케톤생성식이요법에 의한 연령-의존성 케토시스에 대한 연구

Abstract

Purpose：Ketogenic diet (KD) remains a therapy in search of explanation although it is an established treatment for patients with intractable epilepsy. It has been clinically proven more efficacious at younger ages, presumably because of the enhanced ability of the immature brain to extract and utilize ketone bodies. The study was designed to investigate whether ketosis induced by the KD is agedependent. Methods：A KD ([fat]：[protein+carbohydrate] ratio of 4.3：1) was administered to male Sprague-Dawley rats for 3 weeks, while control animals were fed a standard rodent chow. Dietary treatment was initiated at either postnatal 3 or 12 weeks. Blood β-hydroxybutyrate (BHB) levels were assayed from blood obtained via the tail vein with the Keto-SiteTM reflectance meter and test cards on treatment day 21. Results：Blood BHB levels in the KD-treated group were significantly higher than those in the control group in 3 week-old rats (4.18±0.62 [n=30] vs. 0.27±0.02 [n=30] mM, respectively; p< 0.0001) and 12 week-old rats (0.86±0.06 [n=30] vs. 0.22±0.02 [n=30] mM, respectively; p<0.0001). In the KD-treated groups, blood BHB levels of 3 week-old animals were significantly higher than those of 12 week-old ones (p<0.0001), whereas in the control groups, no significant differences in blood BHB levels between the two age groups (p>0.05). Conclusions：The present study demonstrates that the KD induces more severe ketosis in younger rats. Age-dependent differences in the degree of ketosis induced by the KD may explain that the diet is clinically more efficacious at younger ages.