Decimocuarta lección Jesús Culebras. Dieta cetogénica, un tratamiento a medio descubrir / Fourteenth Jesús Culebras Lecture. Ketogenic diet, a half-discovered treatment

La dieta cetogénica constituyó desde su inicio un planteamiento sorprendente para el tratamiento de la epilepsia. Someter al organismo a un cambio en la obtención de energía, pasando de depender de los carbohidratos a hacerlo de las grasas, pone en marcha toda una serie de rutas bioquímicas que, de forma independiente pero también complementaria, dan lugar a un conjunto de efectos que benefician al paciente. Esta búsqueda de su mecanismo de acción, de idear cómo mejorar el cumplimiento y de aprovecharla para otras enfermedades ha marcado su trayectoria. En este artículo se revisan someramente estos aspectos, haciendo hincapié en la importancia de seguir realizando investigación básica y clínica para que este tratamiento pueda aplicarse con bases científicas sólidas.(AU)

The ketogenic diet was an amazing approach to treating epilepsy from its beginning. The body undergoes a change in obtaining energy, going from depending on carbohydrates to depending on fats, and then a whole series of biochemical routes are launched that, independently but also complementary, give rise to a set of effects that benefit the patient. This search for its mechanism of action, of devising how to improve compliance and take advantage of it for other diseases has marked its trajectory. This article briefl y reviews these aspects, emphasizing the importance of continuing to carry out basic and clinical research so that this treatment can be applied with solid scientific bases.(AU)

[Fourteenth Jesús Culebras Lecture. Ketogenic diet, a half-discovered treatment]. / Decimocuarta Lección Jesús Culebras. Dieta cetogénica, un tratamiento a medio descubrir.

Introduction: The ketogenic diet was an amazing approach to treating epilepsy from its beginning. The body undergoes a change in obtaining energy, going from depending on carbohydrates to depending on fats, and then a whole series of biochemical routes are launched that, independently but also complementary, give rise to a set of effects that benefit the patient. This search for its mechanism of action, of devising how to improve compliance and take advantage of it for other diseases has marked its trajectory. This article briefly reviews these aspects, emphasizing the importance of continuing to carry out basic and clinical research so that this treatment can be applied with solid scientific bases.

Introducción: La dieta cetogénica constituyó desde su inicio un planteamiento sorprendente para el tratamiento de la epilepsia. Someter al organismo a un cambio en la obtención de energía, pasando de depender de los carbohidratos a hacerlo de las grasas, pone en marcha toda una serie de rutas bioquímicas que, de forma independiente pero también complementaria, dan lugar a un conjunto de efectos que benefician al paciente. Esta búsqueda de su mecanismo de acción, de idear cómo mejorar el cumplimiento y de aprovecharla para otras enfermedades ha marcado su trayectoria. En este artículo se revisan someramente estos aspectos, haciendo hincapié en la importancia de seguir realizando investigación básica y clínica para que este tratamiento pueda aplicarse con bases científicas sólidas.

Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease.

Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from abnormal mitochondrial function. Currently, there is no causal treatment for MDs. The aim of the study was to assess the effectiveness and safety of the ketogenic diet (KD) in patients with MD and to analyse selected biochemical and clinical parameters evaluating the effectiveness of KD treatment in patients with MDs. A total of 42 paediatric patients were assigned to four groups: group 1-patients with MD in whom KD treatment was started (n = 11); group 2-patients with MD remaining on an ordinary diet (n = 10); group 3-patients without MD in whom KD treatment was initiated (n = 10), group 4-patients without MD on a regular diet (n = 11). Clinical improvement was observed in 9/11 patients with MD treated with KD. Among patients with MD without KD, the clinical condition deteriorated in 7/10 patients, improved in 2/10 patients, and remained unchanged in one patient. Adverse events of KD occurred with a comparable frequency in groups 1 and 3. There was no significant difference in changes in biomarker concentrations over the course of the study among patients treated and untreated with KD.

Dietary restriction and hepatic cancer: Systematic review and meta-analysis of animal studies.

