Body weight and height were assessed at screening visit, starting from baseline, body composition was measured using the Tanita 418 BC MA scale (Tanita Europe BV, 1101 BE Amsterdam, The Netherlands). Furthermore, patients were provided with a center-based diet diary for documentation of hunger, overall well-being, potential additional foods deviant from the allocated diet and the daily ketosis measurements. Patients in the interventional diet groups were provided with recipes for permitted snacks as well as protein bars (Adonis Smart Foods) which could be consumed in case of an untamable hunger. The diet was offered to be vegetarian and through a high percentage of vegetarian recipes, patients were encouraged to limit meat intake. Visit 6 was scheduled to assess a 4-week follow-up period (FU) after return to a carbohydrate (CHO) rich diet. Moreover, both diet groups performed two daily at-home acetone breath analyses.The second case was a 39-year-old woman who had suffered from treatment-resistant psychotic symptoms for 20 years.Obesity has a clear correlation with the incidence of cardiovascular disorders including hypertension, coronary artery disease, heart failure and sudden death, and many patients with insulin resistance, the main etiology of T2DM, tend to have high triglyceride and low HDL levels 53,54,55.On the other hand, our ketogenic diet regimen has no calorie restriction, with a clear target value and period for carbohydrate restriction.Daily mean values of acetone levels are shown.(C) Average feasibility scores of each diet group are displayed, queried with a dedicated feasibility questionnaire.Quantitative synthesis and evidence grading for meta-analyses of the combination of diet and…Moreover, we will understand if the MeDi-KD and the MeDi-MCT can elevate blood ketone bodies to clinically relevant levels, while remaining feasible and safe.Additional psychological techniques, such as integrated motivational interviewing and cognitive behavior therapy, can lead to improvements in diet adherence . While the mechanisms for this response are not entirely clear, preclinical studies from our group and others suggest that the ketone, beta-hydroxybutyrate (βHB), inhibits histone deacetylases which have been shown to preserve muscle in aging rodents . In addition, it will be important to examine tolerability of the KD in different types of cancers and treatments. The hypothesized benefit of any low carbohydrate or low glycemic index diet is that the removal of processed foods containing sugar, added sugar, and lowering of starch-based carbohydrates reduce the amount of insulin required to clear a meal in the postprandial state. Indeed, because of the vast heterogeneity of the human clinical trial literature, the validity of the published systematic reviews and meta-analytic reviews is highly questionable. Therefore, more preclinical studies should be performed to elaborate the antitumor effect of KD in the future (p. 11).” Twenty-four SRMAs were selected which encompassed a total of 255 original studies. We conducted an overview on MEDLINE, EMBASE, Cochrane Database of Systematic Review, and Web of Science from database inception to 3 September 2020. We aim to evaluate the quality of the systematic reviews and meta-analyses (SRMAs) of KDT for epilepsy and summarize the evidence on their effects. Vitaflo are independent to the study design and scientific content of this pilot study. MDJ, AGM, CTS and KJM receive funding from Vitaflo (International) Ltd. for KJM PhD studies. The primary differences are in the maximum limit of carbohydrate and protein, the timing of feeding, and intermittent calorie restriction, as well as the underlying food selection to accommodate personal dietary preferences. It is unclear, however, whether short-term decreases in the GKI value via supplemental MCTs or exogenous ketones, without a global metabolic transition to therapeutic ketosis by chronic KDs and/or fasting (increased oxidative efficiency of fat-derived metabolites), would retain protective effects against SLP inhibition in normal cells . After setting a carbohydrate limit to induce ketogenesis and calculating protein needs to preserve muscle mass, the energy density of the diet will be adjusted by total fat intake. In contrast, KDs consumed in calorically restricted amounts, resulting in a gradual, deliberate reduction of fat mass (with preserved muscle mass), could produce better cumulative, steady-state GKI values, in tandem with the underlying metabolic and signaling effects, such as insulin suppression 102, 134, 224, 225. Preclinical and clinical evidence suggests that patients should aim for the lowest, physiologically safe and sustainable glucose and insulin levels 198,199,200,201,202, where the proxy indicating effective insulin suppression is via elevated blood ketone levels throughout the day, especially during the evening pre-prandial time 203, 204. Feasibility in the general population cannot be assumed from this study.But they come with the same risks if you overdo it on fats and proteins and lay off the carbs.Notably, several reports describe the increased risk for euglycemic DKA in individuals with diabetes treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors and KD (140, 141).Create healthy, balanced meals using this visual guide as a blueprint.Changes in cardiovascular risk factors were mostly favourable and adverse effects were mild.The sum of all safety relevant events in the superordinate groups are shown per study arm.Our evidence-based guides are updated at least once per year to reflect and reference the latest science on the topic.All our evidence-based health guides are written or reviewed by medical doctors who are experts on the topic.The use of ketogenic supplements was discouraged. During treatment, potassium chloride and statins were administered orally for mild hypokalemia and hyperlipidemia, respectively, but no serious side effects were observed. In the previous report, 55 patients met the entry criteria and were enrolled in the trial. The assignment of these weights to the study population generates the “pseudo-population” in which the imbalance of a set of observed covariates is expected to become balanced between two groups. A total of 55 patients with advanced cancer were enrolled from February 2013 to December 2018 and followed up by November 2019. In recent years, the importance of proper nutrition in supporting the treatment of patients with malignant tumors has been emphasized . Current evidence suggests KD may work best in combination with conventional or targeted treatments, and may have the greatest benefit when initiated early in cancer progression (92). The potent weight-loss effect of KD makes it an attractive approach to reduce cancer risk by decreasing obesity. Such research might help to make KD more acceptable in the medical