34 research outputs found
Dysphagia Affecting Quality of Life in Cerebellar Ataxia—a Large Survey
Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients’ health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment
Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study
BACKGROUND:
Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression.
METHODS:
This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed.
DISCUSSION:
Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS
Metabolic, mental and immunological effects of normoxic and hypoxic training in multiple sclerosis patients: a pilot study
Background: Physical activity might attenuate inflammation and neurodegeneration in multiple sclerosis (MS). Erythropoietin, which is produced upon exposure to hypoxia, is thought to act as a neuroprotective agent in MS. Therefore, we studied the effects of intermittent hypoxic training on activity energy expenditure, maximal workload, serum erythropoietin, and immunophenotype focusing on regulatory and IL-17A-producing T cells. Methods: We assigned 34 relapsing-remitting MS patients within a randomized, single blind, parallel-group study to either normoxic (NO) or hypoxic (HO) treadmill training, both 3 times/week for 1 h over 4 weeks (Clinicaltrials.gov identifier: NCT02509897). Before and after training, activity energy expenditure (metabolic chamber), maximal workload (incremental treadmill test), walking ability, depressive symptoms (Beck Depression Inventory I), serum erythropoietin concentrations, and immunophenotype of peripheral blood mononuclear cells (PBMCs) were assessed. Results: Energy expenditure did not change due to training in both groups, but was rather fueled by fat than by carbohydrate oxidation after HO training (P = 0.002). Maximal workload increased by 40 Watt and 42 Watt in the NO and HO group, respectively (both P < 0.0001). Distance patients walked in 6 min increased by 25 m and 27 m in the NO and HO group, respectively (NO P = 0.02; HO P = 0.01). Beck Depression Inventory score markedly decreased in both groups (NO P = 0.03; HO P = 0.0003). NO training shifted Treg subpopulations by increasing and decreasing the frequency of CD39(+) and CD31(+) Tregs, respectively, and decreased IL-17A-producing CD4(+) cells. HO training provoked none of these immunological changes. Erythropoietin concentrations were within normal range and did not significantly change in either group. Conclusion: 4 weeks of moderate treadmill training had considerable effects on fitness level and mood in MS patients, both under normoxic and hypoxic conditions. Additionally, NO training improved Th17/Treg profile and HO training improved fatty acid oxidation during exercise. These effects could not be attributed to an increase of erythropoietin
Metabolic, Mental and Immunological Effects of Normoxic and Hypoxic Training in Multiple Sclerosis Patients: A Pilot Study
Background: Physical activity might attenuate inflammation and neurodegeneration in multiple sclerosis (MS). Erythropoietin, which is produced upon exposure to hypoxia, is thought to act as a neuroprotective agent in MS. Therefore, we studied the effects of intermittent hypoxic training on activity energy expenditure, maximal workload, serum erythropoietin, and immunophenotype focusing on regulatory and IL-17A-producing T cells.Methods: We assigned 34 relapsing-remitting MS patients within a randomized, single blind, parallel-group study to either normoxic (NO) or hypoxic (HO) treadmill training, both 3 times/week for 1 h over 4 weeks (Clinicaltrials.gov identifier: NCT02509897). Before and after training, activity energy expenditure (metabolic chamber), maximal workload (incremental treadmill test), walking ability, depressive symptoms (Beck Depression Inventory I), serum erythropoietin concentrations, and immunophenotype of peripheral blood mononuclear cells (PBMCs) were assessed.Results: Energy expenditure did not change due to training in both groups, but was rather fueled by fat than by carbohydrate oxidation after HO training (P = 0.002). Maximal workload increased by 40 Watt and 42 Watt in the NO and HO group, respectively (both P < 0.0001). Distance patients walked in 6 min increased by 25 m and 27 m in the NO and HO group, respectively (NO P = 0.02; HO P = 0.01). Beck Depression Inventory score markedly decreased in both groups (NO P = 0.03; HO P = 0.0003). NO training shifted Treg subpopulations by increasing and decreasing the frequency of CD39+ and CD31+ Tregs, respectively, and decreased IL-17A-producing CD4+ cells. HO training provoked none of these immunological changes. Erythropoietin concentrations were within normal range and did not significantly change in either group.Conclusion: 4 weeks of moderate treadmill training had considerable effects on fitness level and mood in MS patients, both under normoxic and hypoxic conditions. Additionally, NO training improved Th17/Treg profile and HO training improved fatty acid oxidation during exercise. These effects could not be attributed to an increase of erythropoietin.Clinical Trial Registration: ClinicalTrials.gov; NCT02509897; http://www.clinicaltrials.go
Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation
The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation
studies on patients with multiple sclerosis and spinocerebellar ataxia type 1
Neurologische Erkrankungen können zu strukturellen und funktionellen
Veränderungen von motorischen, sensorischen und vegetativen Neuronen führen.
