A small study comparing people with alcohol use disorder to healthy participants found that a single dose of a ketone ester supplement significantly reduced alcohol craving in participants with alcohol use disorder and shifted brain energy use from glucose to ketone bodies. The paper is Psychiatric research: neuroimaging.
Ketone esters are synthetic compounds designed to increase the levels of ketone bodies in the blood without the need for fasting or a strict ketogenic diet. Ketones are alternative energy molecules naturally produced by the liver when carbohydrate intake is low, especially on an empty stomach or during prolonged exercise.
The rationale behind this study comes from how alcohol changes brain metabolism. People who drink heavily are accustomed to using acetate (a byproduct of alcohol) for brain energy instead of glucose. When a person stops drinking, a sudden lack of acetate creates an energy deficit in the brain, which is thought to cause withdrawal symptoms and severe alcohol cravings. The researchers hypothesized that ketones, which act similarly to acetic acid, could serve as an alternative brain fuel that safely bridges this energy gap.
Ketone ester supplements typically contain molecules such as beta-hydroxybutyric acid (BHB) attached to alcohol, which is quickly converted into ketones that can be used by the body. These supplements quickly induce a state of nutritional ketosis within minutes of consumption.
Unlike ketone salts, ketone esters do not contain large amounts of minerals, making them more efficient at delivering higher ketone levels. May be used by athletes to (potentially) improve endurance performance by providing an alternative fuel source. Some studies suggest that it may also affect cognitive function by providing a stable energy substrate to the brain. However, the taste of ketone ester supplements is unpleasant (to most people) and can cause gastrointestinal discomfort in some users.
Study author Xinyi Li and colleagues wanted to investigate the effects of a single dose of ketone ester supplements. The researchers note that previous studies have shown that a single dose of a ketone ester supplement increases BHB levels in the blood 30 minutes after ingestion, and its effects peak 45 to 60 minutes after ingestion. This study investigated the effects on brain glucose metabolism in people with alcohol use disorder and healthy people. They also investigated how alcohol cravings changed after taking this supplement.
Study participants included five people with alcohol use disorders and five healthy people. Participants were between 21 and 65 years old. Three of them were women and seven were men. The average age of healthy participants was 36 years, while the average age of those with alcohol use disorder was 31 years.
There were two treatment conditions: no ketone ester supplement (baseline) and 395 mg/kg ketone ester supplement. All participants experienced both conditions over two visits to the laboratory, but the order in which they received treatments was randomly determined for each participant. At each visit, they completed a PET scan.
The ketone ester supplement that participants ingested was diluted with diet soda or carbonated water and given to participants 1 hour before undergoing a PET scan. The PET scan portion of the study was open-label, meaning no intervention was administered at the baseline visit and participants knew when to take their supplements. Study participants had blood samples taken upon arrival at the lab, before the injection of radioactive glucose (required for the PET scan to work), 30 minutes later, and 60 minutes later.
Participants with alcohol use disorder also underwent magnetic resonance spectroscopy (MRS), allowing the study authors to directly measure BHB levels in the brain. Unlike the PET scan, this MRS portion of the study was double-blind and placebo-controlled. Participants ingested either a ketone ester or a taste-matched bitter glucose placebo 45 minutes before the scan.
Results showed that ketone ester supplements lowered blood sugar levels and increased BHB levels in both groups. Brain scans revealed a 17% reduction in glucose metabolism, particularly in the frontal, occipital, and cingulate cortex, as well as the hippocampus, amygdala, and insular regions of the brain.
Ketone ester supplements significantly reduced self-reported alcohol craving in participants with alcohol use disorder. They also tripled BHB levels in the cingulate cortex region of the brain, proving that the supplement successfully crossed the blood-brain barrier.
“These findings suggest that a single dose of KE (ketone ester) can rapidly shift brain energy use from glucose to ketones, which may help reduce craving in AUD (alcohol use disorder), supporting its potential as a therapeutic approach,” the study authors concluded.
This study contributes to the scientific understanding of the physiological and psychological effects of ketone ester supplements. However, it should be noted that this study was conducted with a very small number of participants. Therefore, very large scale effects were required to detect an effect.
The authors of this paper are Xinyi Li, Anthony J. Young, Zhenhao Shi, Juliana Byanyima, Sianneh Vesslee, Rishika Reddy, Timothy Pond, Mark Elliott, Ravinder Reddy, Robert K. Doot, Jan-Willem van der Veen, Henry R. Kranzler, Ravi Prakash Reddy Nanga, Jacob G. Dubroff, and Corinde E. Weirs.
