Ketogenic diet has a positive association with mental and emotional well-being in the general population.

OBJECTIVES: A ketogenic diet reduces pathologic stress and improves mood in neurodegenerative and neurodevelopmental disorders. However, the effects of a ketogenic diet for people from the general population have largely been unexplored. A ketogenic diet is increasingly used for weight loss. Research in healthy individuals primarily focuses on the physical implications of a ketogenic diet. It is important to understand the holistic effects of a ketogenic diet, not only the physiological but also the psychological effects, in non-clinical samples. The aim of this cross-sectional study with multiple cohorts was to investigate the association of a ketogenic diet with different aspects of mental health, including calmness, contentedness, alertness, cognitive and emotional stress, depression, anxiety, and loneliness, in a general healthy population. METHODS: Two online surveys were distributed: cohort 1 used Bond-Lader visual analog scales and Perceived Stress Scale (n = 147) and cohort 2 the Depression Anxiety Stress Scale and revised UCLA Loneliness Scale (n = 276). RESULTS: A ketogenic diet was associated with higher self-reported mental and emotional well-being behaviors, including calmness, contentedness, alertness, cognitive and emotional stress, depression, anxiety, and loneliness, compared with individuals on a non-specific diet in a general population. CONCLUSION: This research found that a ketogenic diet has potential psychological benefits in the general population.

Graph Theory-Based Electroencephalographic Connectivity and Its Association with Ketogenic Diet Effectiveness in Epileptic Children.

Ketogenic diet therapies (KDTs) are widely used treatments for epilepsy, but the factors influencing their responsiveness remain unknown. This study aimed to explore the predictors or associated factors for KDTs effectiveness by evaluating the subtle changes in brain functional connectivity (FC) before and after KDTs. Segments of interictal sleep electroencephalography (EEG) were acquired before and after six months of KDTs. Analyses of FC were based on network-based statistics and graph theory, with a focus on different frequency bands. Seventeen responders and 14 non-responders were enrolled. After six months of KDTs, the responders exhibited a significant functional connectivity strength decrease compared with the non-responders; reductions in global efficiency, clustering coefficient, and nodal strength in the beta frequency band for a consecutive range of weighted proportional thresholds were observed in the responders. The alteration of betweenness centrality was significantly and positively correlated with seizure reduction rate in alpha, beta, and theta frequency bands in weighted adjacency matrices with densities of 90%. We conclude that KDTs tended to modify minor-to-moderate-intensity brain connections; the reduction of global connectivity and the increment of betweenness centrality after six months of KDTs were associated with better KD effectiveness.

Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice.

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body's metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.

Adherence to Ketogenic and Mediterranean Study Diets in a Crossover Trial: The Keto-Med Randomized Trial.

Adherence is a critical factor to consider when interpreting study results from randomized clinical trials (RCTs) comparing one diet to another, but it is frequently not reported by researchers. The purpose of this secondary analysis of the Keto-Med randomized trial was to provide a detailed examination and comparison of the adherence to the two study diets (Well Formulated Ketogenic Diet (WFKD) and Mediterranean Plus (Med-Plus)) under the two conditions: all food being provided (delivered) and all food being obtained by individual participants (self-provided). Diet was assessed at six time points including baseline (×1), week 4 of each phase when participants were receiving food deliveries (×2), week 12 of each phase when participants were preparing and providing food on their own (×2), and 12 weeks after participants completed both diet phases and were free to choose their own diet pattern (×1). The adherence scores for WFKD and Med-Plus were developed specifically for this study. Average adherence to the two diet patterns was very similar during both on-study time points of the intervention. Throughout the study, a wide range of adherence was observed among participants-for both diet types and during both the delivery phase and self-provided phase. Insight from this assessment of adherence may aid other researchers when answering the important question of how to improve behavioral adherence during dietary trials. This study is registered at clinicaltrials.gov NCT03810378.

A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer.

