Search

The amount of time spent in poor health at the end of life is increasing. This narrative review summarizes consistent evidence indicating that healthy dietary patterns and maintenance of a healthy weight in the years leading to old age are associated with broad prevention of all the archetypal diseases and impairments associated with aging including: noncommunicable diseases, sarcopenia, cognitive decline and dementia, osteoporosis, age-related macular degeneration, diabetic retinopathy, hearing loss, obstructive sleep apnea, urinary incontinence, and constipation. In addition, randomized clinical trials show that disease-specific nutrition interventions can attenuate progression—and in some cases effectively treat—many established aging-associated conditions. However, middle-aged and older adults are vulnerable to unhealthy dietary patterns, and typically consume diets with inadequate servings of healthy food groups and essential nutrients, along with an abundance of energy-dense but nutrient-weak foods that contribute to obesity. However, based on menu examples, diets that are nutrient-dense, plant-based, and with a moderately low glycemic load are better equipped to meet the nutritional needs of many older adults than current recommendations in US Dietary Guidelines. These summary findings indicate that healthy nutrition is more important for healthy aging than generally recognized. Improved public health messaging about nutrition and aging, combined with routine screening and medical referrals for age-related conditions that can be treated with a nutrition prescription, should form core components of a national nutrition roadmap to reduce the epidemic of unhealthy aging.Healthy nutrition has a broad, underrecognized role in preventing aging-related diseases and conditions. Updated public health recommendations on nutrition are needed to support healthy aging.

The amount of time spent in poor health at the end of life is increasing. This narrative review summarizes consistent evidence indicating that healthy dietary patterns and maintenance of a healthy weight in the years leading to old age are associated with broad prevention of all the archetypal diseases and impairments associated with aging including: noncommunicable diseases, sarcopenia, cognitive decline and dementia, osteoporosis, age-related macular degeneration, diabetic retinopathy, hearing loss, obstructive sleep apnea, urinary incontinence, and constipation. In addition, randomized clinical trials show that disease-specific nutrition interventions can attenuate progression—and in some cases effectively treat—many established aging-associated conditions. However, middle-aged and older adults are vulnerable to unhealthy dietary patterns, and typically consume diets with inadequate servings of healthy food groups and essential nutrients, along with an abundance of energy-dense but nutrient-weak foods that contribute to obesity. However, based on menu examples, diets that are nutrient-dense, plant-based, and with a moderately low glycemic load are better equipped to meet the nutritional needs of many older adults than current recommendations in US Dietary Guidelines. These summary findings indicate that healthy nutrition is more important for healthy aging than generally recognized. Improved public health messaging about nutrition and aging, combined with routine screening and medical referrals for age-related conditions that can be treated with a nutrition prescription, should form core components of a national nutrition roadmap to reduce the epidemic of unhealthy aging.

Effective, standardized, and easily accessible weight management programs are urgently needed for military beneficiaries. Videoconference interventions have the potential for widespread scaling, and can provide both real time interaction and flexibility in delivery times regardless of location, but there is little information on their effectiveness and acceptability.

•Student dialog sessions held in Boston, MA, reveal new insight toward equitable obesity prevention.•Focus on weight stigma and eating disorders to reduce harm while promoting healthy weight.•Increase training and research on racism and discrimination as obesity determinants.•Improve communication of strengths and limitations of BMI for assessing population health.

For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals.

Purpose: Programs focused on employee well-being have gained momentum in recent years, but few have been rigorously evaluated. This study evaluates the effectiveness of an intervention designed to enhance vitality and purpose in life by assessing changes in employee quality of life (QoL) and health-related behaviors.Design: A worksite-based randomized controlled trial.Setting: Twelve eligible worksites (8 randomized to the intervention group [IG] and 4 to the wait-listed control group [CG]).Participants: Employees (n = 240) at the randomized worksites.Intervention: A 2.5-day group-based behavioral intervention.Measures: Rand Medical Outcomes Survey (MOS) 36-item Short-Form (SF-36) vitality and QoL measures, Ryff Purpose in Life Scale, Center for Epidemiologic Studies questionnaire for depression, MOS sleep, body weight, physical activity, diet quality, and blood measures for glucose and lipids (which were used to calculate a cardiometabolic risk score) obtained at baseline and 6 months.Analysis: General linear mixed models were used to compare least squares means or prevalence differences in outcomes between IG and CG participants.Results: As compared to CG, IG had a significantly higher mean 6-month change on the SF-36 vitality scale (P= .003) and scored in the highest categories for 5 of the remaining 7 SF-36 domains: general health (P= .014), mental health (P= .027), absence of role limitations due to physical problems (P= .026), and social functioning (P= .007). The IG also had greater improvements in purpose in life (P< .001) and sleep quality (index I, P= .024; index II, P= .021). No statistically significant changes were observed for weight, diet, physical activity, or cardiometabolic risk factors.Conclusion: An intensive 2.5-day intervention showed improvement in employee QoL and well-being over 6 months.

