Fat-rich versus carbohydrate-rich nutrition in ALS: a randomised controlled study.

OBJECTIVE: There is growing evidence that the course of amyotrophic lateral sclerosis (ALS) may be influenced beneficially by applying high-caloric food supplements (HCSs). However, it is unknown which composition of nutrients offers optimal tolerability and weight gain. METHODS: We conducted a randomised controlled study (Safety and Tolerability of Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS); TOLCAL-ALS study) in 64 patients with possible, probable or definite ALS according to El Escorial criteria. Patients were randomised into four groups: a high-caloric fatty supplement (HCFS; 405 kcal/day, 100% fat), an ultra-high-caloric fatty supplement (UHCFS; 810 kcal/day, 100% fat), an ultra-high-caloric, carbohydrate-rich supplement (UHCCS; 900 kcal/day, 49% carbohydrates) and an open control (OC) group without any supplement. The primary endpoint was tolerability. Patients were followed up over 4 weeks. RESULTS: Gastrointestinal side effects were most frequent in the UHCFS group (75.0%), while loss of appetite was most frequent in the UHCCS group (35.3%). During intervention, patients gained +0.9 kg/month of body weight (IQR -0.9 to 1.5; p=0.03) in the HCFS group and +0.9 kg/month (IQR -0.8 to 2.0; p=0.05) in the UHCFS group. A non-significant trend for weight gain (+0.6 kg/month (IQR -0.3 to 1.9; p=0.08)) was observed in the UHCCS group. Patients in OC group continued to lose body weight (-0.5 kg/month, IQR -1.4 to 1.3; p=0.42). INTERPRETATION: The findings suggest that HCSs frequently cause mild to moderate tolerability issues in patients with ALS, most notably gastrointestinal symptoms in high-fat supplements, and loss of appetite in high-carbohydrate supplements. All three HCSs tested are suited to increase body weight.

Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-Blind Therapeutic Trial After Curcumin Supplementation.

OBJECTIVE: To investigate the efficacy of curcumin oral supplementation (600 mg/day, Brainoil), a natural antioxidant compound, in Amyotrophic Lateral Sclerosis (ALS). METHODS: Patients were randomized into two groups: Group A received placebo for 3 months, then Brainoil for the following 3 months, Group B took Brainoil for 6 months. The evaluations were conducted at basal (T0), after 3 months of double blinded Brainoil or placebo treatment (T1), and after the 3 month open-label phase (T2). Clinical evaluations and oxidative stress biomarkers, including oxidative protein products (AOPPs), ferric reducing ability (FRAP), total thiols (T-SH) and lactate, were evaluated, compared to a control group, during an incremental forearm exercise test. RESULTS: Over the entire study Group B showed a stable score of the ALS-FRS-r which decreased in Group A (p<0.01), in parallel with a reduction of AOPPs (p<0.01) which was not detected into Group A. Also FRAP exercise values remained stable in Group B, while in Group A they were reduced without treatment at T1 (0.05T0 exercise lactate was lower compared to Group A (p<0.01). Compared to controls, the whole ALS population showed a greater oxidative stress (p<0.001), those treated with curcumin (Group B) exhibiting decreased exercise AOPPs at T2 with values approaching those of controls. CONCLUSION: Although further studies are needed to confirm these data, treatment with curcumin shows encouraging results indicating a slight slowdown in disease progression, improving aerobic metabolism and oxidative damage, this also contributing to deepen knowledge into the pathogenic mechanisms of ALS.

A Novel Iron Chelator-Radical Scavenger Ameliorates Motor Dysfunction and Improves Life Span and Mitochondrial Biogenesis in SOD1G93A ALS Mice.