establishment as an efficacious dietary approach for individuals living with obesity and diabetes. This means that clinicians cannot and should not dismiss KD as a dietary approach to treat diabetes. Protocol amendments will be communicated to all relevant parties in writing (Sponsor, REC, HRA, Trial registry, investigators, participants and journals). All data will be pseudo anonymised in order to maintain patient confidentiality. Vitaflo also supplied the nutritional product, however, did not contribute to or influence this trial protocol or publication. Funding for the trial was received from Vitaflo (International) Ltd. via a PhD Studentship for KJM. A PPI event was undertaken, seeking the active involvement of patients and public in identifying research priorities and outcome measures for KD in GB. Indeed, the authors admitted later that their study diet would be more appropriately termed a “coconut oil-enriched Mediterranean diet” (28). The exception was the study published by Benlloch et al. (27), in which the ketogenic ratio was far below 1. KD regimens used in these studies were heterogeneous, including variants such as a modified Atkins diet (3) and medium-chain triglyceride (MCT)–based KD modified from the Wahls Paleo Diet (21). To prevent the acidosis, it has been suggested that dietary protein, which is a source of endogenous acidic metabolites, is maintained at the level of 1–2 g/kg/d, and consumption of alkaline mineral–rich green vegetables is maximized (15). It has been suggested that KD might exert anti-inflammatory and neuroprotective effects in patients with various neurological disorders (9–13), including progressive MS (14). However, studies point toward an overall improvement of body composition and blood parameters , , . Owing to its high fat content, there is a general concern among clinicians that a KD may cause deterioration of certain metabolic markers, especially cholesterol and triglycerides. Besides the traditional use of the KD in therapy-resistant epilepsy, patients with malfunctions in glucose metabolism such as glucose transporter 1, pyruvate carboxylase, or pyruvate dehydrogenase deficiency benefit from a KD , . The shift from glucose to ketones and fatty acids as the main source of energy can take up to one week . Prior to baseline testing (BL), a dietary education session was provided to ensure participants understood the guiding principles to a WFKD and were comfortable with adhering to the diet for 10–12 weeks. Rigorous diagnostic assessments of mental health and dietary adherence were implemented. Given the likelihood that dysregulated metabolic function may be a modulator exacerbating depression, nutrition-focused interventions may augment the effects of psychotherapy and pharmacological interventions for depression . However, pharmacological intervention may be accompanied by anxiety, decreased libido, nausea, insomnia, and decreased metabolic health 6, 7, which may exacerbate depressive symptoms . Several practical aspects, especially of ketogenic diets, warrant consideration.However, the difference in HDL is clinically insignificant, and there was no effect on LDL.There are various types of KDs, offering varying contents of fat and carbohydrate.The ketogenic diet in that study was maintained only for 48 h, and results may differ after prolonged ketosis as in this study (134).More and more evidence highlights the importance of nutrition in maintaining mental health.For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a double-edged sword.Table 1 Inclusion and exclusion criteria for the trial.The median overall survival (OS) in this subset of 37 patients was 25.1 months and the 5-year survival rate was 23.9%.Following treatment, she sees a therapist weekly for supportive psychotherapy, although during the COVID-19 pandemic visits have occurred by telemedicine. The remaining reads are taxonomically classified with the MiniKraken2_v1 database (79). With respect to the latter, the participants will be instructed to place that portion of the sample into their home freezer immediately after collection and transport the sample on ice to our lab where it will be stored at -80 degrees Celsius. To collect the samples, the participants will be instructed to scoop a sample of their fecal matter and place the scoop into the provided container. A ketogenic diet is a process that simulates hunger and forces fat to fuel the body by limiting carbohydrate supply. A ketogenic diet (KD) was defined as any dietary manipulation of high fats, moderate proteins, and very low carbohydrates . Further studies are warranted to determine the long-term sustainability of a ketogenic diet and its effects on the more clinically important endpoints such as obesity-related morbidity and mortality. In light of numerous study results, a ketogenic diet can provide promising effects in many disorders including obesity, cardiovascular disorders, T2DM, and possibly cancer. Based on our study results, patients with overweight or obesity and with underlying T2DM are more likely to receive benefits in terms of weight loss, improvement of glycemic and lipid controls from ketogenic diets. Cancer therapy with metformin is being evaluated in an expanding number of clinical trials due to its good safety profile, mostly as a synergistic addition to SOC 580, 581. Dietary KMT shifts whole-body physiology to an evolutionarily conserved metabolic state of nutrient scarcity that is inhospitable to tumor growth, but facing advanced disease will require multimodal and combinatorial strategies 103, 105, 162, 576, 577. In other types of cancer, KDs and fasting have been proposed as feasible and potentially effective radiotherapy adjuncts, acting as radiosensitizers while mitigating adverse effects 541,542,543. Despite short-term cytotoxicity to cancer cells, ionizing radiation induces metabolic reprogramming in the tumor niche, negatively influences the phenotype of recurrence, and triggers secondary inflammatory responses in the peritumoral tissue 521,522,523,524,525,526, while also damaging normal brain parenchyma and blood vessels 527,528,529. Initial weight loss during the transition to nutritional ketosis and fasting is mostly due to increased diuresis (water loss) and fat loss, not LBM 102, 496. Ketogenic diet in clinical populations—a narrative review Laboratory studies of the effect of KDs in glioma mouse models have demonstrated increased survival , enhanced radiotherapy sensitivity , improved chemotherapy signalling and reduced peritumoural oedema . Several recent trials investigating newer chemotherapy agents (e.g. RTOG 0825–Bevacizumab trial ) and targeted therapies (e.g., CENTRIC–Celengitide trial ) have not resulted in any improvement to prognosis. Despite current treatment options including maximal safe resection, radiotherapy and temozolomide chemotherapy , overall survival