Department of Psychology and Neuroscience Program, Trinity College, Hartford, Connecticut, United States of America.
PLoS One. 2009 Dec 23;4(12):e8349. doi: 10.1371/journal.pone.0008349.
The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow) or ketogenic diet (79% fat) ad libitum for 3-4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund's adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature) as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.
生酮饮食是一种高脂肪、低碳水化合物的饮食方案，它迫使细胞代谢以酮体而非葡萄糖为基础。临床上，生酮饮食的维持已被证明在治疗小儿癫痫和 2 型糖尿病方面有效，最近的基础研究提供了证据，表明生酮策略在减少脑损伤方面有希望。生酮代谢可能通过减少活性氧物种和增加中枢腺苷来减轻疼痛和炎症，这一假说所假设的细胞机制为生酮饮食治疗的成功提供了依据。为了直接测试基于酮的代谢对疼痛和炎症的影响，我们让幼年和成年大鼠自由摄取对照饮食（标准啮齿动物饲料）或生酮饮食（79%脂肪）3-4 周。然后，我们量化了后爪热痛觉作为疼痛测量指标，以及完全弗氏佐剂诱导的局部后爪肿胀和血浆渗出（血管内液体流动）作为炎症测量指标。独立于年龄，生酮饮食的维持显著降低了外周炎症反应，表现为爪肿胀和血浆渗出减少。生酮饮食还诱导了明显的热痛觉低下，表现为热板痛觉测试中后爪潜伏期延长。抗炎和镇痛饮食作用在幼鼠中更为明显。生酮饮食在两个年龄组中均使血浆酮体水平升高相似，但仅在幼鼠中导致体重增长缓慢。这些数据表明，应用生酮饮食或利用与酮体代谢相关的细胞机制为控制疼痛和外周炎症提供了新的治疗机会，这种代谢策略可能为儿童和成人带来显著益处。
