Ketogenic Diet Research Articles

Acetoacetate and D- and L-β-hydroxybutyrate have distinct effects on basal and insulin-stimulated glucose uptake in L6 skeletal muscle cells.

Ketone bodies (acetoacetate and β-hydroxybutyrate) are oxidized in skeletal muscle mainly during fasting as an alternative source of energy to glucose. Prior studies suggest that there is a negative relationship between increased muscle ketolysis and muscle glucose metabolism in mice with obesity and/or type 2 diabetes. Therefore, we investigated the connection between increased ketone body exposure and muscle glucose metabolism by measuring the effect of a 3-hour exposure to ketone bodies on glucose uptake in differentiated L6 myotubes. We showed that exposure to acetoacetate at a typical concentration (0.2 mM) resulted in increased basal glucose uptake in L6 myotubes, which was dependent on increased membrane GLUT4 translocation. Basal and insulin-stimulated glucose uptake was also increased with a concentration of acetoacetate reflective of diabetic ketoacidosis or a ketogenic diet (1 mM). We found that β-hydroxybutyrate had a variable effect on basal glucose uptake, in that a racemic mixture of the two β-hydroxybutyrate enantiomers (D and L) appeared to decrease basal glucose uptake, while 3 mM D-β-hydroxybutyrate alone increased basal glucose uptake. However, the effects of the ketone bodies individually were not observed when acetoacetate was present in combination with β-hydroxybutyrate. These results provide insight that will help elucidate the effect of ketone bodies in the context of specific metabolic diseases and nutritional states (e.g., type 2 diabetes and ketogenic diets).

Abstract PO3-02-03: Ketogenic diet and letrozole to inhibit PI3K signaling in ER+ breast cancer

Abstract Obesity is associated with an increased risk of breast cancer recurrence, similar in magnitude to the reduction in risk seen with the use of adjuvant chemotherapy. However, whether and how obesity causes that increased risk of recurrence remains unknown. Plausible mechanisms include obesity-mediated increases in estrogen signaling, inflammatory conditions resulting from obesity, or effects on insulin or other growth factor signaling pathways resulting from the insulin-resistant state that often accompanies obesity. While phosphatidyl inositol 3-kinase (PI3K) signaling is the normal, biological effector of insulin signaling, abnormal activation of PI3K is of particular concern in breast cancer, where it is associated with resistance to endocrine therapies and HER2-targeted therapies. We hypothesize that at least part of the adverse outcome associated with obesity results from aberrant activation of PI3K signaling in tumors. This may confer resistance to established therapies, or directly stimulate tumor growth (particularly in tumors with existing PI3K pathway mutations), or both. We tested a dietary intervention designed to alter insulin resistance pathophysiology coupled with endocrine therapy in the well-established neoadjuvant treatment paradigm in breast cancer. This will allow us to study the effects of the dietary intervention directly on tumor biology. The primary objective of this neoadjuvant study was to assess feasibility and tolerability of 2 weeks of a very low-carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+ disease. Up to 36 patients will be enrolled for this pilot and feasibility study (24 in the treatment group and 12 controls). Baseline metabolic parameters will be measured and the treatment group will begin a dietitian-supervised 2-week diet to induce a ketogenic state, along with letrozole 2.5 mg daily. The control group will receive only letrozole. At the end of 2 weeks, patients will proceed with surgical treatment of their breast cancer. We will report the primary outcome measure of feasibility, assessed by determining 1) the proportion of patients in the diet group achieving ketosis, 2) adherence to the diet and 3) participant-reported measures of stress, fatigue, and emotional health. For both groups, cell proliferation will be measured in a tumor biopsy obtained from the surgical specimen and compared with the pre-treatment diagnostic biopsy. Correlative studies will evaluate tumor markers of insulin/PI3K signaling before and after the intervention and between diet and control. Citation Format: Brent Rexer, Vandana Abramson, Sara Nunnery, Sonya Reid, Laura Kennedy, Melinda Sanders, Jessica Bennett, Paula Gonzalez-Ericsson, Violeta Sanchez. Ketogenic diet and letrozole to inhibit PI3K signaling in ER+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-03.

