Ketogenic Diet Research Articles

Metabolic Reprogramming via Ketogenic Diet: A Novel Approach to Combating Neurological Diseases

Epilepsy is a chronic neurological disorder characterized by a persistent tendency for the brain to generate seizures, affecting approximately 0.5–1% of the global population. Despite advances in pharmacological treatments and surgical interventions, around 30% of individuals with epilepsy continue to experience seizures, leading to significant impacts on quality of life. Among these individuals, many suffer from drug-resistant epilepsy (DRE), where seizures persist despite optimal drug therapy or surgical interventions.In recent years, the ketogenic diet (KD)—a high-fat, low-carbohydrate dietary regimen—has emerged as an effective non-pharmacological strategy for managing DRE. The KD works by inducing ketosis, a metabolic state where the body uses fat as the primary energy source instead of carbohydrates, which has been associated with neuroprotective effects and significant seizure reduction. Variants of the KD, such as the Modified Atkins Diet (MAD) and Low Glycemic Index Treatment (LGIT), offer less restrictive alternatives that have shown similar efficacy in reducing seizure frequency.This review explores the cellular and molecular mechanisms of the KD, evaluates its safety and tolerability across different age groups, and assesses its efficacy in treating epilepsy, particularly DRE. The findings underscore the potential of personalized dietary interventions to serve as effective adjunctive therapies in the management of epilepsy, offering new hope for individuals who do not respond to conventional treatments.

Пути оптимизации антропометрических параметров у детей с фармакорезистентной эпилепсией, получающих кетогенную диетотерапию

Ketogenic diet (KD) whilst being an effective method of diet therapy for drug-resistant epilepsy (DRE) is nevertheless accompanied by a significant number of side effects that include the possibility for the delayed physical development in pediatric patients. The problem is multifactorial and is primarily associated with the non-physiological nature of the ketogenic diet itself. Foreign studies on the KD effect on the physical development in children are contradictory and there are none domestic ones. The purpose of this research was to study the dynamics of anthropometric parameters in children with DRE against the background of KD and to assess the possibilities of the alimentary factor in its improvement. Materials and methods used: single-center retrospective cohort study had been carried out on the basis of the Russian Federal Research Centre for Nutrition, Biotechnology and Food Safety (Moscow, Russia) in 2016-2024. The study included patients with an established diagnosis of DRE against the background of KD aged 1 to 18 y/o. Patients were monitored for 24 months as follows: quarterly during the first year and semiannually during the second year of observation, using anthropometric, clinical-laboratory and clinical-instrumental research methods. Results: by the 3rd month of KD, out of 174 pediatric patients, the diet was effective in 105 (60%); by 12th month, 100% control over attacks was achieved in 11 (6%). Analysis of anthropometric parameters made it possible to establish that at the initial point of observation, in accordance with the z-score of the body mass index (BMI), 108 (64%) had normal nutritional status, 22 (13%) had malnutrition and 40 (24%) were overweight/obese. When studying the dynamics of weight and height indicators of children who were on KD throughout the observation period, it was found that the median BMI z-score statistically significantly changed upward (p=0.047), which was largely due to growth retardation, with a decrease in the height/age z-score throughout the observation period (p<0.001). It was found that the protein component of the diet, as well as the level of ketonemia, have a significant impact on the dynamics of the BMI z-score in KD patients. The amount of protein in the diet at 6% to 7% of the energy value contributed to the maintenance of optimal growth parameters in children within this research. Conclusion: the significance of the BMI indicator in assessing the nutritional status over KD decreases against the background of growth retardation. Taking into account the value of the protein/energy indicator when calculating nutrition helps in maintaining of the physical development rate in such patients.

