Ketogenic Diet In Adults Research Articles

DDRE-17. A PHASE I CLINICAL TRIAL OF DOSE-ESCALATED METABOLIC THERAPY COMBINED WITH CONCOMITANT RADIATION THERAPY IN HIGH-GRADE GLIOMA

BACKGROUNDAnimal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We sought to assess the feasibility of combined radiation, KD and metformin in adults with high grade gliomas.METHODSA prospective single-institution phase I clinical trial of combined metabolic therapy and radiotherapy. Radiotherapy was either 60Gy over six weeks or 35Gy over two weeks for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a KD supplemented with medium chain triglycerides (MCT). There were three cohorts 1) dietary intervention alone, 2) low-dose metformin combined with dietary intervention and 3) high-dose metformin combined with dietary intervention. Clinicaltrials.gov NCT02149459.RESULTSA total of 13 patients were accrued, median age 61 years, of whom 6 had newly diagnosed and 7 with recurrent disease. All completed radiation therapy; 5 patients stopped the metabolic intervention early. Metformin 850mg three-times daily was poorly tolerated. There were no grade 4 / 5 adverse events, and only one grade 3 event (nausea). The median level of ketones during the intervention was 0.5 mM. Ketone levels were associated with dietary factors (high fat, low carbohydrates, MCT intake), use of metformin and low insulin levels. Median progression free survival was 10 months for newly diagnosed disease and 4 months for recurrent disease.CONCLUSIONSThe intervention was fairly well tolerated, however only moderate ketones levels were obtained. Metformin use and dietary intake were associated with higher serum ketone levels. The recommended phase II dose is the 8 weeks of a low-carbohydrate diet combined with 850mg metformin twice daily.

Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist.

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis.

Isocaloric Ketogenic Diet in Adults with High-Grade Gliomas: A Prospective Metabolic Study

The use of the ketogenic diet (KD) as an adjuvant therapy in high-grade gliomas (HGG) is supported by preclinical studies, but clinical data on its effects on metabolism are currently lacking. In this study, we describe the effects of a KD on glucose profile, ketonemia, energy metabolism, and nutritional status, in adults affected by HGG. This was a single-arm prospective study. An isocaloric 3:1 KD was administered for 1 mo. Glucose profile was assessed by using fasting glycemia, insulin, and glycated hemoglobin. To evaluate ketonemia changes, a hand-held ketone meter was used from home. Energy metabolism was assessed by indirect calorimetry. Nutritional status was evaluated through changes in body composition and in lipid and hepatic profile. No changes in fasting glycemia were observed; however, insulinemia dropped to half of baseline levels. The KD shifted the metabolism, rising ketonemia and decreasing glucose oxidation rate to a quarter of the initial values. Moreover, the KD was generally safe. One-month intervention with the KD was able to act upon key metabolic substrates potentially involved in HGG metabolism. The lack of a significant reduction in fasting glycemia should be investigated in future studies.

Cognitive Effects of a Ketogenic Diet on Neurocognitive Impairment in Adults Aging With HIV: A Pilot Study.

We assessed a ketogenic diet (KD) intervention protocol and the cognitive effects of KD in older adults with HIV-associated neurocognitive impairment. Adults older than 50 years and living with HIV and mild-to-moderate neurocognitive impairment were randomized to either a KD or a patient-choice diet for 12 weeks followed by a 6-week washout period. A neurocognitive battery was administered at baseline, Week 12, and Week 18. Paired t tests compared groups at baseline, and multivariate analyses of covariance were used to assess between-group differences on primary outcome variables at Weeks 12 and 18. We enrolled 17 participants, and 14 completed the study. No between-group baseline differences were noted. The KD group demonstrated improved executive function and speed of processing at Week 12, which were negated after participants resumed their usual diets. Our study supports the potential efficacy of a KD for the treatment of HIV-associated neurocognitive impairment.

Effectiveness, retention, and safety of modified ketogenic diet in adults with epilepsy at a tertiary-care centre in the UK

With the rising demand for ketogenic diet therapy in adult epilepsy, there is a need for research describing the real-life effectiveness, retention, and safety of relevant services. In this 1-year prospective cohort study we present outcomes of the first 100 referrals for modified ketogenic diet (MKD) at the UK’s largest tertiary-care epilepsy centre, where patients received dietetic review up to twice per week. Of the first 100 referrals, 42 (31 females, 11 males; mean age 36.8 [SD ± 11.4 years]) commenced MKD, having used a mean of 4 (SD ± 3) previous antiepileptic drugs. Retention rates were: 60% at 3 months, 43% at 6 months, and 29% at 12 months. 60% of patients reported an improvement in seizure frequency, 38% reported a > 50% reduction, and 13% reported a period of seizure freedom; 30% reported a worsening in seizure frequency at some point during MKD therapy. The most common reasons for discontinuing MKD were side effects and diet restrictiveness. The most common side effects were weight loss, gastrointestinal symptoms and low mood. The likelihood of discontinuing MKD was significantly decreased by experiencing an improvement in seizure frequency (p ≤ 0.001). This study demonstrates that MKD can be effective in adults, although, even with regular dietetic support, retention rates remain low, and periods of worsening seizure frequency are common.

