Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

Abstract 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 (FD) and ketogenic diets (KD) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KD and FD 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 if 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. The dietary interventions are 1) a KD with a restricted carbohydrate intake of 20-40 g/day, 2) a FD with a 7 day fast every 6 months and 14 hours daily intermittent fasting in between, and 3) 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 KD and 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 FD on disease progression of MS. Trial Registration: ClinicalTrials.gov; NCT03508414; Registered 25 April 2018, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03508414

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Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

10.21203/rs.2.12185/v1 ◽

2019 ◽

Author(s):

Lina Samira Bahr ◽

Markus Bock ◽

Daniela Liebscher ◽

Judith Bellmann-Strobl ◽

Liane Franz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Study ◽

Disease Progression ◽

Clinical Evidence ◽

Controlled Study ◽

Intermittent Fasting ◽

Therapeutic Effects ◽

Dietary Interventions ◽

Randomized Controlled ◽

Markers Of Inflammation

Abstract 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 (FD) and ketogenic diets (KD) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KD and FD 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 if 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 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 dietary interventions over 18 months. Dietary interventions are 1) a KD with a carbohydrate intake of 20-40 g/day, 2) a FD with 7 days of fasting every 6 months and 14 hours intermittent fasting daily in between, and 3) a fat-modified SD as recommended by the German Nutrition Society. 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 KD and 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 FD on disease progression of MS. Trial Registration ClinicalTrials.gov; NCT03508414; Registered 25 April 2018, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03508414

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Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

Trials ◽

10.1186/s13063-019-3928-9 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 5

Author(s):

Lina Samira Bahr ◽

Markus Bock ◽

Daniela Liebscher ◽

Judith Bellmann-Strobl ◽

Liane Franz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Study ◽

Disease Progression ◽

Clinical Evidence ◽

Controlled Study ◽

Intermittent Fasting ◽

Therapeutic Effects ◽

Randomized Controlled ◽

Markers Of Inflammation ◽

Ketogenic Diets

Abstract 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. Trial registration ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.

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Treatment of Multiple Sclerosis By Antigen Specific Tolerance Induction with Synthetic Peptide Mbp8298: Hla-Dr Specific Delay of Disease Progression in a Phase LI Clinical Study

Clinical Immunology ◽

10.1016/j.clim.2006.04.417 ◽

2006 ◽

Vol 119 ◽

pp. S46

Author(s):

Mark Krantz ◽

Kenneth Warren ◽

Ingrid Catz ◽

Les Ferenczi

Keyword(s):

Multiple Sclerosis ◽

Clinical Study ◽

Disease Progression ◽

Synthetic Peptide ◽

Tolerance Induction ◽

Hla Dr ◽

Specific Tolerance

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Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666211209155333 ◽

2021 ◽

Vol 16 ◽

Author(s):

Lina María González ◽

Laura Natalia Ospina ◽

Laura Elena Sperling ◽

Orlando Chaparro ◽

Jaison Daniel Cucarián

Keyword(s):

Multiple Sclerosis ◽

Stem Cells ◽

Physical Exercise ◽

Disease Progression ◽

Neuronal Damage ◽

Experimental Studies ◽

Chronic Inflammatory Disease ◽

Therapeutic Effects ◽

Local Inflammatory Response ◽

Neuroinflammatory Response

Multiple sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by central nervous system (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

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