Ketogenic Diet Improves Sleep Quality and Daytime Sleepiness in Chronic Migraine: A Pilot Study

Aims: The aim of this study is to assess the sleep quality and daytime sleepiness improvement in chronic migraineurs after 6 months of a 2:1 KD (ketogenic diet) and LGID (low-glycemic-index diet). Methods: Twenty-six patients underwent 2:1 KD (11 patients) and LGID (15 patients). PSQI (Pittsburgh sleep quality index) and ESS (Epworth sleepiness scale) were administered at the baseline and the 3-month and 6-month follow-up. MIDAS (Migraine Disability Assessment), HIT-6 (Headache Impact Test 6), migraine frequency (migraine days per month), migraine intensity, BMI (Body Mass Index), FM (Fat Mass), and FFM (Fat-Free Mass) were also assessed. Results: PSQI (F1.544, 38.606 = 7.250; p = 0.004), ESS (F1.988, 49.708 = 9.938; p < 0.001), HIT-6 (F1.432, 35.805 = 12.693; p < 0.001), migraine frequency (F1.522, 38.041 = 23.070; p < 0.001), migraine intensity (F1.949, 48.721 = 18.798; p < 0.001), BMI (F1.274, 31.857 = 38.191; p < 0.001), and FM (F1.245, 31.134 = 45.487; p < 0.001) improved significantly. The MIDAS (F1.005, 25.121 = 3.037; p = 0.093) and the FMM (F1.311, 32.784 = 1.741; p = 0.197) did not improve significantly. The ESS (p = 0.712) and PSQI (p = 0.776) data at 3-month and 6-month follow-ups did not differ significantly, as well as for migraine frequency, migraine intensity, BMI, FM, and HIT-6. A mild correlation emerged between the mean FM and mean ESS reduction during the 6 months (r = 0.497, p = 0.010). Conclusions: Six months of LGID and 2:1 KD can improve sleep quality and daytime sleepiness in patients with chronic migraine. The effectiveness on migraine, sleep quality, and daytime sleepiness does not differ significantly between the 3-month and 6-month follow-up periods.

Dietary Antioxidants and Natural Compounds in Preventing Thrombosis and Cardiovascular Disease

Reactive oxygen species (ROS) contribute to endothelial dysfunction, platelet activation, and coagulation abnormalities, promoting thrombus formation. Given the growing interest in non-pharmacological approaches to modulate oxidative stress, we examine the potential of various dietary interventions and antioxidant supplementation in reducing oxidative damage and preventing thrombotic events. Key dietary patterns, such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and ketogenic diets, as well as antioxidant-rich supplements like curcumin, selenium, and polyphenols, demonstrate promising effects in improving oxidative stress markers, lipid profiles, and inflammatory responses. This review highlights recent advances in the field, drawing from in vitro, ex vivo, and clinical studies, and underscores the importance of integrating dietary strategies into preventive and therapeutic approaches for managing thrombosis and cardiovascular health. Further research is needed to better understand long-term effects and personalize these interventions for optimizing patient outcomes.

Element Changes Occurring in Brain Point at the White Matter Abnormalities in Rats Exposed to the Ketogenic Diet During Prenatal Life.

A large number of clinical studies demonstrate that the ketogenic diet (KD) may be an effective approach to the reduction of epileptic seizures in children and adults. Such dietary therapy could also help pregnant women with epilepsy, especially since most antiseizure drugs have teratogenic action. However, there is a lack of medical data, considering the safety of using KD during gestation for the progeny. Therefore, we examined the influence of KD used prenatally in rats on the elemental composition of the selected brain regions in their offspring. For this purpose, synchrotron radiation-induced X-ray fluorescence (SR-XRF) microscopy was utilized, and elements such as P, S, K, Ca, Fe, and Zn were determined. Moreover, to verify whether the possible effects of KD are temporary or long-term, different stages of animal postnatal development were taken into account in our experiment. The obtained results confirmed the great applicability of SR-XRF microscopy to track the element changes occurring in the brain during postnatal development as well as those induced by prenatal exposure to the high-fat diet. The topographic analysis of the brains taken from offspring of mothers fed with KD during pregnancy and appropriate control individuals showed a potential influence of such dietary treatment on the brain levels of elements such as P and S. In the oldest progeny, a significant reduction of the surface of brain areas characterized by an increased P and S content, which histologically/morphologically correspond to white matter structures, was noticed. In turn, quantitative elemental analysis showed significantly decreased levels of Fe in the striatum and white matter of 30-day-old rats exposed prenatally to KD. This effect was temporary and was not noticed in adult animals. The observed abnormalities may be related to the changes in the accumulation of sphingomyelin and sulfatides and may testify about disturbances in the structure and integrity of the myelin, present in the white matter.