Background: There is no consensus over best approaches to reliably prevent malnutrition in rural communities in low-income countries.Objective: We compared the effectiveness of 2 lipid-based ready-to-use supplementary foods (RUSFs) differing in dairy protein content to improve the nutritional status of mothers and at-risk infants and young children in rural Guinea-Bissau.Methods: A 3-month cluster-randomized controlled pilot trial of 2 RUSFs was conducted with 692 mothers and 580 mildly or moderately malnourished infants (6-23 months) and children (24-59 months) from 13 villages. The RUSFs contained either 478 (mothers, children) or 239 kcal/d (infants) with 15% or 33% of protein from dairy and were distributed at community health centers 5 d/wk. Controls were wait-listed to receive RUSF. Primary outcomes were mid-upper arm circumference (MUAC) in mothers, and weight-for-age and height-for-age z-scores (WAZ and HAZ) in infants and children.Results: There was a significant effect of the RUSF-33% on MUAC in mothers (P= .03). The WAZ and HAZ increased substantially, by ≈1 z-score, in infants and children (P< .01) independent of group randomization. In children, but not infants, baseline WAZ and change in maternal MUAC were associated with change in WAZ (β = .07, P= .02).Conclusion: Ready-to-use supplementary foods with higher dairy protein content had a significant benefit in village mothers, supporting a comparable recent finding in preschool children. In addition, supplementation of children <2 years resulted in improved growth independent of family nutritional status, whereas success in older children was associated with change in maternal nutrition, suggesting the need for community-level education about preventing malnutrition in older, as well as younger, children.

Background: The nutrition status of primary schoolchildren in Africa has received relatively little attention in comparison to that of younger children. We surveyed primary school students in Guinea-Bissau, a nation that is among the poorest in the world.Objective: Anthropometry and prevalence of anemia and vitamin A deficiency were assessed in schoolchildren participating in International Partnership for Human Development’s school feeding program in 2 regions of Guinea-Bissau.Methods: A cross-sectional survey of 32 schools in the regions of Cacheu and Oio was conducted in November 2011. Variables included age, gender, weight, height, hemoglobin, and retinol-binding protein concentrations. Zscores for height for age (HAZ), body mass index for age (BAZ), and weight for age were calculated using World Health Organization reference data.Results: Anthropometric assessment of 4784 students revealed stunting (HAZ < -2) in 15.5%, thinness (BAZ < -2) in 13.2%, and anemia in 42.0%. Stunting, thinness, and anemia were significantly more common in males, in students from Oio, and in older students. Vitamin A deficiency, detected in 21.5% of the population, was the only assessment that did not demonstrate significant differences between genders or regions. About 61.1% of all children had 1 or more indicators of undernutrition.Conclusion: There are substantial rates of stunting, thinness, underweight, anemia, and vitamin A deficiency in primary schoolchildren in Guinea-Bissau, even among those participating in a school lunch program and particularly among males and older students. The results suggest the need for evaluating feeding programs and other methods to improve nutrition status in primary school students, especially in older students.

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.

