No Effect of Calorie Restriction or Dietary Patterns on Spatial Working Memory During a 2-Year Intervention: A Secondary Analysis of the CALERIE Trial.

BACKGROUND: The effect of calorie restriction (CR) on cognitive function is not well understood, and the impact of the dietary patterns consumed during CR has not been investigated. OBJECTIVES: We analyzed the combined association of CR and dietary quality with spatial working memory (SWM) in healthy adults without obesity. METHODS: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial was a 2-y, multisite clinical trial. This trial was registered at clinicaltrials.gov as NCT00427193. Participants were randomized to a 25% reduction in EI (n = 143) or an ad libitum Control (n = 76). The Dietary Inflammatory Index (DII) and the Healthy Eating Index (HEI) captured dietary quality, with a lower DII and higher HEI score indicating a healthier diet. The Cambridge Neuropsychological Test Automated Battery battery was used to assess SWM. Longitudinal associations between each dietary pattern index and SWM for CR and Control were assessed by multivariable negative binomial models that included baseline, 12-mo, and 24-mo visits. RESULTS: Participants were aged 38.1 ± 7.2 y with a BMI of 25.1 ± 1.7 kg/m2. A total of 70% of the participants were female. Baseline mean DII and HEI scores were -0.15 (range: -3.77, 4.21) and 59.1 (24.1, 91.0) and did not differ between groups. Improvements in DII and HEI were significantly different between CR and Control over 2 y (both P-interaction = 0.001). In longitudinal analyses, there was no association of either index with SWM. Furthermore, though within-group improvements in SWM were observed at 12 mo, there was no statistically significant difference between CR (SWM errors: 9.0; 95% CI: 1.9, 41.6) and Control (11.7; 95% CI: 2.6, 53.5; P > 0.99), holding DII constant. Comparable results were observed at 24 mo and for the HEI. CONCLUSIONS: Dietary quality during CR was not associated with measures of SWM over 2 y in healthy adults without obesity. These results suggest that, in healthy populations, dietary patterns and CR may have a limited impact on working memory. Further research is required to understand the concurrent effect of these nutritional strategies.

Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition.

BACKGROUND: Weight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects. OBJECTIVES: This study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses' Health Study II cohort. METHODS: The examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause. RESULTS: In longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations. CONCLUSION: Yogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

Greater male variability in daily energy expenditure develops through puberty.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

Sex Differences Across the Life Course: A Focus On Unique Nutritional and Health Considerations among Women.

In the United States, women, while having a longer life expectancy than men, experience a differential risk for chronic diseases and have unique nutritional needs based on physiological and hormonal changes across the life span. However, much of what is known about health is based on research conducted in men. Additional complexity in assessing nutritional needs within gender include the variations in genetics, body compositions, hormonal milieus, underlying chronic diseases, and medication usage, with this list expanding as we consider these variables across the life course. It is clear women experience nutrient shortfalls during key periods of their lives, which may differentially impact their health. Consequently, as we move into the era of precision nutrition, understanding these sex- and gender-based differences may help optimize recommendations and interventions chosen to support health and weight management. Recently, a scientific conference was convened with content experts to explore these topics from a life-course perspective at biological, physiological, and behavioral levels. This publication summarizes the presentations and discussions from the workshop and provides an overview of important nutrition and related lifestyle considerations across the life course. The landscape of addressing female-specific nutritional needs continues to grow; now more than ever, it is essential to increase our understanding of the physiological differences between men and women, and determine how these physiological considerations may aid in optimizing nutritional strategies to support certain personal goals related to health, quality of life, sleep, and exercise performance among women.

Variability in energy expenditure is much greater in males than females.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

Evaluation of PIQNIQ, a Novel Mobile Application for Capturing Dietary Intake.

