The Origin of Nutritional Psychiatry Revealed by Ketone Bodies in Fetuses and Newborns —Molecular Basis of Perinatal Metabolic Environment and Brain Development—

Abstract

This study proposes a novel perspective on the unique characteristics of energy metabolism in h uman brain development, based on perinatal clinical data and molecular biological findings. The c oncentrations of ketone bodies in umbilical cord blood and intervillous space blood measured by t he authors in fetuses and newborns were markedly higher than adult reference levels, ranging fro m several hundred to several thousand µmol/L. This suggests that fetuses and newborns utilize not only glucose but also ketone bodies as major energy sources and as substrates for lipid synthesis required for brain structure formation. β-hydroxybutyrate functions not merely as an alternative fu el but as a signaling molecule, contributing to anti-inflammatory and antioxidant effects and the m aintenance of synaptic plasticity through inhibition of histone deacetylases and suppression of the NLRP3 inflammasome. Excessive glucose-dependent models may impair physiological ketosis and i ncrease the risk of neurodevelopmental disorders and future psychiatric diseases. From the perspect ive of the DOHaD (Developmental Origins of Health and Disease) hypothesis, which addresses ho w the perinatal metabolic environment affects mental resilience, this study reconsiders the origin o f nutritional psychiatry.