Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats

Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wörtwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D.; Fink-Jensen, Anders

doi:10.1111/acer.13560

Cited by 33 publications

(33 citation statements)

References 46 publications

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“…For example, it is unclear if a diet high in fat is necessary to trigger reduced alcohol drinking behavior or if a diet high in sugar would induce the same effect. While a recent study showed a reduction of alcohol withdrawal syndrome following a high fat/ketogenic diet intake [62], studies exist demonstrating that excessive consumption of palatable/sweet food could curb alcohol drinking behavior in human alcoholics [10,11] which also agrees with the Alcoholics Anonymous recommendation of eating more sweet/palatable food to reduce alcohol craving [63]. These data collectively suggest that palatable food may compete with propensity to drink alcohol as both are capable of interacting with the brain reward circuitry.…”

Section: Discussionmentioning

confidence: 99%

Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats

et al. 2019

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We have previously shown that 6 weeks of intermittent high-fat diet (Int-HFD) pre-exposure significantly reduced alcohol drinking in rats, providing preliminary evidence of the effectiveness of a dietary intervention in reducing alcohol intake. However, the functional framework and underlying neurobiological mechanisms of such dietary intervention are unknown. Here, we examined the impact of Int-HFD pre-exposure duration on alcohol drinking, plasma feeding peptides, and central neurotransmitter receptors gene expression. Male Long Evans rats (n = 6–7/group) received no pre-exposure, 1 or 2 weeks pre-exposure to Int-HFD and alcohol drinking (two-bottle choice) was evaluated. We observed HFD pre-exposure-dependent decrease in alcohol drinking, with a significant decrease observed following 2 weeks of Int-HFD pre-exposure. No significant between-group differences in plasma feeding peptides (i.e., ghrelin, leptin, insulin) were detected. A PCR array revealed that the expression of several neurotransmitter receptors was significantly (p < 0.05 and ≥2-fold) altered in the striatum and ventral tegmental area compared to controls. These data suggest that pre-exposure to a palatable diet is critical to reduce alcohol drinking in rats, possibly through genetic alterations in the brain reward circuitry. Importantly, the present study is a step forward in identifying the critical framework needed to evaluate the therapeutic potential of nutritional contingency in the management of alcoholism.

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Section: Discussionmentioning

confidence: 99%

Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats

et al. 2019

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“…Previous studies have demonstrated that in addition to lactate, chronic EtOH exposure increases the production of ketone bodies (Kreisberg, ). Ketogenic diets and ketone supplementation have been demonstrated to improve memory, enhance hippocampal long‐term potentiation, and reduce the severity of EtOH withdrawal syndrome (Dencker et al., ; Hernandez et al., ; Newman et al., ). Similarly, astrocyte‐neuron lactate transfer is necessary for long‐term memory formation and long‐term potentiation (Suzuki et al., ).…”

Section: Discussionmentioning

confidence: 99%

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Lindberg

Peyton

et al. 2019

Alcoholism Clin & Exp Res

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Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones.Methods: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs.Results: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs.Conclusion: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.

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“…97 The concomitant consumption of a KD exacerbates the risk, and it is therefore to be recommend against the prescription of a KD to those with a history of alcohol and substance abuse where relapse seems possible, especially in the absence of adequate support. Noteworthy, a ketogenic diet seems to be effective in suppressing alcohol cravings both at a preclinical level and in subjects with obesity, 98,99 although it should be kept in mind that the physiology underlying such association might be very different across species, as the link in rodent models seems to be an elevation in Fibroblast Growth Factor 21 levels, 78,100 whereas such elevation following a ketogenic diet is not observed in human beings. 101…”

Section: Frail Elderly Patients History Of Mental Disorders and Sumentioning

confidence: 99%

Scientific evidence underlying contraindications to the ketogenic diet: An update

et al. 2020

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Summary First identified as a feasible treatment for intractable epilepsy, the ketogenic diet (KD) has recently gained popularity thanks to growing evidence on applications such as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and chronic pain. As with any treatment, whether pharmacologic or not, the KD might not be an appropriate intervention for every individual, and a number of contraindications have been proposed, now deeply rooted into clinical practice, excluding de facto many patients that could benefit from its use. However, many of these concerns were expressed due to the absence of clinical studies conducted on fragile populations, and an assessment of lately emerged evidence relative to KD safety is currently lacking and much needed. We herein provide a critical revision of the literature behind each safety alert, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation. Based on available evidence, the possible use of this diet as a therapeutic intervention should be assessed on a patient‐to‐patient basis by adequately skilled medical doctors, keeping in mind current recommendations, but reading them through the knowledge of the current state of the art.

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Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats

Abstract: Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans.

Cited by 33 publications

References 46 publications

Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats

Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Scientific evidence underlying contraindications to the ketogenic diet: An update

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