Brain glutamate and sleep efficiency associations following a ketogenic diet intervention in individuals with Alcohol Use Disorder

Authors

Xinyi Li, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Zhenhao Shi, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Juliana Byanyima, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Peter T. Morgan, Department of Psychiatry, Yale University, New Haven, CT, 06519, USA.
Jan-Willem van der Veen, National Institute of Mental Health, Bethesda, MD, 20892, USA.
Rui Zhang, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
Erin Deneke, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Gene-Jack Wang, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
Nora D. Volkow, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
Corinde E. Wiers, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Document Type

Article

Publication Title

Drug and alcohol dependence reports

Abstract

BACKGROUND: We previously showed that ketogenic diet (KD) was effective in curbing alcohol withdrawal and craving in individuals with alcohol use disorder (AUD). We hypothesized that the clinical benefits were due to improvements in sleep. To test this, we performed a secondary analysis on the KD trial data to (1) examine the effects of KD on total sleep time (TST) and sleep quality and (2) investigate the association between KD-induced alterations in cingulate glutamate concentration and changes in TST and sleep quality. METHODS: AUD individuals undergoing alcohol detoxification were randomized to receive KD (n=19) or standard American diet (SA; n=14) for three weeks. TST was measured weekly by self-report, GENEActive sleep accelerometer, and X4 Sleep Profiler ambulatory device. Sleep quality was assessed using subjectively ratings of sleep depth and restedness and Sleep Profiler (Sleep Efficiency [%]). Weekly H magnetic resonance spectroscopy scans measured cingulate glutamate levels. RESULTS: TST was lower in KD than SA and increased with effect of time. Sleep depth, restedness, and Sleep Efficiency improved with time, but exhibited no effect of diet. In KD and SA combined, week 1 cingulate glutamate levels correlated positively with Sleep Efficiency, but not with TST. CONCLUSIONS: Although cingulate glutamate levels correlated positively with Sleep Efficiency in week 1, KD-induced glutamate elevation did not produce significant sleep improvements. Rather, KD was associated with lower TST than SA. Given the well-established associations between sleep and alcohol relapse, longer follow up assessment of KD's impact on sleep in AUD is warranted.

DOI

10.1016/j.dadr.2022.100092

Publication Date

12-1-2022

Recommended Citation

Li, Xinyi; Shi, Zhenhao; Byanyima, Juliana; Morgan, Peter T.; van der Veen, Jan-Willem; Zhang, Rui; Deneke, Erin; Wang, Gene-Jack; Volkow, Nora D.; and Wiers, Corinde E., "Brain glutamate and sleep efficiency associations following a ketogenic diet intervention in individuals with Alcohol Use Disorder" (2022). Randomized Controlled Trial. 11.
https://scholar.bridgeporthospital.org/randomized_trial/11

Identifier

36311277 (pubmed); NIHMS1837450 (mid); PMC9601174 (pmc); 10.1016/j.dadr.2022.100092 (doi); 100092 (pii)