Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial.

BACKGROUND: Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options. OBJECTIVES: We compared 2 low-carbohydrate diets with 3 key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and 3 key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM. METHODS: Keto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the 3 key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake. RESULTS: The primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, -16% (SEM, 4%) compared with -5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with -5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable. CONCLUSIONS: HbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable. This trial was registered at clinicaltrials.gov as NCT03810378.

Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19.

Anorexia and fasting are host adaptations to acute infection, and induce a metabolic switch towards ketogenesis and the production of ketone bodies, including ß-hydroxybutyrate (BHB)1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we show that the production of BHB is impaired in individuals with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) but not in those with  influenza-induced ARDS. We found that BHB promotes both the survival of and the production of interferon-γ by CD4+ T cells. Applying a metabolic-tracing analysis, we established that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but could be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we show in mice that a ketogenic diet and the delivery of BHB as a ketone ester drink restores CD4+ T cell metabolism and function in severe respiratory infections, ultimately reducing the mortality of mice infected with SARS-CoV-2. Altogether, our data reveal that BHB is an alternative source of carbon that promotes T cell responses in pulmonary viral infections, and highlight impaired ketogenesis as a potential confounding factor in severe COVID-19.

From the Ketogenic Diet to the Mediterranean Diet: The Potential Dietary Therapy in Patients with Obesity after CoVID-19 Infection (Post CoVID Syndrome).

PURPOSE OF REVIEW: This review primarily examines the evidence for areas of consensus and on-going uncertainty or controversy about diet and physical exercise approaches for in the post-CoVID. We propose an ideal dietary and physical activity approach that the patient with obesity should follow after CoVID-19 infection in order to reduce the clinical conditions associated with post-CoVID syndrome. RECENT FINDINGS: The CoVID-19 disease pandemic, caused by the severe acute respiratory syndrome coronavirus-2, has spread all over the globe, infecting hundreds of millions of individuals and causing millions of death. It is also known to be is associated with several medical and psychological complications, especially in patients with obesity and weight-related disorders who in general pose a significant global public health problem, and in specific affected individuals are on a greater risk of developing poorer CoVID-19 clinical outcomes and experience a higher rate of mortality. Little is still known about the best nutritional approach to be adopted in this disease especially in the patients post-CoVID syndrome. To the best of our knowledge, no specific nutritional recommendations exist to manage in the patients post-CoVID syndrome. We report a presentation of nutritional therapeutic approach based on a ketogenic diet protocol followed by a transition to the Mediterranean diet in patients post-infection by CoVID, combined to a physical activity program to address conditions associated with post-CoVID syndrome.

Telemedicine- versus outpatient-based initiation and management of ketogenic diet therapy in children with drug-resistant epilepsy during the COVID-19 pandemic.

INTRODUCTION: Initiation of ketogenic diet therapies (KDT) for pediatric epilepsy is usually done on an inpatient basis and the diet is managed during clinical appointments following a protocol of visits and routine tests. Because of the 2019 coronavirus disease (COVID-19) pandemic and the associated lock-down measures, we switched from outpatient to telemedicine-based KDT initiation. OBJECTIVE: To explore the feasibility, effectiveness, and safety of online KDT initiation and follow-up by comparing a group of children with drug-resistant epilepsy that was managed by telemedicine compared to a group that was treated on an outpatient basis. MATERIALS AND METHODS: An observational study was conducted in two groups of patients with drug-resistant epilepsy who initiated KDT and were followed up with an online versus an outpatient modality by the interdisciplinary KDT team of Hospital Pediatria JP Garrahan in Buenos Aires, Argentina. Dietary compliance, ketosis, retention rate, adverse effects, number of contacts, and clinical outcome were evaluated at 1, 3, and 6 months on the diet. RESULTS: Overall, 37 patients were included, of whom 18 started the KD by telemedicine and 19 on an outpatient basis. Minimum follow-up of the patients was 6 months. All patients received the classic ketogenic diet. No statistical differences between the two groups regarding efficacy and safety of the diet were found. CONCLUSIONS: Our results support the feasibility and safety of initiating and management of KDT by telemedicine. Patients and their families should be carefully selected in order to guarantee a good outcome.