at 2 years remains poor (median survival of 12–14 months ). Patient impact will be assessed through quality of life and food acceptability questionnaires, gastrointestinal side effects and changes to biochemical markers and anthropometric measures, assessed at regular intervals. Though a popular version of the ketogenic diet is heavy on meat, that may not be the best option for all people with kidney disease. There is no one ketogenic diet to fit all, however, according to Weimbs. "To everyone's great surprise, kidney function actually improved with the ketogenic diet," said Wiembs. If you are new to a ketogenic diet, read our beginner’s guide and get all your questions answered. This change in metabolic fuel from glucose to ketones leads to a myriad of changes in central nervous system neurotransmitters such as adenosine and gamma-aminobutyric acid (GABA), as well as neuropeptides such as leptin, adiponectin, and growth hormone-releasing peptides (10). We report a case of severe and chronic AN treated successfully by adopting a ketogenic (KG) diet for 3 months followed by a series of intravenous ketamine infusions. Although these treatments were used sequentially the relationship between these modalities, and possible synergy, is unclear, and deserves further study. Serial MRI imaging reveals minimal impact of ketogenic diet on established liver tumor growth. Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Other scientists are studying the diet's effect on neurotransmitters like GABA — which acts as a kind of brake in the brain. Much of the data on how the diet affects the brain comes from research into epilepsy and other neurological diseases like Alzheimer's and Parkinson's. Keto diet followers have to get used to embracing larger amounts of fat in their diet. "Once you trend towards more normal mitochondrial function and metabolic health, that's restoring neurotransmitter systems, it's even restoring blood flow to the brain," says D'Agostino. Capillary ketones and glucose. We demonstrated that a three-month highly supervised WFKD, followed by a three-month self-administered WFKD, was a well-tolerated and sustainable dietary approach for most women with MBC undergoing chemotherapy. Detailed information regarding the study design and de-identified data are publicly available in the supplement (S1 and S2 Files and the online dataset . Regional fat mass and lean body mass were quantified from a whole-body scan at each visit (CoreScan™ enCORE software version 14.10). As participants demonstrated that they could maintain capillary ketone concentrations of ≥0.5 mM βHB, they transitioned to a hybrid approach where the study team provided them with weekly groceries and meal/recipe guidance to prepare WFKD meals at home. At the beginning of Phase I, participants relied heavily on the fresh and frozen meals provided by the study to achieve nutritional ketosis. The potential therapeutic effects in many chronic conditions have led to the gaining popularity of the KD. To learn more about the Baszucki Family Foundation's initiatives in mental health, visit baszuckigroup.com/our-work/. "This grant is instrumental in allowing us to extend our work into potential benefits on mental health, specifically the application of these therapies for managing major depression in college-aged adults." Limiting circulating blood glucose supply while conversely elevating circulating ketone bodies via dietary intervention may stop cancer cell proliferation. This dietary combination decreases available glucose in the blood and increases the production of ketone bodies through the breakdown of fatty acids. Subjects who consent to be in the TKD Study Arm will complete 14 weeks of therapeutic ketogenic diet (TKD), weekly weight and ketone measurements, weekly behavioral assessments, and meetings with the study doctor and dietician every week, and peer counseling sessions. The results of the study support the need for larger studies in anorexia nervosa to test the effectiveness of ketogenic diet and ketamine. During the 2-day immersion program, all study staff (including psychiatrist, internist, experienced ketogenic dietitian/nutritionist, and peer support counsellor), participants, and their support persons met informally, prepared all meals together, and ate together. The KD could improve health-related quality of life, including mental health, after 24 weeks in overweight volunteers. The study assessing the type of fatty acids used in the KD showed a reduction in depressive behavior in animals, regardless of whether they were fed long-chain triglyceride or medium-chain triglyceride fatty acids . The KD and other types of diets based on restricted carbohydrate intake may prevent the occurrence of MDD, reduce depression symptoms, cause a mood improvement, and lower the risk of cognitive impairment . Over 12 months, the patient has maintained a low-carbohydrate KD without a recurrence of symptoms, and her excessive weight has been reduced. Individuals who followed the program lost body weight (12%) and reduced their body mass index (BMI) (12%), waist circumference (13%), and visceral adipose tissue (36%). It is therefore possible that some of the interventions may have been a low carbohydrate rather than a ketogenic diet. However, there is no widely accepted definition of a ketogenic diet, carbohydrate intake was not reported in five studies and confirmation of ketosis was incomplete (blood ketone testing in two studies, urinary ketone testing in five, no confirmation in five). Given this background, the aim of the current study was to systematically review low carbohydrate and ketogenic interventions in adults with mood and anxiety disorders to direct further avenues for research and to highlight uncertainties for clinical practice. Indeed, animal models of depression suggest that a ketogenic diet might exert an antidepressant or anxiolytic effect.48 Case studies have also reported amelioration of psychotic symptoms following initiation of a ketogenic diet.49 However, randomised controlled trials (RCTs) are required to establish efficacy in reducing depression, anxiety and psychotic symptoms in psychiatric populations. Nevertheless, ketogenic diets are increasingly used for medication-resistant epilepsy, and there has been an increase in specialist ketogenic diet services.24 Together, research from epilepsy as well as studies describing improvements in mood and cognition in type 2 diabetes and obesity has stimulated interest in ketogenic diets for various psychiatric and neurological disorders, including cerebral glioma, Parkinson's disease, multiple sclerosis, chronic fatigue25,26 and mood disorders.26–28 Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial): study protocol for a randomised pilot study The authors affirm that human research participants provided informed consent for publication of