IMPORTANCE: Calorie restriction (CR) increases longevity in many species and reduces risk factors for chronic diseases. In humans, CR may improve health span, yet concerns remain about potential negative effects of CR. OBJECTIVE: To test the effect of CR on mood, quality of life (QOL), sleep, and sexual function in healthy nonobese adults. DESIGN, SETTING, AND PARTICIPANTS: A multisite randomized clinical trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 [CALERIE 2]) was conducted at 3 academic research institutions. Adult men and women (N = 220) with body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 22.0 to 28.0 were randomized to 2 years of 25% CR or an ad libitum (AL) control group in a 2:1 ratio favoring CR. Data were collected at baseline, 12 months, and 24 months and examined using intent-to-treat analysis. The study was conducted from January 22, 2007, to March 6, 2012. Data analysis was performed from July 18, 2012, to October 27, 2015. INTERVENTIONS: Two years of 25% CR or AL. MAIN OUTCOMES AND MEASURES: Self-report questionnaires were administered to measure mood (Beck Depression Inventory-II [BDI-II], score range 0-63, higher scores indicating worse mood, and Profile of Mood States [POMS], with a total mood disturbance score range of −32 to 200 and higher scores indicating higher levels of the constructs measured), QOL (Rand 36-Item Short Form, score range 0-100, higher scores reflecting better QOL, and Perceived Stress Scale, score range 0-40, higher scores indicating higher levels of stress), sleep (Pittsburgh Sleep Quality Index [PSQI], total score range 0-21, higher scores reflecting worse sleep quality), and sexual function (Derogatis Interview for Sexual Function–Self–report, total score range 24-188, higher scores indicating better sexual functioning). RESULTS: In all, 218 participants (152 women [69.7%]; mean [SD] age, 37.9 (7.2) years; mean [SD] BMI, 25.1 [1.6]) were included in the analyses. The CR and AL groups lost a mean (SE) of 7.6 (0.3) kg and 0.4 (0.5) kg, respectively, at month 24 (P &lt; .001). Compared with the AL group, the CR group had significantly improved mood (BDI-II: between-group difference [BGD], −0.76; 95% CI, −1.41 to −0.11; effect size [ES], −0.35), reduced tension (POMS: BGD, −0.79; 95% CI, −1.38 to −0.19; ES, −0.39), and improved general health (BGD, 6.45; 95% CI, 3.93 to 8.98; ES, 0.75) and sexual drive and relationship (BGD, 1.06; 95% CI, 0.11 to 2.01; ES, 0.35) at month 24 as well as improved sleep duration at month 12 (BGD, −0.26; 95% CI, −0.49 to −0.02; ES, −0.32) (all P &lt; .05). Greater percent weight loss in the CR group at month 24 was associated with increased vigor (Spearman correlation coefficient, ρ = −0.30) and less mood disturbance (ρ = 0.27) measured with the POMS, improved general health (ρ = −0.27) measured with the SF-36, and better sleep quality per the PSQI total score (ρ = 0.28) (all P &lt; .01). CONCLUSIONS AND RELEVANCE: In nonobese adults, CR had some positive effects and no negative effects on health-related QOL. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00427193

ABSTRACTDaclatasvir (DCV) is a first-in-class hepatitis C virus (HCV) nonstructural 5A replication complex inhibitor (NS5A RCI) that is clinically effective in interferon-free combinations with direct-acting antivirals (DAAs) targeting alternate HCV proteins. Recently, we reported NS5A RCI combinations that enhance HCV inhibitory potential in vitro, defining a new class of HCV inhibitors termed NS5A synergists (J. Sun, D. R. O’Boyle II, R. A. Fridell, D. R. Langley, C. Wang, S. Roberts, P. Nower, B. M. Johnson F. Moulin, M. J. Nophsker, Y. Wang, M. Liu, K. Rigat, Y. Tu, P. Hewawasam, J. Kadow, N. A. Meanwell, M. Cockett, J. A. Lemm, M. Kramer, M. Belema, and M. Gao, Nature 527:245–248, 2015, doi:10.1038/nature15711). To extend the characterization of NS5A synergists, we tested new combinations of DCV and NS5A synergists against genotype (gt) 1 to 6 replicons and gt 1a, 2a, and 3a viruses. The kinetics of inhibition in HCV-infected cells treated with DCV, an NS5A synergist (NS5A-Syn), or a combination of DCV and NS5A-Syn were distinctive. Similar to activity observed clinically, DCV caused a multilog drop in HCV, followed by rebound due to the emergence of resistance. DCV–NS5A-Syn combinations were highly efficient at clearing cells of viruses, in line with the trend seen in replicon studies. The retreatment of resistant viruses that emerged using DCV monotherapy with DCV–NS5A-Syn resulted in a multilog drop and rebound in HCV similar to the initial decline and rebound observed with DCV alone on wild-type (WT) virus. A triple combination of DCV, NS5A-Syn, and a DAA targeting the NS3 or NS5B protein cleared the cells of viruses that are highly resistant to DCV. Our data support the observation that the cooperative interaction of DCV and NS5A-Syn potentiates both the genotype coverage and resistance barrier of DCV, offering an additional DAA option for combination therapy and tools for explorations of NS5A function.

Cancer diagnosis and treatment may influence dietary intake. The validity of using self-reported methods to quantify dietary intake has not been evaluated in childhood cancer survivors. We validated total energy intake (EI) reported from Food Frequency Questionnaire (FFQ) and repeated 24-hour diet recalls (24HRs) against total energy expenditure (TEE) measured using the doubly labeled water method in 16 childhood cancer survivors. Dietary underreporting, assessed by (EI-TEE)/TEE?×?100%, was 22% for FFQ and 1% for repeated 24HRs. FFQ significantly underestimates dietary intake and should not be used to assess the absolute intake of foods and nutrients in childhood cancer survivors.

Childhood cancer survivors are at an increased risk of obesity but causes for this elevated risk are uncertain. We evaluated total energy expenditure in childhood cancer survivors using the doubly labeled water method in a cross-sectional study of 17 survivors of pediatric leukemia or lymphoma (median age, 11.5 y). Mean total energy expenditure was 2073 kcald, which was nearly 500 kcald lower than estimated energy requirements with recommended levels of physical activity. This energy gap is likely to contribute to the risk of obesity in this population and future trials are needed to assess implications and potential treatment strategies.

