Ketogenic Diet Research Articles

Refractory Epilepsy in Adult Patient With COQ8A Variant Improves With CoQ10 Supplementation: A Case for Exome Sequencing in the ICU.

Describe a case of stroke-like episodes and refractory status epilepticus diagnosed with primary CoQ10 deficiency-4 (COQ10D4) using whole-exome sequencing in the intensive care unit (ICU), with treatment implications. A patient presented to the emergency department with 1 month of progressively worsening focal motor status epilepticus and stroke-like imaging abnormalities. Multiple seizure medications, ketogenic diet, and elective intubation for anesthetic drips failed to achieve sustained seizure freedom. Genetic testing was pursued for prognostic information and identified potential treatment. Whole-exome sequencing revealed compound heterozygous variants of COQ8A, including 1 allele not previously described as pathogenic. The patient's history, imaging, and genetic testing supported a diagnosis of COQ10D4. High-dose coenzyme Q10 supplementation was started with gradual clinical improvement. Whole-exome sequencing is a fast and cost-effective means to diagnose rare neurologic disease in critically ill patients and can uncover treatment options. While primarily used in the neonatal ICU, appropriately selected adult patients may also benefit.

MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine

MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.

The impact of a ketogenic diet on weight loss, metabolism, body composition and quality of life

The impact of a ketogenic diet on weight loss, metabolism, body composition and quality of life

Keto-therapy: Unveiling the potential of ketogenic diet in psychiatric care – A systematic review

Keto-therapy: Unveiling the potential of ketogenic diet in psychiatric care – A systematic review

A Ketogenic Diet Alters Liver Cyst Progression in a Rodent Model of Polycystic Kidney Disease and Is Dependent on GPR109A

A Ketogenic Diet Alters Liver Cyst Progression in a Rodent Model of Polycystic Kidney Disease and Is Dependent on GPR109A

Early Insights from Grease II: Safety and Efficacy of a Ketogenic Diet in ADPKD

Early Insights from Grease II: Safety and Efficacy of a Ketogenic Diet in ADPKD

The gut microbiome without any plant food? A case study on the gut microbiome of a healthy carnivore

Objective The carnivore diet is a ketogenic diet based exclusively on the consumption of food of animal origin. While the impact of various diets on the gut microbiome is extensively documented, the effects of a carnivore diet remain unclear. To address this gap, we conducted a pilot study on the gut microbiome of an individual following a carnivore diet and compared it with that of a subgroup of healthy individuals. Methods A stool sample was collected from a healthy 32-year-old male adhering to a carnivore diet and was sequenced using 16S DNA Amplicon Sequencing. The results were then compared to those from three control groups possessing similar anthropometric characteristics and differing in their frequency of meat consumption. Results The gut microbiome of the carnivore was dominated by the phylum Firmicutes and the genera Faecalibacterium, Blautia, unspecific Lachnospiraceae, Bacteroides, and Roseburia—bacteria known for fiber degradation. Furthermore, neither alpha- nor beta-diversity, nor the functional capacity of the gut microbiome, showed differences when compared to the control groups. Additionally, the gut microbiome of the carnivore showed the least similarities with the microbiome of the cohort consuming meat on a daily basis. Conclusions In our study, we showcase the compositional and functional characteristics of the gut microbiome in an individual on a carnivorous diet, finding no differences in comparison to a control cohort. Further research is needed to investigate the short- and long-term impacts of a carnivorous diet on gut health through cross-sectional and longitudinal studies. Significance statement To the best of our knowledge this is the first study to report on the composition of the gut microbiome of a person adhering long-term to the carnivore diet.

