In a recent study published in the journal Frontiers in Nutritiona group of researchers investigated whether a ketogenic diet (KD) reduces the neurobiological craving signature (NCS) and self-reported alcohol craving in patients undergoing inpatient treatment for alcohol use disorder (AUD).
Study: Ketogenic diet reduces neurobiological craving signature in inpatients with alcohol use disorder. Image credit: Lightspring / Shutterstock
Record
AUD poses a major global health problem, responsible for 5% of deaths worldwide. Characterized by intense craving and continued consumption despite adverse consequences, current treatments are limited. A new approach involving a high-fat, low-carb diet shows promise by boosting brain energy, potentially reducing withdrawal symptoms and cravings. Recent studies, including research demonstrating a reduction in withdrawal symptoms and craving among AUD patients with CD, highlight its potential efficacy. Additionally, an NCS detected via brain imaging provides insight into the intensity of craving. Further research is needed to fully understand the mechanisms by which a KD affects NCS and to investigate its long-term efficacy and applicability in different AUD populations.
About the study
The present study provides a secondary analysis of functional magnetic resonance imaging (fMRI) data on alcohol reactivity, originally collected in a clinical trial, to investigate the effects of a KD versus a standard American diet (SA) in individuals with AUD. Participants, admitted to the National Institute on Alcohol Abuse and Alcoholism for up to four weeks, were randomly assigned to either diet within two days of admission. Both diets were isocaloric, ensuring that any observed effects could be attributed to diet composition rather than caloric intake.
Participants were rigorously screened to ensure they met study inclusion criteria, excluding those with MRI contraindications or serious medical conditions. The study’s dietary intervention was carefully designed, with the KD providing a 4:1 ratio of fat to carbohydrate and protein and the SA diet providing a more balanced caloric distribution. Meals were prepared by the Metabolic Kitchen Nutrition Department, ensuring precise nutritional control.
Blood ketone levels were monitored throughout the study, providing biochemical evidence of the physiological effects of the diet. Participants’ desire for alcohol was assessed using the Desire for Alcohol Questionnaire, and intelligence, drinking history, and severity of dependence were also assessed using standardized questionnaires.
MRI scans were performed at three intervals during the dietary intervention, with preprocessing and analysis tailored to explore the NCS. This involved comparing patterns of brain activation in response to alcohol versus food cues, seeking to understand how KD might modulate this neurobiological response to reduce alcohol craving.
Study results
The study showed a significant increase in serum beta-hydroxybutyrate (BHB) levels in the KD group compared to those on the SA diet, indicating successful induction of dietary ketosis. At baseline, there was no difference in blood ketone levels between the groups. However, as the study progressed, KD participants experienced a marked increase in BHB levels, peaking in the second week and declining slightly in the third week, which was attributed to minor non-adherence in some participants. In contrast, the SA group maintained low BHB levels throughout, confirming adherence to the non-ketogenic diet.
Regarding self-reported alcohol craving, measured by the Alcohol Craving Questionnaire (DAQ), there was a trend toward a decrease over time, particularly in the KD group, suggesting a possible effect of diet in reducing alcohol craving. This trend, however, did not reach statistical significance when the two dietary interventions were directly compared.
The study also assessed participants’ reactivity to alcohol cues using fMRI, revealing a decrease in wanting alcohol cues over time in the KD group, an effect not seen in the SA group. The difference between groups over time was statistically significant, underscoring the potential of KD in reducing alcohol craving in AUD patients. Interestingly, this effect was specific to alcohol cues, as no significant changes were observed in response to food cues, nor were there significant differences in valence ratings of alcohol or food cues.
A key finding of this analysis was a significant effect of dietary groups on NCS for alcohol relative to food cues, with the KD group showing lower NCS levels than the SA group, suggesting reduced neural craving in response to alcohol cues among them who had KD. However, no significant time-dependent changes in NCS were observed, indicating that the effect of KD in reducing neurobiological craving was consistent throughout the study period. Additionally, a correlation between mean serum BHB levels and NCS scores suggested a link between higher ketone levels and lower alcohol craving, aligning with the hypothesis that nutritional ketosis could modulate craving responses in AUD.