The role of dietary energy density (ED) in the regulation of energy intake (EI) is controversial. Methodologically, there is also debate about whether beverages should be included in dietary ED calculations. To address these issues, studies examining the effects of ED on EI or body weight in nonelderly adults were reviewed. Different approaches to calculating dietary ED do not appear to alter the direction of reported relations between ED and body weight. Evidence that lowering dietary ED reduces EI in short-term studies is convincing, but there are currently insufficient data to determine long-term effectiveness for weight loss. The review also identified key barriers to progress in understanding the role of ED in energy regulation, in particular the absence of a standard definition of ED, and the lack of data from multiple long-term clinical trials examining the effectiveness of low-ED diet recommendations for preventing both primary weight gain and weight regain in nonobese individuals. Long-term clinical trials designed to examine the impact of dietary ED on energy regulation, and including multiple ED calculation methods within the same study, are still needed to determine the importance of ED in the regulation of EI and body weight.

Adult civilian dependents of active duty military personnel (ADMP) may play a central role in influencing the home food environment and the risk of overweight and obesity in American Warfighters and military families. However, there is no information on whether this group would be receptive to weight control programs. We conducted a survey to determine the level of interest of adult civilian dependents of ADMP in participating in a group weight control program. Subjects were a convenience sample of 191 adult civilian dependents of ADMP (94% women, 6% men) based in Massachusetts and aged 33.8 ± 8.4 years, body mass index 25.5 ± 5.5 kg/m(2). Overall, there was a significant effect of body mass index on interest in program participation (p = 0.004). Eighty five percent of overweight participants and 100% of obese participants reported being Moderately Likely or Very Likely to participate in a provided weight control program. In overweight and obese survey respondents there was no significant effect of ADMP rank on interest in program participation (p = 0.34). These findings suggest that overweight and obese adult civilian dependents of ADMP may be very receptive targets for programs to control overweight and obesity in military families.

IMPORTANCE National recommendations for the prevention and treatment of obesity emphasize reducing energy intake through self-monitoring food consumption. However, little information is available on the energy content of foods offered by nonchain restaurants, which account for approximately 50% of restaurant locations in the United States. OBJECTIVE To measure the energy content of foods from independent and small-chain restaurants that do not provide stated information on energy content. DESIGN We used bomb calorimetry to determine the dietary energy content of the 42 most frequently purchased meals from the 9 most common restaurant categories. Independent and small-chain restaurants were randomly selected, and 157 individual meals were analyzed. SETTING Area within 15 miles of downtown Boston. PARTICIPANTS A random sample of independent and small-chain restaurants. MAIN OUTCOMES AND MEASURES Dietary energy. RESULTS All meal categories provided excessive dietary energy. The mean energy content of individual meals was 1327 (95% CI, 1248-1406) kcal, equivalent to 66% of typical daily energy requirements. We found a significant effect of food category on meal energy (P ≤ .05), and 7.6% of meals provided more than 100% of typical daily energy requirements. Within-meal variability was large (average SD, 271 kcal), and we found no significant effect of restaurant establishment or size. In addition, meal energy content averaged 49% greater than those of popular meals from the largest national chain restaurants (P &lt; .001) and in subset analyses contained 19% more energy than national food database information for directly equivalent items (P &lt; .001). CONCLUSIONS AND RELEVANCE National chain restaurants have been criticized for offering meals with excess dietary energy. This study finds that independent and small-chain restaurants, which provide no nutrition information, also provide excessive dietary energy in amounts apparently greater than popular meals from chain restaurants or information in national food databases. A national requirement for accurate calorie labeling in all restaurants may discourage menus offering unhealthy portions and would allow consumers to make informed choices about ordering meals that promote weight gain and obesity.

The relative influence of genetics and the environment on factors associated with cardiovascular disease (CVD) and metabolic syndrome (MetS) remains unclear. We performed model-fitting analyses to quantify genetic, common environmental, and unique environmental variance components of factors associated with CVD and MetS [waist circumference, blood pressure, fasting plasma glucose and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and fasting plasma lipids] in adult male and female monozygotic twins reared apart or together. We also investigated whether MetS components share common influences. Plasma cholesterol and triglyceride concentrations were highly heritable (56–77%, statistically significant). Waist circumference, plasma glucose and insulin, HOMA-IR, and blood pressure were moderately heritable (43–57%, statistically significant). Unique environmental factors contributed to the variance of all variables (20–38%, perforce statistically significant). Common environmental factors contributed 23, 30, and 42% (statistically significant) of the variance of waist circumference, systolic blood pressure, and plasma glucose, respectively. Two shared factors influenced MetS components; one influenced all components except HDL cholesterol, another influenced only lipid (triglyceride and HDL cholesterol) concentrations. These results suggest that genetic variance has a dominant influence on total variance of factors associated with CVD and MetS and support the proposal of one or more underlying pathologies of MetS.