BACKGROUND & AIMS: Ketogenic diets (KDs) have been proposed as complementary nutritional treatments for cancer patients. Because it is important to gain knowledge about the safety of KDs adopted during cancer therapy, we studied the effects of KDs on quality of life and blood parameters in women with early-stage breast cancer undergoing radiotherapy. METHODS: A total of 29 patients consuming a KD were compared to 30 patients consuming their standard diet (SD) with respect to EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters that were obtained prior to, in the middle of and at the end of radiotherapy. Baseline-to-end differences were assessed using Wilcoxon tests, and longitudinal changes were analyzed using linear mixed effects models. RESULTS: Compared to the SD, women consuming a KD experienced significant improvements in emotional functioning, social functioning, sleep quality, future perspectives and systemic therapy side effects (all p-values <0.01). While breast symptoms increased significantly in both groups, the increase was less pronounced in the KD group. There was no hint of a detrimental effect of the KDs on either liver or kidney function; in contrast, biomarkers of metabolic health (gamma-glutamyl-transpeptidase, creatinine, triglycerides, IGF-1, free T3) significantly improved in the KD, but not the SD group. CONCLUSIONS: These data support the hypothesis that consuming a KD during radiotherapy is safe for women with breast cancer and has the potential to improve quality of life and metabolic health. CLINICALTRIALS. GOV IDENTIFIER: NCT02516501.

Ketogenic therapy in neurodegenerative and psychiatric disorders: From mice to men.

Ketogenic diet is a low carbohydrate and high fat diet that has been used for over 100 years in the management of childhood refractory epilepsy. More recently, ketogenic diet has been investigated for a number of metabolic, neurodegenerative and neurodevelopmental disorders. In this comprehensive review, we critically examine the potential therapeutic benefits of ketogenic diet and ketogenic agents on neurodegenerative and psychiatric disorders in humans and translationally valid animal models. The preclinical literature provides strong support for the efficacy of ketogenic diet in a variety of diverse animal models of neuropsychiatric disorders. However, the evidence from clinical studies, while encouraging, particularly in Alzheimer's disease, psychotic and autism spectrum disorders, is limited to case studies and small pilot trials. Firm conclusion on the efficacy of ketogenic diet in psychiatric disorders cannot be drawn due to the lack of randomised, controlled clinical trials. The potential mechanisms of action of ketogenic therapy in these disorders with diverse pathophysiology may include energy metabolism, oxidative stress and immune/inflammatory processes. In conclusion, while ketogenic diet and ketogenic substances hold promise pre-clinically in a variety of neurodegenerative and psychiatric disorders, further studies, particularly randomised controlled clinical trials, are warranted to better understand their clinical efficacy and potential side effects.

Ketogenic and low-sugar diets for patients with cancer: perceptions and practices of medical oncologists in Canada.

PURPOSE: Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. METHOD: A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. RESULTS: Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. CONCLUSION: The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.

No improvement in quality of life in children with epilepsy treated with the low glycemic index diet.

BACKGROUND: Up to 30% of children with epilepsy show a poor therapeutic response to pharmacologic treatment. Ketogenic diets, including the less strict low glycemic index treatment (LGIT), may improve seizure control in pharmacoresistant epilepsy. However, little is known about the quality of life (QoL) in children on LGIT. To explore psychosocial implications of the LGIT on pediatric patients and their caregivers, we have conducted a pilot study to explore the QoL of children and adolescents on the diet. METHODS: Pediatric patients on LGIT and their parents completed standardized, validated QoL questionnaires (Pediatric Quality of Life Epilepsy Module), one retrospectively and one while being on LGIT. An additional questionnaire included two open-ended questions in order to gain a better understanding of personal experiences of families. RESULTS: We enrolled six patients with epilepsy on LGIT between the age of 3 and 13 years. Self-reported QoL decreased in all adolescents, regardless of improvement in seizure control. Parent-reported QoL improved in three of six participants, remained stable in one, and decreased in two patients (both displayed no seizure improvement). Parents and adolescents reported positive experiences of trying new foods and being more health conscious, as well as negative themes such as social isolation and meal preparation difficulties. CONCLUSIONS: The lack of improvement in patient-reported QoL points towards an overall negative impact of the LGIT on patient well-being, despite positive effects on seizure control. Our preliminary results indicate that the benefits of seizure control may subjectively be outweighed by adverse social effects of the LGIT. Families should be made aware of psychosocial risks of the diet. Whenever possible, children should be part of the therapeutic decision-making process. Larger prospective studies are required to fully assess the overall impact of the LGIT.

The behavioural and pathophysiological effects of the ketogenic diet on mild traumatic brain injury in adolescent rats.