The aim of the present study was to evaluate the therapeutic effect of the novel neuroprotective multitarget brain permeable monoamine oxidase inhibitor/iron chelating-radical scavenging drug, VAR10303 (VAR), co-administered with high-calorie/energy-supplemented diet (ced) in SOD1G93A transgenic amyotrophic lateral sclerosis (ALS) mice. Administration of VAR-ced was initiated after the appearance of disease symptoms (at day 88), as this regimen is comparable with the earliest time at which drug therapy could start in ALS patients. Using this rescue protocol, we demonstrated in the current study that VAR-ced treatment provided several beneficial effects in SOD1G93A mice, including improvement in motor performance, elevation of survival time, and attenuation of iron accumulation and motoneuron loss in the spinal cord. Moreover, VAR-ced treatment attenuated neuromuscular junction denervation and exerted a significant preservation of myofibril regular morphology, associated with a reduction in the expression levels of genes related to denervation and atrophy in the gastrocnemius (GNS) muscle in SOD1G93A mice. These effects were accompanied by upregulation of mitochondrial DNA and elevated activities of complexes I and II in the GNS muscle. We have also demonstrated that VAR-ced treatment upregulated the mitochondrial biogenesis master regulator, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and increased PGC-1α-targeted metabolic genes and proteins, such as, PPARγ, UCP1/3, NRF1/2, Tfam, and ERRα in GNS muscle. These results provide evidence of therapeutic potential of VAR-ced in SOD1G93A mice with underlying molecular mechanisms, further supporting the importance role of multitarget iron chelators in ALS treatment.

Assessment and nutrition education in patients with amyotrophic lateral sclerosis.

Neurological patients with amyotrophic lateral sclerosis (ALS)often deteriorate to a worsening nutritional status. The aim of this study was to compare the nutritional status and food intake after nutrition education in patients with ALS. Clinical, anthropometric and functional variables were analyzed. Fifty-three patients were monitored at an early stage of the disease. The average score on the functionality scale was 33 points. Initially only 3.8% were classified as low body weight. After three months, 50% showed significant variation in anthropometric measures related to muscle mass and body fat reserves without association with clinical variables. After nutritional guidance, there was an increase in the intake of all food groups, especially the dairy group (p <0.05).The change of the nutritional status occurs early in patients with amyotrophic lateral sclerosis, even in those previously eutrophic or over weight. There was an increase in food intake after nutritional guidance according to the food guide adapted to the Brazilian population.

Assessment and nutrition education in patients with amyotrophic lateral sclerosis / Avaliação e educação nutricional em pacientes com esclerose lateral amiotrófica

ABSTRACT Neurological patients with amyotrophic lateral sclerosis (ALS)often deteriorate to a worsening nutritional status. The aim of this study was to compare the nutritional status and food intake after nutrition education in patients with ALS. Clinical, anthropometric and functional variables were analyzed. Fifty-three patients were monitored at an early stage of the disease. The average score on the functionality scale was 33 points. Initially only 3.8% were classified as low body weight. After three months, 50% showed significant variation in anthropometric measures related to muscle mass and body fat reserves without association with clinical variables. After nutritional guidance, there was an increase in the intake of all food groups, especially the dairy group (p <0.05).The change of the nutritional status occurs early in patients with amyotrophic lateral sclerosis, even in those previously eutrophic or over weight. There was an increase in food intake after nutritional guidance according to the food guide adapted to the Brazilian population.

RESUMO Pacientes neurológicos com esclerose lateral amiotrófica frequentemente evoluem com piora do estado nutricional. O objetivo desse estudo foi comparar o estado nutricional e a ingestão alimentar depois da orientação nutricional em pacientes com ELA. Variáveis clínicas,antropométricas e funcionais foram analisadas. 53 pacientes foram avaliados na fase inicial da doença. A pontuação média da escala de funcionalidade foi de 33 pontos. Inicialmente apenas 3,8% foram classificados como baixo peso. Após três meses, 50% apresentaram variação significativa nas medidas antropométricas relacionadas com reservas de massa muscular e gordura corporal, sem associação com variáveis clínicas. Após orientação nutricional, houve um aumento na ingestão de alimentos de todos os grupos com relevância para o grupo de lacticínios (p <0,05). A mudança do estado nutricional ocorre precocemente em pacientes com ELA, mesmo naqueles anteriormente eutróficos ou sobrepeso. Houve um aumento na ingestão de alimentos após orientação nutricional de acordo com o guia alimentar adaptado da população brasileira.