The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to evaluate the effect of restrictive diets on the development and progression of liver cancer in animal models. We did a meta-analysis using the Cochrane Collaboration's Review Manager software, with the random effects model and the inverse variance technique. We examined 19 studies that were conducted between 1983 and 2020. Of these, 63.2% investigated calorie restriction, 21.0% experimented with a ketogenic diet, and 15.8% investigated the effects of fasting. The intervention lasted anything from 48 h to 221 weeks. Results showed that restrictive diets may reduce tumor incidence and progression, with a significant reduction in the risk of liver cancer development. Thereby, our results suggest that putting limits on what you eat may help treat liver cancer in more ways than one.

Tolerance, adherence, and acceptability of a ketogenic 2.5:1 ratio, nutritionally complete, medium chain triglyceride-containing liquid feed in children and adults with drug-resistant epilepsy following a ketogenic diet.

OBJECTIVE: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. METHODS: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8-46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. RESULTS: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). SIGNIFICANCE: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. PLAIN LANGUAGE SUMMARY: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.

Ketogenic diet attenuates cognitive dysfunctions induced by hypoglycemia via inhibiting endoplasmic reticulum stress-dependent pathways.

Hypoglycemia can potentially cause severe damage to the central nervous system. The ketogenic diet (KD), characterized by high-fat and extremely low-carbohydrate content, can modulate homeostasis and nutrient metabolism, thereby influencing body health. However, the effects and underlying mechanisms of KD on hypoglycemia-induced brain injury have not been thoroughly investigated. We aimed to explore the modulating effects of KD on cognitive functions and elucidate the underlying mechanisms. In this study, one-month-old mice were fed with KD for 2 weeks, and the changes in the gut microbiota were detected using the 16S rRNA gene amplicon sequencing method. The hypoglycemic model of mice was established using insulin, and the potential protective effect of KD on hypoglycemia-induced brain injury in mice was evaluated through immunofluorescence staining, western blotting, transmission electron microscopy, and Golgi staining. Our results showed that the intestinal flora of Dorea increased and Rikenella decreased in KD-fed mice. KD can not only alleviate anxiety-like behavior induced by hypoglycemia, but also increase the proportion of mushroom dendritic spines in the hippocampus by modulating changes in the gut microbiota. KD regulated synaptic plasticity by increasing the levels of SPN, PSD95, and SYP, which relieve cognitive impairment caused by hypoglycemia. Moreover, KD can promote the proliferation and survival of adult neural stem cells in the hippocampus, while reducing apoptosis by suppressing the activation of the IRE1-XBP1 and ATF6 endoplasmic reticulum stress pathways in mice with hypoglycemia. This study provides new evidence for demonstrating that KD may alleviate cognitive dysfunctions caused by hypoglycemia by modulating the gut microbiota.

Modulation of beta-hydroxybutyrate in traumatic brain injury.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a significant public health concern with substantial morbidity and mortality rates in the United States. Current management strategies primarily focus on symptomatic approaches and prevention of secondary complications. However, recent research highlights the potential role of ketone bodies, particularly beta-hydroxybutyrate (BHB), in modulating cellular processes involved in TBI. This article reviews the metabolism of BHB, its effect in TBI, and its potential therapeutic impact in TBI. RECENT FINDINGS: BHB can be produced endogenously through fasting or administered exogenously through ketogenic diets, and oral or intravenous supplements. Studies suggest that BHB may offer several benefits in TBI, including reducing oxidative stress, inflammation, controlling excitotoxicity, promoting mitochondrial respiration, and supporting brain regeneration. Various strategies to modulate BHB levels are discussed, with exogenous ketone preparations emerging as a rapid and effective option. SUMMARY: BHB offers potential therapeutic advantages in the comprehensive approach to improve outcomes for TBI patients. However, careful consideration of safety and efficacy is essential when incorporating it into TBI treatment protocols. The timing, dosage, and long-term effects of ketone use in TBI patients require further investigation to fully understand its potential benefits and limitations.

Efficacy and safety of a smartphone application-based treatment of ketogenic diet in pediatric refractory epilepsy.