Ketorash: An underdiagnosed entity

Ketoacidosis-Induced Prurigo Pigmentosa is a rare, inflammatory disease characterized by pruritic, erythematous papules with a reticulate pattern on the torso and neck. It affects predominantly young adult Asian women with risk factors for metabolic ketosis, such as Diabetes Mellitus, anorexia nervosa, bariatric surgery and ketogenic diet. A 26-year-old female being treated for refractory focal frontal and generalized epilepsy with ketogenic diet for four months was consulted due to a three-month-long dermatosis which started in the anterior and posterior cervical region and progressed towards the dorsal midline area. Skin lesions were papular and erythematous, often merging with a vaguely reticulated pattern. These lesions were highly pruriginous and worsened during periods ofhigher ketonemia. Histological examination of a cutaneous biopsy sample was compatible with Ketorash. The patient suspended ketogenic diet and was medicated with topical erythromycin, with full resolution of the lesions and no recurrences after 8 months.

Intermittent Fasting on Cancer: An Update

Intermittent fasting (IF) has garnered considerable interest as a dietary intervention with potential therapeutic benefits for various medical conditions, particularly cancer. This review provides a comprehensive update on the effects of IF on cancer, emphasizing its impact on metabolic, hormonal, and cellular mechanisms. IF has been shown to improve glycemic control and reduce liver enzyme levels in patients with non-alcoholic fatty liver disease (NAFLD), suggesting a reduction in liver cancer risk. It can significantly reduce tumor growth and enhance apoptosis in breast cancer by lowering insulin-like growth factor 1 (IGF-1) levels. In patients with polycystic ovary syndrome (PCOS), IF offers superior metabolic and hormonal regulation, potentially lowering cancer risk. IF mitigates chemotherapy-related toxicities, thereby improving patient quality of life. It modulates metabolic pathways, reduces inflammation, and enhances drug delivery in cancer therapy. Personalized dietary strategies, including IF and ketogenic diets, are crucial in cancer care. IF also benefits liver conditions by reducing inflammation and fibrosis, preventing the progression to hepatocellular carcinoma. In obesity-induced triple-negative breast cancer, IF disrupts critical processes involved in cancer progression. In addition, aligning IF with circadian rhythms has shown promise in treating lung cancer. Patient perspectives reveal that IF is feasible and acceptable, improving treatment adherence and quality of life. Overall, IF represents a multifaceted approach to cancer prevention and therapy. This review advocates for further research to establish standardized guidelines for implementing IF in oncology, aiming to develop more effective and holistic cancer treatment strategies.

Trends and hotspots on the relationship between gut microbiota and Parkinson's Disease: a bibliometric analysis.

Parkinson's disease (PD) is a neurodegenerative disorder that significantly impacts patients' quality of life. Recent evidence has highlighted a complex relationship between the gut microbiota (GM) and PD. Understanding this relationship is crucial for potentially targeting GM in PD treatment and expanding therapeutic options. This study aimed to comprehensively analyze the global landscape, trends, and research focus on GM and PD using bibliometric analysis. Utilizing publications from the Web of Science Core Collection (WsSCC), bibliometric tools such as the R package 'Bibliometrix,' VOS viewer, and CiteSpace software were employed to assess parameters like yearly publications, countries/regions, institutions, and authors. Research trends and hotspots were identified through keyword analysis. The results revealed 1,161 articles published between 2013-2023, with China leading in publications (n=352, 30.31% of total), while the United States had a higher influence (H-index=58). The University of California System was the top institution in terms of publications (n=35), with the National Natural Science Foundation of China funding the most projects (n=172). Keshavarzian A and Sampson TR were the authors with the highest publication and co-citation counts, respectively. The International Journal of Molecular Sciences had the most articles published (n=48). Keyword analysis identified parkinson's disease, gut microbiota, short-chain fatty acids, inflammation, and probiotics as main research topics. Biomarkers, ketogenic diet, and NF-κB were recent research hotspots and trends (2021-2023). The current study conducts an objective and comprehensive analysis of these publications, identifying trends and hotspots in the field of research. The findings offer valuable insights to scholars globally and in-vestigate potential therapeutic strategies for Parkinson's Disease.

POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic-atonic seizures and ataxia.

POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures. The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants. We used online gene-matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas. All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic-atonic, atypical absence, or tonic-clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic-atonic seizures (EMAtS) in seven patients and "probable EMAtS" in two more. Seizures were treatment resistant in all cases. Three patients became seizure-free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset. Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3). Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13). POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients.

Study on the influence of ketogenic diet and intermittent fasting on the change of body fat rate

The purpose of this study is to explore the influence of ketogenic diet and intermittent fasting on the change of body fat rate, and to provide more scientific and effective methods for obese people to lose weight. Through randomized controlled trial design, 120 overweight or obese subjects were recruited and randomly divided into four groups for 12 weeks of dietary intervention. The control group kept their daily eating habits, while the ketogenic diet group adopted a diet scheme of high fat, low carbohydrate and moderate protein. The intermittent fasting group chose two days a week for light fasting, while the combined group used ketogenic diet and intermittent fasting at the same time. The research results show that both the ketogenic diet group and the intermittent fasting group can effectively reduce the weight and body fat percentage of the subjects, and the combination of the two has the most significant effect. The ketogenic diet group showed the greatest decrease in body weight and body fat percentage, at -3.5 ± 1.2kg and -4.8 ± 1.5%, respectively, while the combined group showed a more significant decrease, reaching -4.7 ± 1.4kg and -6.3 ± 1.8%, respectively. Regression analysis shows that ketogenic diet, intermittent fasting and their combination have significant effects on body fat rate, and the increase of weekly exercise time is also significantly related to the decrease of body fat rate. The study also found that ketogenic diet and intermittent fasting have their own advantages in reducing body fat rate, but they may also bring certain health risks, such as hypoglycemia and ketoacidosis. Therefore, doctors or nutritionists should tailor the diet plan according to individual conditions and pay attention to its potential side effects. This study provides a new weight loss option for obese people and provides a direction for future research.

Severe carbohydrate restriction augments the antiproliferative effect of hormonal therapy in a murine model of Ehrlich breast adenocarcinoma: histological and immunohistochemical investigations

BackgroundMalignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group.ResultsCR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased.ConclusionsThe combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect.

Classic ketogenic diet-induced ketoacidosis in the treatment of pyruvate dehydrogenase deficiency: a case report and literature review

BackgroundAs a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD.Case presentationHerein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient.ConclusionsThis rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

The Efficacy of Ketogenic Diets (Low Carbohydrate; High Fat) as a Potential Nutritional Intervention for Lipedema: A Systematic Review and Meta-Analysis.

Lipedema is a frequently misdiagnosed condition in women, often mistaken for obesity, which significantly deteriorates both quality of life and physical health. Recognizing the necessity for holistic treatment strategies, research has increasingly supported the integration of specific dietary approaches, particularly ketogenic diets focusing on low-carbohydrate and high-fat intake. to evaluate the impact of ketogenic diets on women with lipedema through a systematic review and meta-analysis. A systematic review and meta-analysis were conducted by reviewing published, peer-reviewed studies addressing the implications of a low-carbohydrate, high-fat (LCHF) ketogenic diet in managing lipedema following comprehensive scrutiny of digital medical databases, such as PubMed, PubMed Central, Science Direct, and the Web of Science. This research was governed by specified parameters, including an established search string composed of search terms and an eligibility criterion (PICO) as denoted by the principal authors. Statistical analysis was carried out using RevMan 5.4.1 software with the Newcastle-Ottawa Scale utilized for quality appraisal of the included studies. Seven studies reporting statistical outcomes were included in the systematic review and meta-analysis following a rigorous quality appraisal and data identification process. Three hundred and twenty-nine female participants were diagnosed with lipedema and treated using a low-carbohydrate, high-fat diet. Data analysis identified the high-fat diet with a mean study duration of 15.85 weeks. Mean Differences (MDs) on changes pre- and post-intervention showed significant reductions in BMI and total body weight [4.23 (95% CI 2.49, 5.97) p < 0.00001 and 7.94 (95% CI 5.45, 10.43) p < 0.00001 for BMI and body weight, respectively]. Other anthropometric measurements, such as changes in waist/hip circumferences and waist/hip ratios, showed a significant reduction in these parameters, with an MD of 8.05 (95% CI 4.66, 11.44) p < 0.00001 and an MD of 6.67 (95% CI 3.35, 9.99) p < 0.0001 for changes in waist and hip circumferences from baseline, respectively. Lastly, changes in pain sensitivity were statistically significant post-intervention [MD 1.12 (95% CI, 0.44, 1.79) p = 0.001]. All studies scored fair on the Newcastle-Ottawa Scale. despite the limited studies and low number of study participants, the review observed a significant reduction in anthropometric and body composition metrics, indicating a potentially beneficial association between LCHF ketogenic diets and lipedema management.

