Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
The Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
J Inherit Metab Dis. 2020 Jul;43(4):778-786. doi: 10.1002/jimd.12223. Epub 2020 Feb 24.
Glycogen storage disease type V (GSDV) is a rare inborn error of carbohydrate metabolism. Patients present with exercise intolerance due to blocked glycogen breakdown in skeletal muscle. Introducing alternative fuel substrates, such as ketone bodies (KBs), could potentially alleviate muscle symptoms. This pilot study investigates which of three different modified ketogenic diet regimes is optimal for GSDV-patients to follow in a future large-scale study. Participants were randomised to follow one of three diet regimes for 3 weeks (#1: 65%/15%/20%; #2: 75%/15%/10%, or #3: 80%/15%/5%, fat/protein/carbohydrate). The primary outcome was exercise tolerance assessed by heart rate (HR) changes during constant load cycling. Secondary outcomes included levels of ketosis, and changes in perceived exertion and indirect calorimetry measures during exercise. Ten GSDV-patients were included. Eight completed the study. The other two were excluded. Diet #3 showed the highest average KB level (1.1 mmol/L) vs #2 (0.5 mmol/L) and #1 (0.3 mmol/L). Five patients reported subjective symptom relief, all of whom were on diets #2 and #3. All diet regimes seemed to improve fatty acid oxidation rates and exercise capacity as indicated by a small decrease in HR and perceived exertion. The results of this open-label pilot study show that diets #2 and #3 induce ketosis and improve symptoms and exercise capacity in GSDV-patients. Diet #2 had the highest acceptability score and was superior or equal to diet #3 in all other parameters, except level of ketosis. Based on this, we suggest testing diet #2 in a large-scale, placebo-controlled study in GSDV.
糖原贮积病 V 型（GSDV）是一种罕见的碳水化合物代谢先天性缺陷。患者由于骨骼肌中糖原分解受阻而出现运动不耐受。引入替代燃料底物，如酮体（KBs），可能会缓解肌肉症状。这项初步研究旨在探讨三种不同改良生酮饮食方案中哪一种最适合 GSDV 患者在未来的大规模研究中遵循。参与者被随机分配遵循三种饮食方案中的一种 3 周（#1：65%/15%/20%；#2：75%/15%/10%，或#3：80%/15%/5%，脂肪/蛋白质/碳水化合物）。主要结局是通过恒负荷踏车运动时的心率（HR）变化评估运动耐量。次要结局包括酮症水平，以及运动时感知用力和间接量热法测量的变化。10 名 GSDV 患者入组。8 名完成了研究。另外两名被排除。方案 #3 的平均 KB 水平最高（1.1mmol/L），与方案 #2（0.5mmol/L）和方案 #1（0.3mmol/L）相比。有 5 名患者报告主观症状缓解，他们都在方案 #2 和 #3 中。所有饮食方案似乎都改善了脂肪酸氧化率和运动能力，表现为 HR 和感知用力的小幅度降低。这项开放标签初步研究的结果表明，方案 #2 和 #3 诱导酮症并改善 GSDV 患者的症状和运动能力。方案 #2 的可接受性评分最高，除了酮症水平外，在所有其他参数上均优于或等同于方案 #3。基于此，我们建议在 GSDV 中进行一项大型、安慰剂对照研究来测试方案 #2。