BACKGROUND: Accurate measurement of dietary intake is vital for providing nutrition interventions and understanding the complex role of diet in health. Traditional dietary assessment methods are very resource intensive and burdensome to participants. Technology may help mitigate these limitations and improve dietary data capture. OBJECTIVE: Our objective was to evaluate the accuracy of a novel mobile application (PIQNIQ) in capturing dietary intake by self-report. Our secondary objective was to assess whether food capture using PIQNIQ was comparable with an interviewer-assisted 24-h recall (24HR). METHODS: This study was a single-center randomized clinical trial enrolling 132 adults aged 18 to 65 y from the general population. Under a provided-food protocol with 3 menus designed to include a variety of foods, participants were randomly assigned to 1 of 3 food capture methods: simultaneous entry using PIQNIQ, photo-assisted recall using PIQNIQ, and 24HR. Primary outcomes were energy and nutrient content (calories, total fat, carbohydrates, protein, added sugars, calcium, dietary fiber, folate, iron, magnesium, potassium, saturated fat, sodium, and vitamins A, C, D, and E) captured by the 3 methods. RESULTS: The majority of nutrients reported were within 30% of consumed intake in all 3 food capture methods (n = 129 completers). Reported intake was highly (>30%) overestimated for added sugars in both PIQNIQ groups and underestimated for calcium in the photo-assisted recall group only (P < 0.001 for all). However, in general, both PIQNIQ methods had similar levels of accuracy and were comparable to the 24HR except in their overestimation (>30%) of added sugars and total fat (P < 0.001 for both). CONCLUSIONS: Our results suggest that intuitive, technology-based methods of dietary data capture are well suited to modern users and, with proper execution, can provide data that are comparable to data obtained with traditional methods. This trial was registered at clinicaltrials.gov as NCT03578458.

Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial.

BACKGROUND/OBJECTIVES: Obesity is associated with reduced neurocognitive performance. Individuals with obesity show decreased activation in the left dorsolateral prefrontal cortex (DLPFC), a key brain region relevant to the regulation of eating behavior. Transcranial direct current stimulation (tDCS) has emerged as a potential technique to correct these abnormalities. However, there is limited information to date, particularly in clinical settings and regarding long-term effects of tDCS. This study aimed to investigate the effects of DLPFC-targeted tDCS in young women with obesity. SUBJECT/METHODS: Randomized, double-blind, sham-controlled parallel-design clinical trial conducted in 38 women, aged 20-40 years, with BMI 30-35 kg/m2. STUDY DESIGN: Phase I: target engagement (immediate effects of tDCS on working memory performance), Phase II: tDCS only (ten sessions, 2 weeks), Phase III: tDCS + hypocaloric diet (six sessions, 30% energy intake reduction, 2 weeks, inpatient), Phase IV: follow-up at 1, 3, and 6 months. PRIMARY OUTCOME: change in body weight. SECONDARY OUTCOMES: change in eating behavior and appetite. Additional analyses: effect of Catechol-O-methyl transferase (COMT) gene variability. Data were analyzed as linear mixed models. RESULTS: There was no group difference in change in body weight during the tDCS intervention. At follow-up, the active group lost less weight than the sham group. In addition, the active group regained weight at 6-month follow-up, compared with sham. Genetic analysis indicated that COMT Met noncarriers were the subgroup that accounted for this paradoxical response in the active group. CONCLUSION: Our results suggest that in young women with class I obesity, tDCS targeted to the DLPFC does not facilitate weight loss. Indeed, we found indications that tDCS could have a paradoxical effect in this population, possibly connected with individual differences in dopamine availability. Future studies are needed to confirm these findings.

Food cravings: Associations with dietary intake and metabolic health.

