Phosphorus Additives and Albuminuria in Early Stages of CKD: A Randomized Controlled Trial.

BACKGROUND: Little is known about the effects of phosphorus additives on patients with kidney disease. STUDY DESIGN: Randomized, double-blind, crossover trial. SETTING & PARTICIPANTS: 31 adults with early stages of presumed chronic kidney disease (estimated glomerular filtration rate ≥ 45mL/min/1.73m2; urine albumin-creatinine ratio sex-specific cutoff points: men ≥ 17mg/g, women ≥ 25mg/g). INTERVENTION: Higher versus lower phosphorus intake for 3 weeks. Higher phosphorus intake was achieved by the addition of commercially available diet beverages and breakfast bars to diet. OUTCOMES: Change in 24-hour urine albumin excretion and plasma fibroblast growth factor 23 level. MEASUREMENTS: Two 24-hour urine collections and a single fasting blood draw at the end of each period. RESULTS: Mean baseline values for phosphorus intake, 24-hour urine phosphorus excretion, and estimated glomerular filtration rate were 1,113±549 (SD) mg/d, 688±300mg/d, and 74.6±22.0mL/min/1.73m2. Median urine albumin excretion of 82.7 (IQR, 39.6-174.1) mg/d. Although phosphorus intake from study products increased by 993mg/d (P<0.001) during the higher compared to lower phosphorus additive period, background phosphorus intake decreased by 151mg/d (P=0.004). Higher phosphorus additive consumption increased 24-hour urine phosphorus excretion by 505 (95% CI, 381 to 629) mg/d (P<0.001), but did not significantly increase albuminuria (higher vs lower: 14.3%; 95% CI, -2.5% to 34.0%; P=0.1) or fibroblast growth factor 23 level (higher vs lower: 3.4%; 95% CI, -5.9% to 13.6%; P=0.4). LIMITATIONS: Small sample size, short duration of intervention, changes in background diet during the intervention. CONCLUSIONS: A 3-week consumption of higher phosphorus food additives did not significantly increase albuminuria. Further studies are needed to confirm these results.

Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges.

OBJECTIVES: Over 250 medical centers worldwide offer ketogenic diets to children with epilepsy; however, access to these therapies has been extremely limited for adults until recent years. We examine our 5-year experience creating and implementing a dedicated Adult Epilepsy Diet Center designed to provide adults with epilepsy access to ketogenic diets. MATERIAL AND METHODS: Outpatients seen at the Johns Hopkins Adult Epilepsy Diet Center from August 2010 thru September 2015 age 18years and older were enrolled in a prospective open-label observational study. Patients that also enrolled in ongoing clinical diet trials were excluded from this study. Participant demographics, diet type, urine and/or serum ketones, laboratory studies, seizure frequency, diet duration, reason for discontinuing diet therapy, and side effects were recorded. A subgroup analysis of participants that met International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy (DRE) and were treated de novo with a Modified Atkins Diet (MAD) was performed to compare outcomes with the current literature regarding efficacy of other antiseizure treatments for DRE. RESULTS: Two hundred and twenty-nine adults attended the Adult Epilepsy Diet Center, and 168 met inclusion criteria. Two-thirds (n=113, 67%) were women with an age range of 18-86years at the initial visit. Thirty-five participants (21%, n=133) were already on a therapeutic diet while 79% (n=133) were naïve to diet therapy at the time of the initial visit. Diet-naïve participants were typically prescribed MAD (n=130, 98%), unless unable to intake adequate oral nutrition, in which case they were prescribed KD (n=1) or a combination of oral MAD and ketogenic formula (n=2). Twenty-nine of 130 (22%) participants prescribed MAD elected not to start or were lost to follow-up, and 101 (78%) began MAD. A subgroup analysis was performed on one hundred and six participants naïve to diet therapy that met International League Against Epilepsy criteria for DRE, were able to tolerate oral nutrition, and were prescribed a MAD. Relative to the number of enrolled participants who had reliable follow-up results for a given duration (including those that ultimately elected not to start or were later lost to follow-up), at 3months, 36% of these participants responded (≥50% seizure reduction) to diet therapy, and 16% were seizure-free. At 1year, 30% responded, and 13% were seizure-free. At 4years, 21% responded, and 7% were seizure-free. Hyperlipidemia was the most common side effect (occurring in 39% of screened participants, including those on a therapeutic diet prior to the initial visit). Weight loss was also common (occurring in 19% of all participants treated with a ketogenic diet therapy) yet was often an intended effect. SIGNIFICANCE: This study, the largest series of adults with epilepsy treated with ketogenic diet therapies to date, provides evidence that ketogenic diets may be feasible, effective, and safe long-term in adults, although long-term adherence was limited and further adequately controlled studies are necessary to determine the efficacy of ketogenic diets in the treatment of adults with epilepsy.

