The impact of time restricted eating on appetite and disordered eating in adults: A mixed methods systematic review.

This mixed-methods systematic review evaluated the effect of Time Restricted Eating (TRE) on adult participants' experience of hunger, appetite, and disordered eating. PubMed, CINAHL Plus with Full Text, PscyINFO, and Web of Science were searched for quantitative and qualitative original research articles in human adults that had an intervention with a daily eating window of ≤12 h and outcome measures related to hunger, appetite, or disordered eating. Differences in quantitative measures during TRE and qualitative themes were summarized. Qualitative and quantitative data were synthesized by assessing for convergence and divergence. Sixteen studies were included. TRE was associated with higher appetite at bedtime, and lower or unchanged morning fasting appetite. Evening results were mixed. Disordered eating questionnaires were not different as a result of TRE except in one study that found TRE associated with lower hunger. Qualitative themes converged with these findings, however also showed fear of hunger, eating in the absence of hunger, and eating-related stressors. TRE did not result in major changes to appetite or disordered eating symptoms. Bedtime hunger was higher in TRE. Assessment of subtle alterations in eating behavior, such as eating in the absence of hunger, would be beneficial for future research and intervention design.

Diet quality scores associated with improved cardiometabolic measures among African American adolescents.

BACKGROUND: The Reversing the Negative cardiovascular Effects on Weight (ReNEW) Clinic is a prospective cohort study in children and adolescents (≤21 years) at the Johns Hopkins Children's Center. METHODS: Cross-sectional analysis between diet quality using the Alternative Healthy Eating Index (AHEI-2010), pro-inflammatory potential using the Children's Dietary Inflammatory Index (C-DII), and cardiometabolic outcomes. AHEI-2010 and C-DII scores were assessed by median intake determined from the sample distribution and associated with cardiometabolic measures using linear regression models. Changes in measures were evaluated in a sub-sample of participants invited to attend follow-up visits due to the presence of hypertensive blood pressure (n = 33). RESULTS: Participants (n = 90) reported an average energy intake of 1790 kcal/day (SD ± 734), AHEI-2010 score of 55.04 (SD ± 9.86) (range: 0 to 110) and C-DII score of -0.12 (±0.86) (range -5 to 5). Participants with higher quality/anti-inflammatory diets trended towards more favorable cardiometabolic measures at baseline. Among the sub-sample (n = 33), there was a significant reduction in total energy (m = -302 kcal/day; p-value= 0.03) but no change in AHEI-2010 (p-value = 0.73) or C-DII score (p-value = 0.85) over follow-up. CONCLUSIONS: Despite stable diet quality scores, outpatient dietary and behavioral counseling may be an effective tool to reduce energy intake in youth with overweight/obesity and elevated blood pressure. IMPACT: Diet quality scores among obese, hypertensive, African American adolescents were low and reflect a pro-inflammatory diet. Reported intake was negligible for fruits, whole grains, nuts, and legumes, and well above the daily limit for sodium and saturated fat. Participants with high quality/anti-inflammatory diet quality scores trended toward improved cardiometabolic measures. Outpatient dietary counseling resulted in reduced total energy intake.

Six-month effects of modified Atkins diet implementation on indices of cardiovascular disease risk in adults with epilepsy.

BACKGROUND/AIMS: Ketogenic diet therapies (KDTs) offer a needed therapeutic option for patients with drug-resistant epilepsy. The current study investigated biochemical and anthropometric indices of cardiovascular disease (CVD) risk in adults with epilepsy treated with KDT over 6 months. METHOD: 65 adults with epilepsy naïve to diet therapy were enrolled in a prospective longitudinal study and instructed on modified Atkins diet (MAD) use. Seizure frequency, anthropometric measures, blood levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 and B, and lipoprotein sub-fractions were assessed at baseline, 3 months, and 6 months. RESULTS: Subsequent to study enrollment, 34 participants were lost to follow-up, elected not to start, or stopped MAD prior to study completion, leaving a total of 31 participants in the study at 6 months. Compared to baseline, participants on MAD showed significant reductions in median seizure frequency/week, weight, body mass index, waist and hip circumference, and percent body fat at 3 and 6 months. Compared to baseline, participants on MAD for 3 months showed significantly increased levels of total, small and medium LDL particles, ApoB and ApoB/A1 ratio. At 6 months, only small LDL particles and ApoB levels remained elevated and levels of ApoA1 had risen, suggesting possible compensatory adaptation over time. CONCLUSIONS: This study provides evidence demonstrating the efficacy and cardiovascular safety of 6 months of MAD use by adults with epilepsy. It also highlights an index of CVD risk - small LDL particles - that should be closely monitored.Trial registration: ClinicalTrials.gov identifier: NCT02694094..

Ketogenic diet therapy provision in the COVID-19 pandemic: Dual-center experience and recommendations.