OBJECTIVE: We aimed to find predictors for smartphone application-based ketogenic diet (KD) treatment effectiveness and safety. METHODS: The efficacy was evaluated according to the reduction in seizure frequency after the intervention of KD; safety was evaluated based on adverse effects. The ordinal logistic regression analysis was used to explore the influencing factors of efficacy. RESULTS: The study sample included 116 males and 65 females with a median age of 2.27 years. The baseline frequency of seizure was more than five times/day in 123 children, 50.83% of them received three or more antiepileptic drugs (AEDs). Seventy-two patients' KD initiation mode was outpatient, and 73 completed the 12-month follow-up. A total of 88 (48.62%) patients had reported a reduction in seizure ≥50%. Compared with 12 months, those who had received KD therapy for only 3 (P = 0.009) and 6 months (P = 0.005) were more likely to show negative outcomes. Outpatient initiation had better outcomes (P = 0.029) than inpatient initiation. For the number of AEDs applied, patients on two AEDs were more likely to achieve better outcomes (P = 0.001). Adverse events had been noted among 77 patients; BMI Z-score at KD initiation was associated with adverse effects (P = 0.003). SIGNIFICANCE: Our study suggested that outpatient initiation and long-term treatment of KD should be encouraged. PLAIN LANGUAGE SUMMARY: Our research shows that the KD is a helpful treatment for children with refractory epilepsy, reducing seizures by more than 50% in nearly half of the cases, with some experiencing complete seizure freedom. We used a smartphone app to improve communication between patients and their healthcare teams, resulting in a high retention, and app usage was linked to reduced adverse effects. We recommend early consideration of KD treatment for patients failing two AED, encourage outpatient initiation, and advocate for longer-term KD use.

Sleep effects of Ketogenic diet in pediatric patients with migraine: Preliminary data of a prospective study.

OBJECTIVE/BACKGROUND: Ketogenic dietary therapies' effects on sleep have been poorly investigated up to date. Preliminary results of a prospective study aimed at evaluating possible sleep changes in pediatric patients with migraine treated with classic ketogenic diet are presented. PATIENTS/METHODS: Included patients were aged 14-18 years and had a diagnosis of chronic migraine. A customized classic ketogenic diet was drawn up for all patients and all participants underwent neurological, nutritional and subjective and objective sleep assessment at baseline and after three months of follow-up (standardized sleep questionnaires, polysomnography, actigraphy). RESULTS: The majority of patients reported an improvement in migraine symptoms and quality of life. As far as sleep effects, a possible sleep stabilization was evidenced according to actigraphic data, and polysomnographic data showed a slight increase in total sleep time and sleep efficiency together with a reduction in waking time during night and a trend of NREM stage 1 decrease and REM increase. CONCLUSIONS: Future analyses on a broader population are needed to shed light on the ketogenic dietary therapies' effects on sleep and future research should be devoted to identify influence of possible individual and diet characteristics, and biochemical related changes.

Clinical effectiveness and cost-impact after 2 years of a ketogenic diet and virtual coaching intervention for patients with diabetes.

AIM: We previously evaluated the impacts at 5 months of a digitally delivered coaching intervention in which participants are instructed to adhere to a very low carbohydrate, ketogenic diet. With extended follow-up (24 months), we assessed the longer-term effects of this intervention on changes in clinical outcomes, health care utilization and costs associated with outpatient, inpatient and emergency department use in the Veterans Health Administration. MATERIALS AND METHODS: We employed a difference-in-differences model with a waiting list control group to estimate the 24-month change in glycated haemoglobin, body mass index, blood pressure, prescription medication use, health care utilization rates and associated costs. The analysis included 550 people with type 2 diabetes who were overweight or obese and enrolled in the Veterans Health Administration for health care. Data were obtained from electronic health records from 2018 to 2021. RESULTS: The virtual coaching and ketogenic diet intervention was associated with significant reductions in body mass index [-1.56 (SE 0.390)] and total monthly diabetes medication usage [-0.35 (SE 0.054)]. No statistically significant differences in glycated haemoglobin, blood pressure, outpatient visits, inpatient visits, or emergency department visits were observed. The intervention was associated with reductions in per-patient, per-month outpatient spending [-USD286.80 (SE 97.175)] and prescription drug costs (-USD105.40 (SE 30.332)]. CONCLUSIONS: A virtual coaching intervention with a ketogenic diet component offered modest effects on clinical and cost parameters in people with type 2 diabetes and with obesity or overweight. Health care systems should develop methods to assess participant progress and engagement over time if they adopt such interventions, to ensure continued patient engagement and goal achievement.

Evaluating the efficacy of a ketogenic diet in managing drug resistant paediatric DEDPC5-related epilepsy.