Food cravings are a desire for specific foods which, if uncontrolled may lead to excess energy intake and weight gain. However, information on the relation between food cravings, dietary intake, and indices of metabolic health is limited. This study used baseline data from females (n = 229; aged 40.9 ± 0.7 years; BMI 34.7 ± 6.4 kg/m2) who were dependents of active duty and retired military personnel, and enrolled in the Healthy Families Healthy Forces weight loss and maintenance study. Measures obtained included food cravings using the Food Craving Questionnaire-Trait (which provides a habitual and stable measure of food cravings), dietary composition and eating patterns from three 24-h dietary recalls and the Stanford 7-day Physical Activity Recall, body composition from anthropometric measures, cardiometabolic risk factors from blood measures, and demographic information from questionnaires. Linear, quantile, or logistic regression models were used to examine the association of total food craving scores on dietary intake, and indices of metabolic health. In individuals reporting plausible energy intake (n = 146; 2210 ± kcals/day) higher food craving scores were associated with a lower diet quality (P < 0.05), higher eating frequency (P = 0.02), longer daily eating interval (P < 0.05), and a lower likelihood of following a time restricted eating pattern (P = 0.02). Food cravings were also positively associated with BMI (P = 0.03) and waist circumference (P = 0.01), but not with measures of cardiometabolic risk (LDL, HDL, total cholesterol:HDL, triglycerides, glucose, glycated hemoglobin, insulin and C-reactive protein concentrations, blood pressure, metabolic syndrome). Our findings of significant associations of food cravings with lower diet quality, poor eating patterns, and unfavorable body composition strongly support efforts of targeting cravings in behavioral programs for weight management.

Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity.

Calorie restriction (CR) enhances longevity in humans who are normal weight, overweight and obese. While dietary regimens can change self-efficacy, eating behaviors, and food cravings in individuals with obesity, the responses of these measures to prolonged CR in individuals who are exclusively not obese is unknown. The aim of this analysis was to test the effects of a two-year CR intervention on self-efficacy and eating attitudes and behaviors in humans without obesity by analyzing data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study. Participants (n = 218, BMI range = 21.3-29.0 kg/m2) were randomized to a 25% CR group or an ad libitum (AL) group. Eating attitudes and behaviors and self-efficacy were assessed using validated questionnaires at baseline, month 12, and month 24. Dietary restraint and self-efficacy increased in the CR compared to the AL group (ES ≥ 0.32). Increased self-efficacy was negatively related to weight change (ρ < -0.24). In the CR group, males showed a reduction in cravings for carbohydrates and fats at month 24, whereas females did not. The CR group showed elevations in state hunger, which were transient, and disinhibited eating (ES ≥ 0.37). In individuals without obesity, dietary restraint and self-efficacy could be important in promoting long-term CR for individuals looking to use CR as a tool to improve longevity.

Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: A randomized clinical trial.

The regulation of appetite is supported by dopamine-modulated brain circuits. Recent studies have shown that transcranial direct current stimulation (tDCS) aimed at increasing the excitability of the dorsolateral prefrontal cortex can reduce appetite, but the underlying mechanisms remain unknown, and response variability is large. The aim of this study was to determine whether individual differences in Catechol-O-methyl transferase (COMT) Val158Met polymorphism can influence tDCS effects on appetite. Thirty-eight adult women with obesity, classified as carriers or non-carriers of the Met allele, underwent a randomized, double-blind, sham-controlled tDCS intervention involving three phases: Phase I, target engagement (immediate effects of tDCS on working memory performance), Phase II, tDCS only (10 sessions, two weeks), and Phase III, tDCS + hypocaloric diet: (6 sessions, two weeks, 30% energy intake reduction, inpatient). Data were analyzed using linear mixed-effects models and mixed ANCOVA. Appetite was evaluated using visual analogue scales. We found that Met-carriers receiving active tDCS were the only participants who experienced a significant reduction of appetite over time. Conversely, Met non-carriers maintained high levels of appetite during the intervention; this effect was driven by a delayed paradoxical rise in appetite after stimulation. Working memory task performance at phase I correlated with subsequent appetite change in a COMT-dependent manner: speed improvements during the task predicted appetite increase in Met carriers and appetite reduction in Met non-carriers. Our findings suggest that genotype differences impacting dopamine levels influence prefrontal tDCS effects on appetite. This source of variability should be considered in the design of future studies.