The current coronavirus-19 pandemic has changed dramatically how neurologists care for children and adults with epilepsy. Stay-at-home orders and resistance to hospitalizations by patients have led epileptologists to engage in telemedicine and reevaluate how to provide elective services. Ketogenic diet therapy is often started in the hospital, with families educated in hospital-based classes, but this is difficult to do in this current pandemic. At our two academic centers, both our pediatric and adult epilepsy diet centers have had to quickly consider alternative methods to both start and maintain ketogenic diet therapy. This paper provides several examples of how ketogenic diet therapy can be provided to patients in unique ways, along with recommendations from other experts and patients, learned over the past few months.

Birth History and Cardiovascular Disease Risk Among Youth With Significant Obesity.

Children born prematurely have greater lifetime risk for hypertension. We aimed to determine (1) the association between prematurity and cardiovascular disease (CVD) risk factors among 90 children with obesity and elevated blood pressure and (2) if dietary sodium intake modified these associations. Multivariable regression analysis explored for associations between prematurity (<37 weeks gestation; early gestational age) and low birth weight (<2.5 kg) with hypertension, left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). Effect modification by dietary sodium intake was also explored. Patients were predominately male (60%), black (78%), adolescents (13.3 years), and with substantial obesity (body mass index: 36.5 kg/m2). Early gestational age/low birth weight was not an independent predictor for hypertension, LVMI, or LVH. There was no effect modification by sodium load. Our results suggest the increased CVD risk conferred by prematurity is less significant at certain cardiometabolic profiles. Promoting heart-healthy lifestyles to prevent pediatric obesity remains of utmost importance to foster cardiovascular health.

Predictors of elevations in fasting lipid levels in adults with epilepsy on a modified Atkins diet.

BACKGROUND: Ketogenic diet therapies can improve seizure control in patients with drug-resistant epilepsy (DRE). The current study investigated whether dietary fat composition is associated with elevations in serum lipid levels in adults with epilepsy who began a modified Atkins diet (MAD). METHODS: Adults with DRE were instructed to follow the MAD. Food records collected at baseline and follow-up were analyzed to extract median daily macro- and micronutrient composition. Total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, triglyceride (TG), high-density lipoprotein (HDL) cholesterol, non-HDL and TC/HDL ratio were measured at baseline and follow-up. RESULTS: Study participants initiating MAD showed higher fat intake at 1 month (p<0.001) and 2 months (p<0.001) and lower carbohydrate intake at 1 month (p<0.001) and 2 months (p<0.001) compared to baseline. Study participants also showed higher intake of cholesterol (p<0.001), saturated fatty acid (p<0.001) and monounsaturated fatty acid (p<0.001) over time. Following MAD initiation, study participants showed significant increases in levels of TC (p = 0.007), LDL (p<0.001), and non-HDL (p = 0.009) over time. Dietary intake variables, including cholesterol and fat subtypes, were significantly associated with difference in 1 month TC and LDL levels from baseline but not absolute 1 month lipid values. In a sub-analysis, participants with baseline dyslipidemia showed smaller changes in lipid values during diet use. CONCLUSIONS: Adults with DRE starting MAD increased fat intake, particularly saturated and monounsaturated fat subtypes, and reduced carbohydrate intake. Changes in TC and LDL levels 1 month after MAD initiation are associated with dietary intake of cholesterol and fat.

Association of Sodium and Sugar-Sweetened Beverage Intake With Cardiovascular Disease Risk Factors in Adolescents and Young Adults With Obesity.

Cardiovascular disease (CVD) risk factors in children have increased in prevalence. Dietary intake may modify risk. Data collected during a randomized trial testing the effect of a behavioral intervention on adiposity, blood pressure (BP), and left ventricular mass index (LVMI) were analyzed using multivariable regression to determine independent associations of sodium, sugar-sweetened beverage (SSB), and artificially sweetened beverage (ASB) intake with outcomes. High sodium intake (≥3.5 g) was associated with hypertensive BP (odds ratio 12.8; P = .027) in minimally adjusted models. High SSB intake (≥4 oz) was independently associated with body mass index z-score (ß = .34; P = .035) and waist circumference z-score (ß = .49; P = .022) in fully adjusted models. Any ASB intake was associated with LVMI in fully adjusted model (% change 38.22; P = .004). There was no effect modification between sodium and SSB on outcomes. Dietary factors explored in this study independently impacted CVD risk. Further effect measure modification should be explored in larger cohorts.

Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis.

BACKGROUND: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. METHODS: We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a "5:2" style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3+;CD4+ (CD4+) and CD3+;CD4- (as a proxy for CD8+) T cell subsets including effector memory, central memory, and naïve cells. FINDINGS: 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4-EM: -3.82%; 95%CI: -7.44, -0.21; for CD4-: -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4-: 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets. INTERPRETATION: In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers. FUNDING: National MS Society, NIH, Johns Hopkins Catalyst Award.

The Feasibility and Tolerability of Medium Chain Triglycerides in Women with a Catamenial Seizure Pattern on the Modified Atkins Diet.