A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. β-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3months and 4-6months. It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

Abstract PO5-12-02: Landscape analysis of oncology nutrition research among patients being treated for breast cancer

Abstract The American Institute for Cancer Research/World Cancer Research Fund and the American Cancer Society regularly conduct systematic reviews on the evidence supporting nutrition interventions during cancer treatment. These reviews have found that the evidence to support clinical oncology nutrition practice guidelines is limited. It is unclear how many oncology nutrition studies are currently being conducted, especially among patients being treated for breast cancer. The goal of this project was to conduct a landscape analysis of nutrition research being conducted among breast cancer patients over the past 10 years. Methods: This analysis was part of a larger effort to describe the oncology nutrition research landscape for all cancer sites. Searches of ClinicalTrials.gov were performed on 1/8/2023 using the following search terms/combinations: “cancer AND nutrition”, “cancer nutrition”, “oncology AND nutrition”, “diet AND cancer”, “cancer, oncology, neoplasms, nutrition, diet”. Search results were downloaded as .csv files and uploaded to RStudio for merging and data cleaning (elimination of duplicates, and exclusion of studies registered in ClinicalTrials.gov before 1/1/2013 or after 12/31/2022). The resulting harmonized dataset was then uploaded to REDCap, and each entry was reviewed for eligibility by one of the authors. To be included in this landscape analysis, studies must have included data collection from patients who were actively receiving cancer treatment at the time of the study and the study had to be first posted to ClinicalTrials.gov between 1/1/2013 and 12/31/2022. Studies were excluded if they: 1) focused on the role of diet in primary cancer prevention, 2) focused on cancer survivors who had completed primary treatment for their cancers. Following eligibility review, the study datafile was returned to RStudio for further cleaning and analysis. Results: The initial ClinicalTrials.gov search identified 4,345 unique study listings. After review, 1,267 studies met the inclusion criteria, of which 132 (10.4%) studies were specific to breast cancer (117 intervention studies and 15 observational studies). Among breast cancer studies, reasons for exclusion were: study focused on diet/nutrition in the prevention of a primary cancer diagnosis (n=40), study participants had already completed their cancer treatment (n=128), study did not include a diet/nutrition intervention or assessment (n=31). The largest number of breast cancer specific studies were based in the United States (n=55, 41.6%), Italy (n=11, 8.3%), France (n=10, 7.6%) and Canada (n=9, 6.8%). Dietary supplement interventions were the most common type of intervention (n=50 studies, 42.7%), followed by behavior change interventions (n=22, 18.8%), diet in relation to a drug intervention (n=25, 21.4%), diet in relation to a device/procedure/radiation intervention (n=16, 14%), fasting/time-restricted feeding studies (n=13, 11.1%) and ketogenic diet interventions (n=3, 2.6%). Changes in weight or body composition (n=52, 39.4%), quality of life (n=45, 34.1%), adverse events (n=24, 18.2%), survival (n=20, 15,2%) and fatigue (n=17, 12.9%) were the most common outcome measures. Sixteen (12.1%) studies were supported by NIH funding and 9 (6.8%) studies were industry funded, although the majority (n=124, 93.9%) reported funding from “other” sources. Of the 41 studies that started between 2013-2017 (five years prior to the January 2023 ClinicalTrials.gov search), only 21 (51.2%) were listed as being “completed” and of those, only 7 were listed as “has results”. Conclusion: More research is needed to support evidence-based supportive care guidelines for oncology nutrition interventions during breast cancer treatment. Efforts should be made to support researchers in completing studies and disseminating research findings. Citation Format: Kim Robien, Heather Wopat. Landscape analysis of oncology nutrition research among patients being treated for breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-02.

Drug-resistant epilepsy and ketogenic diet therapy – a qualitative study of families’ experiences.

BackgroundA diagnosis of drug-resistant epilepsy is life changing for a family. Ketogenic diet therapy (KDT) can offer hope when other treatments have failed. However, it often requires a significant change in daily routine and dietary habits. This qualitative descriptive study aimed to explore families’ experiences of epilepsy and KDT. MethodsParents of a child aged ≤18 years with epilepsy, currently or recently treated with KDT, were recruited from the UK and internationally via UK Ketogenic Diet (KD) centres, charities, and social media. Semi-structured interviews were audio recorded, transcribed verbatim, anonymised, coded using Nvivo (V12), and inductive thematic analysis undertaken. ResultsTwenty-one parents participated. Four themes and 12 subthemes emerged: 1. ‘Epilepsy is all consuming’ explored the impact of epilepsy on the family. 2. ‘KD provides a window to new opportunities’ explores the motivators for KDT and positive outcomes. 3. ‘The reality of KD’ explores day to day life and how families adapt to KD. 4. ‘Looking to the future’ explores the factors that may make KD easier for families. All were glad their child trialled KD, even when less successful. The importance of a support network including family, friends, charity organisations and the KD team was evident across all themes. ConclusionsWe conclude with five recommendations to help support families in their management of KDT; Improved access to KDT and transition to adult services, access to quality education and support, enhanced variety of KD foods, regular social education and finally consideration of peer mentoring.

