Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans.

Exogenous ketone ester and ketone ester mixed with ketone free acid formulations are rapidly entering the commercial marketspace. Short-term animal and human studies using these products suggest significant potential for primary or secondary prevention of a number of chronic disease conditions. However, a number of questions need to be addressed by the field for optimal use in humans, including variable responses among available exogenous ketones at different dosages; frequency of dosing; and their tolerability, acceptability, and efficacy in long-term clinical trials. The purpose of the current investigation was to examine the tolerability, acceptability, and circulating R-beta-hydroxybutyrate (R-ßHB) and glucose responses to a ketone monoester (KME) and ketone monoester/salt (KMES) combination at 5 g and 10 g total R-ßHB compared with placebo control (PC). Fourteen healthy young adults (age: 21 ± 2 years, weight: 69.7 ± 14.2 kg, percent fat: 28.1 ± 9.3%) completed each of the five study conditions: placebo control (PC), 5 g KME (KME5), 10 g KME (KME10), 5 g (KMES5), and 10 g KMES (KMES10) in a randomized crossover fashion. Circulating concentrations of R-ßHB were measured at baseline (time 0) following an 8-12 h overnight fast and again at 15, 30, 60, and 120 min following drink ingestion. Participants also reported acceptability and tolerability during each condition. Concentrations of R-ßHB rose to 2.4 ± 0.1 mM for KME10 after 15 min, whereas KMES10 similarly peaked (2.1 ± 0.1 mM) but at 30 min. KME5 and KMES5 achieved similar peak R-ßHB concentrations (1.2 ± 0.7 vs. 1.1 ± 0.5 mM) at 15 min. Circulating R-ßHB concentrations were similar to baseline for each condition by 120 min. Negative correlations were observed between R-ßHB and glucose at the 30 min time point for each condition except KME10 and PC. Tolerability was similar among KME and KMES, although decreases in appetite were more frequently reported for KMES. Acceptability was slightly higher for KMES due to the more frequently reported aftertaste for KME. The results of this pilot investigation illustrate that the KME and KMES products used increase circulating R-ßHB concentrations to a similar extent and time course in a dose-dependent fashion with slight differences in tolerability and acceptability. Future studies are needed to examine variable doses, frequency, and timing of exogenous ketone administration for individuals seeking to consume ketone products for health- or sport performance-related purposes.

Using the TIDieR checklist to describe development and integration of a web-based intervention promoting healthy eating and regular exercise among older cancer survivors.

Objective: To facilitate replication and future intervention design of web-based multibehavior lifestyle interventions, we describe the rationale, development, and content of the AiM, Plan, and act on LIFestYles (AMPLIFY) Survivor Health intervention which provides healthy eating and exercise behavior change support for older cancer survivors. The intervention promotes weight loss, improvements in diet quality, and meeting exercise recommendations. Methods: The Template for Intervention Description and Replication (TIDieR) checklist was used to provide a comprehensive description of the AMPLIFY intervention, consistent with CONSORT recommendations. Results: A social cognitive theory web-based intervention founded on the core components of efficacious print and in-person interventions was conceptualized and developed through an iterative collaboration involving cancer survivors, web design experts, and a multidisciplinary investigative team. The intervention includes the AMPLIFY website, text and/or email messaging, and a private Facebook group. The website consists of: (1) Sessions (weekly interactive e-learning tutorials); (2) My Progress (logging current behavior, receiving feedback, setting goals); (3) Tools (additional information and resources); (4) Support (social support resources, frequently asked questions); and (5) Home page. Algorithms were used to generate fresh content daily and weekly, tailor information, and personalize goal recommendations. An a priori rubric was used to facilitate intervention delivery as healthy eating only (24 weeks), exercise only (24 weeks), or both behaviors concurrently over 48 weeks. Conclusions: Our TIDieR-guided AMPLIFY description provides pragmatic information helpful for researchers designing multibehavior web-based interventions and enhances potential opportunities to improve such interventions.

Perspective: Acknowledging a Hierarchy of Social Needs in Diabetes Clinical Care and Prevention.

