Ketone supplements vs. alcohol: New study uncovers a surprising interaction

New findings suggest ketone supplements could significantly impact alcohol consumption and cravings. The research, published in the International Journal of Neuropsychopharmacology, found that ketone supplements not only reduced breath and blood alcohol concentrations but also diminished the subjective appeal of alcohol.

Ketogenic diets have gained significant attention not only for their weight loss benefits but also for their potential therapeutic effects on various health conditions. At their core, ketogenic diets are high in fats, moderate in proteins, and very low in carbohydrates. By drastically reducing carbohydrate intake and replacing it with fat, the body is pushed into a metabolic state known as ketosis.

In this state, the body turns fat into ketones in the liver, which can supply energy for the brain. Ketones are three water-soluble molecules (acetone, acetoacetate, and beta-hydroxybutyrate) that are produced as by-products when fatty acids are broken down for energy. This metabolic process is a natural response to food scarcity, allowing the body to utilize its fat reserves as a primary energy source.

The motivation behind the current study stems from the sobering statistics regarding alcohol use disorder (AUD) and its widespread impact in the United States, where a significant portion of the population engages in binge drinking and exhibits criteria for AUD. Excessive alcohol consumption is linked with a myriad of health risks, including increased reckless behaviors, cognitive decline, liver disease, and various cancers, positioning it as a leading cause of preventable death.

Previous research has highlighted the potential of nutritional ketosis, induced either through ketogenic diets or exogenous ketone supplements, to alleviate symptoms of alcohol withdrawal and reduce alcohol craving and consumption. In their new study, the researchers sought to better understand how consuming exogenous ketones (supplements) might influence physiological and subjective responses to alcohol intake.

Free daily newsletter

“We previously found that a ketogenic diet intervention reduced alcohol withdrawal and alcohol craving in patients with AUD during alcohol detoxification treatment, and in animal models found that a ketogenic diet decreased alcohol consumption,” said study author Corinde E. Wiers, an assistant professor of psychiatry at the University of Pennsylvania.

“Because a ketogenic diet is difficult to maintain, we are studying the use of ketone supplements (Kenetik) for the treatment of alcohol use disorder. Because the ketone supplement and alcohol require similar enzymes in the liver to break down, we wanted to understand how people responded to alcohol after the intake of a ketone supplement. To our surprise, blood and breath levels were significantly lower for the same alcohol dose, when paired with ketones, and alcohol liking and wanting were also down.”

The study was carried out at the University of Pennsylvania and was structured as a single-blinded, cross-over trial, ensuring that each participant served as their own control by receiving both the ketone supplement and a placebo in a randomized order across two separate visits.

Participants were carefully selected to include healthy individuals between the ages of 21 and 50 who had consumed alcohol at least once in the prior month. The study excluded anyone with significant medical conditions, psychiatric or substance use disorders (other than nicotine or cannabis), pregnant or lactating females, individuals over a certain weight threshold, or those with a baseline breath alcohol level above 0.00%. This resulted in a cohort of ten participants who completed the study.

On each study visit, participants were asked to arrive after an overnight fast and were provided with a standardized meal. Approximately one hour after meal consumption, they consumed either the ketone supplement or placebo, followed by an oral dose of alcohol 30 minutes later.

The ketone drink contained ketones and the low-calorie sweetener allulose, whereas the placebo consisted of a non-ketogenic sweet and sour mix. The alcohol dose was adjusted for body weight and sex to target a specific breath alcohol concentration (0.05%), aiming to standardize the alcohol exposure across participants.

The researchers observed significant reductions in both breath and blood alcohol concentrations (BrAC and BAL) following the intake of the ketone supplement compared to the placebo. This indicated that the ketone supplement could attenuate the physiological presence of alcohol in the body.

Subjectively, participants reported a decrease in alcohol liking and wanting and an increase in alcohol disliking after consuming the ketone supplement, suggesting that the supplement could alter the rewarding effects of alcohol.

In addition to these primary outcomes, the study also noted changes in blood glucose and ketone levels, providing insights into the metabolic effects of the ketone supplement. Blood glucose levels were significantly lower following the intake of the ketone supplement, while ketone levels were elevated, reinforcing the metabolic shift induced by the supplement.

The findings suggest that “pairing a ketone supplement with alcohol reduces alcohol intoxication – it makes you less tipsy! We need to understand more whether the supplement slows down the absorption of alcohol in the stomach, and/or if it increases the metabolism of alcohol in the liver,” Wiers told PsyPost.

In parallel to the human study, the researchers conducted a investigation using rodents. This study involved a total of eight Wistar rats, evenly divided by sex. Each rat received one of three treatments via oral gavage: a dose of ketone supplement, allulose, or water (serving as the control). Thirty minutes following this administration, the rats were given a dose of alcohol orally, simulating the human study’s alcohol challenge but adjusted for the physiological differences between species.

Unlike in humans, where the ketone supplement led to significant changes in alcohol sensitivity and subjective responses, the rodent study focused on the physiological metrics of BAL, blood glucose, and ketone levels. The results showed that the ketone supplement significantly reduced BAL compared to both the water and allulose treatments at several time points following alcohol administration.

Notably, the study found no significant effects of the allulose treatment on BAL, indicating that the observed reductions in alcohol levels were specifically attributable to the ketone supplement rather than the sweetener component. Additionally, the study reported significant increases in blood β-hydroxybutyrate levels following ketone administration, confirming the efficacy of the supplement in inducing ketosis in rodents.

“We previously found that rats on a 6-week ketogenic diet could not tolerate alcohol well: Rats on the ketogenic diet vs control diet had 6x higher blood alcohol levels than rats on a regular chow diet,” Wiers noted. “We were wondering if an acute dose of a ketone supplement would also had an effect on blood and breath alcohol levels. With the ketone supplement, we found the exact opposite effect (lower breath and blood alcohol levels, both in humans and rats), which was very surprising to us. The ketogenic diet and ketone supplement affect alcohol metabolism differently.”

The study’s limitations include its small sample size and the focus on healthy volunteers rather than individuals with AUD. Furthermore, the placebo and ketone supplement were not calorically matched, and the unpleasant taste of the ketone supplement may have influenced subjective responses to alcohol.

“We gave very little alcohol” in the current study, Wiers noted. “We are recruiting for a new study now in which we give 3 different diets to social drinkers for 3.5 days: (1) ketogenic diet, (2) control diet, (3) control diet + ketone supplement before breakfast lunch and dinner. We will bring up alcohol levels to approximately 0.08% (the legal drinking limit), so that we can also assess effects of ketosis (diet vs supplement) on alcohol-induced cognitive impairments.”

“The long-term goals are to develop ketone therapy for individuals with alcohol use disorder (reducing alcohol withdrawal, reducing consumption), to improve brain energetics and decrease alcohol consumption/withdrawal in outpatient and inpatient settings e.g.: Mahajan, 2021. The current study may also suggest that ketone drinks could aid in sober drinking cultures.”

The study, “Ketone Supplementation Dampens Subjective and Objective Responses to Alcohol: Evidence From a Preclinical Rat Study and a Randomized, Cross-Over Trial in Healthy Volunteers,” was authored by Xinyi Li, Zhenhao Shi, Dustin R. Todaro, Timothy Pond, Juliana I Byanyima, Sianneh A. Vesslee, Rishika Reddy, Ravi Prakash Reddy Nanga, Gabriel Kass, Vijay Ramchandani, Henry R. Kranzler, Janaina C M Vendruscolo, Leandro F Vendruscolo, and Corinde E. Wiers