The relative influence of genetics and the environment on factors associated with cardiovascular disease (CVD) and metabolic syndrome (MetS) remains unclear. We performed model-fitting analyses to quantify genetic, common environmental, and unique environmental variance components of factors associated with CVD and MetS [waist circumference, blood pressure, fasting plasma glucose and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and fasting plasma lipids] in adult male and female monozygotic twins reared apart or together. We also investigated whether MetS components share common influences. Plasma cholesterol and triglyceride concentrations were highly heritable (56–77%, statistically significant). Waist circumference, plasma glucose and insulin, HOMA-IR, and blood pressure were moderately heritable (43–57%, statistically significant). Unique environmental factors contributed to the variance of all variables (20–38%, perforce statistically significant). Common environmental factors contributed 23, 30, and 42% (statistically significant) of the variance of waist circumference, systolic blood pressure, and plasma glucose, respectively. Two shared factors influenced MetS components; one influenced all components except HDL cholesterol, another influenced only lipid (triglyceride and HDL cholesterol) concentrations. These results suggest that genetic variance has a dominant influence on total variance of factors associated with CVD and MetS and support the proposal of one or more underlying pathologies of MetS.

Objective: We present an updated method for identifying physiologically implausible dietary reports by comparing reported energy intake (rEI) with predicted energy requirements (pER), and we examine the impact of excluding these reports. Research Methods and Procedures: Adult data from the Continuing Survey of Food Intakes by Individuals 1994 to 1996 were used. pER was calculated from the dietary reference intake equations. Within‐subject variations and errors in rEI [coefficient of variation (CV) ∼ 23%] over 2 days (d), pER (CV ∼ 11%), and measured total energy expenditure (mTEE; doubly labeled water, CV ∼ 8.2%) were propagated, where ±1 SD = . Thus, a report was identified as implausible if rEI was not within 78% to 122% of pER. Multiple cut‐offs between ±1 and ±2 SD were tested. Results: %rEI/pER = 81% in the total sample (n= 6499) and progressively increased to 95% in the ±1 SD sample (n= 2685). The ±1 to 1.4 SD samples yielded rEI‐weight associations closest to the theoretical relationship (mTEE to weight). Weak or spurious diet—BMI associations were present in the total sample; ±1 to 1.4 SD samples showed the strongest set of associations and provided the maximum nwhile maintaining biological plausibility. Discussion: Our methodology can be applied to different data sets to evaluate the impact of implausible rEIs on health outcomes. Implausible rEIs reduce the overall validity of a sample, and not excluding them may lead to inappropriate conclusions about potential dietary causes of health outcomes such as obesity.

Objective: We examined relationships of eating patterns and reported energy intake (rEI) with BMI percentile in U.S. children. Research Methods and Procedures: Two 24‐hour dietary recalls from the Continuing Surveys of Food Intakes by Individuals 1994 to 1996 and 1998 (1005 boys, 990 girls) were averaged, and children were categorized into three age groups: 3 to 5 years (n= 1077), 6 to 11 years (n= 537), and 12 to 19 years (n= 381). Physiologically implausible reports due to reporting bias or abnormal intake (rEI outside ±18% to 23% of predicted energy requirements; pER) were identified. Results: rEI averaged 109 ± 34% and 100 ± 10% of pER in the total and plausible samples, respectively. EI was overreported more in younger children and underreported more in overweight older children. Children with plausible rEI (45.3% of sample) averaged 4.7 eating occasions/d, 589 kcal/meal, 223 kcal/snack, and 2038 kcal/d. rEI was not associated with BMI percentile in the total sample. In the plausible sample, rEI, meal portion size, and meal energy were positively associated with BMI percentile in boys 6 to 11 years and in children 12 to 19 years. No relationships were found in children 3 to 5 years and girls 6 to 11 years. Relationships were more consistent and stronger in the plausible compared with the total sample. Discussion: Excluding implausible dietary reports may be necessary for discerning dietary associations with BMI percentile. EI and meal, but not snack, patterns may play a quantitatively greater role in weight regulation as children age.