The glycaemic benefits of a very-low-carbohydrate ketogenic diet in adults with Type 1 diabetes mellitus may be opposed by increased hypoglycaemia risk and dyslipidaemia.

To investigate whether very-low-carbohydrate high-fat diets, typical of ketogenic diets, can improve glycaemic control without causing any ill health effects in adults with Type 1 diabetes. In this observational study, 11 adults with Type 1 diabetes (seven men, four women, mean ± sd age 36.1± 6.8 years, mean ± sd duration of diabetes 12.8 ± 10.3 years), who followed a ketogenic diet (< 55 g carbohydrate per day) for a mean ± sd of 2.6 ± 3.3 years (β-hydroxybutyrate 1.6 ± 1.3 mmol/l), underwent sampling and analysis of fasting blood, and were fitted with a blinded continuous glucose monitor for 7 days to measure glycaemic variability. The mean ± sd HbA1c levels were 35±4 mmol/mol (5.3±0.4%), and participants spent 74±20 and 3±8% of their time in the euglycaemic (4-8 mmol/l) and hyperglycaemic (>10 mmol/l) ranges, respectively, with little daily glycaemic variability (sd 1.5±0.7 mmol/l; coefficient of variation 26±8%). Blood glucose levels were <3.0 mmol/l for 3.6% of the time, and participants experienced a median (range) of 0.9 (0.0-2.0) daily episodes of hypoglycaemia. Total cholesterol, LDL cholesterol, total cholesterol/HDL cholesterol ratio, and triglycerides were above the recommended range in 82%, 82%, 64% and 27% of participants, respectively; however, HDL cholesterol levels were within the recommended range for all participants. Participants displayed no or little evidence of hepatic or renal dysfunction. This study provides the first evidence that, ketogenic diets in adults with Type 1 diabetes are associated with excellent HbA1c levels and little glycaemic variability, but may also be associated with dyslipidaemia and a high number of hypoglycaemic episodes.

The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service

ABSTRACTThere is an increasing interest in the use of the ketogenic diet (KD) as an adjuvant therapy for glioma patients. We assessed the tolerability and feasibility of a modified ketogenic diet (MKD) in patients with glioma, along with willingness of patients to participate in future randomized controlled trials. The study was undertaken in two parts; a patient questionnaire and evaluation of the diet. One hundred and seventy-two questionnaires were completed; 69% (n = 119) of the population reported MKD should be offered to patients with glioma and 73% (n = 125) would be willing to try MKD for 3 months. Six male patients with high grade gliomas tried the diet; 4 completed the 3-month feasibility period. Ketosis was achieved in all patients. The only gastrointestinal side effect was constipation (n = 2). Minimal changes were observed in weight, body mass index, fat mass and cholesterol profiles. MKD was well tolerated, with few side effects and is deliverable within a financially viable, NHS service. There is a high level of interest in the diet within the glioma patient community to ensure adequate recruitment for a clinical trial. Further studies are required to demonstrate efficacy and patient benefit before implementing a service.

The modified ketogenic diet for adults with refractory epilepsy: An evaluation of a set up service

PurposeThe ketogenic diet (KD) has been proven to be effective in children with refractory epilepsy and is recommended by the National Institute of Health and Care Excellence (NICE). There is no randomised control trial (RCT) evidence for the clinical or cost effectiveness of KD in adults, for whom the KD is not currently recommended. We assessed the feasibility of the modified ketogenic diet (MKD) in adults with refractory epilepsy along with the willingness of patients to participate in a future RCT. MethodsThe service evaluation was undertaken in two parts; questionnaire and diet evaluation. Results102 patients completed a questionnaire, of which 51 patients were willing to try the MKD for 3 months to assess effect on seizures. Forty three patients were willing to participate in a clinical trial to investigate deliverability, efficacy and tolerability. Thirty seven of which would still be willing to participate if the trial were randomised. Of the 17 patients who commenced the diet, 9 completed the 12 week period, 7 of which stayed on the diet for the longer term. Constipation (n=6) and loose stools (n=3) were the only reported adverse effects. ConclusionOur results indicate that there is demand for a ketogenic diet service in adults. The MKD is well tolerated, feasible and financially viable to deliver to adults with epilepsy in the NHS. There is also interest in and willingness to participate in a UK based RCT that would ultimately inform decisions about commissioning appropriate services.

Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults

BackgroundThe ketogenic diet (KD) is a very low-carbohydrate, high-fat and adequate-protein diet that without limiting calories induces different metabolic adaptations, eg, increased levels of circulating ketone bodies and a shift to lipid metabolism. Our objective was to assess the impact of a 6-week non-energy-restricted KD in healthy adults beyond cohorts of athletes on physical performance, body composition, and blood parameters.MethodsOur single arm, before-and-after comparison study consisted of a 6-week KD with a previous preparation period including detailed instructions during classes and individual counselling by a dietitian. Compliance with the dietary regimen was monitored by measuring urinary ketones daily, and 7-day food records. All tests were performed after an overnight fast: cardiopulmonary exercise testing via cycle sprioergometry, blood samples, body composition, indirect calorimetry, handgrip strength, and questionnaires addressing complaints and physical sensations.ResultsForty-two subjects aged 37 ± 12 years with a BMI of 23.9 ± 3.1 kg/m2 completed the study. Urinary ketosis was detectable on 97% of the days, revealing very good compliance with the KD. Mean energy intake during the study did not change from the habitual diet and 71.6, 20.9, and 7.7% of total energy intake were from fat, protein, and carbohydrates, respectively. Weight loss was −2.0 ± 1.9 kg (P < 0.001) with equal losses of fat-free and fat mass. VO2peak and peak power decreased from 2.55 ± 0.68 l/min to 2.49 ± 0.69 l/min by 2.4% (P = 0.023) and from 241 ± 57 W to 231 ± 57 W by 4.1% (P < 0.001), respectively, whereas, handgrip strength rose slightly from 40.1 ± 8.8 to 41.0 ± 9.1 kg by 2.5% (P = 0.047). The blood lipids TG and HDL-C remained unchanged, whereas total cholesterol and LDL-C increased significantly by 4.7 and 10.7%, respectively. Glucose, insulin, and IGF-1 dropped significantly by 3.0, 22.2 and 20.2%, respectively.ConclusionsWe detected a mildly negative impact from this 6-week non-energy-restricted KD on physical performance (endurance capacity, peak power and faster exhaustion). Our findings lead us to assume that a KD does not impact physical fitness in a clinically relevant manner that would impair activities of daily living and aerobic training. However, a KD may be a matter of concern in competitive athletes.Trial registrationDRKS00009605, registered 08 January 2016.

Ketogenic diet and other dietary treatments for epilepsy.

The ketogenic diet (KD), being high in fat and low in carbohydrates, has been suggested to reduce seizure frequency. It is currently used mainly for children who continue to have seizures despite treatment with antiepileptic drugs. Recently, there has been interest in less restrictive KDs including the modified Atkins diet (MAD) and the use of these diets has extended into adult practice. To review the evidence for efficacy and tolerability from randomised controlled trials regarding the effects of KD and similar diets. We searched the Cochrane Epilepsy Group's Specialized Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 30 March 2015), MEDLINE (Ovid, 30 March 2015), ClinicalTrials.gov (30 March 2015) and the WHO International Clinical Trials Registry Platform (ICTRP, 30 March 2015). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies. Studies of KDs and similar diets for people with epilepsy. Two review authors independently applied pre-defined criteria to extract data and assessed study quality. We identified seven randomised controlled trials that generated eight publications.All trials applied an intention-to-treat analysis with varied randomisation methods. The seven studies recruited 427 children and adolescents and no adults. We could not conduct a meta-analysis due to the heterogeneity of the studies.Reported rates of seizure freedom reached as high as 55% in a 4 : 1 KD group after three months and reported rates of seizure reduction reached as high as 85% in a 4 : 1 KD group after three months.One trial found no significant difference between the fasting-onset and gradual-onset KD for rates of seizure freedom and reported a greater rate of seizure reduction in the gradual-onset KD group.Studies assessing the efficacy of the MAD reported seizure freedom rates of up to 10% and seizure reduction rates of up to 60%. One study compared the MAD to a 4 : 1 KD, but did not report rates of seizure freedom or seizure reduction.Adverse effects were fairly consistent across different dietary interventions. The most commonly reported adverse effects were gastrointestinal syndromes. It was common that adverse effects were the reason for participants dropping out of trials. Other reasons for drop-out included lack of efficacy and non-acceptance of the diet.Although there was some evidence for greater antiepileptic efficacy for a 4 : 1 KD over lower ratios, the 4 : 1 KD was consistently associated with more adverse effects.No studies assessed the effect of dietary interventions on quality of life, or cognitive or behavioural functioning. The randomised controlled trials discussed in this review show promising results for the use of KDs in epilepsy. However, the limited number of studies, small sample sizes and a sole paediatric population resulted in a poor overall quality of evidence.There were adverse effects within all of the studies and for all KD variations, such as short-term gastrointestinal-related disturbances, to longer-term cardiovascular complications. Attrition rates remained a problem with all KDs and across all studies, reasons for this being lack of observed efficacy and dietary tolerance.There was a lack of evidence to support the clinical use of KD in adults with epilepsy, therefore, further research would be of benefit.Other more palatable but related diets, such as the MAD ketogenic diet, may have a similar effect on seizure control as classical KD but this assumption requires more investigation. For people who have medically intractable epilepsy or people who are not suitable for surgical intervention, a KD remains a valid option; however, further research is required.

Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a meta-analysis.

Background and PurposeDespite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice.MethodsElectronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes.ResultsIn total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%.ConclusionsThe results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.

Ketogenic diet in adolescents and adults with epilepsy

PurposeThe ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy. MethodTwenty-nine adult and adolescent patients (mean age 32 years, range 11–51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet. ResultsFifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13–35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects. ConclusionThe ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment.

Ketogenic diet for adults in super-refractory status epilepticus

To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE.

Use of the Ketogenic Diet in Adults

The ketogenic diet is a high-fat, low-carbohydrate diet that has been used primarily to treat difficult-to-control (refractory) epilepsy in children. There are case reports and other evidence that adults with epilepsy may benefit from the diet. A less-strict regimen, such as a modified Atkins or low glycemic index treatment, may also be effective. Clinical trials and studies in animal models suggest that ketogenic diets provide neuroprotective and disease-modifying benefits for a number of adult neurodegenerative disorders. A review of the literature, case studies, and sample low-carbohydrate menus are included.

Intérêt du régime cétogène dans le traitement d’un état de mal épileptique résistant de l’adulte

Introduction Ketogenic diets have been employed for the treatment of intractable epilepsiy in children since 1921, although underlying mechanism remains unknown. Observation We report the case of a 54-year-old man with partial refractory status epilepticus who exhibited a favourable outcome about seven days after introduction of a ketogenic diet in association with antiepileptic drugs. Discussion Although its efficiency was largely demonstrated in children, little is known about the impact of a ketogenic diet in adults with refractory epilepsy. Conclusion Introduction of a ketogenic diet requires a multidisciplinary approach. Its usefulness in adult intractable epilepsy and/or refractory status epilepticus merits further study into its efficacy in reducing the frequency of seizures and a possible prolonged effect.

The ketogenic diet for intractable epilepsy in adults: preliminary results.

Little is known concerning the efficacy and adverse effects of the ketogenic diet in adults with refractory epilepsy. This review reports preliminary results in 11 adults prospectively treated with the diet who had previously failed to gain seizure control with two or more medications and/or surgery. Eleven patients nine women, two men), median age, 32.2 years (range, 19-45 years) were treated with the ketogenic diet with a 4:1 ratio with fluid restriction. Six patients had symptomatic partial epilepsy, and five had symptomatic generalized epilepsy. The diet was administered in addition to antiepileptic medication by a multidisciplinary team geared exclusively to adult patients. Medications were not changed while on the diet. Seizure frequency at 8-month follow-up was compared with frequency during a baseline period. At 8 months of follow-up, three patients had a 90% seizure decrease, three patients had a 50-89% decrease in seizure frequency, one patient had <50% seizure decrease, and four patients discontinued the diet. Of the four patients who discontinued the diet, two had no appreciable change in their seizures despite high ketone levels. Two patients were unable to maintain persistent ketosis at home, despite having done so in the hospital. All seizure types responded to the diet. Common adverse effects included constipation and menstrual irregularities in women. Most patients reported a subjective improvement in concentration. Serum cholesterol and triglycerides increased while on the diet as well as cholesterol high-density lipoprotein (HDL) ratios. The ketogenic diet shows promise in both adult generalized and partial epilepsy. Persistent ketosis was possible in adults, and the diet was tolerable for most patients. Further study assessing the efficacy of the ketogenic diet, and the cognitive and long-term effects is ongoing.