ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026
A ketogenic diet reduces hepatic alcohol metabolism and alcohol consumption in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Previous work showed that rats that were exposed to a high-fat, low-carbohydrate/protein ketogenic diet (KD) exhibited elevated blood alcohol levels following alcohol exposure compared with rats fed regular chow. Additionally, the administration of a KD prior to alcohol exposure (i.e., a history of KD) reduced alcohol consumption in alcohol-dependent rats that were no longer on the diet. In the present study, we investigated the mechanisms by which a KD alters alcohol metabolism and tested whether ongoing KD exposure reduces alcohol consumption in rats. We hypothesized that chronic KD exposure alters hepatic alcohol-metabolizing enzymes, slows alcohol metabolism, and reduces alcohol self-administration in alcohol-dependent rats. We found that male and female rats maintained on a KD had higher blood alcohol levels, lower hepatic alcohol dehydrogenase 1 protein levels, and a higher nicotinamide adenine dinucleotide [NAD+]/[NADH] ratio in the liver cytoplasm compared with chow-fed control rats. Furthermore, KD-fed rats demonstrated lower brain glucose uptake relative to chow-fed control rats. In a model of alcohol dependence, the KD reduced alcohol consumption in male, but not female, rats compared with chow-fed rats. These findings suggest that a KD alters brain energetics and alcohol metabolism, which may contribute to reduced alcohol consumption in male rats.
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