the data gathered in this study. Animal research implicated ketogenic diet and ketamine as potentially beneficial to normalize brain dysfunction and behaviors in models for anorexia nervosa. That individual did not remain on TKD and it can be speculated whether she would have remained significantly improved had she stayed on the ketogenic diet. All study participants reported improvement after TKD and more so after addition of the ketamine intervention. Weight remained largely stable in this cohort and the treatment did not result in any severe adverse effects that would have required stopping the trial. Meta-regression and subgroup analyses were not performed for these outcomes because of the limited number of studies included. Animal studies reporting the effect of the KD on tumor growth and survival. The characteristics of all included studies are described in Table 1 and the detailed composition of KD involved in meta-analysis are listed in Supplementary Table 2. Findings were therefore synthesised narratively, clustered by study type and then stratified as either ‘no efficacy’ or ‘possible efficacy’ of the intervention. Owing to the heterogeneity in study designs, we did not provide a quality score for each study and instead provided a qualitative assessment.56 None of the studies employed representative sampling techniques and confounders were not controlled for. The studies comprised nine case reports, two cohort studies and one observational study. The 12 eligible studies are summarised in Table 2, stratified by study design. Common adverse effects reported with the use of KDT for RSE/SRSE in studies of five or more patients have included metabolic derangements like acidosis and hypoglycemia, hyperlipidemia and elevated triglycerides, and gastrointestinal symptoms similar to those reported in the outpatient setting, while pancreatitis and nephrolithiasis have been rare.86 However, in some cases the KDT was administered intravenously or via total parental nutrition when enteral access was not immediately available and then later converted.78,80-82,84 The largest studies of KDT use for pediatric status epilepticus management, with ≥10 patients each, included one multicenter study83 and three single-center studies.74,81,85 In the first large retrospective case series, of 10 children with RSE treated with an enteral KDT, 100% (10/10) achieved ketosis in a mean of 3 days (range 2–4 days), 20% (2/10) had seizure resolution, and 50% (5/10) demonstrated 50 to 75% seizure reduction at a mean of 5 days (range 5–7 days) following diet onset.74 The diet was discontinued within 7 days in the three children with 83 Although KDT in this study was not initiated until a median of 13 days of RSE (range 3–39 days), ketosis was achieved in a median of 2 days (range 0–10 days), and in 76% of patients (11/14) continuous anesthetic infusions could be weaned off within 2 weeks of KDT initiation. Summary of published randomized controlled trials of ketogenic diet therapy efficacy for seizure management in children and adults A random effects model or fixed effects model was used according to the heterogeneity. Outcome measures, including tumor weight, tumor volume, and survival time were included in the meta-analysis. Literature search, data extraction, and quality assessment were completed independently by two authors (J.L. and H.Y.Z.) according to the inclusion criteria. In addition, some studies have demonstrated that KD could increase the sensitivity of tumor cells to classic chemotherapy and radiotherapy when used in combination (8–10). A possible drawback of a diet enriched in purified MCTs, as opposed to naturally occurring high-fat foods, is that they are comparatively devoid of micronutrients, particularly liposoluble vitamins.Interestingly, the study conducted by Westman et al. showed that a ketogenic diet changed the composition of LDL subclasses, increasing the proportion of large-sized buoyant LDL with cardiovascular protective effects while significantly decreasing small-sized dense LDL, which is the primary cause of atherogenesis in the arterial intima.To assess the potential clinical relevance of increase in cholesterol levels observed in the KD group, we performed nuclear magnetic resonance (NMR) measurements of 52 lipid parameters using serum samples at BL and EOT.Originally developed in the 1920s to treat patients with epilepsy, and more recently touted as a way to combat obesity, the keto diet is limited to foods that are very low in carbohydrates, high in fat, and moderate to low in protein.In the MeDi-MCT group, the participants will adhere to the MeDi diet as described above, but with a greater allowance for carbohydrates and natural sweets such as fresh fruits.She was discharged to home after attaining a weight of 54.4 kg (120 lbs.) with a BMI of 20.6.Dietary intake data were collected through two 24-hour retrospective NHANES surveys conducted by trained dietary investigators. A recent study in cancer patients showed that negative affect was negatively correlated with glucose metabolism across cortical and subcortical brain regions, indicating global effects (79). The ketogenic diet showed promising potential as it succeeded in reducing weight, improving glycemic control, and decreasing diabetic-related medication; however, this review is just opening the door for further studies with more rigorous research methodology. While both diets were low in carbohydrates and excluded added glucose and refined grains, the ketogenic diet was stricter, eliminating legumes, fruits, and whole grains. In a 2022 RCT, Li et al. assigned 60 newly diagnosed adults (aged 16-50) with overweight or obese and had no history of hypoglycemic drug use to either a ketogenic diet (30-50g carbohydrates) or a standard diabetes diet. 1. Etiopathogenesis and Potential Role of the Ketogenic Diet As such, various dietary compositions have been proposed for reducing cancer risk and as potential adjuvant therapies. Body weight decreased 10% after three-months, primarily from body fat. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three- and six-months. Gastrointestinal side effects will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE, version 4, ), and dietary adjustments will be made to aid symptom relief when possible. Billingham et al. demonstrate a median sample size of 30 (range 8–114 participants) for UK pilot studies, whilst Hertzog reports on the statistical adequacy for sample sizes of 10–40, thus further justifying a sample size of 12 for the current trial. In our cohort, 32 participants (50.79%) were men, and the study cohort had a mean age of 41.41 ± 9.55 years. Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies. "Anything that improves metabolic health in general is probably going to improve brain health anyway," Sethi said. Thus, combining the KD with standard therapy or even novel treatment approaches to enhance the therapeutic response in humans should be a research focus in this field . Thus, the ROS inducing potential of the KD may explain its additive effects on radiotherapy . In line with this hypothesis, the combination of a KD and radiation therapy increased the level of oxidative stress and reduced tumor growth in lung and pancreatic cancer-bearing mice , . In contrast, it has been hypothesized that increased ROS production of cancer cells may be compensated by the generation of reducing equivalents through elevated glycolysis and pentose phosphate pathway activity . Moreover, in a glioma mouse model, the KD induced antitumor effects and decreased the production of ROS in tumor cells by altering the expression of genes involved in modulating ROS levels and oxidative stress , . Environmental factors, including thin-body messages from the media, may trigger those thoughts and condition a fear response (45–47). Those mechanisms apply to AN, where fear of weight gain causes food and eating to become conditioned fear-inducing stimuli, leading to negative ruminations and ambiance (40, 41). Brain research from various groups over the past decades has provided empirical data to better understand symptoms and behaviors in AN. AN is a chronic disorder with frequent relapse, high disease burden, and treatment cost (2–6). Studies have suggested that metabolic factors could contribute to developing and maintaining AN pathophysiology. Beyond comorbid metabolic disorders characterized by insulin resistance, MDD and BPD medications frequently negatively impact metabolism (Chokka et al., 2006; Gramaglia et al., 2018). Ketogenic diets have been shown to improve mitochondrial energy metabolism, inflammatory processes, oxidative stress, monoaminergic activity, and neuro-degeneration (Norwitz et al., 2020). Unfortunately, many of these individuals do not receive adequate psychiatric care, representing a critical public health issue. This was a significant medical breakthrough at a time when few treatments for epilepsy existed. In 1911 the first research study on fasting in epilepsy was published (Guelpa, 1911). For instance, CEA and CA 19-9 were both described only in one RCT which talked about pancreatobiliary cancer, while PSA was shown in another RCT for prostate cancer and with no other comparison. The results showed that all the lipid profile contents including TC, HDL, LDL, TG, BW, FBG, and insulin had no proven statistical significance and, therefore, showing no difference in effects between the KD group and non-KD group. While studying the level of ketosis achieved between the subgroups, the KD group had a statistically higher occurrence of ketosis than the non-KD group. When comparing the tumor marker PSA between subgroups (non-KD and KD groups), those who were in the non-KD group had a better effect on their diet than the KD group. The findings of this review were obtained through careful studying of each paper and their results by comparing the lipid profiles, tumor markers, ketosis, level of satisfaction, and the presence of adverse events. 1. Participants and Design The ketogenic diet is typically a high-fat, moderate-protein, and very low–carbohydrate diet. However, the findings from this meta-analysis with respect to the impact of a ketogenic diet on those surrogate markers can validate and provide insight into the effects of a ketogenic diet on the more clinically important endpoints. Interestingly, the study conducted by Westman et al. showed that a ketogenic diet changed the composition of LDL subclasses, increasing the proportion of large-sized buoyant LDL with cardiovascular protective effects while significantly decreasing small-sized dense LDL, which is the primary cause of atherogenesis in the arterial intima. One of the suggested reasons for the diminished effects of KD with time is the difficulty in long-term adherence to KD (52, 54), however adherence was not evaluated in this analysis (52). However, there is limited research evidence that these beneficial outcomes persist in long-term KD treatment. The benefits of KD for individuals with T2D also include increased lipolysis, significant weight-loss and reduction of blood triglycerides (TG), and together with other changes these result in decreased insulin resistance (47). In fact, CHO restriction as a form of diabetes treatment is not a new concept and was the only available treatment in the pre-insulin era. KD seems to be beneficial for controlling blood glucose primarily due to the restricted CHO and reliance on ketones for energy production. More recent data from open clinical trials have pointed toward a dramatic reduction in psychotic, affective, and metabolic symptoms in both schizophrenia and bipolar affective disorder. Recent research shows that a ketogenic diet (KD) might ease cancer symptoms and reduce tumour size. Going forward, a larger collection of clinical trials will be needed to standardize the implementation of GKI-adjusted dietary KMT with concurrent SLP targeting. Cancer metabolism was not the primary target in the aforementioned proof-of-concept studies, and they did not include a “metabolic priming” dietary baseline. Given the conflicting effects on cancer metabolism described below, in the specific context of future research evaluating diet-drug KMT as the primary treatment modality, a proposal to modify the timing of radiotherapy could be requested by the investigators if biologically justified. Previous studies have determined that 50 g of MCT per day is safe and well tolerated by the participants (76). The dose titration during the first week should minimize the risk of developing GI symptoms, however, we will monitor the participants for such symptoms throughout the intervention period. Furthermore, the RD will continuously monitor the participants’ safety while coaching them to ensure continuous adherence to the interventions using motivational counselling techniques. Despite meeting the inclusion criteria for clinical intervention and ketone measurement, the cited studies exhibited significant variability in several key aspects. Alongside concerns about LMM loss, several studies documented mild or no side effects from the KD, such as headaches, fatigue, and gastrointestinal discomfort, mostly during the adaptation phase 8, 16, 24–27, 45, 46. Wu et al., found that participants receiving the GLP-1RA medication beinaglutide did not achieve statistically superior outcomes in BW, total FM, body fat, BFP, or VAT compared to those following a KD without medication. Only a few studies have examined the impact of sex on weight loss outcomes following a KD intervention. Falkenhain et al., , analyzed data from a digital KD intervention and observed that higher ketone levels were strongly correlated with greater weight loss. Other studies examining practice effects on