Mild traumatic brain injury (mTBI), caused by an insult to the head, results in a cascade of molecular imbalance that includes altered glucose metabolism, mitochondrial dysfunction, and increases in reactive oxygen species. Although glucose is the primary energy source for the brain, it becomes an inefficient substrate following injury, and the brain is primed to use alternative substrates (such as ketones). The ketogenic diet (KD), a high-fat, low-carbohydrate diet, forces the brain to utilize ketones over glucose for energy. Given that mTBIs are commonly experienced during adolescence, our study sought to examine the effects of the KD on recovery from mTBI in adolescent rats. This was done via two experiments; the first of which animals were fed the KD prior to a mTBI in order to investigate the neuroprotective potential of the diet, and the second the animals were fed the KD following a mTBI to examine the therapeutic potential. Male and female Sprague Dawley rats were assigned to receive a control standard diet or the KD (either pre-injury or post-injury), then further randomized to receive a sham or mTBI. Animals were tested on 6 behavioural measures designed to examine post-concussive symptomology, and mRNA analysis of the brain and small intestine were performed. Pre-injury exposure to the KD offered some neuroprotection, reducing balance and motor impairments while increasing exploratory behaviour and telomere length. Consumption of the KD following the injury also provided some therapeutic benefit, reducing both anxiety- and depressive-like behaviours. The timing of KD administration also differentially modified expression of prefrontal cortex, hippocampus, and intestinal mRNA for our genes of interest (Fgf2, Iba1, Opa1, Sirt1, Claudin3, OCC, and ZO1) This study demonstrates the neuroprotective and therapeutic potential of the KD for mTBI and warrants further investigation.

Quality of Life in Chronic Ketogenic Diet Treatment: The GLUT1DS Population Perspective.

BACKGROUND: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare, genetically determined neurological disorder, for which Ketogenic Diet (KD) represents the gold standard life-long treatment. The aim of this study is to investigate health related quality of life in a well characterized cohort of patients affected by GLUT1DS treated with KD, evaluating factors that can influence patients' and parents' quality of life perception. METHODS: This is a double center exploratory research study. A postal survey with auto-administrable questionnaires was conducted among 17 subjects (aged 3-22 years) with diagnosis of GLUT1DS, receiving a stable KD treatment for more than 1 year. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales was adopted. Clinical variables analyzed in relation to quality of life were frequency of epileptic seizures and movement disorder since KD introduction, presence of intellectual disability (ID), and KD ratio. RESULTS: Quality of life global scores were impaired both in parents' and children's perspectives, with a significant concordance. Taking into consideration subscales, the average was 64.17 (range 10-100) for physical functioning, 74.23 (range 30-100) for emotional functioning, 62.64 (range 10-100) for social functioning, and 56 (range 15-92) for school functioning. CONCLUSIONS: In patients with GLUT1DS the quality of life perception is comparable to that of other patients with chronic disease. In our sample, the presence of movement disorder seems to be a crucial element in quality of life perception.

A ketogenic diet diminishes behavioral responses to cocaine in young adult male and female rats.

Ketogenic diets (KDs) are high fat, low carbohydrate formulations traditionally used to treat epilepsy; more recently, KDs have shown promise for a wide range of other neurological disorders. Drug addiction studies suggest that repeated exposure to drugs of abuse, including cocaine, results in a suite of neurobiological changes that includes neuroinflammation, decreased glucose metabolism, and disordered neurotransmission. Given that KDs positively regulate these factors, we addressed whether administration of a KD has potential as a novel therapy for drug addiction. In this study, male and female Sprague-Dawley rats were placed on a KD or a control diet (CD), beginning at five weeks of age and continuing through the end of behavioral testing. Three weeks after initiation of dietary treatments, rats received daily i.p. injections of cocaine (15 mg/kg) or saline vehicle for one week, were drug free for a subsequent week, and then all animals received a final challenge injection of 15 mg/kg cocaine. In the absence of cocaine injections, stereotyped locomotor responses were minimal and were unaffected by dietary treatment. In contrast, both males and females fed a KD exhibited decreased cocaine-induced stereotyped responses as compared to CD-fed rats. The sensitization of ambulatory responses was also disrupted in KD-fed rats. These results suggest that KDs directly impact dopamine-mediated behaviors, and hence may hold potential as a therapy for drug addiction.

Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients.