The influence of the initial state of nutrition on the lifespan of patients with amyotrophic lateral sclerosis (ALS) during home enteral nutrition / La influencia del estado inicial de la nutrición en la esperanza de vida de pacientes con esclerosis lateral amiotrófica (ALS) durante la nutrición enteral en casa

Aim: Amyotrophic lateral sclerosis (ALS) is a chronic, neurodegenerative disease, which leads to development of malnutrition. The main purpose of this research was to analyze the impact of malnutrition on the course of the disease and long-term survival. Material and methods: A retrospective analysis has been performed on 48 patients (22 F [45,83%] and 26 M [54,17%], the average age of patients: 66,2 [43-83]) in 2008-2014.The analysis of the initial state of nutrition was measured by body mass index (BMI), nutritional status according to NRS 2002, SGA and concentration of albumin in blood serum. Patients were divided into two groups, depending on the state of nutrition: well-nourished and malnourished. The groups were created separately for each of these, which allowed an additional comparative analysis of techniques used for the assessment of nutritional status. Results: Proper state of nutrition was interrelated with longer survival (SGA: 456 vs. 679 days, NRS: 312 vs. 659 vs. 835 days, BMI: respectively, 411, 541, 631 days, results were statistically significant for NRS and BMI). Concentration of albumin was not a prognostic factor, but longer survival was observed when level of albumin was increased during nutritional therapy. Conclusions: The initial nutrition state and positive response to enteral feeding is associated with better survival among patients with ALS. For this reason, nutritional therapy should be introduced as soon as possible (AU)

Objetivo: la esclerosis lateral amiotrófica (ELA) es una enfermedad crónica, neurodegenerativa que genera malnutrición. El objetivo principal de este estudio es analizar el impacto de la malnutrición en el curso de la enfermedad y la sobrevida a largo plazo. Materiales y métodos: se realizó un análisis retrospectivo de 48 pacientes (22 mujeres [45.83%] y 26 hombres [54.17%], con un promedio de edad de 66,2 [43-83]) del 2008 al 2014. El análisis del estado nutricional inicial se midió utilizando el índice de masa corporal (IMC), el estado nutricional de acuerdo al NRS 2002, la valoración global subjetiva (VGS) y la concentración sérica de albúmina. Los pacientes se dividieron en dos grupos, dependiendo del estado nutricional en el que se encontraban: bien nutridos o malnutridos. Los grupos se crearon por separado, lo que permitió un análisis comparativo adicional de las técnicas utilizadas para la evaluación del estado nutricional. Resultados: un estado nutricional adecuado se relaciona con mayor sobreviva a largo plazo (456 vs. 679 días, NRS 312 vs. 659 vs. 835 días, IMC respectivamente: 41, 541, 631 días, resultados estadísticamente significativos para NRS e IMC). Las concentraciones de albúmina no fueron un factor pronóstico, pero se observó mayor sobrevida si las concentraciones de albúmina incrementaban durante el tratamiento nutricional. Conclusiones: el estado nutricional inicial y la respuesta positiva a la alimentación enteral están asociados a mayor sobrevida en pacientes con ELA, razón por la cual, la terapia nutricional debe de iniciarse lo antes posible (AU)

Atención clínica, toma de decisiones y soporte nutricional en pacientes con esclerosis lateral amiotrófica / Clinical care, decision making and nutritional support in patients with amyotrophic lateral sclerosis