AbstractObjective:To review existing methods and illustrate the use of a new, simple method for identifying inaccurate reports of dietary energy intake (rEI).Design:Comparison of rEI with energy requirements estimated by using total energy expenditure predicted (pTEE) from age, weight, height and sex using a previously published equation. Propagation of error calculations was performed and cut-offs for excluding rEI at plus or minus two standard deviations (?2 SD) and ?1 SD for the agreement between rEI and pTEE were established.Setting:Dietary survey in a US national cohort: the Continuing Survey of Food Intakes by Individuals (CSFII), 1994?96.Subjects:Men and non-pregnant, non-lactating women aged 21?45 years in the CSFII who provided two multiple-pass 24-hour recalls, height and weight(n= 3755).Results:Average rEI was 77% of pTEE in men, and 64% of pTEE in women. Calculated cut-offs were rEI <40% or >160% of pTEE (?2 SD) and <70% or >130% of pTEE (?1 SD), respectively. Use of only the ?1 SD cut-offs, not the ?2 SD cut-offs, resulted in a relationship between rEI and body weight similar to what was expected (based on an independently calculated relationship between rEI and measured TEE). Exclusion of rEI outside either the ?2 SD (11% of subjects) or ?1 SD (57% of subjects) cut-offs did not affect mean reported macronutrient intakes, but did markedly affect relationships between dietary composition and body mass index.Conclusions:When examining relationships between diet and health, use of ?1 SD cut-offs may be preferable to ?2 SD cut-offs for excluding inaccurate dietary reports.

We review evidence regarding the influence of dietary fat, fiber, the glycemic index and sugar on energy intake and body weight. Although data from comprehensive long-term studies are lacking, published investigations suggest that the previous focus on lowering dietary fat as a means for promoting negative energy balance has led to an underestimation of the potential role of dietary composition in promoting reductions in energy intake and weight loss. More randomized clinical trials are needed to examine the relative utility of different putative dietary factors in the treatment of obesity.

As a result of the rising prevalence of overweight and obesity in the United States, more and more individuals are attempting to lose weight by modifying dietary intake. Total energy intake remains the most important factor in dietary interventions, but strategies based on emerging factors such as glycemic index, fiber intake, dietary variety, and energy density may improve efficacy and tolerability of energy restriction. Many popular diets remain untested by prospective randomized trials, and concerns exist about the effects of these diets on long-term health issues such as lipid profiles, micronutrient intake, bone health, and renal function. Recent developments in the dietary treatment of obesity are reviewed, and potential mechanisms by which dietary strategies influence weight loss and compliance with reductions in energy intake are discussed.

Objectives:To investigate the effects of oats, a cereal rich in soluble fiber, on body composition changes and dietary compliance during consumption of a weight loss diet.Methods:Subjects were 41 healthy men and women aged 18 to 78 years. Weight maintenance energy requirements were established over two weeks during consumption of a control diet with low soluble fiber content. Subjects then consumed a hypocaloric diet for six weeks, either consuming a low soluble fiber control diet or a diet containing 45 g/1000 kcal rolled oats, a whole grain cereal rich in soluble fiber (mean energy deficit −895 ± 18 kcal/day relative to weight maintenance energy requirements). Changes in body fat and fat-free mass were determined by underwater weighing, and dietary compliance was assessed using the urinary osmolar excretion rate technique. In a final phase of the study, subjects ate ad libitumfor six months, and changes in body weight and composition were monitored.Results:There was no significant effect of the oat-containing diet on body weight or composition changes during the hypocaloric regimen or in the subsequent ad libitumperiod. In addition, fecal energy excretion was not significantly different between groups. However, there were non-significant trends indicating reduced hunger in the oat group compared to controls (frequency of hunger 2.5±0.5 vs.3.6±0.4, P=0.1). In addition, fewer oat subjects were non-compliant (four versus seven subjects dropped out or had urinary osmolar excretions greater than 130% of values predicted from dietary intake), but again the difference was not significant.Conclusions:These results suggest that use of a cereal rich in soluble fiber in a closely monitored hypocaloric feeding regimen does not improve weight loss or dietary compliance. Further studies are needed to examine the possibility that cereals containing soluble fiber may have effects on hunger and dietary compliance that could be important in less tightly controlled protocols than the one described here.

β-Amyloid (Aβ) accumulation is believed to contribute to neuronal cell death in Alzheimer's disease. To understand the role of cAMP in the regulation of Aβ induced cell death, we used 8-chlorophenylthio-cAMP (8-CPT-cAMP, a cAMP analog) to raise intracellular cAMP levels. Exposure of rat cortical neurons to Aβ(25-35) resulted in a gradual increase in lactate dehydrogenase (LDH) over 48 h, which was preceded by a transient elevation in caspase-3-like activity. In the presence of 8CPT-cAMP, both caspase-3 activity and LDH release was significantly reduced. These data suggest that elevation of intracellular cAMP levels attenuate Aβ-induced neurotoxicity and may delay or prevent the onset of Aβ-induced neurode-generation.

