Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents

Abstract

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower “wanting” and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.

Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice

“…To date, few studies have explored the relationship between alcohol consumption and KD, most of them focusing on ketoacidosis, a state in which the body’s insulin is so low that the liver produces excess levels of ketone bodies that would have neurotoxic properties [ 68 ]. Nevertheless, only a few studies have evaluated the interaction between KD and EtOH, one of them focused on the reduction of alcohol intake in rodents [ 51 ]. In this study, animals were first trained to lever press for alcohol in the vapor self-administration paradigm.…”

“…Martínez and co-workers [ 48 ] showed that animals on a KD showed decreased cocaine-induced stereotypies and sensitization in male and female rats, suggesting that the KD modulates the dopaminergic system. Regarding alcohol, KD has been reported to decrease alcohol withdrawal symptoms in rats [ 49 ] and mice [ 50 ], as well as reduce alcohol consumption in rats [ 51 ]. The recently published work by Wiers and co-workers [ 51 ] combines a preclinical and a clinical study.…”

“…Regarding alcohol, KD has been reported to decrease alcohol withdrawal symptoms in rats [ 49 ] and mice [ 50 ], as well as reduce alcohol consumption in rats [ 51 ]. The recently published work by Wiers and co-workers [ 51 ] combines a preclinical and a clinical study. In relation to the clinical study, Wiers and co-workers [ 51 ] also found that people with alcohol-use disorder who were on a KD had fewer withdrawal symptoms and required fewer medication the first week of detoxification than those following a standard American diet [ 51 ].…”

Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder

“…Several advantages of ketone supplementation, specifically with D-BHB, over the traditionally used KD have been described. Within 30 min of its administration, KE (which is commercially available in a slightly bitter but palatable liquid) induces levels of plasma ketone bodies similar to those observed after 2 weeks of KD, with the effects maintained for 4-5 h with no further dietary manipulation (8,15). Although KEs anecdotally are more effective in fasted states, their use, in contrast to KDs, does not require drastic carbohydrate restriction (39).…”

“…Recent preclinical and clinical studies show beneficial effects of a nutritional state of ketosis on alcohol withdrawal symptoms (6)(7)(8). Ketosis is characterized by elevated plasma and brain levels of ketone bodies (acetoacetate [AcAc], β-hydroxybutyrate [BHB] and acetone) that can be induced by prolonged or intermittent fasting, consumption of a low-carbohydrate, high-fat Ketogenic Diet (KD), a nutritional Ketone Ester (KE) supplement, Medium Chain Triglyceride (MCT) oils, or D-β-hydroxybutyrate (D-BHB) ketone salts.…”