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The impact of ketogenic diet on the onset and progression of multiple sclerosis.

ABSTRACT: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. Current research suggests that diet may influence disease course, severity of symptoms, and quality of life in MS patients. The ketogenic diet (KD) has been used for more than a century as a therapeutic approach for various medical conditions. It was originally developed in the 1920s as a treatment option for epilepsy, and especially in the last 30 years, has gained popularity for its potential benefits in a variety of neurological conditions other than epilepsy. This prompted us to perform a literature survey regarding the effect of KD on the onset and progression of MS. The here reviewed 15 original research articles including in vitro, preclinical, and clinical studies provide evidence for the safety and feasibility of the KD in MS, showing potential neuroprotective effects and positive impacts on cellular metabolism and disease outcome. Since the literature is limited and most studies were conducted with low numbers of MS patients and rather exploratory in nature, further studies with larger cohorts are needed to gain a better understanding of the mechanisms by which the improvements of the MS disease course are achieved.

SUBMITTER: Brockhoff JD

PROVIDER: S-EPMC10578139 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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The impact of ketogenic diet on the onset and progression of multiple sclerosis.

Brockhoff Jurij D JD Bereswill Stefan S Heimesaat Markus M MM

European journal of microbiology & immunology 20230904 2

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. Current research suggests that diet may influence disease course, severity of symptoms, and quality of life in MS patients. The ketogenic diet (KD) has been used for more than a century as a therapeutic approach for various medical conditions. It was originally developed in the 1920s as a treatment option for epilepsy, and especially in the last 30 year ...[more]

PMID: 37665667

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Project description:BackgroundKetogenic diets (KDs) are safe and tolerable in people with multiple sclerosis (MS). While many patient-reported and clinical benefits are noted, the sustainability of these diets outside of a clinical trial is unknown.AimsEvaluate patient perceptions of the KD following intervention, determine the degree of adherence to KDs post-trial, and examine what factors increase the likelihood of KD continuation following the structured diet intervention trial.MethodsSixty-five subjects with relapsing MS previously enrolled into a 6-month prospective, intention-to-treat KD intervention. Following the 6-month trial, subjects were asked to return for a 3-month post-study follow-up, at which time patient reported outcomes, dietary recall, clinical outcome measures, and laboratory values were repeated. In addition, subjects completed a survey to evaluate sustained and attenuated benefits following completion of the intervention phase of the trial.ResultsFifty-two subjects (81%) returned for the 3-month post-KD intervention visit. Twenty-one percent reported continued adherence to a strict KD and an additional 37% reported adhering to a liberalized, less restrictive form of the KD. Those subjects with greater reductions in body mass index (BMI) and fatigue at 6-months on-diet were more likely to continue on KD following trial completion. Using intention-to-treat analysis, patient-reported and clinical outcomes at 3-months post-trial remained significantly improved from baseline (pre-KD), though the degree of improvement was slightly attenuated relative to outcomes at 6-months on KD. Regardless of diet type following the KD intervention, dietary patterns shifted toward greater protein and polyunsaturated fats and less carbohydrate/added sugar consumption.ConclusionsFollowing the 6-month KD intervention study, the majority of subjects elected to continue on KD, though many pursued a more liberal limit for carbohydrate restriction. Those who experienced a greater reduction in BMI or fatigue were more likely to continue with strict KD. The 6-month KD intervention induced persistent changes to dietary habits in the months following study completion.Trial registration informationRegistered on Clinicaltrials.gov under registration number NCT03718247, posted on Oct 24, 2018. First patient enrollment date: Nov 1, 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

Project description: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.

Project description:The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys [median (IQR) 5.03 (3.71, 6.34)], MSWS-12 [median (IQR) 5.28 (3.62, 6.94)] and HADS-Depression [median (IQR) 0.71 (0.47, 0.96)] scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores [median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively] while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis.

Dataset Information

The impact of ketogenic diet on the onset and progression of multiple sclerosis.

Publications

The impact of ketogenic diet on the onset and progression of multiple sclerosis.

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