Ãœber die Auswirkungen einer autonomen Dysfunktion auf den Energiestoffwechsel
von neurologischen Patienten und mögliche Vorteile diätetischer Interventionen
ist derzeit wenig bekannt. Deshalb soll in dieser Arbeit der
Energiestoffwechsel bei einer zentralen und einer spinocerebellären
neurodegenerativen Erkrankung modellhaft charakterisiert werden. Multiple
Sklerose (MS) ist eine chronisch-entzündliche Erkrankung des zentralen
Nervensystems. Zahlreiche Betroffene leiden unter einem subjektiven Mangel
körperlicher und mentaler Energie (Fatigue), der ihre Leistungsfähigkeit und
aktive Teilnahme am sozialen Leben deutlich beeinträchtigt. Von Grüntee-
Extrakten ist bekannt, dass sie den Energiestoffwechsel gesunder Probanden in
Ruhe und während körperlicher Aktivität verbessern. Spinocerebelläre Ataxie
Typ 1 (SCA1) ist eine seltene, erblich bedingte neurodegenerative Erkrankung.
Bei der klinischen Beobachtung von Personen mit SCA1 (PSCA1) fällt häufig ein
nachteiliger Gewichtsverlust im Verlauf der Erkrankung auf. Daher sollten
folgende Hypothesen geprüft werden: a) systemischer und lokaler
Energiestoffwechsel von Personen mit MS (PMS) sind gestört und beinträchtigen
die Leistungsfähigkeit während körperlicher Aktivität; b) ein Grüntee-Extrakt
reich an Epigallocatechin-3-Gallat (EGCG) verbessert den Energiestoffwechsel
in PMS; c) in PSCA1 liegt eine negative Energiebilanz vor, die den häufig
beobachteten Gewichtsverlust teilweise erklärt. Es wurde der
Energiestoffwechsel in Ruhe und während körperlicher Aktivität von 16 PMS bzw.
10 PSCA1 im Vergleich zu gesunden Kontrollen charakterisiert. In einer
doppelblinden, randomisierten, cross-over Studie nahmen 18 PMS über drei
Monate 600 mg EGCG/d und Placebo ein. Bei PMS war in Ruhe, nach 12h
Nahrungskarenz sowie nach einem Glucose-Trunk, die systemische Lipidoxidation
im Vergleich zu Kontrollen vermindert. Die Lipidmobilisation war im abdominal
subkutanen Fettgewebe gesteigert. Während moderater körperlicher Aktivität
deuteten der systemische Energieumsatz und die Substratoxidation auf eine
verminderte Leistungsfähigkeit der PMS hin. Interessanterweise führte die
Einnahme von EGCG insbesondere bei Männern mit MS zu einer Harmonisierung
dieser Befunde auf das Kontroll-Niveau. Bei PSCA1 vs. Kontrollen waren der
Ruhe-Nüchtern-Umsatz um 22 % und die Lipidoxidation um 28 % erhöht.
Zusammengefasst zeigten sich auch in gering bis moderat fortgeschrittenen
Stadien der hier untersuchten neurologischen Erkrankungen deutliche
Veränderungen des Energiestoffwechsels im Vergleich zu Gesunden. Die positive
Wirkung von EGCG auf den Energiestoffwechsel während körperlicher Aktivität
könnten PMS im Alltag ebenso durch das Trinken von grünem Tee erzielen. Bei
PSCA1 scheint eine regelmäßige Kontrolle von Körpergewicht und
Körperzusammensetzung aufgrund ihrer katabolen Stoffwechsellage sinnvoll,
besonders im Hinblick auf ihren erhöhten Energieverbrauch während körperlicher
Aktivität (Gehen).Neurological diseases can lead to structural and functional changes in
motoric, sensory and vegetative neurons. However, little is known how
autonomic dysfunction affects energy metabolism in neurological patients and
if they could benefit from dietary interventions. Therefore, we characterized
energy metabolism in a central and a spinocerebellar neurodegenerative
disease. Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the
central nervous system. The commonly experienced subjective lack of physical
and mental energy (fatigue) in persons with MS (PMS) has a negative impact on
their physical activity level as well as their social life. Green tea extracts
are known to improve energy metabolism at rest and during exercise in healthy
subjects. Spinocerebellar ataxia type 1 (SCA1) is a rare hereditary
neurodegenerative disease. Within the disease course, clinicians often observe
a detrimental weight loss in persons with SCA1 (PSCA1). Thus, we tested the
hypotheses that: a) systemic and local energy metabolism in PMS are impaired
which affects working efficiency during physical activity, b) a green tea
extract rich in epigallocatechin-3-gallate (EGCG) improves energy metabolism
in PMS, and c) PSCA1 present a negative energy balance, either caused by
decreased energy intake or increased energy expenditure, partly explaining the
often observed weight loss. We characterized resting and physical activity
energy metabolism of 16 PMS and 10 PSCA1 compared to healthy controls matched
for age, sex, and body composition. In a randomized, double-blind, cross-over
trial, 18 PMS took 600 mg EGCG/d and placebo for three months. At rest, both
after a 12h overnight fast and an oral glucose load, systemic lipid oxidation
was decreased while adipose tissue lipid mobilization was increased in PMS vs.