Introducción: En los pacientes afectos de Esclerosis Lateral Amiotrófica, es indispensable ofertar una adecuada información, que conlleve una acertada toma de decisiones, debido a las situaciones de alta complejidad que presentan durante su enfermedad. Con esta idea de fondo, se creó en nuestro Hospital Universitario Puerta del Mar de Cádiz un equipo interdisciplinar e interniveles para la atención de pacientes con esta entidad. Objetivos: Comparar variables relacionadas con la evolución clínica y la de toma de decisiones antes y después de la creación del equipo. Material y Método: Estudio descriptivo, observacional. Se comparan variables, pre y post intervención, destacando: sintomatología que motiva la consulta o el ingreso, episodios de atención en el hospital, interconsultas a profesionales, registro en la historia clínica de haber proporcionado información sobre la posibilidad de expresar la Voluntad Vital Anticipada y/o la existencia de la misma, soporte nutricional recibido. Resultados: Se obtuvieron 15 pacientes en el primer grupo y 13 en el segundo. Existe mejora en los porcentajes obtenidos en todas las variables, destacando el registro de voluntades vitales, toma de decisiones y soporte nutricional. Discusión-Conclusiones: La creación de un equipo interdisciplinar que hace partícipe al paciente de todo su proceso, además de asegurar una adecuada toma de decisiones por parte del paciente, conlleva la mejora de los resultados de indicadores clínicos (AU)

Background: In cases of ALS, due to the highly complex situations arising during the disease, it is essential to provide adequate information to the patient, so they can make suitable decisions concerning quality of life and symptom management over the course of their disease. To this end, an interdisciplinary and interlevel team has been created in the Hospital Universitario Puerta del Mar of Cádiz to provide the best care for people living with ALS. Objectives: Compare variables related to the clinical outcome and decision in-making before and after the creation of the team. Methods: Descriptive and observational study. Variables under evaluation were compared pre- and post- intervention, including: symptoms at the admission or consultation stages, care taking episodes in the hospital, interdepartmental clinical issues, entries in the medical record of existence or prospect of completing the advance health care directive, decision-making and nutritional support. Result: For sake of comparison, two groups were formed, the first one was made of 15, whereas the second one composed of 13 patients. There was a significant improvement in all the variables under study. It is especially remarkable the advance in the living will records, decision-making and nutritional support. Discussion-Conclusion: The creation of an interdisciplinary team capable fo engaging the patient of ALS in the clinical issues and symptom management over the course of the disease, not only ensures an adequate decision-making by the patient, but improves the results of the corresponding clinical indicators (AU)

Body mass index and dietary intervention: implications for prognosis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an adult onset, neurodegenerative disease that is characterized by the loss of upper (corticospinal) and lower motor neurons. ALS is a multifactorial disease whereby a combination of genetic and environmental factors may contribute to disease pathogenesis. While the majority of studies indicate that the underlying causes for ALS pathology may be due to multiple defects at the cellular level, factors that have recently been identified to be associated with survival could lead to the development of beneficial interventions. In ALS, a higher pre-morbid body mass index (BMI) and the maintenance of BMI and nutritional state is associated with improved outcome. This review will focus on the associations between body composition and adiposity relative to disease duration and risk, and will discuss current evidence that supports the benefits of improving energy balance, and the maintenance of body mass through nutritional intervention in ALS.

Nutritional care in motor neurone disease/ amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis (ALS) often present changes in nutritional status. Based on weight loss and on difficulty in nutritional management, this study aims to review the different possibilities and to present guidelines concerning nutritional treatment to such patients. Diet characteristics, types of treatment and nutritional therapy indicating administration routes and discussing the details of the disease are described herein. Nutritional therapy has been a substantial therapeutic resource for ALS development.

Dietary restriction in cerebral bioenergetics and redox state.

The brain has a central role in the regulation of energy stability of the organism. It is the organ with the highest energetic demands, the most susceptible to energy deficits, and is responsible for coordinating behavioral and physiological responses related to food foraging and intake. Dietary interventions have been shown to be a very effective means to extend lifespan and delay the appearance of age-related pathological conditions, notably those associated with brain functional decline. The present review focuses on the effects of these interventions on brain metabolism and cerebral redox state, and summarizes the current literature dealing with dietary interventions on brain pathology.

