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The NEW CNP Keto Diet and Mental Health Research Category consolidates research exploring the interconnected relationship between dietary intake and our environment. To view each original study on the open internet, click “Original.” To view the CNP-written abstract summary, click “CNP Summary.” While only some of the CNP-written abstract summaries are available below for free, all abstract summaries are available to CNP members through the CNP Library Membership.
The ketogenic diet (KD) has a long history of use in treating epileptic conditions in both children and adults. More recently, it has gained renewed interest for its potential therapeutic effects on cardiometabolic diseases. Furthermore, the anti-inflammatory and neuroprotective qualities of KD have demonstrated promise, indicating its uses in the prevention and/or treatment of a range of mental illnesses. The goal of this thorough literature analysis by Chrysafi et al. (2024) is to assess clinical evidence and previous studies about the possible advantages of KD for treating stress, anxiety, depression, bipolar disorder, and schizophrenia. A thorough literature search was conducted to encompass the breadth of research in this area and identify gaps in the current scientific knowledge. A thorough search of Scopus, PubMed, and Web of Science was conducted using pertinent keywords for relevant animal and clinical human research. An increasing amount of studies on the effects of KD on depression, anxiety, stress, schizophrenia, and bipolar illness have been conducted recently on both people and animals. Animal studies have consistently shown promising results, indicating a potential to alleviate symptoms of these psychiatric disorders. However, translating these findings to clinical practice poses challenges. Many clinical studies are of moderate quality, often lacking proper controls and assessing only the short-term effects of KD. Additionally, issues such as high dropout rates, poor compliance measurement, and methodological heterogeneity are prevalent. While the available evidence is promising, larger, longer-term, randomized, double-blind, controlled clinical trials with prospective designs are needed to establish definitive conclusions regarding the potential preventive or adjunctive role of the KD in treating stress, anxiety, depression, schizophrenia, and bipolar disorder. It is also necessary to do further fundamental research in animal models to clarify the biochemical processes that underlie the KD's impacts on various mental illnesses. [NPID: Ketogenic diet, depression, anxiety, stress, schizophrenia, bipolar disorder, animal studies, clinical human studies, psychiatric disorders, carbohydrates restriction]
Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice
Aging adversely affects brain function, leading to cognitive decline. While a cyclic ketogenic diet (KD) has been shown to enhance memory in aged mice with prolonged use, its short-term effects later in life and the underlying molecular mechanisms are poorly understood. This study by Acuña-Catalán et al. (2024) investigates the impact of a short-term KD treatment initiated during the elderly stage on brain function in aged mice. Behavioral tests and long-term potentiation (LTP) recordings demonstrate that KD improves working memory and enhances hippocampal LTP. Moreover, analysis of synaptosome proteome in aged mice on long-term KD reveals significant changes primarily in the presynaptic compartment, particularly associated with the protein kinase A (PKA) signaling pathway. In vivo western blot analysis supports these findings, showing increased levels of brain-derived neurotrophic factor (BDNF) and phosphorylation of PKA substrates. In conclusion, the authors demonstrate that even short-term administration of KD modifies brain function in aged mice and mirrors molecular changes observed with long-term KD use, notably involving the PKA signaling pathway. These alterations promote synaptic plasticity in the advanced stages of life. [NPID: BDNF, LTP, PKA, aging, brain-derived neurotrophic factor, ketogenic diet, long-term potentiation, protein kinase A, proteomics, β-hydroxybutyrate]
CNP Research Summary can be found in the CNP Library Membership
Ketone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer’s disease