Use of an mHealth Ketogenic Diet App Intervention and User Behaviors Associated With Weight Loss in Adults With Overweight or Obesity: Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Low-carbohydrate ketogenic diets are a viable method to lose weight that have regained popularity in recent years. Technology in the form of mobile health (mHealth) apps allows for scalable and remote delivery of such dietary interventions and are increasingly being used by the general population without direct medical supervision. However, it is currently unknown which factors related to app use and user behavior are associated with successful weight loss. OBJECTIVE: First, to describe and characterize user behavior, we aim to examine characteristics and user behaviors over time of participants who were enrolled in a remotely delivered clinical weight loss trial that tested an mHealth ketogenic diet app paired with a breath acetone biofeedback device. Second, to identify variables of importance to weight loss at 12 weeks that may offer insight for future development of dietary mHealth interventions, we aim to explore which app- and adherence-related user behaviors characterized successful weight loss. METHODS: We analyzed app use and self-reported questionnaire data from 75 adults with overweight or obesity who participated in the intervention arm of a previous weight loss study. We examined data patterns over time through linear mixed models and performed correlation, linear regression, and causal mediation analyses to characterize diet-, weight-, and app-related user behavior associated with weight loss. RESULTS: In the context of a low-carbohydrate ketogenic diet intervention delivered remotely through an mHealth app paired with a breath acetone biofeedback device, self-reported dietary adherence seemed to be the most important factor to predict weight loss (ß=-.31; t54=-2.366; P=.02). Furthermore, self-reported adherence mediated the relationship between greater app engagement (from c=-0.008, 95% CI -0.014 to -0.0019 to c'=-0.0035, 95% CI -0.0094 to 0.0024) or higher breath acetone levels (from c=-1.34, 95% CI -2.28 to -0.40 to c'=-0.40, 95% CI -1.42 to 0.62) and greater weight loss, explaining a total of 27.8% and 28.8% of the variance in weight loss, respectively. User behavior (compliance with weight measurements and app engagement) and adherence-related aspects (breath acetone values and self-reported dietary adherence) over time differed between individuals who achieved a clinically significant weight loss of >5% and those who did not. CONCLUSIONS: Our in-depth examination of app- and adherence-related user behaviors offers insight into factors associated with successful weight loss in the context of mHealth interventions. In particular, our finding that self-reported dietary adherence was the most important metric predicting weight loss may aid in the development of future mHealth dietary interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04165707; https://clinicaltrials.gov/ct2/show/NCT04165707. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19053.

About gladiators and a sacred disease.

In this special edition of the Biomedical Journal the reader gains an insight into drug-resistant epilepsy and according treatment approaches involving deep brain stimulation, the ketogenic diet and fecal microbiota transplant. Another emphasis is put on personalized medicine strategies, and covered in articles about the use of natriuretic peptides against cancer, along with an article about companion diagnostics involving extracellular vesicles. Recurrent infection with Clostridium difficile, associated risk factors and therapeutic options are discussed. We learn about a mechanism that helps Leishmania evade a host control mechanism, receive an update about human adenovirus and are presented with characteristic magnetic resonance neuroimaging in COVID-19 pediatric patients. An advanced assessment in pediatric septic shock and an improved model for a pediatric early warning system are proposed. Some of the genetic causes of renal hypomagnesemia are explored, the impact of air pollution on children is examined, and an antisiphon device is described for surgical treatment of hydrocephalus. The relation between energy metabolism, circadian rhythm and its influence on the ATPase in the SCN are investigated, and among others some of the genetics influencing smoking duration and lung cancer. Finally it is discussed how embryo quality can be improved in in vitro fertilization, and what impact high estradiol has on blastocyst implantation. The outcome of surgery to correct mandibular deficiency is assessed, and in two letters the inclusion of observational studies in the evaluation of clinical trials related to COVID-19 is elaborated.

Very-Low-Calorie Ketogenic Diet: A Potential Treatment for Binge Eating and Food Addiction Symptoms in Women. A Pilot Study.