McCRORY, MEGAN A., PAUL J. FUSS, NICHOLAS P. HAYS, ANGELA G. VINKEN, ANDREW S. GREENBERG, AND SUSAN B. ROBERTS. Overeating in America: association between restaurant food consumption and body fatness in healthy adult men and women ages 19 to 80. Obes Res. Purpose: To examine the association between the frequency of consuming restaurant food and body fatness in adults. Research Methods and Procedures: Usual free‐living dietary intake and the frequency of consuming food from seven different restaurant types (fried chicken, burger, pizza, Chinese, Mexican, fried fish, and “other”) were assessed by food frequency questionnaire in 73 healthy men and women [ages 19 to 80, body mass index (BMI) 18 to 331. In addition, body fatness (percent weight) was determined by hydrostatic weighing, and physical activity and other lifestyle parameters were assessed by questionnaire. The relationship between the frequency of consuming restaurant food and body fatness was determined after controlling for age, sex, and other confounders by using multiple regression techniques. Results: Restaurant food consumption averaged 7.5±8.5 (Standard Deviation) timedmonth. After controlling for age and sex, the frequency of consuming restaurant food was positively associated with body fatness (partial r= 0. 36, p= 0. 003). The strength of this association did not change after controlling for education level, smoking status, and alcohol intake, but after additionally controlling for physical activity, the partial rincreased to 0. 42 (p= 0. 004). Total daily intakes of energy, fat, and fiber were significantly associated with restaurant food consumption frequency (r = 0. 59, 0. 28, and −0.45, respectively, p= 0.02 to 0.0001). Discussion: The frequency of consuming restaurant food was positively associated with increased body fatness in adults. The increasing proportion of household food income spent on food prepared away from home in the United States may therefore help explain the rising national prevalence of obesity.

Research indicates that lower extremity muscle weakness in the elderly is consistently related to impaired mobility and fall risk. Reversible components of the muscle weakness of aging include underuse syndromes and undernutrition, both of which are prevalent in nursing home populations. The Boston FICSIT study is a nursing home‐based intervention to improve muscle strength through progressive resistance training of the lower extremities and/or multi‐nutrient supplementation in chronically institutionalized subjects aged 70–100. Baseline measurements of falls, medical status, psychological variables, functional status, nutritional intake and status, body composition, muscle mass and morphology, muscle function, and gait and balance are taken. The nursing home residents are then randomly assigned to one of four treatment groups for 10 weeks: (1) high intensity progressive resistance training of the hip and knee extensors 3 days per week; (2) multi‐nutrient supplementation with a 360‐kcal high carbohydrate, low fat liquid supplement every day; (3) a combination of groups (1) and (2); and (4) a control group. Both non‐supplemented groups receive a liquid placebo every day, and both non‐exercising groups attend three sessions of “leisure activities” every week in order to control for the attentional aspects of the exercise and nutritional interventions. At the end of the 10‐week period, all baseline measurements are re‐assessed.

A double‐blind study was conducted to determine between‐laboratory variability in the doubly labeled water method for measurement of total energy expenditure in humans, and to compare the accuracy and precision of three widely‐used procedures for calculating rates of carbon dioxide production from the original isotope data. Eighteen laboratories from five countries participated in the study. All laboratories were provided with five water standards containing varying amounts of 2H and 18O, and in addition 11 laboratories were provided with urine and dose specimens from one (six laboratories) or two (five laboratories) healthy elderly subjects of normal height and weight undergoing a calorimetric validation of the doubly labeled water method. The data from the five water standards were analyzed to predict between‐laboratory variability in the doubly labeled water technique in all laboratories. In addition, data from the subjects were analyzed using the “slope‐intercept”, “2‐point” and “modified” methods of calculation. The results confirm that the doubly labeled water method can be an accurate technique for the measurement of energy expenditure in adult human subjects in some laboratories. However, there was substantial between‐laboratory variability in the results and some laboratories returned physiologically impossible results. There was no significant effect of calculation procedure on the accuracy of the technique in this limited comparison, although the slope‐intercept procedure appeared to be more susceptible to analytical error than the other procedures. The isotope standards analyzed by participants in this study will be made available to other investigators on request.

The role of energy expenditure in the development of obesity remains unclear. This issue is examined using data from prospective studies of energy expenditure and obesity, the effects of overfeeding and diet composition on energy expenditure, and studies of the relationship between energy expenditure for physical activity and body composition. The combined results from these investigations strongly support the view that low energy expenditure can facilitate rapid weight gain in susceptible individuals. It is speculated that, in susceptible individuals, low energy expenditure for resting energy expenditure as well as physical activity are part of a range of mechanisms available for providing surplus energy for rapid weight gain. In addition, both cross‐sectional and intervention studies indicate that there is an equilibration between the level of energy expenditure for physical activity and body fat content. While genetic and other factors clearly play an important role in this relationship, it appears that a modest reduction in body fat content can be achieved by increasing energy expenditure for physical activity in physical exercise programs.