The evidence of suboptimal social determinants of health (SDoH) on poor health outcomes has resulted in widespread calls for research to identify ways to measure and address social needs to improve health outcomes and reduce disparities. While assessing SDoH has become increasingly important in diabetes care and prevention research, little guidance has been offered on how to address suboptimal determinants in diabetes-related clinical care, prevention efforts, medical education and research. Not surprisingly, many patients experience multiple social needs - some that are more urgent (housing) than others (transportation/resources), therefore the order in which these needs are addressed needs to be considered in the context of diabetes care/outcomes. Here we discuss how conceptualizing diabetes related health through the lens of Maslow's hierarchy of needs has potential to help prioritize individual social needs that should be addressed to improve outcomes in the context of population-level determinants in the communities where people live.

The Changing Landscape of Nutrition in Cystic Fibrosis: The Emergence of Overweight and Obesity.

Cystic fibrosis has historically been characterized by malnutrition, and nutrition strategies have placed emphasis on weight gain due to its association with better pulmonary outcomes. As treatment for this disease has significantly improved, longevity has increased and overweight and obesity have emerged issues in this population. The effect of excess weight and adiposity on CF clinical outcomes is unknown but may produce similar health consequences and obesity-related diseases as those observed in the general population. This review examines the prevalence of overweight and obesity in CF, the medical and psychological impact, as well as the existing evidence for treatment in the general population and how this may be applied to people with CF. Clinicians should partner with individuals with CF and their families to provide a personalized, interdisciplinary approach that includes dietary modification, physical activity, and behavioral intervention. Additional research is needed to identify the optimal strategies for preventing and addressing overweight and obesity in CF.

Ketogenic Diet for Cancer: Critical Assessment and Research Recommendations.

Despite remarkable improvements in screening, diagnosis, and targeted therapies, cancer remains the second leading cause of death in the United States. It is increasingly clear that diet and lifestyle practices play a substantial role in cancer development and progression. As such, various dietary compositions have been proposed for reducing cancer risk and as potential adjuvant therapies. In this article, we critically assess the preclinical and human trials on the effects of the ketogenic diet (KD, i.e., high-fat, moderate-to-low protein, and very-low carbohydrate content) for cancer-related outcomes. The mechanisms underlying the hypothesized effects of KD, most notably the Warburg Effect, suggest that restricting carbohydrate content may impede cancer development and progression via several pathways (e.g., tumor metabolism, gene expression). Overall, although preclinical studies suggest that KD has antitumor effects, prolongs survival, and prevents cancer development, human clinical trials are equivocal. Because of the lack of high-quality clinical trials, the effects of KD on cancer and as an adjunctive therapy are essentially unknown. We propose a set of research recommendations for clinical studies examining the effects of KD on cancer development and progression.

A Pilot Study of Associations Between Visceral Fat, IL-6, and Urinary F2-Isoprostanes in Older Adults Exposed to a Diet Intervention.

BACKGROUND: Short-term markers of successful visceral adipose tissue (VAT) loss are needed. Urinary F2-isoprostanes might serve as a marker for intensified lipid metabolism, whereas circulating IL-6 might stimulate fat oxidation and enhance mobilization of VAT. OBJECTIVES: This pilot study was designed to explore the hypotheses that 1) reduction in VAT is associated with increase in IL-6, and 2) that increases in urinary F2-isoprostanes are associated with increases in IL-6 and reduction in VAT. METHODS: Eighteen participants (aged 60-75 y, BMI 30-40 kg/m2) were randomly assigned to either a very-low-carbohydrate diet (VLCD; <10:25:>65% energy from carbohydrate:protein:fat) or a low-fat diet (LFD; 55:25:20%) for 8 wk. Changes in fat distribution were assessed by MRI. Four urinary F2-isoprostane isomers were quantified in 24-h urine collection using LC-MS/MS analyses. Changes in 4 F2-isoprostane isomers were summarized using factor analysis (Δ-F2-isoprostane factor). Statistical significance was set at P < 0.1. RESULTS: Within the VLCD group, change in VAT was inversely associated with change in IL-6 (r = -0.778, P = 0.069) and Δ-F2-isoprostane factor (r = -0.690, P = 0.086), demonstrating that participants who maintained higher concentrations of F2-isoprostane factor across the intervention showed greater decreases in VAT. A positive relation between Δ-F2-isoprostane factor and change in IL-6 was observed (r = 0.642, P = 0.062). In the LFD group, no significant associations between changes in VAT, F2-isoprostane factor, or IL-6 were observed. CONCLUSIONS: Results from this exploratory study in older adults with obesity suggest that, in the context of a VLCD, IL-6 could be involved in VAT mobilization, and urinary F2-isoprostanes could reflect intensified oxidation of mobilized fatty acids.Trial registration: This study is registered at clinicaltrials.gov as NCT02760641.

