改良生酮饮食能否成为麦克尔氏病患者的一种营养策略？一项随机、单盲、安慰剂对照、交叉研究的结果。
Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study.
作者信息
Løkken Nicoline, Nielsen Maja Risager, Stemmerik Mads Godtfeldt, Ellerton Charlotte, Revsbech Karoline Lolk, Macrae Margaret, Slipsager Anna, Krett Bjørg, Beha Gry Hatting, Emanuelsson Frida, van Hall Gerrit, Quinlivan Rosaline, Vissing John
机构信息
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
出版信息
Clin Nutr. 2023 Nov;42(11):2124-2137. doi: 10.1016/j.clnu.2023.09.006. Epub 2023 Sep 20.
BACKGROUND
McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogenolysis in skeletal muscle. Consequently, individuals with McArdle disease have intolerance to physical activity, muscle fatigue, and pain. These symptoms vary according to the availability of alternative fuels for muscle contraction. In theory, a modified ketogenic diet (mKD) can provide alternative fuels in the form of ketone bodies and potentially boost fat oxidation.
METHODS
This randomized, single-blind, placebo-controlled, cross-over study aimed to investigate if a mKD improves exercise capacity in individuals with McArdle disease. Participants were randomized to follow a mKD (75-80% fat, 15% protein, 5-10% carbohydrates) or placebo diet (PD) first for three weeks, followed by a wash-out period, and then the opposite diet. The primary outcome was change in heart rate during constant-load cycling. Secondary outcomes included change in plasma metabolites, perceived exertion, indirect calorimetry measures, maximal exercise capacity, and patient-reported outcomes.
RESULTS
Fifteen out of 20 patients with genetically verified McArdle disease completed all study visits, and 14 were included in the data analyses. We found that the mKD induced a metabolic shift towards increased fat oxidation (∼60% increase), and a 19-fold increase in plasma β-hydroxybutyrate (p < 0.05). The mKD did not improve heart rate responses during constant-load cycling but did improve patient-reported outcomes and maximal exercise capacity (∼20% increase) compared to the PD.
CONCLUSION
The mKD did not alleviate all McArdle disease-related symptoms but did induce some positive changes. To date, no satisfactory treatment options exist other than exercise training. To that end, a mKD can be a possible nutritional strategy for some individuals with McArdle disease who are motivated to undertake a restrictive diet.
CLINICAL TRIAL REGISTRATION
clinical trials.gov: NCT04044508.
背景
麦克尔迪氏病由肌磷酸化酶缺乏引起，导致骨骼肌糖原分解受阻。因此，患有麦克尔迪氏病的个体不耐受体力活动、肌肉疲劳和疼痛。这些症状因肌肉收缩的替代燃料可用性而异。理论上，改良生酮饮食（mKD）可以以酮体的形式提供替代燃料，并可能促进脂肪氧化。
方法
这项随机、单盲、安慰剂对照、交叉研究旨在调查mKD是否能改善麦克尔迪氏病患者的运动能力。参与者被随机分为先遵循mKD（75 - 80%脂肪、15%蛋白质、5 - 10%碳水化合物）或安慰剂饮食（PD）三周，随后是洗脱期，然后是相反的饮食。主要结局是恒负荷骑行期间心率的变化。次要结局包括血浆代谢物的变化、主观用力程度、间接测热法测量、最大运动能力以及患者报告的结局。
结果
20例经基因验证的麦克尔迪氏病患者中有15例完成了所有研究访视，14例纳入数据分析。我们发现mKD诱导了代谢向脂肪氧化增加（约增加60%）的转变，血浆β-羟基丁酸增加了19倍（p < 0.05）。mKD在恒负荷骑行期间并未改善心率反应，但与PD相比，确实改善了患者报告的结局和最大运动能力（约增加20%）。
结论
mKD并未缓解所有与麦克尔迪氏病相关的症状，但确实诱导了一些积极变化。迄今为止，除了运动训练外，没有令人满意的治疗选择。为此，mKD对于一些有动力接受限制性饮食的麦克尔迪氏病患者可能是一种可行的营养策略。
临床试验注册
clinicaltrials.gov：NCT04044508。
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