The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischemic heart failure.

Cardiac energy metabolism is perturbed in ischemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure. C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending (LAD) coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and ß-hydroxybutyrate (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. Mice with heart failure exhibited a 56% drop in ejection fraction which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of key ketone oxidation enzymes. Furthermore, in mice on the ketogenic diet no increase in overall cardiac energy production was observed, and instead there was a shift to an increased reliance on fatty acid oxidation as a source of cardiac energy production. This resulted in a decrease in cardiac efficiency in heart failure mice fed a ketogenic diet. We conclude that the ketogenic diet does not improve heart function in failing hearts, due to ketogenic diet-induced excessive fatty acid oxidation in the ischemic heart and a decrease in insulin-stimulated glucose oxidation.

Dietary intervention in acne management: review of the literature and future prospective

Acne is a common skin disease, affecting millions of subjects worldwide. Several processes and mechanisms have been identified in acne pathogenesis. Among these, it is known that acne or its worsening is also related to metabolic factors and nutritional influences. In this scenario, we carried out a review of the current literature in order to investigate the role of diet in acne disease, offering a wide perspective for possible clinical applications. A total of 55 manuscripts were considered. In particular, the role of the Western diet, glycemic index, glycemic load, dairy products, fats, fatty acids, Mediterranean diet, ketogenic diet, and dietary supplements in acne management has been investigated. On one hand, dairy products, foods with high glycemic load and glycemic index, fatty acids and fats seem to worsen the severity; on the other hand, Mediterranean and ketogenic diet, and oral supplements seem to improve the disease. Despite the conflicting results and conclusions in the scientific literature about the impact of nutrition in acne, mainly related to the severla limitations of the study design, several prospective, controlled, well-designed studies have recently demonstrated the role of some specific nutrition influenced mediators on acne severity.

Opinion: Are mental health benefits of the ketogenic diet accompanied by an increased risk of cardiovascular disease?

Opinion: Are mental health benefits of the ketogenic diet accompanied by an increased risk of cardiovascular disease?

Low-carbohydrate diet - application in the treatment of type 2 diabetes - review

Introduction: A very low carbohydrate diet called the ketogenic diet has been shown to be effective in the management of drug-resistant epilepsy. In the recent years it has been studied as a potential remedy for conditions such as insulin resistance, type 2 diabetes, obesity, cardiovascular diseases as well as various psychological disorders including drug-resistant depression and schizophrenia. This approach seems to be promising in managing abovementioned issues given a sufficient amount of commitment. There is an abundance of papers looking into the said diet yet not many of them seem to have been well deigned and carried out. Methods and materials: A review of chosen literature from PubMed database, GoogleScholar database between the years 2000-2024 was carried out using the following keywords: “low-carbohydrate”, low-carb”, “low carbohydrate diet”, “low-carb diet”, “type 2 diabetes”, “insulin”, “insulin resistance”, “obesity”. Aim of study: Review of the current knowledge on the influence of the therapeutic carbohydrate restriction on health, especially type 2 diabetes. Results: The introduction of the low-carbohydrate diet may have a beneficial influence on metabolism-related diseases. There is quite strong evidence proving it help with the management of type 2 diabetes and limit the amount of medication necessary to manage the disease as well as lower one’s body fat and blood pressure. It is however not an intervention without its limitations. Conclusions: Low carbohydrate diets seem to be safe and effective in the treatment of Type 2 diabetes. Further large-scale, randomized, well-designed studies with clearly set guidelines as to what constitutes a low-carbohydrate intervention using high-quality protein and fat sources are necessary to determine the efficacy and safety of the carbohydrate restriction in the long term.