Nutritional care in motor neurone disease/ amyotrophic lateral sclerosis / Assistencia nutricional nas doencas do neuronio motor/esclerose lateral amiotrofica

Patients with amyotrophic lateral sclerosis (ALS) often present changes in nutritional status. Based on weight loss and on difficulty in nutritional management, this study aims to review the different possibilities and to present guidelines concerning nutritional treatment to such patients. Diet characteristics, types of treatment and nutritional therapy indicating administration routes and discussing the details of the disease are described herein. Nutritional therapy has been a substantial therapeutic resource for ALS development.

Pacientes com esclerose lateral amiotrófica (ELA) frequentemente apresentam alteração do estado nutricional. Baseado na perda ponderal de peso e na dificuldade no manejo nutricional, o objetivo desse estudo é rever as estratégias de tratamento nutricional para a manutenção do estado nutricional desses doentes. Nesse trabalho, descrevem-se as características da dieta, as formas de tratamento e terapia nutricional com indicação das vias de administração, bem como discuti-se as particularidades da doença. A terapia nutricional tem se mostrado um recurso terapêutico primordial atuante na evolução da ELA.

High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: a prospective interventional study.

Weight loss is an independent prognostic factor in amyotrophic lateral sclerosis (ALS). We investigated whether the body weight of ALS patients who previously lost weight can be stabilized by a high-caloric diet. For this purpose we compared two different high-caloric food supplements: one with high fat content and one with high carbohydrate content. Twenty-six patients were randomly allocated to one of the therapeutic groups. Body weight, ALS functional rating scale-revised (ALSFRS-R), static vital capacity (SVC), bioelectrical impedance analysis (BIA), metabolic serum parameters, and adverse events were investigated. Results showed that body weight of ALS patients could be stabilized in both therapeutic groups after 12 weeks of therapy (p = 0.008). The effect was greater in the group with high fat supplement though not statistically significant (p = 0.37). In conclusion, high-caloric food supplements with high fat as well as high carbohydrate content are both suitable to stabilize the body weight of ALS patients. The effect of a high fat diet might be more pronounced. Since body weight is an independent prognostic factor in ALS it is possible that a high-caloric food supplement improves survival in ALS. However, this hypothesis can only be tested by conducting a placebo-controlled double-blinded trial of sufficient power.

Amyotrophic lateral sclerosis treatment with ultramicronized palmitoylethanolamide: a case report.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons which leads to muscular atrophy, paralysis and death in 3-5 years from starting symptoms. This disorder is accompanied by noteworthy spinal inflammation mediated in particular by microglia and mast cells. No effective therapy is available. This report describes the effects of administering the anti-inflammatory agent palmitoylethanolamide in a case of sporadic amyotrophic lateral sclerosis. Palmitoylethanolamide treatment led to an improved clinical picture, as evidenced by electromyographic analysis and pulmonary function. Conceivably, the action of palmitoylethanolamide could result, in part, from its ability to dampen mast cell and microglia activation.

Dietary vitamin D3 supplementation at 10× the adequate intake improves functional capacity in the G93A transgenic mouse model of ALS, a pilot study.

BACKGROUND: Vitamin D has antioxidant, anti-inflammatory, and neuroprotective properties, and may mitigate amyotrophic lateral sclerosis (ALS) pathology. AIMS: To determine the effects of dietary vitamin D(3) (D(3)) at 10-fold the adequate intake (AI) on functional and disease outcomes and lifespan in the transgenic G93A mouse model of ALS. METHODS: Starting at age 40 days, 32 G93A mice (21 M, 11 F) were provided ad libitum with either an adequate (AI; 1 IU/g feed) or high (HiD; 10 IU/g feed) D(3) diet. Differences were considered significant at P≤ 0.10, as this was a pilot study. RESULTS: For paw grip endurance, HiD mice had a 7% greater score between 60-133 d versus AI mice (P= 0.074). For motor performance, HiD mice had a 22% greater score between 60-133 days (P= 0.074) versus AI mice due to changes observed in male mice, where HiD males had a 33% greater score (P= 0.064) versus AI males. There were no significant diet differences in disease onset, disease progression, or lifespan. CONCLUSION: Although disease outcomes were not affected, D(3) supplementation at 10-fold the AI improved paw grip endurance and motor performance in the transgenic G93A mouse model of ALS, specifically in males.