Impressive weight loss induced by a very low-calorie ketogenic diet in a morbidly complex obese patient with a recent episode of acute kidney injury and advanced chronic kidney disease: a case report

The very low-calorie ketogenic diet (VLCKD), characterized by a marked energy restriction that induces rapid weight loss, has recently been proposed as a valid nutritional strategy for managing obesity. VLCKD is commonly considered dangerous for the kidneys due to the misconception that it is high in protein, beyond the risk of electrolyte imbalances and an increase in diuresis. We report a case of safe and effective weight loss induced by VLCKD in a 43-year-old Caucasian woman with a recent episode of acute kidney injury on advanced chronic kidney disease. Surprisingly, we observed that after the diet-induced weight loss, not only did renal function not worsen, but proteinuria also improved. The principal value of this case report is its singular demonstration of impressive weight loss induced by VLCKD in a complex obese patient that was apparently not accompanied by the development of serious adverse sequelae.

Autism Spectrum Disorder: Latest Advances in Treatment

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by deficits in social communication and the presence of restricted, repetitive behaviours. Despite the global prevalence of ASD, its diagnosis and treatment remain challenging due to the absence of specific biomarkers and the heterogeneity of symptoms. ASD is incurable and current management options aim to minimize the symptoms and maximize the patients’ ability to function. There is no one standardized treatment for ASD at present, recommended medical interventions involve various therapies which include cognitive behavioral therapy alongside additional personalized pharmacological symptomatic treatments. New approach for ASD management includes sensory integration therapy (SIT) as well as dietary interventions, like gluten-free, casein-free and ketogenic diets. Other innovative treatment strategies are targeted at gut microbiome and include probiotic treatment and fecal microbiota transplant. In this review possible genetic variants associated with ASD are discussed as well as their influence on the manifestation and management of clinical symptoms. For a better understanding on how genetic variables impact drug effectiveness in individuals and the importance of pharmacogenetics in ASD. This paper aims to explore the available and possible treatment options as well the genetic components associated with ASD. In summary, this paper reviews the current and emerging treatment options for ASD.

Efficacy, Safety, and Tolerability of a Very Low-Calorie Ketogenic Diet in Women with Obesity and Symptomatic Knee Osteoarthritis: A Pilot Interventional Study.

