The ketogenic diet may have mood-stabilizing properties

doi:10.1054/mehy.2001.1446

Medical Hypotheses

Volume 57, Issue 6, December 2001, Pages 724-726

https://doi.org/10.1054/mehy.2001.1446 Get rights and content

Abstract

The ketogenic diet, originally introduced in the 1920s, has been undergoing a recent resurgence as an adjunctive treatment for refractory epilepsy, particularly in children. In this difficult-to-treat population, the diet exhibits remarkable efficacy with two-thirds showing significant reduction in seizure frequency and one-third becoming nearly seizure-free. There are several reasons to suspect that the ketogenic diet may also have utility as a mood stabilizer in bipolar illness. These include the observation that several anticonvulsant interventions may improve outcome in mood disorders. Furthermore, beneficial changes in brain-energy profile are noted in subjects on the ketogenic diet. This is important since global cerebral hypometabolism is a characteristic of the brains of depressed or manic individuals. Finally, the extracellular changes that occur in ketosis would be expected to decrease intracellular sodium concentrations, a common property of all effective mood stabilizers. Trials of the ketogenic diet in relapse prevention of bipolar mood episodes are warranted.

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Cited by (44)

The role of ketogenic therapy in developmental disorders
2023, Journal of Psychiatric Research
The ketogenic diet (KD) has been highlighted as a potential metabolic therapy for both neuropsychiatric and neurodegenerative diseases. Multiple underlying mechanisms have been identified to explain the anti-inflammatory, neuro-protective, anti-depressant and mood stabilizing effects of nutritional ketosis. This short paper examines the proposed mechanisms of KD and ponders about its clinical implications for neurodevelopmental disorders given similarities in pathogenic processes. We briefly review available evidence of the effects of ketogenic diet in ASD, RETT and PWS. Finally, we describe challenges and opportunities in implementation of ketogenic therapy and call for more research to understand the potential therapeutic effects of this dietary intervention in neurodevelopmental disorders.
Influence of anti-obesity strategies on brain function in health and review: A review
2023, Neurochemistry International
The aim of this review was to investigate in the literature the application of strategies such as low carbohydrate diet (LCD), ketogenic diet (KD) and intermittent fasting (IF) and their effects on the CNS. We performed a narrative review of the literature. The search was specifically carried out in PubMed, selecting articles in English, which had the following keywords: obesity, central nervous system, low carb diet, ketogenic diet and intermittent fasting, using the narrative review methodology. The studies found show that the benefits of the LCD, KD and IF strategies, at the CNS level, have a strong influence on the mechanisms of hunger and satiety, as well as on the reduction of food reward and show improvement in memory and mood influenced by the interventions.
Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments
2023, Journal of Affective Disorders Reports
Citation Excerpt :
The ketogenic diet has been used as an effective intervention for epilepsy since the 1920s (Neal et al., 2008). Recently, it has garnered more interest on its potential therapeutic effects on neuropsychiatric disorders and BD (Dsouza et al., 2019; El-Mallakh and Paskitti, 2001). The nutritional plan use fats as its main energy substrates replacing glucose by reducing carbohydrate intake.
Key underlying metabolic pathologies are thought to play a role in bipolar disorder (BD), including dysfunctions in energy metabolism. This review highlights underlying metabolic mechanisms of BD and potential therapeutic effects of a low carbohydrate ketogenic diet (KD) on mood symptoms. Based on its robust effectiveness in treating epilepsy, the KD has garnered recent interest in its application for mood disorders as it may imitate the pharmacological effects of mood stabilizers, commonly prescribed agents in the treatment of both BD and epilepsy, amongst other effects on stabilizing neural networks in the brain.
A literature review was conducted on current metabolic mechanisms of BD and clinical developments in KD.
Recent findings support the idea that BD may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction. A KD provides alternative fuel to the brain and is believed to contain beneficial neuroprotective effects, including neural network stabilization and inflammation reduction. Several beneficial metabolic effects on insulin resistance, weight, and lipid composition have been shown.
Limited case studies on KD treatment in BD have been reported to date.
Preliminary data support further testing of a low carbohydrate KD as a potential therapeutic tool in repairing energy metabolism in bipolar illness. Additionally, it may repair deficits in energy metabolism often seen in BD. Further research and clinical trials are needed to evaluate the efficacy of a KD as a supplemental or co-treatment of bipolar illness and an open-label pilot trial testing the diet in bipolar illness is currently underway at Stanford.
Changes in tryptophan and kynurenine pathway metabolites in the blood of children treated with ketogenic diet for refractory epilepsy
2019, Seizure
Citation Excerpt :
The same mechanism of KD-induced KAT upregulation cannot be ruled out as a driver of the anticonvulsant effect in our patients. It has also been documented that the KD exerts antidepressant and mood-stabilizing properties [20,21]. Similarly, Lee and coworkers suggested that mice fed a high-fat diet who perform aerobic exercise exhibit a rising KYNA/3-OH-KYN ratio, which is believed to be a meaningful anti-aging indicator [22].
There is growing evidence to support the role of the kynurenine pathway in the anticonvulsant efficacy of ketogenic diets (KDs) in refractory epilepsy. The aim of the present study was to measure blood levels of tryptophan (TRP) and its kynurenine derivatives and correlate them with seizure reduction after starting the KD in children with refractory epilepsy.
Sixteen children (9 F/7 M; 7.1 ± 5.1 years) with refractory epilepsy were treated with the KDs. Clinical efficacy and metabolic ketosis were monitored throughout the study; blood levels of TRP, kynurenine (KYN), kynurenic acid (KYNA), and 3-OH-kynurenine (3-OH-KYN) were measured at 3, 6, and 12 months on the diet and compared to the pre-KD levels.
Out of 16 children, 14 attained a ≥50% reduction (responders) in seizure frequency 3 months after starting the KD. In the 14 responders, TRP levels decreased numerically (18–25%) but not significantly (P = 0.077) compared to the pre-KD control values. KYN levels decreased significantly (30–57%; P = 0.001) compared to the pre-KD control levels while KYNA levels significantly increased (38–96%; P < 0.001). KYNA/KYN ratios significantly increased (100–323%; P = 0.003) while 3-OH-KYN levels (P = 0.680) and KYN/TRP ratios (P = 0.385) remained unchanged. Higher concentrations of KYNA and lower concentrations of KYN (P < 0.05) were found in patients who attained a higher reduction in seizure frequencies on the KD.
We report a pattern of changes in the blood level of kynurenines in patients with refractory epilepsy who started the KD. The results of this study further support the role of specific kynurenines (e.g. KYNA) in the efficacy of the KD in refractory epilepsy.
The influence of ketogenic diets on mood stability in bipolar disorder
2019, Asian Journal of Psychiatry
Dietary interventions for autism spectrum disorder: New perspectives from the gut-brain axis
2018, Physiology and Behavior
Citation Excerpt :
A systematic review of the administration of KD to individuals with ASD note positive effects especially for mild and moderate cases and some reports of improvements in seizure symptoms and behavioral deficits [9]. Yet, KD is also reported to lead to adverse effects including constipation, elevated serum cholesterol, decreased serum protein, hemolytic anemia, menstrual irregularities, and hospitalization due to vomiting and dehydration [5, 23]. So, it is important to understand the physiological effects of KD diets before recommending its use in ASD or other disorders.
There is still controversy surrounding the effectiveness of dietary interventions for autism spectrum disorder (ASD), namely the gluten-free/casein free diet and the ketogenic diet. Additionally, as studies mainly investigated their impact on ASD symptoms and behaviors, much remains unknown about their mechanisms of action and physiological effects. Given the recent surge of global interest in the gut-brain axis and its involvement in ASD, we underline the importance of understanding the physiological effects of such restrictive diets that remove certain nutritional items from one's diet. Some evidence has emerged with findings of the gut-microbial, inflammatory, and neuronal effects of these diets. We propose probiotics as a potential alternative that can serve similar biological purposes as these elimination diets and outline different physiological routes whereby probiotics can lead to improvements for individuals with ASD. We hope that future research can delineate the complete physiological effects of these diets. Such knowledge can guide the creation of more informed interventions, which conserve the components resulting in positive behavioral change while being less restrictive and devoid of the harmful effects of limiting certain nutrients.