The impact of mild episodic ketosis on microglia and hippocampal long‐term depression in 5xFAD mice

AbstractKetotherapeutics is a potential metabolic intervention for mitigating dementias; however, its mechanisms and optimal methods of application are not well understood. Our previous in vitro study showed that β‐hydroxybutyrate (BHB), a major ketone body, reverses pathological features of amyloid‐β oligomer (AβO)‐activated microglia. Here we tested the in vivo effects of BHB on microglia and synaptic plasticity in the 5xFAD Alzheimer's disease (AD) mouse model. A short 1‐week regimen of daily intraperitoneal injection of BHB (250 mg/kg), which induced brief and mild daily episodic ketosis, was sufficient to mitigate pro‐inflammatory microglia activation and reduce brain amyloid‐β deposition by enhancing phagocytosis. Remarkably, it mitigated the deficits of hippocampal long‐term depression but not long‐term potentiation, and this effect was linked to suppression of NLRP3 inflammasome‐generated IL‐1β. As ketogenic diets are known for poor compliance, our study opens the possibility for alternative approaches such as short‐term BHB injections or dietary ketone esters that are less restrictive, potentially safer, and easier for compliance.

Ketogenic diet and intermittent fasting - impact on body weight and various diseases

Introduction and purpose: Obesity affects every age group and is associated with many negative health effects. Various diets are used to remove excess body weight. Recently, popular became two diets - intermittent fasting and ketogenic diet. Material and Method: This paper reviews various types of research documents published since 2018. Its main aim is to summarize the latest knowledge of ketogenic diet and intermittent fasting, including contraindications, side effects, impact on body weight and many diseases. It is also aimed to highlight the need for future research of the effects of both diets on various diseases and body weight reduction. Results: Both diets may be effective in weight loss and show other health benefits. Both ketogenic diet and intermittent fasting have proven to be effective in weight reduction. In the case of intermittent fasting the biggest impact on weight loss is calorie restriction. Ketogenic diet is effective as a result of calorie restriction, increased gluconeogenesis and loss of free water through increased diuresis. They can be used in the prevention and treatment of many diseases, including cardiovascular disorders, neurological disorders or potentially cancer. However, they cannot be administered by everyone and may cause dangerous side effects. Conclusion: Ketogenic diet and intermittent fasting are successful strategies for body weight reduction. Moreover, both of them may be used as an additional therapy for various diseases. However, patients should be under supervision.

Exploring Consumption of Ultra‐Processed Foods and Diet Quality in the Context of Popular Low Carbohydrate and Plant‐Based Dietary Approaches

ABSTRACTThis study investigates diet quality across four popular dietary patterns: Ketogenic Diet, Low‐Carbohydrate Healthy‐Fat, Vegetarian, and Vegan, employing the NOVA and Human Interference Scoring System (HISS) classification systems. Utilizing a modified Food Frequency Questionnaire (FFQ) and analyzing 168 participants' dietary habits, the research identifies notable differences in dietary quality among the dietary patterns. While all groups reported lower consumption of UPFs than the general population, plant‐based diets demonstrated higher UPF consumption than ketogenic and low carbohydrate diets. The study reveals that both NOVA and HISS effectively identify UPFs, with significant differences observed at various processing levels, except for UPFs where both systems showed similarity. This research contributes to the detailed understanding of diet quality within popular dietary patterns, highlighting the importance of considering food processing in dietary choices and the need for ongoing research to further elucidate the health implications of different types of UPFs.

The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy.

One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.