the NIH-TB battery reported significant practice effects for Dimensional Change Card Sort Test and Flanker Test and the Pattern Comparison Processing Speed Test over 2-weeks . Sources of practice effects include incidental learning, shift in strategy, or increased familiarity with the test-taking environment and have been reported in nutrition studies . Previous work has reported positive or null effects of a KD on cognitive outcomes in healthy adults. Participants had stable, normal glucose levels throughout the intervention, but their insulin and HOMA-IR values indicated more variability in insulin resistance. Prior research has shown an association between obesity and an increased risk of depression, with higher body fat positively correlated with depressive symptoms 56, 57. EI was individually calculated based on ideal weight and physical activity level Single-center, comparative, two-arm, randomized, open-label trial BK- by the research team- pre- and post-intervention Thus, there is growing evidence that nutrition and mental health are linked, and diet may be particularly appealing as a therapeutic intervention (157). In one study, infusion of BHB ketone bodies reduced brain glucose uptake and enhanced blood flow, supporting the notion of TKD’s neuroprotective effects (133). Only a few human brain imaging studies have investigated glucose metabolism in AN compared to healthy controls, and the samples were generally small and results inconsistent. Those data, together with genetic markers, supported the possibility of critical metabolic targets that need to be identified for successful treatment development for AN (83). To explore associations between depression scores and weight loss and ketones, we performed simple regression using Pearson correlation coefficients. Changes in depression scores in completers were evaluated using an analysis of covariance (ANCOVA), with the baseline score included as a covariate to control for baseline variability between participants. For variables that demonstrated normal distribution at baseline, we used a 1 (condition) x 3 (time) repeated-measures mixed-effects analysis of variance (RM ANOVA). In the second condition, participants were asked to sequence the stimuli from one category (food) in size order and then stimuli from the second category (animals) in size order. In the first condition, participants were instructed to sequence the stimuli in size order, from smallest to biggest. Thus, reducing glucose supply and selectively cutting off the energy source of tumor cells could inhibit tumor growth (4). Recently, it has been found that tumor metabolic reprogramming is a central feature of tumors (2). Cancer is one of the major problems worldwide and is grievously harmful to human health (1). Outcome measures comprised tumor weight, tumor volume, and survival time. More well‐designed studies, taking into consideration energy intake, more detailed assessment of nutrient quality, medication adjustments and physical activity levels, with outcomes at ≥24 months are required to provide more certain evidence of benefit or harm. Social functioning, which assesses whether treatment interferes with social life, and constipation, which is often seen as an adverse event, were considered likely to influence long-term persistence with the ketogenic diet for cancers. To the best of our knowledge, there is no evidence on factors contributing to longer persistence on a ketogenic diet in cancer patients. For patients with lung cancer, six patients remained on the ketogenic diet for more than three months. For patients with colorectal cancer, eight patients remained on the ketogenic diet for more than three months. Differences in study design, sample size, and measurement techniques are common, complicating the interpretation and generalizability of findings. This variability is not unique to the studies included in this review but reflects a broader limitation in KD research. Despite its increasing popularity, many questions persist about the design, effectiveness, and long-term applicability of the KD for weight loss. Gender differences in response to the KD and weight loss remain an important area of investigation, considering the physical and biological disparities between men and women. Assessments evaluated patient cognition, daily function, and quality of life; patients and trial partners were evaluated by the same assessor at baseline and week 12, on the same weekday and hour of the day. By contrast, a ketogenic diet induces a state of “physiological ketosis” in which beta-hydroxybutyrate provides a greater contribution to brain energy metabolism and its blood concentration exceeds 0.5–0.6 mmol/L. Brain energy metabolism is impaired in Alzheimer’s disease (AD), which may be mitigated by a ketogenic diet. To date, the program has announced $8M in funding to McLean Hospital and the University of Pittsburgh for randomized controlled trials combining mechanistic explorations with a clinical ketogenic intervention. “After we witnessed ketogenic therapy send our son’s ‘treatment resistant’ bipolar disorder into complete and lasting remission, we immediately started funding metabolic psychiatry studies like Dr. Sethi’s,” said Jan Ellison Baszucki, co-founder and President of Baszucki Group. The field of psychiatry may have a new ally in the form of a medical ketogenic diet, according to the findings of a pioneering pilot study published in Psychiatry Research and announced today by Stanford Medicine. Some individuals might benefit from switching from KD to other dietary interventions to maintain long-term weight loss. We further emphasize the importance of consultation with healthcare professionals before utilizing KD and any other dietary interventions. The study will be conducted in a university medical environment, showing feasibility and safety in a typical medical setting. Of those 60 participants, 40 of them will participate in the Therapeutic Ketogenic Diet (TKD) Study Arm and 20 subjects will be enrolled in the Treatment as Usual Study Arm. These individuals will be underweight or recently weight-restored and continue to have high impairment from the illness as indicated by an Eating Disorder Examination Questionnaire (EDE-Q) global score greater than 2.09. This follow-up procedure will help determine whether symptom improvement is stable or worsens in individuals who choose to continue or discontinue the TKD intervention and in relation to the control group. Warnock, GI, and Steckler, T. Stress-induced decreases in local cerebral glucose utilization in specific regions of the mouse brain.Although we intended to conduct a two-arm trial, a limitation of this study is the lack of control or standard of care group, which would have provided context for the normal progression of outcomes in women consuming a non-ketogenic eating pattern recruited from this single study site.Dopamine may have a central role in the pathophysiology of AN , and ketogenic diet and ketamine could help normalize altered dopamine function in AN.The KD leads to improved carbohydrate and lipid metabolism, which may inhibit the metabolic disturbances that may occur with many antidepressants and antipsychotic medications 15,30.Delusionality of body image beliefs in eating disorders.Sun et al., found that incorporated exercise training had no additional effects on weight loss.The goal of this review is to offer clarity to physicians counseling patients on the ketogenic diet with the latest literature about benefits and risks.Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. View All Health The Keto Diet intervention will be for an 18-week period and conducted by trained research dietitians. All patients will receive standard of care treatment for their glioblastoma. This is a Phase 2, randomized two-armed, multi-site study of 170 patients with newly diagnosed glioblastoma multiforme. The reduction in glucose levels following CR largely accounts for why tumors grow minimally on either restricted KD or on restricted high carbohydrate standard diets. On the other hand, KDs are known to have an appetite suppressing effect which may contribute to body weight loss (52), while some studies report no significant effect or increase of body weight. In order to enhance the anti-tumor effects of KD, several studies have either increased the proportion of fat, or supplemented KD with MCTs, omega-3 fatty acids or ketone esters (6, 13, 30, 42, 44). This high-fat diet is currently recommended as a treatment for patients with medication-refractory epilepsy 8,9. (4) The effect of a ketogenic diet on cardiovascular and renal risk markers was comparable to that of a low-fat diet. (3) A ketogenic diet for 4 days and up to 2 years led to improved lipid profiles for diabetic patients, such as lower triglyceride and higher HDL levels, whereas for nondiabetic patients an increase in total cholesterol and LDL levels. Subgroup analysis of nondiabetic patients showed no significant decrease in the glycemic index in ketogenic diet groups relative to comparator groups. The comparator group patients received varying types of low-fat diets, such as low-calorie diet, low-fat diet, low-fat low-glycemic index diet, high-carbohydrate low-fat diet, moderate-carbohydrate calorie-restricted low-fat diet, etc. 3% of the preclinical studies did not report data on tumor progression but investigated the effect of the KD on tumor microvasculature, gene expression or glucose up-take.Macronutrient intake, including carbohydrates, fat, and protein, is calculated to match individual factors such as age, weight, and level of physical activity as set out in the guidelines.Full guide to keto fruits DD+ MEMBERSHIPGet instant access to healthy low-carb and keto meal plans, fast and easy recipes, weight loss advice from medical experts, and so much more.Compared to previous studies using combination therapy, our pregnancy rate of 62.5% appears to demonstrate a higher rate of success.The classic KD contains 80% fat, dominated by long-chain fatty acids, 15% protein, and 5% carbohydrates .The kidneys help metabolize protein, and McManus says the keto diet may overload them. A small improvement in mOS is observed in younger patients and high-grade gliomas with specific isocitrate dehydrogenase (IDH) mutations 17, 18. If therapeutic success is defined as long-term survival, it becomes clear that no major advancements have been made in GBM therapy despite a century of cancer research . Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, has one of the highest mortality rates of all cancers. The proposed strategy may be implemented as a synergistic metabolic priming baseline in GBM as well as other tumors driven by glycolysis and glutaminolysis, regardless of their residual mitochondrial function. The glucose-ketone index (GKI) is a standardized biomarker for assessing biological compliance, ideally via real-time monitoring. This safety study will consist of two 8-week interventions (MeDi-MCT and MeDi-KD) in random order separated by 8-weeks washout period (i.e., returning to pre-study dietary habits), using a cross-over design. Emerging evidence suggests that both ketogenic diet (KD) (17–22) and Mediterranean(MeDi) diet (23–29) have beneficial and likely complementary effects in PD. Following the washout period, the participants will start the other dietary intervention for another 8 weeks. Hence, combining the principles of the MeDi and KD may allow us to harness the potential benefits of both these dietary interventions, while maintaining gut health. Dietary interventions such as the Mediterranean (MeDi) diet and the ketogenic diet (KD) have shown promise in alleviating the gastrointestinal symptoms and bioenergetics deficits of PD, respectively. The above strong, converging evidence for the efficacy of ketogenic therapies from pharmacological and genetic animal models paves the way for the introduction of this nutritional/metabolic approach to the clinical management of psychiatric disorders (Kraeuter et al., 2019a; Palmer, 2019a). Animals with the highest blood ketone levels showed the lowest P20/N40 gating ratios, indicating that a ketogenic diet normalizes sensory gating deficits (Tregellas et al., 2015), which are conceptualized as fundamental in the development of hallucinatory episodes in persons with schizophrenia (Javitt and Freedman, 2015). The ketogenic diet prevented the schizophrenia-like abnormal behaviors induced by acute MK-801 administration, including hyperactivity, stereotyped behavior, decreased sociability, working memory deficit, and impaired pre-pulse inhibition of startle in male mice (Kraeuter et al., 2015, 2019c). Nonetheless, given that the primary goal of this study is to establish a safety profile for these interventions, omitting a control treatment in favor of higher analytic power is justifiable. Only the PI and REB-approved study team members will have access to the key that links participant study numbers to their identifying information and the interim and final trial dataset. In-depth unsupervised analyses of clinical phenotypes, microbiome features, and inflammatory markers will be used to identify empirical groupings among features, interventions and patients. Functional analysis of altered microbiome profiles will be used to understand the biological mechanisms triggered by the respective dietary interventions. In addition to strategies mentioned above, the participants will be requested to bring all study supplement bottles (used and unused) to the post-intervention visit where overall compliance will be determined. Subsequently, participants chose food and meals on their own with the exception that we provided a few shelf-stable items such as high-quality