Psychological well-being and hunger and food control are two relevant factors involved in the success of weight-loss therapy in treating obesity. Thus, this study aims to evaluate food and alcohol cravings, physical and sexual activity, sleep, and life quality (QoL) in obese patients following a very low-calorie ketogenic (VLCK) diet, as well as the role of weight lost and ketosis on these parameters. A battery of psychological test was performed in twenty obese patients (12 females, 47.2 ± 10.2 year and BMI of 35.5 ± 4.4) through the course of a 4-month VLCK diet on four subsequent visits: baseline, maximum ketosis, reduced ketosis, and endpoint. Each subject acted as their own control. Relevantly, the dietary-induced changes in body composition (7.7 units of BMI lost, 18 kg of fat mass (1.2 kg of visceral fat mass)) were associated with a statistically significant improvement in food craving scores, physical activity, sleepiness, and female sexual function. Overall, these results also translated in a notable enhancement in QoL of the treated obese patients. Therefore, the rapid and sustained weight and fat mass (FM) loss induced by the VLCK diet is associated with good food control and improvements in the psychological well-being parameters in obese subjects, which could contribute to the long-term success of this therapy.

Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial.

Ketogenic diets (KDs) are gaining attention as a potential adjuvant therapy for cancer, but data are limited for KDs' effects on quality of life. We hypothesized that the KD would (1) improve mental and physical function, including energy levels, (2) reduce hunger, and (3) diminish sweet and starchy food cravings in women with ovarian or endometrial cancer. Participants were randomized to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS: high-fiber, lower-fat). Questionnaires were administered at baseline and after 12 weeks on the assigned diet to assess changes in mental and physical health, perceived energy, appetite, and food cravings. We assessed both between-group differences and within-group changes using ANCOVA and paired t-tests, respectively. After 12 weeks, there was a significant between-group difference in adjusted physical function scores (p < 0.05), and KD participants not receiving chemotherapy reported a significant within-group reduction in fatigue (p < 0.05). There were no significant between-group differences in mental function, hunger, or appetite. There was a significant between-group difference in adjusted cravings for starchy foods and fast food fats at 12 weeks (p < 0.05 for both), with the KD group demonstrating less frequent cravings than the ACS. In conclusion, in women with ovarian or endometrial cancer, a KD does not negatively affect quality of life and in fact may improve physical function, increase energy, and diminish specific food cravings. This trial was registered at ClinicalTrials.gov as NCT03171506.

Development and pilot testing of a parent-reported health-related quality of life measure for children on the ketogenic diet: The KetoQoL.

AIM: The aim of the present study was to develop a parent-reported tool that will measure health-related quality of life (HRQoL) in children following ketogenic diet (KD) therapies for refractory epilepsy once it has been pilot tested and analysed. METHODS: Parents of children following KD therapies for epilepsy were recruited through a public hospital in Queensland, Australia, in 2012 and 2014. Qualitative semistructured interviews were conducted in 2012 with 13 parents who described changes seen in their child's HRQoL while on the KD. A quality of life tool (QoL) was developed by adapting the Quality of Life in Childhood Epilepsy tool based on results and themes analysed from the interviews. The KetoQoL was pilot tested with 18 parents recruited in 2014. Interrelationships between variables and questions were explored with exploratory factor analysis (EFA) to determine which questions had the greatest effect on QoL. RESULTS: The first iteration of the KetoQoL consisted of five main domains: physical, cognitive, social, intrapersonal and effects on the family. The domains were subdivided into 18 variables, totalling 54 items. EFA demonstrated that items from the physical and effects on the family domains had the greatest effect on QoL. CONCLUSIONS: KetoQoL is an HRQoL tool developed using a range of methods and assessed for both face and content validity. Further testing of KetoQoL is required to refine and confirm the factors. This work will enhance the evaluation of treatment effectiveness in children with epilepsy following the KD.

Dietary therapy for epilepsy. / Diettbehandling av epilepsi.

Children with pharmacoresistant epilepsy should be offered ketogenic dietary therapy. The diet, which is rich in fat and low in carbohydrate, has a beneficial effect in reducing seizures in this patient group. It may also have a beneficial effect in adults, but there is less evidence than in children. Dietary treatment of epilepsy is a specialist therapy, and in order to adhere to the diet, strong motivation of the patient and relatives as well as close follow-up from the specialist health service are necessary.

Impact of Child Life Services on Children and Families Admitted to Start the Ketogenic Diet.