Ketone Esters Partially and Selectively Rescue Mitochondrial Bioenergetics After Acute Cervical Spinal Cord Injury in Rats: A Time-Course

Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-β-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4–6 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime.

European Society for the Study of Obesity (EASO) Position Statement on medical nutrition therapy for the management of individuals with overweight or obesity and cancer.

Obesity, a prevalent and multifactorial disease, is linked to a range of metabolic abnormalities, including insulin resistance, dyslipidemia, and chronic inflammation. These imbalances not only contribute to cardiometabolic diseases but also play a significant role in cancer pathogenesis. The rising prevalence of obesity underscores the need to investigate dietary strategies for effective weight management for individuals with overweight or obesity and cancer. This European Society for the Study of Obesity (EASO) position statement aimed to summarize current evidence on the role of obesity in cancer and to provide insights on the major nutritional interventions, including Mediterranean Diet (MedDiet), ketogenic diet (KD), and intermittent fasting (IF), that should be adopted to manage individuals with overweight or obesity and cancer. The MedDiet, characterized by high consumption of plant-based foods and moderate intake of olive oil, fish, and nuts, has been associated with a reduced cancer risk. The KD and the IF are emerging dietary interventions with potential benefits for weight loss and metabolic health. KD, by inducing ketosis, and IF, through periodic fasting cycles, may offer anticancer effects by modifying tumor metabolism and improving insulin sensitivity. Despite the promising results, current evidence on these dietary approaches in cancer management in individuals with overweight or obesity is limited and inconsistent, with challenges including variability in adherence and the need for personalized dietary plans.

The impact of 3 different dietary interventions on overweight or obese adults: A network meta-analysis.

This network meta-analysis aims to investigate and compare the effectiveness of 3 dietary interventions - Mediterranean, ketogenic, and low-fat diet - on overweight and obese adults, with a comparison to traditional low-calorie diet. A systematic review was conducted in both Chinese and English databases, including the China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), SinoMed, PubMed, Web of Science, Cochrane Library and Embase to identify relevant randomized controlled trials (RCTs) up to January 31, 2024. Two researchers independently screened and extracted data from the identified literature. The quality of these studies was assessed using the Cochrane bias risk assessment tool. A random-effects network meta-analysis was performed using Review Manager 5.4.1 and Stata 16.0 software. A total of 17 randomized controlled trials involving 5802 subjects were included in this study. The network meta-analysis revealed a descending order of effectiveness for reducing body weight (BW), body mass index (BMI), and waist circumference (WC): ketogenic diet > low-fat diet > low-calorie diet > Mediterranean diet. The ketogenic diet was identified as the most effective intervention for reducing BW, BMI, and WC in the studied dietary comparisons. It consistently showed superior outcomes, ranking highest in effectiveness among the 4 evaluated dietary approaches. Nevertheless, additional high-quality randomized controlled trials are necessary to validate these findings.

The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system of daf-18/PTEN Caenorhabditis elegans mutants.

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including autism spectrum disorders (ASDs). Mutations in Phosphatase and Tensin Homolog (PTEN), the main negative regulator of the phosphatidylinositol 3-phosphate kinase/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the Caenorhabditis elegans neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that daf-18/PTEN mutations impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The defects observed in the GABAergic system in daf-18/PTEN mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in daf-18/PTEN mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.