The impact of the modified Atkins diet on lipid profiles in adults with epilepsy.

OBJECTIVES: The modified Atkins diet (MAD) is a high fat, low carbohydrate ketogenic diet used to treat intractable seizures in children and adults. The long-term impact on fasting lipid profiles (FLPs) remains unknown. This study was designed to detect significant lipid changes in adults on MAD. METHODS: Patients were observed prospectively. A FLP was obtained in all patients at the first visit then serially. Patients were started on a 20 g per day net carbohydrate limit MAD. They were screened for risk for coronary heart disease and counseled to reduce saturated fats by a registered dietitian if deemed at risk. Patients that remained on MAD for 3 or more months with one or more follow-up FLP were included. RESULTS: Thirty-seven patients (14 male), mean age 33 years (SD 13, range 18-59) met study criteria. Median diet duration was 16 months (range 3-41). Total cholesterol and low-density lipoprotein (LDL) increased significantly over the first 3 months of MAD (P = 0.01 and 0.008, respectively), but were not significantly different from baseline after 1 year of treatment (P = 0.2 and P = 0.5, respectively). High-density lipoprotein levels trended upward in the first 3 months (P = 0.05) and triglycerides remained unchanged (P = 0.5). In 12 patients followed for 3 or more years, no cardiovascular or cerebrovascular events were reported. DISCUSSION: Although total cholesterol and LDL increased over the first 3 months of the MAD, these values normalized within a year of treatment, including in patients treated with MAD for more than 3 years.

Efficacy of dietary therapy for juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is often successfully managed with anticonvulsants; however, some patients may have medically resistant seizures. The modified Atkins diet (MAD) has been reported as effective for idiopathic generalized epilepsy and is increasingly being used in adolescents and adults. Since 2006, 8 adolescents and adults have been started on the MAD for JME at Johns Hopkins Hospital. Of these 8 patients, 6 (75%) were female, with a mean age at seizure onset of 10.5 years (range: 6-13 years) and 24.3 years (range: 15-44 years) at MAD initiation. After 1 month, 6 (75%) patients had >50% seizure reduction, and after 3 months, 5 (63%) patients had >50% improvement. Several patients found the MAD difficult to adhere to, including 3 patients who reported temporarily increased seizures during periods of noncompliance. In this limited experience, the modified Atkins diet was an efficacious adjunctive therapy for young adults with very medically resistant JME.

A decade of the modified Atkins diet (2003­2013): Results, insights, and future directions.

The modified Atkins diet has been used since 2003 for the treatment of children and adults with refractory epilepsy.This "alternative" ketogenic diet is started in clinic, without fasting, hospitalization, and restriction of protein,calories, or fluid intake. Now after 10 years of continued use, approximately 400 patients have been reported in over 30 studies of the modified Atkins diet as treatment for intractable seizures, with results demonstrating similar efficacy to the ketogenic diet and improved tolerability. The modified Atkins diet is being increasingly used in the adult population. Clinical trials have provided insight into the mechanisms of action of dietary therapies overall. This review will discuss the past decade of experience with the modified Atkins diet as well as predictions for its role in the treatment of epilepsy a decade from now.

E-mail management of the modified Atkins Diet for adults with epilepsy is feasible and effective.