An Exploratory Analysis of the Association Between Catechol-O-Methyltransferase and Response to a Randomized Open-Label Placebo Treatment for Cancer-Related Fatigue.

Previous studies have identified catechol-O-methyltransferase (COMT), as a key enzyme influencing sympathetic function. Although the COMT SNP rs4680 and rs4818, are well-studied, little is known about their influence on cancer-related fatigue (CrF) and placebo response. In this study, we examined whether genetic variation in COMT, at the functional SNP rs4680 and linked rs4818, influenced open-label placebo (OLP) responses found in cancer survivors reporting moderate to severe CrF. We randomized cancer survivors (N = 74) reporting moderate-to-severe CrF to receive OLP or to treatment-as-usual (TAU) and assessed if rs4680 and rs4818 were associated with changes in fatigue severity and fatigue-distressed quality of life. At the end of the initial 21 days, the treatments were crossed over and both groups were re-assessed. Participants with the rs4680 high-activity G-allele (G/G or G/A) or rs4818 C/G genotypes reported significant decreases in fatigue severity and improvements in fatigue-distressed quality of life. The COMT rs4818 findings replicated findings in a similar study of OLP in cancer fatigue. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02522988.

Geospatial analysis of Mediterranean diet adherence in the United States.

OBJECTIVE: The current study aims to describe the Mediterranean diet (MD) adherence across the US regions, and explore the predictive factors of MD adherence among US adults. DESIGN: Cross-sectional secondary data analysis. MD adherence score (0-9) was calculated using the Block 98 FFQ. Hot spot analysis was conducted to describe the geospatial distribution of MD adherence across the US regions. Logistic regression explored predictors of MD adherence. SETTING: Nationwide community-dwelling residency in the USA. PARTICIPANTS: Adults aged ≥45 years (n 20 897) who participated in the REasons for Geographic and Racial Differences in Stroke study and completed baseline assessment during January 2003 and October 2007. RESULTS: The mean of MD adherence score was 4·36 (sd 1·70), and 46·5 % of the sample had high MD adherence (score 5-9). Higher MD adherence clusters were primarily located in the western and northeastern coastal areas of the USA, whereas lower MD adherence clusters were majorly observed in south and east-north-central regions. Being older, black, not a current smoker, having a college degree or above, an annual household income ≥ $US 75K, exercising ≥4 times/week and watching TV/video <4 h/d were each associated with higher odds of high MD adherence. CONCLUSIONS: There were significant geospatial and population disparities in MD adherence across the US regions. Future studies are needed to explore the causes of MD adherence disparities and develop effective interventions for MD promotion in the USA.

Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial.