Traditionally the ketogenic diet is started as an inpatient admission to the hospital. Starting in January 2015, child life services were made formally available during ketogenic diet admissions to help families cope. One-page surveys were then provided to 15 parents on the day of discharge and again after 3 months. Every family believed that the child life services were helpful. Children who were developmentally appropriate/mildly delayed had higher parent-reported anxiety scores than those who were moderate to severely delayed (4.4 vs 1.0, P = .02). At 3 months, child life services were deemed very helpful for the parents (mean score: 8.9, range: 5-10), and were more helpful for the parent than the child (mean 6.2, range 1-10, P = .047). One of the most helpful services was a prior phone call to parents 1 week prior. In this small pilot study, child life involvement during the start of the ketogenic diet was highly useful.

Changes in quality of life as a result of ketogenic diet therapy: A new approach to assessment with the potential for positive therapeutic effects.

There are difficulties inherent in measuring Quality of life (QoL) in patients with chronic illness, including agreement on definitions of quality of life and the type of measure used, disease specific or generic. Well validated QoL instruments for epilepsy exist but focus on capturing common themes pertinent to children and families as a group instead of focusing on themes important to individual patients and their families/carers. In addition, it is common for numerous items on these inventories to be left incomplete or responded to with "not applicable" since many of the items are not suitable for children with disabilities and their families. This led us to devise a way to capture individual quality-of-life measures that are linked to parental/carer expectations in families of children undergoing ketogenic diet therapy for epilepsy. As part of our routine clinical assessment, parents/carers were asked to describe what they would like to see happen or change as a result of their child being on ketogenic diet therapy. A simple unstructured form was designed to facilitate the assessment process. Parents were then asked to rate their own QoL against these criteria on a Likert scale of 0-10 prior to commencement of the diet. This assessment was repeated at subsequent visits with parents/carers initially blinded to their original responses. Our assessments indicated that ketogenic diet therapy improves quality of life over a twelve-month period when measured against parental expectations. This ideographic approach has demonstrated changes in parental Qol and parental perceptions of their child's quality of life that would not have been captured by other validated measures. A lengthy questionnaire is avoided and is replaced by a skilled supportive conversation that identifies goals for treatment that are important to parents. This helps parents to reflect on the progress their child makes on the diet by revisiting their previously stated aspirations, and assessing whether they have been achieved. This is particularly helpful for those parents who express a sense of failure or helplessness relating to their child's intractable epilepsy. As a result, future work will center on developing this approach as a clinical tool.

The Ketogenic Diet and Sport: A Possible Marriage?

The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

Assessing parents' attitudes towards ketogenic dietary therapies.

We aimed to assess and quantify parental beliefs regarding ketogenic dietary therapies (KDTs). We also aimed to determine whether beliefs were related to response to KDTs. Adapted versions of the Beliefs about Medicine Questionnaire were completed by parents of children following KDTs for epilepsy. Demographic and clinical data were collected from hospital records. Ketogenic dietary therapy response was defined as ≥50% seizure reduction compared to baseline. Many parents had a positive perception of KDTs and were convinced of the necessity of KDTs for their children, although beliefs were wide-ranging. Over half of parents reported concerns about the potential long-term effects of KDTs. Parental beliefs about KDTs were significantly correlated with patient response. This was an attempt to quantify parents' beliefs regarding the use of KDTs for their child's epilepsy. The questionnaire may be used to identify individuals with a less positive attitude towards KDTs and who may be less likely to report a favorable response to KDTs. It is unknown whether people who have positive beliefs about KDTs engage in less nonadherent behavior or whether beliefs regarding KDTs simply reflect outcomes. The evidence behind the long-term side effects of KDTs should be emphasized when counseling patients and their families.

Epilepsy characteristics and psychosocial factors associated with ketogenic diet success.

The ketogenic diet is an effective therapy for childhood epilepsy, but its important impacts on families could affect successful treatment. We assessed medical and psychosocial factors associated with successful ketogenic diet treatment. A total of 23 families of patients treated with ketogenic diet completed questionnaires (30% response), including inquiries about challenges to successful dietary treatments and validated family functioning scales. Of these, 14 were considered successful (diet discontinued once the child was seizure-free or continued as clinically indicated). Family-identified challenges were food preparation time (n = 11) and that the diet was too restrictive (n = 9). Neither Medicaid insurance nor family functioning scale scores were significantly associated with successful treatment. Lower seizure frequency prior to ketogenic diet initiation (P = .02) and postdiet seizure improvement (P = .01) were associated with increased odds of success. Effective ketogenic diet treatment is dictated both by psychosocial and epilepsy-related influences. A focus on understanding the psychosocial issues may help to improve families' experiences and success with the ketogenic diet.