Ketogenic diets are high-fat, low-carbohydrate, moderate protein diets used as a treatment option for drug-resistant epilepsy. These diets are the treatment of choice for rare, neurometabolic disorders, such as glucose transport type 1 deficiency syndrome and pyruvate dehydrogenase deficiency, and are effective in reducing seizure frequency in approximately 40% of patients with epilepsy. In a ketogenic diet, circulating ketone bodies increase the acidic milieu of the body and thus, the risk of metabolic acidosis, with the potential consequences of nephrolithiasis, nephrocalcinosis, and bone mineral density loss. Oral citrate supplementation may be given to individuals on ketogenic diet therapy as an alkalizing agent to treat metabolic acidosis and also prophylactically, particularly when used alongside concomitant carbonic anhydrase inhibitors (topiramate, zonisamide, or acetazolamide). These can independently increase the risk of nephrolithiasis and, potentially, worsen pre-existing metabolic acidosis. Bjurulf et al. present findings that none of 22 individuals following a ketogenic diet for epilepsy and receiving potassium citrate supplementation developed uncompensated metabolic acidosis, including clinical symptoms, compared to 10 out of 29 individuals who received no supplementation. Potassium citrate supplementation did not affect serum beta-hydroxybutyrate concentrations or 7-month efficacy rates. This study adds to the body of literature showing the effectiveness of prophylactic potassium citrate supplementation in preventing nephrolithiasis in individuals taking carbonic anhydrase inhibitors or other antiseizure drugs. It also provides reassurance that supplementation does not affect ketogenic diet efficacy. The authors rightly highlight that a higher median age at diet initiation in the group receiving supplementation compared to the nonsupplemented group could have influenced results, potentially due to different ketogenic ratios and acidic load per unit of body weight. However, the proportion of patients taking carbonic anhydrase inhibitors should have been stated and controlled for in the analyses. Whether citrate supplementation should be used for everybody commencing a ketogenic diet, just for those at increased risk of metabolic acidosis or related complications, or solely to treat ketogenic diet-related adverse events, requires clarification. International best practice guidelines state that oral citrates help prevent renal stone formation, but give no other specific recommendations. Current practice depends on centre-specific clinical protocols. The long-term effects of chronic, low-grade pH reduction associated with ketogenic diet therapy are largely unknown, as are the long-term effects of citrate supplementation. It is of interest to know whether prophylactic supplementation effects long-term efficacy rates, particularly within specific phenotypic subgroups. This knowledge would provide further insight into the mechanisms of action of ketogenic diets. Bjurulf et al. present interesting findings and, although not novel nor likely to immediately change clinical practice, we welcome the study as an addition to the collective evidence regarding this controversial issue.

中文翻译：

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补充柠檬酸钾与生酮饮食疗法治疗耐药性癫痫

生酮饮食是高脂肪、低碳水化合物、中等蛋白质的饮食，用作耐药性癫痫的治疗选择。这些饮食是治疗罕见的神经代谢疾病（如 1 型葡萄糖转运缺陷综合征和丙酮酸脱氢酶缺乏症）的首选，可有效降低约 40% 的癫痫患者的癫痫发作频率。在生酮饮食中，循环中的酮体会增加身体的酸性环境，从而增加代谢性酸中毒的风险，并可能导致肾结石、肾钙质沉着症和骨矿物质密度损失。口服柠檬酸盐补充剂可以给予接受生酮饮食疗法的个体作为碱化剂来治疗代谢性酸中毒，也可以预防性地，特别是与伴随的碳酸酐酶抑制剂（托吡酯、唑尼沙胺或乙酰唑胺）一起使用时。这些可以独立地增加肾结石的风险，并可能使先前存在的代谢性酸中毒恶化。Bjurulf 等。目前的研究结果表明，在接受生酮饮食治疗癫痫并接受柠檬酸钾补充的 22 个人中，没有一个人发生未代偿性代谢性酸中毒，包括临床症状，而 29 个人中没有接受补充的 10 个人。柠檬酸钾补充剂不影响血清 β-羟基丁酸浓度或 7 个月的有效率。该研究补充了大量文献，表明预防性补充柠檬酸钾对预防服用碳酸酐酶抑制剂或其他抗癫痫药的个体肾结石的有效性。它还保证补充剂不会影响生酮饮食的功效。作者正确地强调，与未补充组相比，接受补充组的饮食开始时的中位年龄可能会影响结果，这可能是由于不同的生酮比例和每单位体重的酸负荷。然而，应在分析中说明和控制服用碳酸酐酶抑制剂的患者比例。每个开始生酮饮食的人都应该补充柠檬酸盐吗？只是对于那些代谢性酸中毒或相关并发症风险增加的人，或仅用于治疗与生酮饮食相关的不良事件，需要澄清。国际最佳实践指南指出，口服柠檬酸盐有助于预防肾结石的形成，但没有给出其他具体建议。当前的实践取决于中心特定的临床协议。与生酮饮食疗法相关的慢性、低度 pH 值降低的长期影响在很大程度上是未知的，柠檬酸补充剂的长期影响也是如此。了解预防性补充是否会影响长期有效率是很有趣的，尤其是在特定的表型亚组中。这些知识将提供对生酮饮食作用机制的进一步了解。Bjurulf 等。展示有趣的发现，并且，