Energy intake in short bowel syndrome: assessment by 24-h dietary recalls compared with the doubly labelled water method.

Short bowel syndrome (SBS) represents a serious intestinal absorption disorder, and patients may be prone to severe malnutrition. Dietetic therapy is critically important both for immediate prognosis and successful long-term rehabilitation. To maintain energy balance, an accurate assessment of energy intake is required. Our objective was to compare energy intake (EI) assessed by 24-h dietary recalls (EIrecall), a standard clinical assessment, with the total energy expenditure measured by the doubly labelled water (TEEdlw) method in SBS patients and matched controls. A total of twenty-two participants (eleven each in the SBS and control groups (CG), six female and five male) were evaluated; CG were matched to SBS patients on the basis of age, BMI and sex. TEE was measured by DLW and compared with EI determined by four 24-h dietary recalls using the USDA Automated Multiple-Pass Method. Bland-Altman plots and paired Student's t test were used to compare EIrecall with TEEdlw (P<0·05). Participants' mean age was 53 (sd 8) years. TEEdlw (7·85 (SD 1·16) MJ/d, 0·14 (SD 0·02) MJ/kg per d) was significantly lower (P=0·014) compared with EIrecall (11·07 (SD 3·45) MJ/d, 0·21 (SD 0·08) MJ/kg per d) in the SBS group. On the other hand, in the CG group TEEdlw (10·02 (SD 1·86) MJ/d, 0·18 (SD 0·03) MJ/kg per d) was significantly higher (P=0·001) compared with EIrecall (7·19 (SD 1·68) MJ/d, 0·13 (SD 0·03) MJ/kg per d). In SBS patients, reported EI is higher than DLW-measured EI. Therefore, providing or prescribing energetic intake based on EIrecall without accounting for potential malabsorption-related losses can compromise the energy needs in SBS patients and affect nutritional status in the long term.

Association of nutrition club membership with markers of health: a cross sectional study.

BACKGROUND: Nutrition clubs (NC) operate in community settings and provide members with nutrition education and meal replacements for weight management. NC are owned and operated by distributors of Herbalife products. There are over 6200 NC in the US, but there has been no independent assessment of the association of these NC with biomarkers of health. METHODS: We conducted a cross-sectional pilot study to compare the health status of 100 NC members to 100 community-matched controls (CC) in the greater Boston area. Each CC was matched to a NC member for community of residence (zip code), age category, gender, BMI category, race/ethnicity, education level (category), and readiness to make health changes. Measures obtained included cardio-metabolic risk factors, body composition, markers of nutritional status, reported health status, dietary intake, physical activity, sleep and depression. RESULTS: Participants were predominantly female (64%) and Hispanic (73%). NC members had significantly lower fasting insulin (P < 0.001) and lower HbA1c (P = 0.008), higher levels of 25 hydroxy-vitamin D (P = 0.001), and vitamin E:cholesterol ratio (P < 0.001), and lower prevalence of metabolic syndrome (P = 0.02) compared to CC. In addition, most of the NC members (99%) were satisfied with Herbalife NC membership for themselves and their families. A higher percentage of NC members (86%) compared to CC (32%) reported being in much better or somewhat better health compared to a year ago (P < 0.001); and they reported significantly better physical health (P = 0.03), and fewer sleep problems (P = 0.03). CONCLUSION: Herbalife NC membership was positively associated with perceived health and measured cardiometabolic benefits. However, causality cannot be inferred from these findings.

The doubly labeled water method produces highly reproducible longitudinal results in nutrition studies.

