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study.

Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time-condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.

Vitamin B1 Intake in Multiple Sclerosis Patients and its Impact on Depression Presence: A Pilot Study.

Vitamin B1, or thiamine, is one of the most relevant vitamins in obtaining energy for the nervous system. Thiamine deficiency or lack of activity causes neurological manifestations, especially symptoms of depression, intrinsic to multiple sclerosis (MS) and related to its pathogenesis. On this basis, the aim of this study was to determine the possible relationship between the nutritional habits of patients with MS and the presence of depression. Therefore, a cross-sectional and observational descriptive study was conducted. An analysis of dietary habits and vitamin B1 consumption in a Spanish population of 51 MS patients was performed by recording the frequency of food consumption. Results showed a vitamin B1 intake within the established range, mainly provided by the consumption of ultra-processed products such as cold meats or pastries, and a total carbohydrate consumption lower than recommended, which stands out for its high content of simple carbohydrates deriving from processed foods such as dairy desserts, juice, snacks, pastries, chocolate bars, soft drinks and fermented alcohol. In addition, a significant negative correlation between depression and the intake of thiamine and total carbohydrates was observed. These findings could explain the influence of MS patients' eating habits, and consequently vitamin B1 activity, on depression levels.

The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.

BACKGROUND: Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS: A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS: State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS: EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.

Therapeutic alternative of the ketogenic Mediterranean diet to improve mitochondrial activity in Amyotrophic Lateral Sclerosis (ALS): A Comprehensive Review.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease which is pathogenically based on the mitochondrial alteration of motor neurons, causing progressive neuron death. While ALS is characterized by enormous oxidative stress, the Mediterranean diet has been seen to have high antioxidant power. Therefore, the aim of this study is to determine how the Mediterranean diet can improve mitochondrial activity, establishing the specific nutrients and, in addition, observing the pathogenic mechanisms related to the disease that would achieve this improvement. To this end, a comprehensive review of the literature was performed using PubMed. KBs have been observed to have a neuroprotective effect to improve energy balance, increasing survival and the number of motor neurons. This ketogenesis can be achieved after following a Mediterranean diet which is associated with great benefits in other neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and ALS. These benefits are due to the high antioxidant power especially based on polyphenols contained mainly in olive oil, wine, nuts, or berries. In short, KBs could be considered as a promising option to treat ALS, representing an alternative source to glucose in motor neurons by providing neuroprotection. In addition, treatment results can be improved as ketogenesis can be achieved (increase in KBs) by following a Mediterranean diet, thanks to the high antioxidant properties which, at the same time, would improve the high oxidative stress that characterizes the disease.

Reply to "When Is a Ketogenic Diet Ketogenic? Comment on Satiating Effect of a Ketogenic Diet and Its Impact on Muscle Improvement and Oxidation State in Multiple Sclerosis Patients. Nutrients 2019, 11, 1156".

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Satiating Effect of a Ketogenic Diet and Its Impact on Muscle Improvement and Oxidation State in Multiple Sclerosis Patients.

BACKGROUND: It was previously established that Multiple sclerosis (MS) generates energy alterations at the mitochondrial level related to the loss of muscle mass. Ketone bodies, mainly beta-hydroxybutyrate (BHB), re-establish this energy alteration causing satiety, changes in body composition and a decrease in hormone-dependant hunger, such as ghrelin. The aim of this study was to establish possible improvements in body composition and the level of oxidation in patients with MS, by means of the satiating effect of a ketogenic diet. METHODS: A pilot study was carried out with 27 MS patients who were given a Mediterranean isocaloric and ketogenic diet for 4 months. Anthropometric measurements, as well as satiety and hunger perception (VAS scale), were taken. In addition, BHB and paraoxonase 1 (PON1), as an oxidation marker, were measured by spectrophotometric automated assays, and ghrelin was determined by an enzyme immunoassay in the serum. All measurements were taken before and after the intervention. RESULTS: A significant increase in satiety perception at lunch and dinner and of BHB in the blood was obtained. Hunger perception decreased significantly at lunch and dinner with similar levels of ghrelin. In addition, an important increase in lean mass and PON1 was observed. To our knowledge, this is the first study addressing improvements in body composition, oxidation state and metabolism in MS patients, based on the satiating effect of a Mediterranean isocaloric diet. CONCLUSION: A ketogenic diet increases lean mass and decreases inflammation and oxidation possibly as a consequence of an increase in satiety and decrease in hunger in MS patients.

Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health's candidate drug EH301 in people with ALS (PALS). METHODS: This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS were recruited thanks to the collaboration of the Spanish Foundation for ALS Research (FUNDELA). Study participants were randomized to receive either EH301 or placebo and underwent evaluation for 4 months. Differences between EH301 and placebo-treated participants were evaluated based on standard clinical endpoints, including the revised ALS functional rating scale (ALSFRS-R), forced vital capacity (FVC), and the Medical Research Council (MRC) grading scale. RESULTS: Compared to placebo, participants treated with EH301 demonstrated significant improvements in the ALSFRS-R score, pulmonary function, muscular strength, and in skeletal muscle/fat weight ratio. EH301 was shown to significantly slow the progression of ALS relative to placebo, and even showed improvements in several key outcome measures compared with baseline. CONCLUSIONS: This study provides evidence in support of the disease-modifying effects of EH301 for the treatment of ALS.