View all citing articles on Scopus

^f1: Correspondence to: Rif S. El-Mallakah MD, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA

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Regular ArticleThe ketogenic diet may have mood-stabilizing properties

Abstract

J Am Diet Assoc

Pediatr Neurol

Epilepsy Res

J Urol

J Am Diet Assoc

MAGMA

Biol Psychiatry

J Affect Disord

Ketogenic diet in the treatment of epilepsy

N Engl J Med

Higher ketogenic diet ratios confer protection from seizures without neurotoxicity

Epilepsy Res

The ketogenic diet for intractable epilepsy in adults: preliminary results

Epilepsia

Complications of the ketogenic diet

Epilepsia

Cardiac complications in pediatric patients on the ketogenic diet

Neurology

An interdisciplinary team approach to implementing the ketogenic diet for the treatment of seizures

Pediatr Nurs

The efficacy of the ketogenic diet – 1998: a prospective evaluation of intervention in 150 children

Pediatrics

A multicenter study of the efficacy of the ketogenic diet

Arch Neurol

The ketogenic diet in refractory epilepsy: the experience of Children's Hospital of Pittsburgh

Clin Pediatr Philadelphia

Medication cost reduction in children on the ketogenic diet: data from a prospective study

J Child Neurol

Carbamazepine in manic-depressive illness: a new treatment

Am J Psychiatry

Carbamazepine versus lithium in mania: a double-blind study

J Clin Psychiatry

Valproate in the treatment of acute mania: a placebo-controlled study

Arch Gen Psychiatry

Regular Article
The ketogenic diet may have mood-stabilizing properties