BACKGROUND: Insulin resistance and accumulation of visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) place aging adults with obesity at high risk of cardio-metabolic disease. A very low carbohydrate diet (VLCD) may be a means of promoting fat loss from the visceral cavity and skeletal muscle, without compromising lean mass, and improve insulin sensitivity in aging adults with obesity. OBJECTIVE: To determine if a VLCD promotes a greater loss of fat (total, visceral and intermuscular), preserves lean mass, and improves insulin sensitivity compared to a standard CHO-based/low-fat diet (LFD) in older adults with obesity. DESIGN: Thirty-four men and women aged 60-75 years with obesity (body mass index [BMI] 30-40 kg/m2) were randomized to a diet prescription of either a VLCD (< 10:25:> 65% energy from CHO:protein:fat) or LFD diet (55:25:20) for 8 weeks. Body composition by dual-energy X-ray absorptiometry (DXA), fat distribution by magnetic resonance imaging (MRI), insulin sensitivity by euglycemic hyperinsulinemic clamp, and lipids by a fasting blood draw were assessed at baseline and after the intervention. RESULTS: Participants lost an average of 9.7 and 2.0% in total fat following the VLCD and LFD, respectively (p < 0.01). The VLCD group experienced ~ 3-fold greater loss in VAT compared to the LFD group (- 22.8% vs - 1.0%, p < 0.001) and a greater decrease in thigh-IMAT (- 24.4% vs - 1.0%, p < 0.01). The VLCD group also had significantly greater thigh skeletal muscle (SM) at 8 weeks following adjustment for change in total fat mass. Finally, the VLCD had greater increases in insulin sensitivity and HDL-C and decreases in fasting insulin and triglycerides compared to the LFD group. CONCLUSIONS: Weight loss resulting from consumption of a diet lower in CHO and higher in fat may be beneficial for older adults with obesity by depleting adipose tissue depots most strongly implicated in poor metabolic and functional outcomes and by improving insulin sensitivity and the lipid profile. TRIAL REGISTRATION: NCT02760641. Registered 03 May 2016 - Retrospectively registered.

Does Adherence to Mediterranean Diet Mediate the Association Between Food Environment and Obesity Among Non-Hispanic Black and White Older US Adults? A Path Analysis.

PURPOSE: This study aims to test the hypothesis that in addition to a direct effect of food environment on obesity, food environment is indirectly associated with obesity through consuming Mediterranean diet (MD). DESIGN: Cross-sectional secondary data analysis. SETTING: Nationwide community-dwelling residency. SAMPLE: A total of 20 897 non-Hispanic black and white adults aged ≥45 years who participated in the REasons for Geographic and Racial Differences in Stroke study and completed baseline assessment during January 2003 and October 2007. MEASURES: The Modified Retail Food Environment Index (mRFEI; 0-100) was used as food environment indicator. The MD score (0-9) was calculated to indicate the dietary pattern adherence. Body mass index (BMI; kg/m2) was used to estimate obesity. ANALYSIS: Path analysis was used to quantify the pathways between food environment, MD adherence, and obesity. Proper data transformation was made using Box-Cox power transformation to meet certain analysis assumptions. RESULTS: The participants were from 49 states of the United States, with the majority (64.42%) residing in the South. Most of the participants were retired, female, white, married, having less than college graduate education, having annual household income ≤75 000, and having health insurance. The means of mRFEI was 10.92 (standard deviation [SD] = 10.19), MD score was 4.36 (SD = 1.70), and the BMI was 28.96 kg/m2 (SD = 5.90). Access to healthy food outlets (ß = .04, P < .0001) and MD adherence (ß = .08, P < .0001) had significant and inverse relationships with BMI, respectively. Mediterranean diet adherence mediated the relationship between food environment and obesity among a subpopulation who had an annual household income of <$75 000 (ß = -.02, P = .0391). CONCLUSION: Population-tailored interventions/policies to modify food environment and promote MD consumption are needed in order to combat the obesity crisis in the United States.

A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial.

Ketogenic diets (KDs) are emerging as effective therapies for several chronic diseases, including cancer. However, concerns regarding safety and adherence may prevent clinicians from prescribing KDs. We hypothesized that a KD does not negatively affect blood lipid profile compared to a lower-fat diet in ovarian and endometrial cancer patients, and that KD subjects would demonstrate acceptable adherence. Subjects were randomized to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (ACS; high-fiber and lower-fat). Blood lipids and ketones were measured at baseline and after 12 weeks of the assigned intervention. Adherence measures included urinary ketones in the KD and 4 days' diet records. Diet records were also examined to identify general patterns of consumption. Differences between the diets on blood lipids and dietary intake were assessed with Analysis of covariance and independent t-tests. Correlation analyses were used to estimate associations between dietary intake and serum analytes. At 12 weeks, there were no significant differences between diet groups in blood lipids, after adjusting for baseline values and weight loss. Adherence among KD subjects ranged from 57% to 80%. These findings suggest that KDs may be a safe and achievable component of treatment for some cancer patients.