Effects of a Carbohydrate Meal on Lipolysis

Background: Due to the increasing prevalence of obesity and type 2 diabetes, effective dietary recommendations are needed. Previously, we developed the low-insulin method: by avoiding insulinogenic, i.e., insulin-release-triggering foods, insulin secretion becomes reduced, lipolysis is stimulated, and energy production is shifted to ketosis with excess ketone bodies exhaled in the form of acetone. Now, we investigate how quickly stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm) is achieved, whether and for how long a carbohydrate meal inhibits ketosis, and whether the responses differ in healthy adults with different insulin levels. Methods: An oral glucose tolerance test was conducted, and body composition and fasting insulin were determined at the beginning and end of the 14-day study. Participants (n = 10) followed a ketogenic diet and performed continuous glucose monitoring. Ketosis levels were determined by measuring breath acetone concentrations. On day 8, two white bread rolls with jam (72 g carbohydrates) were consumed for breakfast. Results: After seven days, all participants achieved stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm), which dropped from 8.2 to 5.7 ppm (p = 0.0014) after the carbohydrate meal. It took five days to achieve stable ketosis again. The stratification of participants into tertiles according to their fasting insulin levels demonstrated that individuals with low fasting insulin levels achieved stable ketosis again after two days and those with medium insulin levels after five days, while those with high baseline values did not reach stable ketosis by the end of the study. Conclusions: By carbohydrate restriction, stable ketosis can be achieved within one week. However, a single carbohydrate meal inhibits ketosis for several days. This effect is pronounced in individuals with elevated fasting insulin levels.

The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system of daf-18/PTEN Caenorhabditis elegans mutants

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including autism spectrum disorders (ASDs). Mutations in Phosphatase and Tensin Homolog (PTEN), the main negative regulator of the phosphatidylinositol 3-phosphate kinase/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the Caenorhabditis elegans neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that daf-18/PTEN mutations impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The defects observed in the GABAergic system in daf-18/PTEN mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in daf-18/PTEN mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.

Oral Administration of a Novel, Synthetic Ketogenic Compound Elevates Blood β-Hydroxybutyrate Levels in Mice in Both Fasted and Fed Conditions.

Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2-3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2-3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis.

Ketogenic Approaches for the Treatment of Alzheimer's Disease.

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.

Investigating the impact of ketogenic diets.

Exposure to ketone bodies in early development can reduce neurological impairments in a strain of the nematode C. elegans with PTEN defects.

Role of the ketogenic diet in the treatment of epilepsy

role of the ketogenic diet in the treatment of epilepsy

Exploring the role of ketogenic diet in ADPKD treatment: A promising avenue

Dear Editor, This letter intends to highlight the importance of the keto diet in the treatment and slowing the progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD). We aim to increase awareness about this newly advertised nutrition plan for ADPKD patients. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a disease that continuously expands multiple cysts in both kidneys. Clinical symptoms (Flanks pain, haematuria, hypertension) mostly develop in the fourth decade of life and around 50% of almost 12 million worldwide affected people will go into end-stage renal disease (ESRD) in their sixth decade of life.1 In 2015, EMA approved the use of Vasopressin receptor antagonists, i.e., tolvaptan, for the treatment of ADPKD in adults with CKD stages 1-3 and with rapidly progressive disease.2 However, these drugs are associated with side effects such as transient extracellular volume reduction and continuous symptoms of increased aquaresis, liver toxicity, avoiding pregnancy and breastfeeding and drug interactions.2 Moreover, strict criteria for patient selection such as GFR values, changes in GFR, patient age and cost-effectiveness needed to be fulfilled before commencing this particular therapy.2 The ongoing advancements in medical sciences have recently provided evidence that introducing the keto diet in patients with ADPKD can lead to a decline in the reduction rate of GFR and to a reduced rate of increasing kidney volume.3,4 A small study published in November 2023 compared the effects of the keto diet (KD) with control and water fasting groups.5 KD group surprisingly showed a decrease in height-adjusted total kidney volume by 0.55% and height-adjusted total liver volume by 4.7%.5 The most important observed effect was an increase in eGFR by 5.5% compared to the other groups, which showed a decrease in eGFR.5 Serum levels of Beta Hydroxy Butyrate were used to evaluate the ketosis state.5 The most commonly reported side effect was transiently occurring keto flu. However, one patient developed appendicitis and one patient also had nephrolithiasis.5 This three-month duration study overall shows good outcomes in ADPKD patients. We encourage physicians and the broader community of nephrologists to prioritise and carry out larger-scale randomised controlled trials based on the previously mentioned study using the keto diet in the management of ADPKD patients. This will require not only the aggressive participation of physicians in carrying out the research study but also the active education of the general public about this newly introduced nutrition plan. ---Continue