The ketogenic diet and MetSyn in Parkinson’s disease – Symptoms, biomarkers, depression and anxiety: A case study

The use of therapeutic carbohydrate restriction (TCR) in the form of a ketogenic diet (KD) in neurodegenerative disorders such as Parkinson’s disease (PD) is increasing as an alternative treatment for primary and secondary symptoms. There exists a gap in the literature on symptoms of PD in the setting of metabolic syndrome (MetSyn) and possible comorbid impact on symptoms, biomarkers of health, cardiac risk, depression and anxiety. This case report documents a 24-week KD intervention for a 53-year-old man with multiple comorbid diagnoses, PD (Hoehn-Yahr stage IIa) with a history of morbid obesity with increased waist circumference, prediabetes, hyperinsulinaemia and significantly impaired mobility with chronic back pain, anxiety disorder and depression. Baseline cardiac risk ratios (CRR = triglycerides/HDL) were calculated and compared. The KD approach involved a well-formulated, ketogenic diet (fats 70%; protein 25%; carbohydrates 5% according to total daily energy intake for 24 weeks). Baseline, 12-week and 24-week biomarkers and scores on scales were compared. Clinically significant results were found when baseline biomarker results and scales were compared with 12-week results. Positive trends were seen for all variables at 24 weeks. Improvements in health biomarkers, including HbA1C, high sensitivity C-reactive protein (hs-CRP), triglycerides, fasting insulin, weight loss, waist circumference and cardiac risk were observed at 12 and 24 weeks. Some improvements in scores on an anxiety scale were seen. Based on our findings, KD is safe and effective for improving health biomarkers and symptoms of MetSyn, depression, anxiety and symptoms of PD. Future clinical trial studies for more generalisable results are needed.

Application and Effectiveness of Dietary Therapies for Pediatric Migraine

Migraine is a representative type of primary headache and a common chronic neurological disease that accounts for a large proportion of headaches in children, adolescents, and adults. Unlike migraine in adulthood, pediatric migraine occurs when brain development is not yet complete. This characteristic may require a new perspective for the treatment and management of pediatric migraine. Dietary therapies, mainly the ketogenic diet and its variants, can have positive effects on pediatric migraine. Several recent studies have revealed that dietary therapies, such as the classic ketogenic diet, modified Atkins diet, and low glycemic index diet, improve various neurological diseases by improving dysbiosis of microbiota, reducing proinflammatory cytokines, and increasing mitochondrial function. Nonetheless, the mechanism through which active dietary therapy affects pediatric migraine requires further research. To achieve this, an important role is played by the neuro-nutritional team, which can develop and manage tolerable diets for pediatric migraine patients through mutual collaboration among pediatric neurologists, nurses, and nutritionists.

Specifically formulated ketogenic, low carbohydrate, and carnivore diets can prevent migraine: a perspective

This article presents a hypothesis explaining the cause of migraines, suggesting that electrolyte imbalance, specifically a lack of sufficient sodium in the extracellular space of sensory neurons, leads to failed action potentials. The author argues that migraines are triggered when sodium channels fail to initiate action potentials, preventing communication between neurons. The article discusses the evolutionary perspective of the migraine brain, stating that migraineurs have a hypersensitive brain with more sensory neuronal connections, making them more reactive to environmental stimuli and in need of more minerals for the increased sensory neuronal communication. Since glucose is often used to reduce serum hypernatremia, it follows that a high carbohydrate diet reduces sodium availability for use in the brain, causing an electrolyte imbalance. Low carbohydrate diets, such as ketogenic, low carb-high fat (LCHF), and carnivore (all animal products), can be beneficial for migraineurs by reducing/eliminating carbohydrate intake, thereby increasing sodium availability. In support, many research papers and some anecdotal evidences are referred to. The article concludes by proposing lifestyle modifications, such as dietary changes and sodium intake management. These will provide migraineurs with a long-term healthy metabolic foundation helping them to maintain strong nutritional adherence and with that aiding continued proper neuronal functioning and migraine free life.

