Keto diets may be much more than a weight loss fad — cutting out carbs and eating foods rich in healthy fats may also help people with alcohol use disorder (AUD) manage their withdrawal symptoms and cravings while they undergo treatment, according to a new study of 33 patients in the April 9 issue of Science Advances.
The study found that patients who went on a ketogenic diet for three weeks required fewer benzodiazepine drugs to manage their alcohol withdrawal symptoms within the first week of treatment than those on a standard American diet. Patients on the keto diet also reported reduced cravings when exposed to alcohol cues over three weeks and tended to have lower withdrawal scores.
Furthermore, experiments in rats suggested that a ketogenic diet could offer long-lasting benefits for those with AUD, even after a return to a standard diet.
"Even though our study needs to be replicated, ideally in an outpatient setting, I predict that some clinicians might start recommending a keto diet to their patients, since this diet is already being used for the treatment of epilepsy and is generally safe," said Nora Volkow, director of the National Institute on Drug Abuse and chief of the Laboratory of Neuroimaging at the National Institute on Alcohol Abuse and Alcoholism and one of the senior authors of the study.
More Than a Trendy Diet
In recent years, the keto diet has experienced a boom in popularity as a trendy weight loss tool used by stars like Vanessa Hudgens, world-class athletes like LeBron James, and anybody looking to burn fat and build muscle. The diet emphasizes healthy fat and proteins, such as eggs, meat, butter, avocados, and nuts, while minimizing carbohydrates. This way, the body relies less on glucose for energy and instead enters a metabolic state called ketosis, converting fat into energy molecules called ketones.
While a body of evidence does support that a keto diet promotes weight loss, it was not previously known whether it could help addiction sufferers overcome AUD. However, Volkow and colleagues had reason to believe it might. The researchers had previously performed brain imaging studies that showed alcohol markedly reduced glucose metabolism by the brain, with more pronounced reductions in people with AUD than in non-drinkers. Noting that these non-drinkers became intoxicated with doses of alcohol that barely affected those with the disorder, they corroborated their hypothesis that the brain uses acetate instead of glucose during intoxication and that those with AUD more readily switch to metabolizing acetate.
"We reasoned that during withdrawal, as alcohol leaves the body, the brain of a person with AUD would be in a state of energy deprivation contributing to the withdrawal symptoms and neurotoxicity," said Volkow. "This led us to hypothesize that, by providing ketone bodies, a ketogenic diet would help avoid the state of energy deprivation to the brain and improve withdrawal symptoms and brain recovery."
Double-Blind Diet Shakes
To investigate whether an energy deficit state emerges in the brain when patients with AUD detox and to determine if a keto diet might help, the researchers placed 19 treatment-seeking patients on a keto diet and 14 on a standard American diet for three weeks. Dieticians at the National Institutes of Health clinic prepared the patients either a keto diet shake, which contained 80% fat, 15% protein and 5% carbohydrates, or a shake with 50% calories from carbohydrates, 15% protein and 35% fat. Patients in both groups also ate ketogenic snacks for breakfast, lunch, and dinner.
"We tested shakes to aim for a double-blind study approach: neither the investigators nor the patients knew if they were on the ketogenic diet or the standard American control diet," said Corinde Wiers, assistant professor of psychiatry at the University of Pennsylvania's Perelman School of Medicine and former postdoctoral fellow at NIAAA and the lead author of the study.
The researchers measured ketones in the patients' urine each day before breakfast and performed weekly scans to measure levels of brain ketones, amino acids, and markers of neuroinflammation. They also took weekly measurements of serum ketone, a hallmark of ketosis. Each week, the participants also rated their alcohol cravings using a questionnaire, and each day before and after breakfast and dinner they were asked to rate other feelings, including how alert, tired, anxious, or irritable they felt and their sugar cravings.
Since this clinical study could not evaluate whether the keto diet reduced alcohol intake, the researchers also conducted experiments in rats. They trained 36 adult male rats to access alcohol or water using levers, then fed 18 rats a keto diet and 18 a regular chow diet. They found that rats that had been on a ketogenic diet six to seven weeks previously before resuming a regular diet consumed significantly less alcohol than those only fed the regular diet, hinting that the special diet could confer long-lasting benefits.
"We were not surprised by the clinical findings since we had hypothesized the results and these were also consistent with prior preclinical work," said Volkow. "However, we were surprised by the reduction in alcohol consumption that [study co-authors] Dr. Vendruscolo and Dr. Koob uncovered in the rats that had been exposed to a ketogenic diet. "
Next, Wiers plans to test a dietary supplement to raise ketones in place of the keto diet, which could make it easier for patients to comply and receive the diet's benefits.