Ketosis Elevates Antioxidants and Enhances Neural Function Through Improved Bioenergetics: A ¹ H MR Spectroscopy Study

Ketosis is known to alter the balance of neuroactive amino acids and enhance neural function when compared to a glycolytic condition. However, its influence on other metabolites, such as antioxidants and neural energy markers, and the mechanisms by which ketosis improves neural function remain unclear. Here, we measure the neurochemical effects of acute ketosis on the human brain using ultra-high-field ¹ H MR Spectroscopy (MRS) and investigate the subsequent impact on neural function through resting-state functional magnetic resonance imaging (rsfMRI). In a within-subjects design, N = 63 healthy adults from across the lifespan underwent ¹ H MRS and rsfMRI scans before and after consuming individually weight-dosed and calorically-matched ketone monoester or glucose drinks. Ketone monoester administration, but not glucose, significantly elevated cerebral antioxidants and energy markers while decreasing GABA, glutamate, and glutamine levels in the posterior cingulate cortex (PCC). Notably, increased bioenergetics, specifically an increase in total creatine, correlated with greater improvements in neural function as measured using rsfMRI. Our results integrate metabolic and functional neuroimaging findings, offering a comprehensive understanding of ketosis-induced changes in brain chemistry and functional network dynamics, yielding valuable insights into potential mechanisms by which ketosis imparts its neural benefits.