AIM: To evaluate the effectiveness of the ketogenic diet treatment in a cohort of patients with drug-resistant epilepsy with a mutation in the DEPDC5 gene. MATERIALS AND METHODS: We followed four paediatric patients with drug resistant DEPDC5-related epilepsy through a ketogenic diet (KD) treatment course. We analyzed the following parameters of their clinical profiles: past medical history, clinical characteristics of seizure morphology, EEG records pre- and post-KD treatment, the results of MRI head and neurological and psychological examinations (pre-treatment and throughout treatment course). We evaluated the effectiveness of previous therapeutic approaches and the current treatment with ketogenic diet alongside results of neuroimaging studies. Effect of KD on co-morbid behavioural and psychiatric symptoms, as well as adverse effects from KD were also assessed. RESULTS: In three patients, the introduction of the ketogenic diet resulted in the cessation of seizures, while in 1 patient with co-morbid cortical dysplasia, epileptic seizures of lesser severity returned after an initial seizure-free period of several weeks. Further, 1 patient was able to transition to a KD-only treatment regimen. The remaining patients were able to reduce the number of antiseizure medicine (ASM) to a monotherapy. In all cases we observed improvements in EEG results. Our cohort included one patient whose MRI head showed cortical dysplasia. However, no patients demonstrated any neurological signs in neurological examination. Psychological examination showed normal intellectual development in all patients, although behavioral disorders and difficulties at school were observed. The introduction of KD treatment correlated with improvement in school performance and improved behavioral regulation. No clinically significant adverse events were observed. CONCLUSIONS: KD seems to be both effective and well tolerated in young patients with DEPDC5-related epilepsy, both as a monotherapy and as an adjunct to ASM. We recommend an early adoption of this therapeutic approach in this patient demographic. Our results demonstrate that the positive effects of KD treatment encompass improvements in general functioning, particularly in the context of school performance and behavior, in addition to the achievement of good seizure control.

The Ketogenic Diet in the Prevention of Migraines in the Elderly.

Migraines display atypical age dependence, as the peak of their prevalence occurs between the ages of 20-40 years. With age, headache attacks occur less frequently and are characterized by a lower amplitude. However, both diagnosis and therapy of migraines in the elderly are challenging due to multiple comorbidities and polypharmacy. Dietary components and eating habits are migraine triggers; therefore, nutrition is a main target in migraine prevention. Several kinds of diets were proposed to prevent migraines, but none are commonly accepted due to inconsistent results obtained in different studies. The ketogenic diet is featured by very low-carbohydrate and high-fat contents. It may replace glucose with ketone bodies as the primary source of energy production. The ketogenic diet and the actions of ketone bodies are considered beneficial in several aspects of health, including migraine prevention, but studies on the ketogenic diet in migraines are not standardized and poorly evidenced. Apart from papers claiming beneficial effects of the ketogenic diet in migraines, several studies have reported that increased levels of ketone bodies may be associated with all-cause and incident heart failure mortality in older adults and are supported by research on mice showing that the ketogenic diets and diet supplementation with a human ketone body precursor may cause life span shortening. Therefore, despite reports showing a beneficial effect of the ketogenic diet in migraines, such a diet requires further studies, including clinical trials, to verify whether it should be recommended in older adults with migraines.

The Real-Life Use of a Protein-Sparing Modified Fast Diet by Nasogastric Tube (ProMoFasT) in Adults with Obesity: An Open-Label Randomized Controlled Trial.

BACKGROUND: Protein-sparing modified fast (PSMF) diet is a very-low-carbohydrate ketogenic diet administered to patients with obesity, which preserves lean mass and suppresses appetite as well as continuous enteral feeding. Thus, we aim to evaluate the effect of the PSMF diet administered continuously by nasogastric tube (NGT) or orally. METHODS: Patients with a body mass index (BMI) > 34.9 kg/m2 were randomly assigned to receive a whey protein PSMF formula through NGT (ProMoFasT) or orally. Data were collected at baseline and after 150 days. The endpoints were assessed in the intention-to-treat population. RESULTS: We enrolled 20 patients in the ProMoFasT group and 24 in the oral group. No differences in body weight, BMI or waist circumference between the two groups were found after 150 days. At follow-up, FFM (%) and MM (%) results were higher in the ProMoFasT group than the oral group (63.1% vs. 52.9%, p = 0.012 and 45.0% vs. 36.1%, p = 0.009, respectively) and FM (kg) and FM (%) were significantly lower in the ProMoFasT group (36.9 kg vs. 44.0 kg, p = 0.033 and 37.4% vs. 44.9%, p = 0.012, respectively). Insulin levels were lower in the ProMoFasT group than the oral group at follow-up (11.8 mU/L vs. 28.0 mU/L, p = 0.001, respectively). CONCLUSION: The ProMoFasT is more effective in improving body composition and glucometabolic markers than the same diet administered orally.