Lipedema and Nutrition: High Fat Ketogenic Diet as Treatment of Choice

Background: Lipedema is a disease of the subcutaneous adipose tissue that was first clinically recognized in the mid-1900s. Lipedema can have a significant impact on physical appearance, mental health, and well-being: people with lipedema, lovingly called “Lippies”, not only complain about their physical appearance, but also the presence of a bunch of symptoms that worsen the quality of life, which is why it is important to study treatments that may have positive effects mainly in the affected areas. Reducing inflammation is the main target of the multidisciplinary treatment of lipedema. Many studies have shown a significant reduction in body fat and in the painful component of lipedema following integrated treatment and, above all, the high fat ketogenic diet. Therefore, we compared the efficacy of a High Fat Ketogenic Diet (HFKD) in patients suffering from lipedema to test the hypothesis that this approach is more effective than a Low Carb Antinflammatory non-ketogenic Diet (LCAD) on reducing the anthropometric measures in the affected areas and on improving symptoms.

Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets influences intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate−dextran (FITC–dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC–dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.

Carbohydrate reduction for metabolic disease is distinct from the ketogenic diet for epilepsy

Recent reviews of using therapeutic carbohydrate reduction to treat metabolic disease in paediatric patients have consistently made errors in the form of bias against recommending this nutrient-dense eating pattern despite strong evidence for its use in adults and emerging evidence in paediatric patients. The purpose of this perspective is to review these errors, which include conflating 4:1 ketogenic diets with well-formulated ketogenic diets and the needless medicalisation of using therapeutic carbohydrate reduction in paediatric populations.

Ketogenic Diets Hold Therapeutic Potential Against Periodontal Inflammation

Abstract Purpose of Review Periodontitis, one of the most prevalent diseases in the world, is caused by the accumulation of dysbiotic microbial biofilm on the teeth leading to chronic inflammation of the tissues surrounding the teeth. Type 2 diabetes mellitus (T2DM), obesity, chronic stress, and smoking are some of the risk factors for the disease. A high-carbohydrate diet also increases the risk of periodontal inflammation. Modifying diet and nutrition could serve as a preventive and therapeutic tool to target multiple risk factors simultaneously. Recent Findings Emerging evidence shows that the ketogenic diet induces hormetic stress and switches on various cell-protective anti-inflammatory and antioxidant mechanisms. The ketogenic diet also improves mitochondrial function, DNA repair, and autophagy. The diet can effectively treat periodontitis risk factors such as T2DM and obesity. By restricting carbohydrates, the diet improves glycaemic control in T2DM patients and can effectively produce fat loss and reduce BMI (body-mass index) in obese patients. Poor long-term compliance and high cost are the drawbacks of the diet and the potential of the diet to increase cardiovascular disease risk needs further investigation. Summary Taken together, ketogenic diets, through various mechanisms reduce inflammation, mitigate oxidative stress, improve metabolic health, and can be used as a therapeutic tool to treat periodontal inflammation. Since robust scientific evidence for the ketogenic diet is currently scarce, future research should study the diet's efficacy, effectiveness, and safety in managing periodontal inflammation.

Oxidative Stress in Military Missions—Impact and Management Strategies: A Narrative Analysis

This narrative review comprehensively examines the impact of oxidative stress on military personnel, highlighting the crucial role of physical exercise and tailored diets, particularly the ketogenic diet, in minimizing this stress. Through a meticulous analysis of the recent literature, the study emphasizes how regular physical exercise not only enhances cardiovascular, cognitive, and musculoskeletal health but is also essential in neutralizing the effects of oxidative stress, thereby improving endurance and performance during long-term missions. Furthermore, the implementation of the ketogenic diet provides an efficient and consistent energy source through ketone bodies, tailored to the specific energy requirements of military activities, and significantly contributes to the reduction in reactive oxygen species production, thus protecting against cellular deterioration under extreme stress. The study also underlines the importance of integrating advanced technologies, such as wearable devices and smart sensors that allow for the precise and real-time monitoring of oxidative stress and physiological responses, thus facilitating the customization of training and nutritional regimes. Observations from this review emphasize significant variability among individuals in responses to oxidative stress, highlighting the need for a personalized approach in formulating intervention strategies. It is crucial to develop and implement well-monitored, personalized supplementation protocols to ensure that each member of the military personnel receives a regimen tailored to their specific needs, thereby maximizing the effectiveness of measures to combat oxidative stress. This analysis makes a valuable contribution to the specialized literature, proposing a detailed framework for addressing oxidative stress in the armed forces and opening new directions for future research with the aim of optimizing clinical practices and improving the health and performance of military personnel under stress and specific challenges of the military field.

