Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study
Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study
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DOI：
10.1186/s13063-019-3928-9
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发表时间：
2020-01-02
期刊：
影响因子：
2.5
通讯作者：
Maehler, Anja
中科院分区：
文献类型：
--
作者：
Bahr, Lina Samira;Bock, Markus;Maehler, Anja
多发性硬化（MS）是年轻人中最常见的中枢神经系统炎性疾病，可导致进行性残疾。由于药物治疗可能有很大的副作用，因此需要补充治疗方案，如特定的饮食方法。禁食饮食（FD）和生酮饮食（KD）期间产生的酮体是大脑的一种替代能源，而且可能更有效。对患有实验性自身免疫性脑脊髓炎的小鼠的研究表明，KD和FD对疾病进展、残疾、认知和炎症标志物具有有益作用。然而，这些饮食的临床证据是稀缺的。在这里介绍的临床研究方案中，我们研究了KD和FD在治疗效果和疾病进展方面是否上级标准饮食（SD）。方法本研究为单中心、随机、对照、平行组研究。将111例目前疾病活动且接受稳定免疫调节治疗或未接受疾病改善治疗的复发缓解型MS患者随机分配至3种18个月饮食干预之一：KD，限制碳水化合物摄入量为20-40 g/天; FD，每6个月禁食7天，其间每日间歇性禁食14小时;以及德国营养学会推荐的脂肪改良SD。主要结局指标是18个月后新发T2加权MRI病变的数量。次要终点是安全性、复发率的变化、残疾进展、疲劳、抑郁、认知、生活质量、肠道微生物组的变化以及炎症、氧化应激和自噬的标志物。还将评估安全性和可行性。讨论临床前数据表明，KD和FD可以调节免疫力，降低疾病的严重程度，并促进髓鞘再生的MS小鼠模型，但缺乏临床证据。这项研究是第一项研究KD和FD对MS疾病进展影响的临床研究。
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.