The doubly labeled water (DLW) method is considered the reference method for the measurement of energy expenditure under free-living conditions. However, the reproducibility of the DLW method in longitudinal studies is not well documented. This study was designed to evaluate the longitudinal reproducibility of the DLW method using 2 protocols developed and implemented in a multicenter clinical trial-the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). To document the longitudinal reproducibility of the DLW method, 2 protocols, 1 based on repeated analysis of dose dilutions over the course of the clinical trial (dose-dilution protocol) and 1 based on repeated but blinded analysis of randomly selected DLW studies (test-retest protocol), were carried out. The dose-dilution protocol showed that the theoretical fractional turnover rates for (2)H and (18)O and the difference between the 2 fractional turnover rates were reproducible to within 1% and 5%, respectively, over 4.5 y. The Bland-Altman pair-wise comparisons of the results generated from 50 test-retest DLW studies showed that the fractional turnover rates and isotope dilution spaces for (2)H and (18)O, and total energy expenditure, were highly reproducible over 2.4 y. Our results show that the DLW method is reproducible in longitudinal studies and confirm the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5-4.4 y. The 2 protocols can be adopted by other laboratories to document the longitudinal reproducibility of their measurements to ensure the long-term outcomes of interest are meaningful biologically. This trial was registered at clinicaltrials.gov as NCT00427193.

Effect of glycemic load on eating behavior self-efficacy during weight loss.

High eating behavior self-efficacy may contribute to successful weight loss. Diet interventions that maximize eating behavior self-efficacy may therefore improve weight loss outcomes. However, data on the effect of diet composition on eating behavior self-efficacy are sparse. To determine the effects of dietary glycemic load (GL) on eating behavior self-efficacy during weight loss, body weight and eating behavior self-efficacy were measured every six months in overweight adults participating in a 12-mo randomized trial testing energy-restricted diets differing in GL. All food was provided during the first six months and self-selected thereafter. Total mean weight loss did not differ between groups, and GL-level had no significant effect on eating behavior self-efficacy. In the combined cohort, individuals losing the most weight reported improvements in eating behavior self-efficacy, whereas those achieving less weight loss reported decrements in eating behavior self-efficacy. Decrements in eating behavior self-efficacy were associated with subsequent weight regain when diets were self-selected. While GL does not appear to influence eating behavior self-efficacy, lesser amounts of weight loss on provided-food energy restricted diets may deter successful maintenance of weight loss by attenuating improvements in eating behavior self-efficacy.

Weight Loss Trajectories and Short-Term Prediction in an Online Weight Management Program.

The extent to which early weight loss in behavioral weight control interventions predicts long-term success remains unclear. In this study, we developed an algorithm aimed at classifying weight change trajectories and examined its ability to predict long-term weight loss based on weight early change. We utilized data from 667 de-identified individuals who participated in a commercial weight loss program (Instinct Health Science), comprising 69,363 weight records. Sequential polynomial regression models were employed to classify participants into distinct weight trajectory patterns based on key model parameters. Next, we applied multinomial logistic models to evaluate if early weight loss in the first 14 days and prolonged duration of participation were significantly associated with long-term weight loss patterns. The mean percentage of weight loss was 7.9 ± 5.1% over 133 ± 69 days. Our analysis revealed four main weight loss trajectory patterns: a steady decrease over time (30.6%), a decrease to a plateau with subsequent decline (15.8%), a decrease to a plateau with subsequent increase (46.9%), and no substantial decrease (6.7%). Early weight change rate and total participating duration emerged as significant factors in differentiating long-term weight loss patterns. These findings contribute to support the provision of tailored advice in the early phase of behavioral interventions for weight loss.

Weight history of individuals with and without physical disability in the International Weight Control Registry.