Human milk and breastfeeding during ketogenic diet therapy in infants with epilepsy: Clinical practice guideline.

Ketogenic diet therapy (KDT) is a safe and effective treatment for epilepsy and glucose transporter type 1 (GLUT1) deficiency syndrome in infancy. Complete weaning from breastfeeding is not required to implement KDT; however, breastfeeding remains uncommon. Barriers include feasibility concerns and lack of referrals to expert centres. Therefore, practical strategies are needed to help mothers and professionals overcome these barriers and facilitate the inclusion of breastfeeding and human milk during KDT. A multidisciplinary expert panel met online to address clinical concerns, systematically reviewed the literature, and conducted two international surveys to develop an expert consensus of practical recommendations for including human milk and breastfeeding in KDT. The need to educate about the nutritional benefits of human milk and to increase breastfeeding rates is emphasized. Prospective real-world registries could help to collect data on the implementation of breastfeeding and the use of human milk in KDT, while systematically including non-seizure-related outcomes, such as quality of life, and social and emotional well-being, which could improve outcomes for infants and mothers.

Ketogenic Diet in the Treatment of Epilepsy

Epilepsy is one of the most disabling neurological diseases. Despite proper pharmacotherapy and the availability of 2nd and 3rd generation antiepileptic drugs, deep brain stimulation, and surgery, up to 30–40% of epilepsy patients remain drug-resistant. Consequences of this phenomenon include not only decreased a quality of life, and cognitive, behavioral, and personal disorders, but also an increased risk of death, i.e., in the mechanism of sudden unexpected death in epilepsy patients (SUDEP). The main goals of epilepsy treatment include three basic issues: achieving the best possible seizure control, avoiding the undesired effects of treatment, and maintaining/improving the quality of patients’ lives. Therefore, numerous attempts are made to offer alternative treatments for drug-resistant seizures, an example of which is the ketogenic diet. It is a long-known but rarely used dietary therapy for intractable seizures. One of the reasons for this is the unpalatability of the classic ketogenic diet, which reduces patient compliance and adherence rates. However, its antiseizure effects are often considered to be worth the effort. Until recently, the diet was considered the last-resort treatment. Currently, it is believed that a ketogenic diet should be used much earlier in patients with well-defined indications. In correctly qualified patients, seizure activity may be reduced by over 90% or even abolished for long periods after the diet is stopped. A ketogenic diet can be used in all age groups, although most of the available literature addresses pediatric epilepsy. In this article, we focus on the mechanisms of action, effectiveness, and adverse effects of different variants of the ketogenic diet, including its classic version, a medium-chain triglyceride diet, a modified Atkins diet, and a low glycemic index treatment.

Differentiating non-epileptic seizures from epileptic seizures in Glut1 deficiency syndrome.

To investigate the clinical characteristics of non-epileptic seizures due to transient brain dysfunction caused by energy deficiency after prolonged fasting or exercise in individuals with glucose transporter type 1 deficiency syndrome (Glut1DS), and then elucidate further the seizure features to distinguish non-epileptic seizures from epileptic seizures. This retrospective case-control study included 57 non-epileptic seizures and 23 epileptic seizures (control group) in 14 individuals (11 males, three females; aged 5-44 years, median = 20 years) with Glut1DS, all with a heterozygous pathogenic SLC2A1 mutation. Non-epileptic seizures were classified as paroxysmal altered consciousness (n = 8), movement disorders (n = 35) (eye-head movements, ataxia, spasticity, weakness, involuntary movement), dysaesthesia (n = 8), and vomiting (n = 6) at the peak ages at onset of 5 to 10 years. Ketogenic diet therapy was effective in 33 of 43 (77%) non-epileptic seizures. Providing supplementary food before high-impact exercise or during attacks prevented or mitigated non-epileptic seizures in some individuals. Glut1DS-associated non-epileptic seizures are fundamentally situation-related seizures with specific provoking and ameliorating factors. Non-epileptic seizures can be distinguished from epileptic seizures by the absence of complete consciousness loss and rapid postictal recovery despite prolonged seizures. Non-epileptic seizures are not well recognized but require different therapeutic approaches compared to epileptic seizures. Awareness of the differentiation of non-epileptic seizures from epileptic seizures is essential when performing preventive or therapeutic decision-making for acute exacerbation seizures.