fats (e.g., olive oil), salad dressings, salmon & sardine packets, beef jerky, Whisps cheese crips, nuts and seeds, and an oatmeal alternative.If the development of these parameters also depends on the length of the dietary change is still unknown.Two physicians in Paris reported that seizures were less severe in period of starvation.5 While this was the origin for the ketogenic diet, it wasn’t until 1921 that any physician tried to generate ketosis.In our cohort, 32 participants (50.79%) were men, and the study cohort had a mean age of 41.41 ± 9.55 years.A decrease in bilateral multiple lung metastases 4 years after the start of the ketogenic diet is seen.Danan et al. conducted a one-year analysis of poorly controlled symptoms (despite intensive pharmacological treatment) of severe mental illness, including MDD, following the KD instead of the usual hospital diet.Indigestible (unabsorbed) carbohydrates include insoluble fibers from whole grains, fruits, and vegetables; and sugar alcohols, such as mannitol, sorbitol, and xylitol commonly used in sugar-free diabetic food products.Both patients either purposely or inadvertently stopped the ketogenic diet, and their psychotic symptoms returned quickly. The sample size is likely insufficient for clarification of KD's effects on many MS-related outcomes. Together, these findings suggest that KD can ameliorate MS through its microbiome-modulating effects. The most common adverse events in KD-treated patients were respiratory tract infection ∼67% compared with 75% in control group (17), gastrointestinal symptoms (diarrhea, constipation, nausea; 28 to 40%), and genitourinary problems (ureteric colic, urinary tract infection, menstrual irregularities; 11 to 20%). One study reported a significant decrease of leptin after a 3-mo period of KD (3), which is consistent with the KD-induced changes in anthropometric measures. Therefore, historical controversies regarding the role of OXPHOS in cancer may have originated from imprecise definitions; as stated by Otto Warburg himself, “we have here a perfect example of a dispute about words” 56, 57. While it is possible that insights from in vitro mechanistic studies do not fully translate to the in vivo condition 53,54,55, we hypothesize that the minimal bioenergetic requirements for cell viability (ATP sufficiency) may be applicable across model systems, even if heterogeneity in fuel utilization may arise once energy constraints have been met. Insufficient or “dysfunctional” OXPHOS in cancer cells, as compared to normal cells, is hypothesized to arise from the well-documented and universal abnormalities in the number, structure, dynamics, and collective functional efficiency of the mitochondrial population 39,40,41,42,43,44,45. In this protocol, we favor a functional definition of SLP dependency as the comparatively limited capacity of malignant cells to sustain long-term proliferation when forced to use OXPHOS-exclusive metabolism (e.g., deprivation of glucose and glutamine, the two primary SLP fuels, at the substrate, transport, or utilization level). The mortality rate of AN is among the highest among the psychiatric disorders, but there is no FDA-approved medication for the treatment of AN, and the effectiveness of psychotherapeutic interventions especially for severe and enduring AN is limited . AN often becomes a chronic and enduring illness that is driven by persistent distress over weight gain and body image. Anorexia nervosa (AN) is a severe psychiatric disorder, typically presenting at puberty, marked by self-starvation, fear of weight gain, distortions in body image, and compulsions regarding food and exercise. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Regarding quality of life, stable quality of life to significant improvements have been described for several cancer patients consuming a KD , , , , , , . In two insulin-dependent diabetic cancer patients, insulin requirements decreased by 75% and 100% , respectively. Furthermore, a study in recurrent glioblastoma patients investigated the effect of a KD in combination with intranasal perillyl alcohol . Despite the lack of randomized controlled trials with large patient cohorts, several individual observations that support the antitumor effects of KDs have been reported in humans (Table 2). Moreover, and very importantly, none of the studies reported any serious adverse events or toxicity related to the KD (Table 2), supporting the safety of a KD intervention. Few randomized trials have performed sample size calculations with survival or response rates as primary endpoints 7,20. Several prospective, single-arm trials have also examined survival and response rates. The results for lung cancer and colorectal cancer were shown separately, although their numbers were very small. Chest computed tomography images of a colorectal cancer patient with lung metastases (yellow arrows). A 48-year-old woman was diagnosed with RAS-mutant colon cancer and multiple bilateral lung metastases in December 2016. The keto diet is low in fibrous foods like grains and legumes. The kidneys help metabolize protein, and McManus says the keto diet may overload them. McManus recommends that you keep saturated fats to no more than 7% of your daily calories because of the link to heart disease. But saturated fats from oils (palm, coconut), lard, butter, and cocoa butter are encouraged in high amounts. The fats and proteins are broken down to an intermediate form known as ketones, and so this biochemical pathway is referred to as 'ketogenesis'. DKJM runs a whole-foods coaching business; however, none of her recipes were used in this trial. This trial was approved by the Waikato Maori Consultation Research Review Committee and the Health and Disability Ethics Committee of New Zealand. This trial was supported by a grant from the Waikato Medical Research Foundation. LMD, RM, LJG, KMC, PVS, EJM, JO, SY, VMK, BR, MB, BMC, SS, SL, and JACS were involved in data acquisition. The presence of hypertension, stroke, and cancer/malignancy was determined through questionnaire responses. The Body Mass Index (BMI, kg/cm2) was calculated by dividing the weight by the square of standing height. Standing height (centimeter, cm) and weight (kilogram, kg) were measured at the mobile examination center. Information regarding sociodemographic and lifestyle characteristics was obtained from demographics and questionnaire data. For example, a KD consisting of 10% carbohydrate for a total caloric intake of 2500 kcal/day equals to approximately 60 g/day, which may be incompatible with therapeutic ketosis for most patients. The macronutrient distribution (% energy) of the classic KD is commonly defined as 88–90% fat, 6–8% protein, and 4% carbohydrate. As a long-term therapeutic strategy, dietary KMT may continue as long as there is evidence of persistent disease or risk of recurrence.