BACKGROUND: many patients who struggle to lose weight are unable to cut down certain ultra-processed, refined types of food with a high glycemic index. This condition is linked to responses similar to addiction that lead to overeating. A very-low-calorie ketogenic diet (VLCKD) with adequate protein intake could be considered a valid dietary approach. The aim of the present study was to evaluate the feasibility of a VLCKD in women with binge eating and/or food addiction symptoms. METHODS: subjects diagnosed with binge eating and/or food addiction symptoms (measured with the Binge Eating Scale and the Yale Food Addiction Scale 2.0) were asked to follow a VLCKD with protein replacement for 5-7 weeks (T1) and a low-calorie diet for 11-21 weeks (T2). Self-reported food addiction and binge eating symptoms and body composition were tested at T0 (baseline) and at the end of each diet (T1 and T2 respectively); Results: five women were included in the study. Mean age was 36.4 years (SEM = 4.95) and mean BMI was 31.16 (SEM = 0.91). At T0, two cases of severe food addiction, one case of mild food addiction, one case of binge eating with severe food addiction, and one case of binge eating were recorded. Weight loss was recorded at both T1 and T2 (ranging from 4.8% to 11.6% of the initial body weight at T1 and from 7.3% to 12.8% at T2). No case of food addiction and/or binge eating symptoms was recorded at T2. Muscle mass was preserved. CONCLUSIONS: recent findings have highlighted the potential therapeutic role of ketogenic diets for the treatment of addiction to high-calorie, ultra-processed and high-glycemic food. Our pilot study demonstrates the feasibility of a ketogenic diet in women with addictive-like eating disorders seeking to lose weight.

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.

BACKGROUND: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. AIM: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). MATERIALS AND METHODS: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. RESULTS: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. CONCLUSION: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.

Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues.

BACKGROUND: Obesity increases the severity of SARS-CoV-2 outcomes. Thus, this study tested whether obesogenic and ketogenic diets distinctly affect SARS-CoV-2 entry proteins and the renin-angiotensin system (RAS) in rat pulmonary and cardiac tissues. METHODS: Male Sprague-Dawley rats were fed either standard chow (SC), a high-fat sucrose-enriched diet (HFS), or a ketogenic diet (KD) for 16 weeks. Afterwards, levels of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), RAS components, and inflammatory genes were measured in the lungs and hearts of these animals. RESULTS: In the lungs, HFS elevated ACE2 and TMPRSS2 levels relative to SC diet, whereas the KD lowered the levels of these proteins and the gene expressions of toll-like receptor 4 and interleukin-6 receptor relative to HFS. The diets did not alter ACE2 and TMPRSS2 in the heart, although ACE2 was more abundant in heart than lung tissues. CONCLUSION: Diet-induced obesity increased the levels of viral entry proteins in the lungs, providing a mechanism whereby SARS-CoV-2 infectivity can be enhanced in obese individuals. Conversely, by maintaining low levels of ACE2 and TMPRSS2 and by exerting an anti-inflammatory effect, the KD can potentially attenuate the severity of infection and migration of SARS-CoV-2 to other ACE2-expressing tissues.

[Obesity, inflammation and COVID-19: preventive interest of ketogenic diet?] / Obésité, inflammation et COVID-19 : intérêt préventif de l'alimentation cétogène ?

Obesity is considered a pandemic responsible for millions of deaths worldwide for many years. At the end of 2019, the Coronavirus disease 2019 (COVID-19) appeared, causing the death of more than a million people in less than a year. Numerous studies suggest that obesity could be defined as key to the onset of severe forms of this emerging disease. Indeed, SARS-CoV2 infects the host by binding to ACE2 receptors present on the surface of the cells and causes excessive secretion of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α, which lead to developing acute respiratory distress syndrome (ARDS). It therefore seems essential to make up effective preventive strategies to protect this part of the population from the risk of developing a severe form of COVID-19. The ketogenic diet, which is low in sugars and high in fat, has interesting properties, both in the fight against obesity but also against severe infections. This article focuses on the latest scientific advances that make it possible to consider the ketogenic diet as a preventive strategy that simultaneously reduces the development of obesity while strengthening the immune system, two key actions in the fight against SARS-CoV2 infections and severe forms of COVID-19.