PURPOSE: The modified Atkins Diet (MAD) is an effective dietary treatment for children with epilepsy. However, adults may have limited access to this therapy because of lack of availability of dietitian or nutrition support or familiarity with the diet by their treating neurologist. This study was designed to investigate the tolerability and efficacy of the MAD administered solely via e-mail to adults with pharmacoresistant epilepsy. METHODS: A prospective, open-label, proof-of-principle 3-month study design was employed. Adults were enrolled, instructed on how to self-administer a 20 g carbohydrate per day MAD, and followed by the investigators only via e-mail. There were no clinic visits or dietitian contacts during the study period. KEY FINDINGS: Twenty-five participants (median age 30 years [range 18-66 years], 68% female) consented and 22 started the MAD. The median prior anticonvulsants was 5 (range 2-10) and seizure frequency was 5 per week (range 1-140). Urinary ketosis was achieved in 21 participants (95%), of which 16 (76%) reported at least 40 mg/dl (moderate). Twenty-one participants (95%) remained on the MAD at 1 month and 14 (64%) at 3 months. After 1 month, 9 (41%) had >50% seizure reduction including one (5%) with >90% seizure reduction using intent-to-treat analysis. After 3 months, 6 (27%) had >50% seizure reduction including 3 (14%) with >90% seizure reduction. The mean ketogenic ratio was 1.1:1 (fat:carbohydrates and protein) for those who provided a MAD food record at follow-up. Over the study period, the median number of e-mails sent by the participants was 6 (range 1-19). The most frequent side effect was weight loss. SIGNIFICANCE: E-mail administration of the MAD to adults with refractory epilepsy appears to be feasible and effective. Therefore, when dietitian or physician support is limited for adult patients with epilepsy, remote access via telemedicine could provide an alternative.

Diet Redux: Outcomes from Reattempting Dietary Therapy for Epilepsy.

The outcome for patients attempting dietary therapy for epilepsy a second time is unknown. Twenty-six subjects treated with the ketogenic diet as children who then began either the ketogenic diet or a Modified Atkins Diet (MAD) at least 6 months later were evaluated. The mean age at the first diet trial was 5.6 years and at the second diet trial was 11.5 years. Most restarted dietary therapy because of persistent seizures (65%) or recurrence after seizure freedom (19%). Overall, 77% had a ≥50% seizure reduction with the first diet, and 50% with the second diet, P = .04. Individual subject responses were largely similar, with 14 (54%) having identical seizure reduction both times, 9 worse (35%) with the second attempt, and 3 (16%) improved. The second diet trial was more likely to lead to >50% seizure reduction if the first trial was started at a later age (7.4 vs 3.9 years, P = .04).

Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors.

Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study.

Ketogenic diet for adults in super-refractory status epilepticus.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE.

Transitioning pediatric patients receiving ketogenic diets for epilepsy into adulthood.

PURPOSE: To examine the process for transitioning adolescents on dietary management for intractable epilepsy to adult neurologic care. METHODS: Ten patients, ages 6-16 years when the ketogenic or modified Atkins diet was initiated, were identified; age at transition was 18-43 years. All patients were seen at Johns Hopkins Hospital, Baltimore, Maryland. RESULTS: Seven remain on diets (4 Ketogenic, 3 modified Atkins diet) at this time with mean diet duration of 15.5 years (range 4-32 years). Most patients had excellent but not complete seizure control and several had recurrence or worsening of seizures with attempts to wean dietary therapy, hence the need to continue. Three main transition options were utilized: (1) continue being followed in pediatric clinic (n=2), (2) establish care with an adult neurologist (n=2), or 3) receive care from the Adult Epilepsy Diet Center (n=6). Those patients followed in the Adult Epilepsy Diet Center were slightly more likely to remain on dietary therapy following transition (5/6 vs. 1/4, p=0.12). CONCLUSION: It is important for adolescents with epilepsy receiving ketogenic diets to have transition plans in place for when they become adults. Adult epilepsy diet centers are the ideal option when possible.

Worldwide dietary therapies for adults with epilepsy and other disorders.

During the 3rd International Symposium on Dietary Therapies held in Chicago, Illinois, there was a first-ever, half-day session devoted to the management of adults with epilepsy and other disorders with dietary treatments. Speakers from 3 different continents shared their successes, challenges, and future directions in their management of these patients. Diets used to treat adults included the classic ketogenic diet, the modified Atkins diet, and a low glycemic index treatment. The utility of dietary therapies was demonstrated not only in patients with epilepsy but also patients with propriospinal myoclonus, astrocytoma, type 2 diabetes, obesity, hyperlipidemia, and metabolic disorder. The session provided evidence that dietary therapies are safe and effective in adults.