controls. During moderate physical activity, systemic energy expenditure and
substrate oxidation indicated a decreased working efficiency in PMS vs.
controls. Interestingly, intake of EGCG vs. placebo ameliorated these
findings, especially in men with MS. PSCA1 presented with 22% and 28% higher
resting energy expenditure and lipid oxidation rate, respectively, compared to
closely-matched healthy controls. Taken together, energy metabolism was
considerably altered in mild to moderate stages of MS and SCA1 compared with
healthy controls. By drinking green tea on a regular basis, PMS could benefit
from the effects of EGCG on physical activity energy metabolism in everyday
life. Owing to the increased catabolic state in PSCA1, it seems useful to
monitor body weight and body composition regularly, particularly because of
their increased energy expenditure during physical activity (walking)
Effect of a probiotic on blood pressure in grade 1 hypertension (HYPRO): protocol of a randomized controlled study
Background:
Arterial hypertension is a major risk factor for cardiovascular disease and leads to target organ damage including stroke, heart failure, and kidney disease. About 1.5 billion people worldwide have hypertension, and it is estimated that it causes about 8 million deaths each year. Although there are several drugs available to lower blood pressure (BP), a great proportion of treated patients does not reach recommended treatment targets. Typical antihypertensive drugs target the vessels, the kidneys, and the heart. However, our gut microbiota also influences cardiovascular health, and gut dysbiosis is associated with hypertension. In this study protocol, we investigate the potential BP-lowering effect of a probiotic in patients with grade 1 hypertension.
Methods:
This study is an exploratory, randomized, double-blind, placebo-controlled, parallel-group study. One hundred ten patients with grade 1 hypertension (treated or untreated) will be randomized to either the probiotic Vivomixx® or placebo. The primary endpoint is the nocturnal systolic BP measured by ambulatory blood pressure monitoring after 8 weeks adjusted for the baseline value. The secondary endpoints are changes from baseline in nocturnal diastolic BP, antihypertensive medication, fecal microbiome composition, fecal and serum metabolome, immune cell phenotypes, glucose variability after three standardized breakfasts, and health-related quality of life (PROMIS-29). We also assess the safety profile of the intervention.
Discussion:
We postulate that various administrated bacteria (Lactobacilli, Bifidobacteria, and Streptococcus thermophilus) convert dietary components into active metabolites that positively affect immune cell function. A reduction of pro-inflammatory immune cell function could promote a BP-lowering effect.
Trial registration:
ClinicalTrials.gov NCT03906578. Registered on 08 April 201
Metabolic Barriers to Weight Gain in Patients With Anorexia Nervosa: A Young Adult Case Report
Background: Over-proportionally high energy requirements in some patients with anorexia nervosa (AN) have been reported, but their exact origin remains unclear.Objective: To objectively measure metabolic alterations in an AN patient with high energy requirements as judged by clinical observation.Materials and Methods: We present the case of a young woman with AN (index patient, IP; 19 years, admission BMI 13.9 kg/m2). After 3 months of treatment at BMI 17.4 kg/m2, we assessed her resting energy expenditure (REE), respiratory exchange ratio (RER), diet-induced thermogenesis (DIT), seated non-exercise physical activity (NEPA in Volt by infrared sensors), and exercise activity thermogenesis (EAT) in a metabolic chamber; body composition (bioimpedance analysis), energy intake (15d-food protocol), physical activity (accelerometry) and endocrine parameters. The IP was compared for REE, RER, DIT and seated NEPA to six AN patients (AN-C) and four healthy women (HC-1), and for EAT to another six healthy women (HC-2).Results: Our IP showed high REE (110% of predicted REE according to Harris & Benedict) and high seated NEPA (47% increase over AN-C, 40% over HC-1), whereas DIT (IP: 78 vs. HC-1: 145 ± 51 kJ/180 min) and EAT (IP: 157 vs. HC-2: 235 ± 30 kJ/30 min) were low, when compared with HC. The other AN patients showed a lower REE (AN: 87 ± 2% vs. HC: 97 ± 2% predicted) at increased DIT (AN: 187 ± 91 vs. HC: 145 ± 51 kJ/180 min) when compared with HC. RER of the IP was low (IP: 0.72 vs. 0.77 in AN-C; 0.77 in HC-1 and 0.80 in HC-2).Conclusions: Complex and variable disturbances of energy metabolism might exist in a subgroup of patients with AN during refeeding, which could lead to unexpectedly high energy requirements. Future studies need to confirm the existence, and investigate the characteristics and prevalence of this subgroup.Clinical trial Registry number: NCT02087280, https://www.clinicaltrials.gov