Among the subtypes of dementia, Alzheimer's disease (AD) is the most prevalent kind. AD is a neurological disease that worsens with time and is marked by behavioral abnormalities and cognitive dysfunction, including memory and learning impairments. Changes in fluid biomarkers, such as glial fibrillary acidic protein (GFAP), amyloid beta plaques (Aβ), phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, and neurofilament light (NFL), are linked to neuropathology pathognomonic markers of Alzheimer's disease (AD), including Aβ and neurofibrillary tangles containing the neuron-specific protein tau. Mitochondrial damage and decreased brain glucose metabolism can be seen up to 15 years before clinical signs of AD manifest. Furthermore, neural damage and astrocyte hyperactivation, which can result in elevated pro-inflammatory mediators and oxidative stress, are further pathogenic characteristics of AD. Since the brains of AD patients have trouble using glucose, Ramezani et al. (2023) postulate that ketone bodies (KBs) might be a viable energy source. The β-oxidation of fatty acids produces KBs. β-oxidation can be accelerated after consuming moderate-protein, high-fat, low-carbohydrate ketogenic diets. It has been demonstrated that KBs enhance brain energy metabolism by crossing the blood-brain barrier. The existing body of research on the benefits of increasing KBs for brain energy metabolism is included in this review. Furthermore, the authors highlight that their study addresses for the first time how the ketogenic diet affects potential AD biomarkers such as NFL, GFAP, tau (particularly p-tau 181), Aβ, and NFL. It also addresses the impact of KBs on mitochondrial metabolism, oxidative stress, and neuroinflammation. [NPID: Dementia, Alzheimer's disease, dietary intervention, ketone bodies, ketosis, brain metabolism]
Ketogenic Diet intervention on metabolic and psychiatric health in Bipolar and Schizophrenia: A pilot trial
The ketogenic diet (KD), also referred to as metabolic therapy, has demonstrated efficacy in addressing conditions such as type 2 diabetes, obesity, and epilepsy. Recently, KD has emerged as a promising treatment for psychiatric disorders. We conducted a four-month pilot study to explore the impact of KD on individuals with schizophrenia or bipolar disorder who had preexisting metabolic issues. Twenty-three participants took part in a single-arm trial, revealing notable improvements in metabolic health, with none of the participants meeting the criteria for metabolic syndrome by the study's end. Fidelity to the diet granted the participants substantial decreases in body mass index (BMI, 12%), weight (12%), waist circumference (13%), and visceral adipose tissue (36%). Biomarker improvements were also observed, including a 25% reduction in triglyceride levels and a 27% decrease in HOMA-IR. The overall severity of Clinical Global Impression (CGI) ratings improved by an average of 31%, with 79% of participants who initially presented with elevated symptoms showing improvement of at least one point on CGI. Evaluation of psychiatric variables showed that participants diagnosed with schizophrenia had experienced a 32% reduction in Brief Psychiatric Rating Scale scores. Moreover, the authors noted improved psychiatric outcomes, including improved sleep quality (19%) and increased life satisfaction (17%). The authors conclude that this pilot trial underscores the potential benefits of incorporating ketogenic dietary treatment as an adjunctive therapy for individuals grappling with severe mental illness.
Ketogenic diet has a positive association with mental and emotional well-being in the general population
In this study by Garner et al. (2024), the authors explored the effects of a ketogenic diet on mental health aspects in individuals from the general population, which have been relatively understudied compared to its effects in clinical contexts. While the ketogenic diet is commonly used for weight loss, and its physical effects have been researched in healthy individuals, its holistic impact, including psychological effects, remains less understood. To better understand how a ketogenic diet relates to several mental health markers as tranquility, contentment, alertness, cognitive and emotional stress, sadness, anxiety, and loneliness in a non-clinical population, the authors conducted a cross-sectional research using numerous cohorts. Two separate online surveys were conducted. The first cohort (n = 147) utilized the Perceived Stress and the Bond-Lader visual analog scales. In contrast, the second cohort (n = 276) employed the updated UCLA Loneliness Scale alongside the Depression Anxiety Stress Scale. Following a ketogenic diet was associated with greater levels of mental and emotional well-being on several measures compared to a general population that followed a non-specific diet. This study suggests that a ketogenic diet may offer psychological benefits for individuals in the general population, shedding light on its broader impacts beyond weight loss and physical health. [NPID: Ketogenic diet, depression, loneliness, mood, anxiety, stress]
