β hydroxybutyrate levels in serum and cerebrospinal fluid under ketone body metabolism in rats

A high-fat, low–carbohydrate diet (KD) or calorie restriction in the form of every-other-day fasting (EODF) results in ketone body metabolism with an increasing β-hydroxybutyrate (βOHB) level. Previous studies have supported that a KD and EODF have a neuroprotective effect. However, the βOHB levels in the cerebrospinal fluid (CSF) resulting from a KD and EODF remain unknown. The aim of this study was to detect βOHB levels in rats fed a KD, EODF diet, and every-other-day ketogenic diet (EODKD) and to compare the serum βOHB level with the CSF βOHB level. Twenty-four male Sprague-Dawley rats were randomly divided into KD, EODF, EODKD, and standard diet (SD) groups. A customized food with a ratio of carbohydrates to fats of 1:4 was used in the KD and EODKD groups. The βOHB level was measured using ELISA kits in 200 µl serum and 100 µl CSF samples for each rat after feeding for 2 weeks. The KD, EODF, and EODKD resulted in a significant increase in βOHB levels in both the serum and CSF. The βOHB levels in the EODKD group were the highest. The CSF βOHB level was, on average, 69% of the serum βOHB level. There was a positive correlation between the overall βOHB levels in serum and that in cerebrospinal fluid. This study demonstrated that the KD, EODF, and EODKD resulted in ketone body metabolism, as the βOHB levels increased significantly compared with those resulting from the standard diet. Our results suggested that the serum βOHB level was an indicator of the CSF βOHB level, and that the EODKD was an effective diet to enhance ketogenic metabolism.