Ketogenic therapies in Parkinson's disease, Alzheimer's disease, and mild cognitive impairment: An integrative review.

BACKGROUND: Ketogenic therapies have shown benefit for seizure reduction in epilepsy but their impact on other neurologic conditions is less known. In this literature review, the efficacy of ketogenic therapies were assessed in Parkinson's disease (PD), Alzheimer's disease (AD), and mild cognitive impairment (MCI). METHODS: A literature search was conducted using PubMed, Scopus, and Google Scholar focusing on ketogenic therapies in PD, AD, and MCI. RESULTS: A total of 2565 records were identified with a total of 15 studies (3 for PD and 12 for MCI/AD) meeting criteria for analysis. The ketogenic diet was used in all the PD studies and did show significant improvement in motor function either through vocal quality, gait, freezing, tremor, and/or balance. A variety of ketogenic therapies were utilized in the MCI and AD groups including a ketogenic diet, low-carbohydrate diet, modified Adkins diet, Mediterranean diet with coconut oil supplementation, a ketogenic diet with a ketogenic medium chain triglyceride (kMCT) supplement, as well as ketogenic supplements including a ketogenic drink with kMCT, oral ketogenic compounds (Axona and AC-1202), and MCT oil or emulsion. The ketogenic diet independently showed a non-significant trend towards improvement in cognition. The Mediterranean diet, modified Adkins diet, and low-carbohydrate diet showed statistically significant improvements in some, although not all, of their cognitive measures. Use of ketogenic supplements, drinks, or compounds showed variable results in the AD and MCI groups. The Axona and AC-1202 compounds showed no significant improvement in cognition at the end of their respective 90-day trials. Most MCT supplements did show cognitive improvements, although only after 6 months of adherence. Adherence to the intervention was problematic in most of the diet studies. CONCLUSION: Ketogenic therapies have promise in PD, AD, and MCI for symptom improvement although larger studies are needed to support their implementation in clinical practice.

The Effect of Three Different Ketogenic Diet Protocols on Migraine and Fatigue in Chronic and High-Frequency Episodic Migraine: A Pilot Study.

AIMS: We aimed to evaluate the efficacy of three different ketogenic diets on migraine and fatigue in chronic and high-frequency episodic migraineurs. METHODS: 76 patients with migraine were treated with the KD for at least three months. Three different KD protocols were used (2:1 KD, LGID, and VLCKD). We evaluated the fatigue severity scale (FSS), migraine frequency, migraine intensity, MIDAS, and HIT-6 at the baseline and 3-month follow-up, and we compared the results. We also correlated the mean FSS reduction with the mean migraine frequency, migraine intensity, BMI, fat mass, free-fat mass, MIDAS, and HIT-6 reduction. RESULTS: FSS improved from 4.977 ± 1.779 to 3.911 ± 1.779 at the 3-month follow-up (p < 0.001). This improvement was significant in both high-frequency and chronic migraineurs. Moreover, the three KD protocols effectively improved migraine intensity, frequency, MIDAS, and HIT-6. There was a mild correlation between mean FSS reduction (p < 0.001), mean MIDAS (p = 0.001), and HIT-6 (p = 0.002) reduction. CONCLUSIONS: The VLCKD, LGID, and 2:1 KD may improve migraine intensity, frequency, and fatigue in chronic and high-frequency episodic migraineurs.

Ketogenic Diet and Breast Cancer: Recent Findings and Therapeutic Approaches.

