The regulation of blood-brain barrier permeability of ketone bodies in ketogenic diet.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Kawamura Masahito 東京慈恵会医科大学, 医学部, 准教授 (10408388)
• Co-Investigator(Kenkyū-buntansha): 西 晴久 東京慈恵会医科大学, 医学部, 講師 (70256428)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ketogenic diet / 小児てんかん / 抗けいれん作用

Outline of Final Research Achievements

A ketogenic diet increases ketone bodies in the blood and has been used successfully to treat pediatric epilepsy by mimicking fasting. However, ketogenic diet has the disadvantage that it takes longer to cause antiepileptic effects than fasting. To elucidate the reason for this discrepancy, we examined biokinetics of ketone bodies underlies ketogenic diet and fasting. The ketogenic diet took longer than fasting for the onset of anticonvulsant effects and the increase in cerebrospinal fluid concentrations of ketone body. On the other hand, blood concentrations of ketone body were significantly lower during ketogenic diet than during fasting. The permeability of ketone body was low in the cultured cell model of the blood-brain barrier. The lower increase in blood ketone concentrations during ketogenic diet than during fasting and the low blood-brain barrier permeability of ketone bodies might delay the time to onset of anticonvulsant effects.

Free Research Field

中枢神経薬理

Academic Significance and Societal Importance of the Research Achievements

ケトン食療法は薬剤耐性てんかんに対しても有用であることが示されている。また近年は、自閉症スペクトラム障害や統合失調症などの難治性中枢神経系疾患への治療効果も示唆されており、小児てんかん以外への適応拡大も期待されている。ケトン食療法におけるケトン体の中枢移行性を含めた体内動態を解明することは、難治性中枢神経系疾患に対するケトン食療法の適応拡大への一助になるだけでなく、脳内のエネルギー供給経路を理解するために重要な基盤研究となる。