TITLE: Obésité, inflammation et COVID-19 : intérêt préventif de l'alimentation cétogène ? ABSTRACT: L'obésité est considérée comme une pandémie responsable de plusieurs millions de morts dans le monde depuis de nombreuses années. Fin 2019 est apparue la maladie à Coronavirus 2019 (COVID-19) qui a provoqué la mort de plus d'un million de personnes en moins d'un an. De nombreuses études suggèrent que l'obésité pourrait être un paramètre clé dans l'apparition des formes graves de cette maladie émergente. En effet, le SARS-CoV2 infecte l'hôte en se fixant aux récepteurs ACE2 présents à la surface des cellules et entraîne une sécrétion excessive de cytokines pro-inflammatoires notamment l'IL-1, l'IL-6 et le TNF-α qui conduisent au développement d'un syndrome de détresse respiratoire aigu (SDRA). Il paraît essentiel d'élaborer des stratégies préventives efficaces pour protéger cette partie de la population du risque de développer une forme grave de COVID-19. L'alimentation cétogène, pauvre en sucres et riche en lipides, présente d'intéressantes propriétés, à la fois pour la lutte contre l'obésité mais également contre les infections sévères. Cet article fait le point sur les dernières avancées scientifiques qui permettent d'envisager l'alimentation cétogène comme une stratégie préventive visant à diminuer le développement de l'obésité et à renforcer le système immunitaire, deux actions clés dans la lutte contre l'infection au SARS-CoV2 et le développement de formes graves de COVID-19.

Challenges faced by people with epilepsy on ketogenic diet therapy and their caregivers during the COVID-19 pandemic in Brazil.

BACKGROUND: Although ketogenic diet therapy (KDT) is a well-established, nonpharmacologic therapeutic option for patients with pharmacoresistant epilepsy, its availability is still not widespread. The COVID-19 pandemic may have further restricted the access of people with pharmacoresistant epilepsy (PWE) to KDT. Thus, we evaluated the experiences of Brazilian PWE and their caregivers during the first year of the pandemic. METHODS: An online self-assessed survey containing 25 questions was distributed via social media to be answered by PWE treated with KDT or their caregivers through Google Forms from June 2020 to January 2021. Mental health was assessed using the DASS and NDDI-E scales. RESULTS: Fifty adults (>18 yo), of whom 68% were caregivers, answered the survey. During the pandemic, 40% faced adversities in accessing their usual healthcare professionals and 38% in obtaining anti-seizure medication (ASM). Despite these issues, 66% of those on KDT could comply with their treatment. Those struggling to maintain KDT (34%) named these obstacles mainly: diet costs, social isolation, food availability, and carbohydrate craving due to anxiety or stress. An increase in seizure frequency was observed in 26% of participants, positively associated with difficulties in obtaining ASM [X2 (1, N = 48) = 6.55; p = 0.01], but not with KDT compliance issues. CONCLUSIONS: People with pharmacoresistant epilepsy and undergoing KDT, as well as their caregivers, faced additional challenges during the COVID-19 pandemic, not only difficulties in accessing healthcare and KDT maintenance but also on seizure control and mental health.

Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

Evaluation of E-Health Applications for Paediatric Patients with Refractory Epilepsy and Maintained on Ketogenic Diet.

E-health technologies improve healthcare quality and disease management. The aim of this study was to develop a ketogenic diet management app as well as a website about this dietary treatment and to evaluate the benefits of giving caregivers access to various web materials designed for paediatric patients with refractory epilepsy. Forty families participated in the questionnaire survey, from January 2016 to March 2016. All caregivers were exposed to paper-based materials about the ketogenic diet, whereas only 22 received the app, called KetApp, and videos produced by dieticians. Caregivers with free access to web materials were more satisfied than the others with the informative material provided by the centre (p ≤ 0.001, Mann-Whitney test). Indeed, they showed a better attitude towards treatment, and they became more aware of dietary management in comparison to the control group (p ≤ 0.001). Moreover, caregivers provided with web materials were stimulated to pursue the treatment (p = 0.002) and to introduce it to their children and other people (p = 0.001). Additionally, caregivers supplied with web materials were more willing to help other families in choosing the ketogenic diet (p = 0.004). Overall, these findings indicate that web materials are beneficial for caregivers of paediatric patients with refractory epilepsy in our centres. Thus, the use of e-health applications could be a promising tool in the daily aspects of ketogenic diet management, and it is especially of value in the attempt to start or maintain the diet during the ongoing COVID-19 pandemic crisis.

Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients.

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.

The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet?

The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.

Challenges in telemedicine for adult patients with drug-resistant epilepsy undergoing ketogenic diet treatment during the COVID-19 pandemic in the public healthcare system in Brazil.

Hygienic and sanitary measures and social distancing policies implemented during the new coronavirus disease - COVID-19 - pandemic have altered the care and follow-up provided by healthcare professionals for patients with chronic diseases, including patients with epilepsy (PWEs). Telemedicine has become a solution for the healthcare of PWEs in many developed countries. In this short communication, we trace a particular perspective for the application of telemedicine for PWEs undergoing ketogenic diet (KD) treatment, considering the social and economic difficulties faced by healthcare teams in resource-poor countries, such as Brazil. During the pandemic, financial strain was the main impediment to following KD. The pandemic increased socioeconomic insecurity and access to KD-related products, as well as increasing anxiety in 71% of PWE, impacting their KD treatment follow-up. The challenges of telemedicine in Brazil include not only social and economic issues but also access to food, healthcare services, and education for the population, in addition to digital inclusion.

COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm.

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.

Telemedicine, drug-resistant epilepsy, and ketogenic dietary therapies: A patient survey of a pediatric remote-care program during the COVID-19 pandemic.

OBJECTIVE: The purpose of this study was to assess parent satisfaction with the management of ketogenic diet therapies (KDTs) through telemedicine using WhatsApp as the main tool. METHODS: Parent satisfaction was longitudinally evaluated through questionnaires. The survey was developed with Google Questionnaire forms and sent via WhatsApp. The questionnaire consisted of 13 items concerning the management of KDTs using telemedicine in the context of the coronavirus disease 2019 (COVID-19) pandemic. Our population of patients has limited financial resources and low levels of education. Given that many families did not have either computers or WIFI, or any other access to information or communication technology, WhatsApp was chosen as a tool as it was available on the cell phones of all families and the professionals. RESULTS: Our survey showed that 96.3% of the parents were satisfied with the management of KDTs through telemedicine. The main benefits observed were the possibility of continuing treatment during the COVID-19 pandemic and the ease of accessing the professional team from the comfort of their home. Overall, 72.2% of the families would recommend using telemedicine for KDTs in any situation regardless of the pandemic. None of the families reported that they would recommend against treatment by telemedicine. The availability of a social support network (parents WhatsApp group) coordinated by professionals from the KDT team was considered to be useful by most respondents (90%). CONCLUSIONS: Our study suggests that management of children with DRE on KDTs through telemedicine is feasible, well accepted by the families, and probably as safe as conventional medicine. WhatsApp may be an interesting telemedicine tool to start and maintain KDTs.

Switching Host Metabolism as an Approach to Dampen SARS-CoV-2 Infection.

BACKGROUND: COVID-19 pandemic, a global threat, adversely affects all daily lives, altered governmental plans around the world, and urges the development of therapeutics and prophylactics to avoid the expansion of the viral infection. With the recent gradual opening after long lockdown, several recommendations have been placed, with dietary modification as one of the most important approaches that have been appraised. SUMMARY: Here, we are reviewing how changing the host metabolism, particularly changing the host metabolic state from the carbohydrate-dependent glycolytic state to a fat-dependent ketogenic state, may affect viral replication. Furthermore, the impact of intermittent fasting (IF) in triggering metabolic switch along with the impact of supplementation with medium-chain triglycerides (MCTs) such as lauric acid in repressing the envelope formation and viral replication is also addressed. The amalgamation of IF and a ketogenic diet rich in MCTs is thought to work as a prophylactic measure for normal people and adjunct therapy for infected persons. Key Message: A diet regimen of ketogenic breakfast along with supplementation with two doses of lauric acid-rich MCTs at breakfast and lunch times, followed by 8-12-h IF and a dinner rich with fruits and vegetables, could be a potential prophylactic strategy and adjuvant therapy to combat SARS-CoV-2 infections.