Childhood obesity intervention studies: A narrative review and guide for investigators, authors, editors, reviewers, journalists, and readers to guard against exaggerated effectiveness claims.

Being able to draw accurate conclusions from childhood obesity trials is important to make advances in reversing the obesity epidemic. However, obesity research sometimes is not conducted or reported to appropriate scientific standards. To constructively draw attention to this issue, we present 10 errors that are commonly committed, illustrate each error with examples from the childhood obesity literature, and follow with suggestions on how to avoid these errors. These errors are as follows: using self-reported outcomes and teaching to the test; foregoing control groups and risking regression to the mean creating differences over time; changing the goal posts; ignoring clustering in studies that randomize groups of children; following the forking paths, subsetting, p-hacking, and data dredging; basing conclusions on tests for significant differences from baseline; equating "no statistically significant difference" with "equally effective"; ignoring intervention study results in favor of observational analyses; using one-sided testing for statistical significance; and stating that effects are clinically significant even though they are not statistically significant. We hope that compiling these errors in one article will serve as the beginning of a checklist to support fidelity in conducting, analyzing, and reporting childhood obesity research.

Slow speed resistance exercise training in children with polyarticular juvenile idiopathic arthritis.

Background: Juvenile idiopathic arthritis (JIA) is an inflammatory autoimmune disease that can cause severe impairment and disability. Exercise is recommended to preserve joint mobility and function. Our objectives were to assess the safety, feasibility, and effects of slow speed resistance exercise in children with polyarticular JIA. Methods: Patients were recruited from a pediatric rheumatology clinic at an urban hospital and randomized to exercise or control groups. In the intervention group, slow speed resistance exercise with individualized instruction by a certified trainer was performed 1-2 times per week for 12 weeks. The control group performed home-based aerobic exercise 3 days per week for 12 weeks. Pre and post-body composition measurements by dual-energy X-ray absorptiometry; aerobic fitness by peak oxygen uptake during cycle ergometry; isometric muscle strength; and quality of life measures were obtained. Results: In the exercise group, 9/17 (53%) completed any exercise training. Of these nine subjects, five (55%) completed all 12 weeks of the protocol. In the control group, 8/16 (50%) reported compliance with the recommended aerobic exercise training at least one time per week. Only 2 subjects (12%) reported exercising more than once per week. There was no significant difference between pre- and post-measurements in any category in the exercise group. There was also significantly elevated body fat in both groups with only 17% in the control group and 23% in the exercise group meeting recommended <30% total body fat levels. Conclusions: Children with JIA participated safely in this resistance exercise protocol. The exercise was well-tolerated with no serious adverse events noted. While individual subjects reported improvement in fatigue and improved energy, there was no statistical difference in pre- and post-exercise measures of body composition or quality of life. Identifying ways to improve adherence and encourage exercise in children with JIA is important.

The effect of expectation on transcranial direct current stimulation (tDCS) to suppress food craving and eating in individuals with overweight and obesity.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique with potential to treat eating disorders and obesity. As for any potential treatment, it is important to assess the degree to which expectation effects contribute to its reported efficacy. This study assessed the effect of tDCS on amount of food craving and eating while tightly controlling treatment expectation. N = 74 adults with overweight or obesity were informed of the known effects of tDCS to suppress craving and eating. Once electrodes were on the head, half of the participants were told they were receiving real, and the other half sham tDCS. Within these groups, approximately half actually received real and the other half sham tDCS. Stimulation parameters used were those previously found to reduce craving and eating, including in our lab: 2 mA, anode right/cathode left targeting the dorsolateral prefrontal cortex for 20 min (real), or only for the first and last minute (sham). Analyses controlled for demographics, hunger, trait impulsiveness, eating motives, dieting, binge eating, suggestibility, and baseline craving and eating. Participants told they were receiving real tDCS craved and ate less than participants told they were receiving sham tDCS (both p < 0.01), regardless of tDCS condition administered. There was no main effect of real vs. sham tDCS on craving or eating or an interaction between tDCS condition and expectation. The scientific validation of tDCS as a treatment for eating-related conditions hinges on controlling for the powerful effects of expectation. This can include the type of information provided on consent forms and participants' ability to guess real from sham conditions.

Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

The dietary R-3-hydroxybutyrate- R-1,3-butanediol monoester increases resting energy expenditure (REE) and markers of brown and white adipose thermogenesis in lean mice. The purpose of this investigation was to determine whether the ketone ester, R, S-1,3-butanediol diacetoacetate (BD-AcAc2), increases energy expenditure and markers of adipose tissue thermogenesis in the context of high-fat diet (HFD)-induced obesity. Thirty-five-week-old male C57BL/6J mice were placed on an ad libitum HFD (45% kcal) for 10 wk. The mice were then randomized to 1 of 3 groups ( n = 10 per group) for an additional 12 wk: 1) control (Con), continuous HFD, 2) pair-fed (PF) to ketone ester (KE); and 3) KE: HFD+30% energy from BD-AcAc2. Mean energy intake throughout the study was ∼26% lower in the KE compared to the Con group (8.2 ± 0.5 vs. 11.2 ± 0.7 kcal/d; P < 0.05). Final body weight (26.8 ± 3.6 vs. 34.9 ± 4.8 g; P < 0.001) and fat mass (5.2 ± 1.2 vs. 11.3 ± 4.5 g; P < 0.001) of the KE group was significantly lower than PF, despite being matched for energy provisions. Differences in body weight and adiposity were accompanied by higher REE and total energy expenditure in the KE group compared to PF after adjustment for lean body mass and fat-mass ( P = 0.001 and 0.007, respectively). Coupled or uncoupled mitochondrial respiratory rates in skeletal muscle were not different among groups, but markers of mitochondrial uncoupling and thermogenesis (uncoupling protein-1, deiodinase-2, and peroxisome proliferator-activated receptor γ coactivator-1α) were higher in interscapular brown adipose tissue (BAT) of mice receiving the KE diet. The absence of mitochondrial uncoupling in skeletal muscle and increased markers of mitochondrial uncoupling in BAT suggest that BD-AcAc2 initiates a transcriptional signature consistent with BAT thermogenesis in the context of HFD-induced obesity.-Davis, R. A. H., Deemer, S. E., Bergeron, J. M., Little, J. T., Warren, J. L., Fisher, G., Smith, D. L., Jr., Fontaine, K. R., Dickinson, S. L., Allison, D. B., Plaisance, E. P. Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

Association of community food environment and obesity among US adults: a geographical information system analysis.

BACKGROUND: Emerging studies have investigated the contribution of food environment to obesity in the USA. However, the findings were inconsistent. Methodological explanations for the inconsistent findings included: (1) using individual store/restaurant exposure as food environment indicator, and (2) not accounting for non-stationarity assumption. This study aimed to describe the spatial distribution of obesity and examine the association between community food environment and obesity, and the variation of magnitude and direction of this association across the USA. METHODS: Data from 20 897 adults who participated in the REasons for Geographic and Racial Differences in Stroke study and completed baseline assessment between January 2003 and October 2007 were eligible in analysis. Hot Spot analysis was used to assess the spatial distribution of obesity. The association between community food environment and obesity and the variation of this association across the USA were examined using global ordinary least squares regression and local geographically weighted regression. RESULTS: Higher body mass index (BMI) clusters were more likely to locate in socioeconomically disadvantaged, rural, minority neighbourhoods with a smaller population size, while lower BMI clusters were more likely to appear in more affluent, urban neighbourhoods with a higher percentage of non-Hispanic white residences. There was an overall significant, inverse association between community food environment and obesity (ß=-0.0210; p<0.0001). Moreover, the magnitude and direction of this association varied significantly across the US regions. CONCLUSIONS: The findings underscored the need for geographically tailored public health interventions and policies to address unique local food environment issues to achieve maximum effects on obesity prevention.

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.

A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer.