Ketogenic diet therapy (KDT), particularly modified Atkins diet (MAD), is increasingly recognized as a treatment for adults with epilepsy. Women with epilepsy (WWE) comprise 50% of people with epilepsy and approximately one in three have catamenial epilepsy. The purpose of this study was to determine whether adding a medium chain triglyceride emulsion to MAD to target catamenial seizures was feasible and well-tolerated. This was a prospective two-center study of pre-menopausal WWE with a catamenial seizure pattern on MAD. After a 1-month baseline interval with no changes in treatment, participants consumed betaquik® (Vitaflo International Ltd.) for 10 days each menstrual cycle starting 2 days prior to and encompassing the primary catamenial seizure pattern for five cycles. Participants recorded seizures, ketones, and menses, and completed surveys measuring tolerability. Sixteen women aged 20-50 years (mean 32) were enrolled and 13 (81.2%) completed the study. There was 100% adherence for consuming betaquik® in the women who completed the study and overall intervention adherence rate including the participants that dropped out was 81.2%. The most common side effects attributed to MAD alone prior to starting betaquik® were constipation and nausea, whereas abdominal pain, diarrhea, and nausea were reported after adding betaquik®. The high adherence rate and acceptable tolerability of betaquik® shows feasibility for future studies evaluating KDT-based treatments for catamenial seizures.

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma.

OBJECTIVE: To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma. METHODS: Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8. RESULTS: Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (ß-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB R s = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria. CONCLUSION: The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02286167.

Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease.

Ketone bodies, the products of fat metabolism, are a source of energy for the brain and are available even when glucose supplies are inadequate (such as with severe carbohydrate deprivation) or its metabolism is faulty (as it is in Alzheimer's disease). This phase I/II randomized clinical trial examined the feasibility of using a modified Atkins diet (MAD) to induce ketogenesis in persons with mild cognitive impairment (MCI) or early AD, and the effect of this diet on memory and other clinical outcomes. In the first 2.5 years of active recruitment, only 27 eligible and willing patients enrolled. After extensive assessment and education, they and their study partners were randomly assigned for 12 weeks to either the MAD or the National Institute on Aging (NIA) recommended diet for seniors. As of April 2018, 9 patients in the MAD arm and 5 in the NIA arm have completed the trial. In spite of extensive teaching, coaching, and monitoring, adherence to both diets was only fair. Among those in the MAD arm who generated at least trace amounts of urinary ketones, there was a large (effect size = 0.53) and statistically significant (p = 0.03) increase in Memory Composite Score between the baseline and week-6 assessment. MAD participants also reported increased energy between baseline and week-6 assessment. Despite challenges to implementing this trial, resulting in a small sample, our preliminary data suggest that the generation of even trace ketones might enhance episodic memory and patient-reported vitality in very early AD.

Association of mood disorders with cardiovascular disease risk factors in overweight and obese youth with elevated blood pressure.

The American Heart Association defines mood disorders (MDO) as a tier-II cardiovascular disease risk factor in children. Cross-sectional analysis of overweight/obese children referred to an obesity hypertension clinic revealed 37% had a MDO (defined by clinical diagnosis or Patient Health Questionnaire-9/-A score ≥10), 55% had confirmed hypertension, and 75% left ventricular hypertrophy (LVH). Children with MDOs were older, had greater measures of adiposity, and had a greater prevalence of hypertension (78%) than those without MDOs (42%; P = .04). Hypertensive children were 2.8 times more likely to have a MDO than those without (52% vs 18%; P = .02). Multivariable logistic regression revealed a statistically significant independent association of MDOs with hypertension (Odds Ratio [OR] 6.3, P = .048), but not LVH (LVMI ≥ 51 g/m2.7 ; OR 1.13, P = .88). Overall, the prevalence of MDOs in this group of overweight/obese children with elevated blood pressure was well above national averages, suggesting that at-risk youth, particularly those with confirmed hypertension, should be regularly screened for MDOs.

Improving compliance in adults with epilepsy on a modified Atkins diet: A randomized trial.

PURPOSE: To determine whether use of a ketogenic formula during the first month of the modified Atkins diet (MAD) in adults with drug-resistant epilepsy (DRE) improves seizure reduction and compliance compared to MAD alone. METHODS: Eighty adults (age ≥18 years) with DRE and ≥4 reliably quantifiable seizures/month were enrolled. All participants were trained to follow a 20 g/day net carbohydrate limit MAD. Patients were randomized to receive one 8-ounce (237 mL) tetrapak of KetoCal®, a 4:1 ketogenic ratio formula, daily in combination with MAD during the first month (treatment arm) or second month (control/cross-over arm). Patients recorded urine ketones, weight, and seizure frequency and followed up at 1 and 2 months. RESULTS: By 1 month, 84% of patients achieved ketosis (median of 4-4.5 days). At 1 month, the treatment arm had a significantly higher ketogenic ratio and more patients with a ≥1:1 ketogenic ratio compared to the control arm. There was no difference in median seizure frequency, proportion of responders (≥50% seizure reduction), or median seizure reduction from baseline between groups. However, patients treated with KetoCal® during the first month were significantly more likely to continue MAD for 6 months or more. CONCLUSION: Although supplementing MAD with a ketogenic formula in the first month did not increase the likelihood of reducing seizures compared to MAD alone, significantly more adults remained on MAD long-term with this approach. This suggests a potential strategy for encouraging compliance with MAD in adults with DRE.

Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.