Effect of nutritional supplementation with milk whey proteins in amyotrophic lateral sclerosis patients.

OBJECTIVE: We evaluated the efficacy of oral supplementation with milk whey proteins and modified starch (70%WPI:30%MS), on nutritional and functional parameters of patients with ALS. METHOD: A prospective randomized double-blind study was performed with 16 ALS patients, divided in two groups, the treatment group received (70%WPI:30%MS) and the control group received (maltodextrin). They underwent prospective nutritional and functional assessment for 4 months. RESULTS: Patients in the treatment group presented weight gain, increased body mass index (BMI), increased arm muscle area and circumference, higher albumin, white blood cell and total lymphocyte counts, and reduced creatine-kinase, aspartate aminotransferase and alanine aminotransferase. In the control group, biochemical parameters did not change, but weight and BMI declined. CONCLUSION: Our results indicate that the agglomerate 70%WPI:30%MS may be useful in the nutritional therapy of patients with ALS.

Effect of nutritional supplementation with milk whey proteins in amyotrophic lateral sclerosis patients / Efeito da suplementação nutricional com proteínas do soro de leite em pacientes com esclerose lateral amiotrófica

OBJECTIVE: We evaluated the efficacy of oral supplementation with milk whey proteins and modified starch (70 percentWPI:30 percentMS), on nutritional and functional parameters of patients with ALS. METHOD: A prospective randomized double-blind study was performed with 16 ALS patients, divided in two groups, the treatment group received (70 percentWPI:30 percentMS) and the control group received (maltodextrin). They underwent prospective nutritional and functional assessment for 4 months. RESULTS: Patients in the treatment group presented weight gain, increased body mass index (BMI), increased arm muscle area and circumference, higher albumin, white blood cell and total lymphocyte counts, and reduced creatine-kinase, aspartate aminotransferase and alanine aminotransferase. In the control group, biochemical parameters did not change, but weight and BMI declined. CONCLUSION: Our results indicate that the agglomerate 70 percentWPI:30 percentMS may be useful in the nutritional therapy of patients with ALS.

OBJETIVO: Avaliar a eficácia da suplementação nutricional oral com proteínas do soro do leite e amido modificado (70 por centoWPI:30 por centoMS), nos parâmetros nutricionais e funcionais de pacientes com esclerose lateral amiotrófica (ELA). MÉTODO: Foi realizado estudo randomizado duplo-cego, com 16 pacientes com ELA, divididos em dois grupos, um que recebeu 70 por centoWPI:30 por centoMS e um controle que recebeu maltodextrina. Os pacientes foram submetidos a avaliação nutricional e funcional durante quatro meses. RESULTADOS: Nos pacientes que receberam o suplemento 70 por centoWPI:30 por centoMS, foi observado ganho de peso, aumento na contagem de linfócitos e redução de creatina kinase, aspartato aminotransferase and alanina aminotransferase. No grupo controle, os parâmetros bioquímicos não sofreram modificações; no entanto, peso e índice de massa corporal diminuíram. CONCLUSÃO: Nossos resultados indicam que o aglomerado 70 por centoWPI:30 por centoMS pode ser útil na terapia de pacientes com ALS.

Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation.

We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased N-acetyl aspartate and glutamate and increased glutamine, taurine and myo-inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild-type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%), reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on N-acetyl aspartate loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention, leading to a 13% increase in weight between 120 and 130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models.