Breast cancer (BC), a complex disease with several influencing factors, is significantly impacted by dietary habits. The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has gained attention as a potential therapeutic approach, but its effects on BC remain unclear. This review seeks to summarize the current knowledge on the principles of the KD, its metabolic influence on BC cells, and the findings of recent clinical trials, in order to elucidate the potential therapeutic role of the KD in BC management. For these purposes, a comprehensive literature review was conducted selecting preclinical and clinical studies that investigate the relationship between the KD and BC. The selection criteria prioritized studies exploring the KD's metabolic effects on BC cells and current clinical trials involving the KD in BC management. The reviewed studies provide a diverse range of findings, with some suggesting potential benefits of the KD in inhibiting tumor growth and improving treatment response. However, robust clinical trials providing clear evidence of the KD's efficacy as a standalone therapeutic approach in BC are still lacking. There are also significant concerns regarding the safety and long-term effects of sustained ketosis in cancer patients. The therapeutic potential of the KD in BC remains an area of active research and debate. While preliminary findings are promising, definitive conclusions are hindered by inconsistent results and limited human trial data. Future research, specifically well-structured, large-scale clinical trials, is necessary to provide a comprehensive understanding of the role of the KD in BC treatment. Until then, caution should be exercised in its application, and patients should continue prioritizing evidence-based, standard-of-care treatments.

Ketogenic diet influence on the elemental homeostasis of internal organs is gender dependent.

The ketogenic diet (KD) is a low-carbohydrate and high-fat diet that gains increasing popularity in the treatment of numerous diseases, including epilepsy, brain cancers, type 2 diabetes and various metabolic syndromes. Although KD is effective in the treatment of mentioned medical conditions, it is unfortunately not without side effects. The most frequently occurring undesired outcomes of this diet are nutrient deficiencies, the formation of kidney stones, loss of bone mineral density, increased LDL (low-density lipoprotein) cholesterol levels and hormonal disturbances. Both the diet itself and the mentioned adverse effects can influence the elemental composition and homeostasis of internal organs. Therefore, the objective of this study was to determine the elemental abnormalities that appear in the liver, kidney, and spleen of rats subjected to long-term KD treatment. The investigation was conducted separately on males and females to determine if observed changes in the elemental composition of organs are gender-dependent. To measure the concentration of P, S, K, Ca, Fe, Cu, Zn and Se in the tissues the method of the total reflection X-ray fluorescence (TXRF) was utilized. The obtained results revealed numerous elemental abnormalities in the organs of animals fed a high-fat diet. Only some of them can be explained by the differences in the composition and intake of the ketogenic and standard diets. Furthermore, in many cases, the observed anomalies differed between male and female rats.

Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis.

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.

Feasibility, tolerability and efficacy of the ketogenic diet in children with drug-resistant epilepsy in Vietnam.

OBJECTIVES: According to the WHO, more than 50 million people have epilepsy. Among them, nearly 80% of patients with epilepsy live in developing countries and 75% of them do not have access to treatment. The ketogenic diet (KD) has been shown as an effective alternative for patients with drug-resistant epilepsy. Although it has been studied in Asia, no such studies have been conducted in Vietnam. The purpose of this study was to verify the feasibility and tolerability of KD in children with refractory epilepsies in Vietnam. METHODS: Children with drug-resistant epilepsy followed at Children's Hospital, Vietnam treated by KD were included in a prospective study from June 2019 to October 2021. Side-effects, retention rate, number, and duration of seizures were recorded after 1, 3, 6, 9 and 12 months of KD. Patients were considered as respondents when a 50% seizure frequency was reached. Tolerance and acceptability of the KD were closely monitored. RESULTS: Forty-six children were included but KD was contraindicated for one patient. Due to the COVID pandemic, we had to rely on internet exchanges to stay in touch with families. Meals had to be adapted to Vietnamese culinary habits. The retention rate decreased from 82.2% at 1 month to 40% at 12 months of follow-up. The incidence of side effects was 44.4% and occurred mainly during the first month. Fifteen patients out of 45 were considered as responders after 12 months. SIGNIFICANCE: Our study was the first attempt to introduce KD in Vietnam. It demonstrated that this diet was feasible and well tolerated. The KD diet resulted in significant improvement for 30% of our patients with drug-resistant epilepsy. This percentage is lower than in some studies but warrants the use of KD as a valuable alternative in a country where many patients lack access to recent treatments.

The Ketogenic Diet and Cardiovascular Diseases.

The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.