Background: People with physical disabilities (PWD) have an increased risk of obesity and related comorbidities compared with people without physical disabilities (PWoD). Previously identified contributors to weight loss maintenance pose challenges to PWD. However, it is not known if PWD experience less success in weight management. Methods: Six hundred and nine participants in the International Weight Control Registry (IWCR) were eligible for this analysis (PWD, n = 174; PWoD, n = 435). Self-reported weight history metrics were compared using general linear models. Perceived weight history category was compared using Chi-squared tests. Importance of diet and physical activity strategies for weight management were compared using Wilcoxon rank-signed tests. Results: PWD reported higher current body mass index (BMI) (36.1 ± 0.7 vs. 31.0 ± 0.5; p < 0.0001) and more weight loss attempts (9.1 ± 0.7 vs. 7.1 ± 0.4; p = 0.01) than PWoD. Current weight loss percentage (PWD 13.0 ± 1.0; PWoD, 13.0 ± 0.6; p = 0.97) and weight loss category (χ 2 [3, N = 609] = 2.9057, p = 0.41) did not differ between the groups. There were no differences in any weight strategy between PWD who were successful and those who regained. Conclusions: PWD and PWoD in the IWCR achieved similar levels of weight maintenance success. However, higher BMI and more weight loss attempts suggest that PWD may face challenges with weight management. More research is needed to identify strategies leading to success for PWD.

Development and Feasibility of an eHealth Diabetes Prevention Program Adapted for Older Adults-Results from a Randomized Control Pilot Study.

Lifestyle programs that reduce health risks and support weight loss (WL) in older adults face adherence and attendance challenges due to reduced energy requirements, impaired mobility, lack of transportation, and low social support. Tailored lifestyle and weight management programs are needed to better support healthy aging for older adults. Here, we developed and piloted an age-adapted, remotely delivered modification of the Diabetes Prevention Program (DPP). The modification includes age-appropriate goals, visuals, and examples; flexible dietary composition; remote classroom and fitness-monitoring technology; and standardized online classroom materials employing pedagogical and behavior change theory. The modifications were designed to safeguard fidelity and to boost adherence, engagement, and knowledge integration, with the convenience of a fully remote WL program for diverse older adults. Six-month pilot data are presented from older adults (55-85 years, body mass index (BMI) 27-39.9 kg/m2, N = 20) randomly allocated to an online DPP intervention with weight, diet, and activity monitored remotely, or into a waitlisted control. The intervention achieved 100% attendance and adherence to self-monitoring. The intervention group mean (±SD) body weight change was -9.5% (±4.1); 90% lost ≥ 5%. By contrast, the control group gained 2.4% (±1.8). Once thought incompatible with older adults, remote interventions are feasible for older adults and can support fidelity, adherence, engagement, and clinically significant WL. Standardized materials are provided for future implementation.

Calorie restriction reduces biomarkers of cellular senescence in humans.

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change in HOMA-IR and insulin sensitivity index at 12 and 24 months, and the change in resting metabolic rate residual at 12 months. Finally, using adipose tissue RNA-sequencing data from a subset of participants, we observed a significant reduction in a senescence-focused gene set in response to CR at both 12 and 24 months compared to baseline. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health.

Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis.

Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m2), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR intervention slowed biological aging. Here, we extend these analyses to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12-, and 24-months by quantitative PCR (absolute TL; aTL) and a published DNA-methylation algorithm (DNAmTL). Intent-to-treat analysis found no significant differences in TL attrition across the first year, although there were trends toward increased attrition in the CR group for both aTL and DNAmTL measurements. When accounting for adherence heterogeneity with an Effect-of-Treatment-on-the-Treated analysis, greater CR dose was associated with increased DNAmTL attrition during the baseline to 12-month weight-loss period. By contrast, both CR group status and increased CR were associated with reduced aTL attrition over the month 12 to month 24 weight maintenance period. No differences were observed when considering TL change across the study duration from baseline to 24-months, leaving it unclear whether CR-related effects reflect long-term detriments to telomere fidelity, a hormesis-like adaptation to decreased energy availability, or measurement error and insufficient statistical power. Unraveling these trends will be a focus of future CALERIE™ analyses and trials.