Background: The glycolytic nature of cancer cells presents a potential treatment target that may be addressed by a ketogenic diet (KD). Objective: We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer. Methods: In this randomized controlled trial, women with ovarian or endometrial cancer [age: ≥19 y; body mass index (kg/m2): ≥18.5] were randomly assigned to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS; high-fiber, low-fat). Body composition (DXA) and fasting serum insulin, IGF-I, and ß-hydroxybutyrate were obtained at baseline and at 12 wk; urinary ketones were also measured throughout the intervention. We assessed differences between the diets with ANCOVA and independent t tests. We used correlation analyses to estimate associations between changes in serum analytes and body composition. Results: After 12 wk, the KD (compared with ACS) group had lower adjusted total (35.3 compared with 38.0 kg, P < 0.05) and android (3.0 compared with 3.3 kg, P < 0.05) fat mass. Percentage of change in visceral fat was greater in the KD group (compared with the ACS group; -21.2% compared with -4.6%, P < 0.05). Adjusted total lean mass did not differ between the groups. The KD (compared with ACS) group had lower adjusted fasting serum insulin (7.6 compared with 11.2 µU/mL, P < 0.01). There was a significant inverse association between the changes in serum ß-hydroxybutyrate and IGF-I concentrations (r = -0.57; P < 0.0001). Conclusions: In women with ovarian or endometrial cancer, a KD results in selective loss of fat mass and retention of lean mass. Visceral fat mass and fasting serum insulin also are reduced by the KD, perhaps owing to enhanced insulin sensitivity. Elevated serum ß-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

Body Composition and Mortality in Mexican American Adults: Results from the National Health and Nutrition Examination Survey.

OBJECTIVE: Epidemiologic analyses indicate a lack of association between BMI (kg/m2 ) and mortality among Hispanic adults. Because BMI provides only a surrogate for the real variable of interest, adiposity, this study evaluated associations between measures of body composition and mortality. METHODS: Using data from US-residing Mexican Americans in the National Health and Nutrition Examination Survey (NHANES) III (n = 4,480) and NHANES 1999-2010 (n = 5,849), the association between seven measures of body composition measured via anthropometry and bio-electrical impedance analysis (i.e., waist circumference, waist-to-height ratios [WHtR], skinfolds, lean mass, fat mass, percent body fat, and BMI) and all-cause and cardiovascular and diabetes mortality were examined. Additional analyses were stratified by gender. RESULTS: Waist circumference (hazard ratio [HR]: 1.04, 95% CI: 1.01-1.07) and WHtR (HR: 1.08, 95% CI: 1.03-1.14) were weakly associated with an increased all-cause mortality, while WHtR was associated with an increased risk of diabetes-related death (HR: 1.26, 95% CI: 1.07-1.49). In gender-stratified analyses, there was an increased risk of mortality in females who had increases in WHtR and waist circumference for all-cause mortality and cardiovascular deaths. CONCLUSIONS: Waist circumference and WHtR were associated with increased risk of all-cause and diabetes-related mortality in US-residing Mexican American adults.

Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome.

OBJECTIVE: To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life. STUDY DESIGN: Participants underwent a standardized examination of 11 areas of limb and spine ROM at baseline and at 3- to 6-month intervals for 2 years, resulting in a ROM score that ranged from 0 (normal throughout) to 11 (abnormal ROM in all areas tested). We measured the time until the ROM score was ≤2 (the score in healthy age-matched controls). Change in ROM was measured by subtracting the 24-month from the baseline ROM score and by summing the degrees of change in the 10 tests with continuous outcomes. Health-related quality of life was measured using the Pediatric Quality of Life Inventory 4.0 (PedsQL). RESULTS: The mean age at enrollment was 16.5 years (range 10-23). Two-year follow-up was available for 53 (96%). The proportion with a ROM score of >2 fell gradually over 2 years, from 78% at entry to 20% at 24 months (P < .001). ROM scores improved from a median of 5 at entry to 2 at 24 months (P < .001). The change in the summed degrees of improvement in ROM correlated positively with improvement in the PedsQL physical function subscale (r = 0.30; P < .03). CONCLUSIONS: In association with multimodal therapy, young people with chronic fatigue syndrome experienced progressively less impairment in ROM over 2 years, correlating with improvements in the physical function subscale of the PedsQL.