Obesity is a major risk factor for knee osteoarthritis (OA), and weight loss is crucial for its management. This pilot study explores the effects of a Very Low-Calorie Ketogenic Diet (VLCKD) in women with obesity and symptomatic knee OA. Women with symptomatic knee OA and obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, were eligible for the VLCKD protocol. The intervention included a ketogenic phase from baseline (T0) to the 8th week (T8), followed by a progressive reintroduction of carbohydrates over the next 12 weeks, ending at the 20th week (T20). Body mass index (BMI), the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, the EuroQol 5D (EQ-5D), and the 36-item Short Form Health Survey (SF-36) were assessed at all time points. Generalized estimating equations were used to analyze the association between BMI and patient-reported outcomes across the study period. Twenty participants started the study, but four discontinued the intervention, with two of these being due to adverse effects. The mean age of the 16 patients who completed the 20-week program was 57.3 ± 5.5 years, and their mean BMI was 40.0 ± 4.8 kg/m2. The mean BMI significantly decreased to 37.5 ± 4.5 at T4, 36.3 ± 4.6 at T8, and 34.8 ± 4.8 at T20 (all p < 0.001 compared to baseline). The total WOMAC score improved from a mean of 43.6 ± 16.9 at T0 to 30.2 ± 12.8 at T4 (p = 0.005) and further to 24.7 ± 10.6 at T8 (p = 0.001) and to 24.8 ± 15.9 at T20 (p = 0.005). The reduction in BMI was significantly correlated with the improvements in WOMAC, EQ-5D, and SF-36 over time. No major adverse effects were observed. A 20-week VLCKD in women with obesity and knee OA significantly reduced their weight and improved their outcomes, warranting further research. This trial is registered with number NCT05848544 on ClinicalTrials.gov.

The effects of the ketogenic diet on cancer treatment: a narrative review.

Despite significant advances in therapy, cancer remains the top cause of death in parts of the globe. For many types of cancer, the typical treatment is a combination of surgery, chemotherapy, and radiotherapy. However, this conventional treatment is not successful on its own. As a consequence, innovative approaches that improve treatment efficacy are urgently needed. The ketogenic diet is a high-fat, moderate protein, and low-carbohydrate diet that appears to sensitize most cancers to conventional therapies by exploiting cancer cells' altered metabolism, making it an effective adjuvant cancer treatment alternative. This diet could decrease glucose metabolism while enhancing lipid metabolism, interfering with the Warburg effect, and inhibiting tumor cell proliferation. The anticancer impact of ketogenic diet has been established in numerous animal trials and clinical investigations on a wide range of tumor types, including glioblastoma, pancreatic cancer, head and neck cancer, breast cancer, invasive rectal cancer, ovarian cancer, and endometrial cancer. In this review, we discussed the various types of ketogenic diets, the mechanism of action for ketogenic diet as a cancer therapy, and the data gathered from continuing preclinical and clinical studies, intending to establish a solid theoretical foundation for future research.

The potential protective effect of 3-Hydroxybutyrate against aortic dissection: a mendelian randomization analysis

Background3-Hydroxybutyrate, also called β-hydroxybutyrate, is a significant constituent of ketone bodies. Previous observational and experimental studies have suggested that ketogenic diet, especially 3-hydroxybutyrate, may have a protective effect against cardiovascular disease. However, the relationship between ketone bodies, especially 3-hydroxybutyrate, and aortic dissection remains uncertain.Materials and methodsPublicly accessible data from genome-wide association study (GWAS) was utilized to obtain information on ketone bodies, including 3-hydroxybutyrate, acetoacetate and acetone as exposure respectively, while GWAS data on aortic dissection was used as outcome. Subsequently, two-sample Mendelian randomization (MR) analysis was conducted to examine the potential relationship between ketone bodies and aortic dissection. Then, reverse and multivariate Mendelian randomization analyses were performed. Additionally, sensitivity tests were conducted to assess the robustness of MR study.ResultsThe inverse-variance weighted (IVW) method of Mendelian randomization analysis of gene prediction observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection (OR 0.147, 95% CI 0.053–0.410). Furthermore, consistent findings were obtained through the implementation of the weighted median, simple mode, Mendelian randomization-Egger (MR-Egger), and weighted mode methods. After adjusting acetoacetate (OR 0.143, 95% CI 0.023-0.900) or acetone (OR 0.100, 95% CI 0.025–0.398), MR analysis of gene prediction still observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection. No indications of heterogeneity or pleiotropy among the SNPs were detected.ConclusionThe findings from the MR analysis demonstrated that genetically predicted 3-hydroxybutyrate exhibits a protective effect against aortic dissection.