To investigate the prevalence of obesity and malnutrition in the poor Brazilian population we conducted a survey on the socioeconomic and nutritional status of 535 families (comprising 2 411 individuals) living in shanty towns in the city of São Paulo. There was a 30% prevalence of malnutrition in the children, with chronic malnutrition as the most predominant problem. The prevalence of obesity was 6.4% in boys and 8.7% in girls. Overweight and obesity associated with stunting was found in 5.8% of boys and 6.8% girls. Adolescents showed a higher prevalence of malnutrition when weight‐for‐age distribution was used (boys 46.4%, girls 40.2%), but a right deviation in the distribution was observed with an increase in obesity and a decrease of malnutrition was observed (obesity was 21% in girls and 8.8% in boys; malnutrition was 15.5% in boys and 12.6% in girls) when the weight‐for‐height adjustment was made. Stunting was the most predominant type of malnutrition in both sexes. Obesity associated with stunting was more common than obesity without stunting, both in younger children and adolescents. Adults had a higher prevalence of obesity than malnutrition according to both the Metropolitan Life Insurance tables (1.7% of undernutrition, 16.7% of overweight, and 14.1% of obesity) and Body Mass Index (8.5% of undernutrition, 21.9% of overweight, and 14.6% of obesity). There was an increase in the percentage of obese children when at least one adult in the family was obese and an increased percentage of malnourished children when undernourished adults were present in the family. Obesity among the adults of the family decreased the occurrence of malnutrition among the children. In 9% of families there was a coexistence of obesity in the adults and malnutrition in the children. These results demonstrate a coexistence of malnutrition and obesity in poor urban Brazilian communities.

SUSAN B. ROBERTS, MARGERY NICHOLSON, MYRLENE STATEN, GERALD E. DALLAL, ANA L. SAWAYA, MELVIN B. HEYMAN, PAUL FUSS, ANDREW S. GREENBERG. Relationship between circulating leptin and energy expenditure in adult men and women aged 18 years to 81 years. Recent studies suggest that leptin may be an important metabolic signal for energy regulation in rodents, but the role of leptin in human energy regulation remains uncertain. Because adaptive variations in energy expenditure play an important role in human energy regulation, we investigated the relationship between leptin and energy expenditure parameters in 61 weight‐stable men and women aged 18 years to 81 years who were not obese. Measurements were made of circulating leptin in the fasting state, body fat and fat free mass, resting metabolic rate (n=61), free‐living total energy expenditure (n=52), and the thermic effect of feeding (n=33). After statistically accounting for age, body fat, and fat free mass, there was no association between leptin and any measured energy expenditure parameter. In addition, there was no effect of age on the relationship between circulating leptin and body fat mass. These results indicate that physiological variations in circulating leptin are not linked with adaptive variations in energy expenditure in humans, in contrast to indications of this phenomenon in the ob/obmouse.

Mutations within the β–amyloid precursor protein gene cosegregate with the early–onset form of familial Alzheimer's Disease (FAD). It is not known how these mutations result in disease; however, one early–onset AD mutation in a Swedish kindred increases potentially amyloidogenic fragments and β–protein production in cells expressing the mutant β–APP. Using a novel recombinant reporter system we found a qualitative change in the secreted product, from cleavage within the β–protein sequence to cleavage near the N–terminal region of the β–protein, even though the total amount of secreted mutant product is similar to wild–type. The results suggest that the increased formation of potentially amyloidogenic fragments in cells expressing the Swedish FAD occurs by enzymatic cleavage in the secretory pathway. Alterations in the secretory process may predispose an individual to AD.

Physiologically acceptable methods for estimating milk intake in experimental animals are based on the measurement of rates of disappearance of3H2O from their body-water. This work discusses the problems involved in using methods of this type when steady-states (constant tracee inflow and outflow rates, and constant pool-size) do not exist. Theoretically sound techniques are developed and their use justified.

An investigation was made of long-term variation in oxygen consumption rate (VO2) in preterm infants. Four subjects (gestational age 27–34 weeks, postnatal age 17–38 days, weight at study 1.1–2.6 kg) were studied for 5 days each using open-circuit, indirect calorimetry. The mean VO2 for each subject (11.0–11.5 litres/kg/day) was within the reported range. However, the between-subject coefficient of variation during the study (2.1 %) was smaller than the mean between-measurement coefficient of variation for daily VO2 (3.8%, range 1.7–6.3%). In addition, the between-measurement coefficient of variation was increased further for measurement intervals of less than 24 h (reaching a mean of 8.3% for 1-hour periods), and a relationship between measurement duration and the precision of estimating VO2 over 3 or 5 days is described. Thus, even 24-hour measurements of VO2 in these preterm infants were less representative of the individual’s VO2 over 3 days than the group mean estimate. This finding is of relevance to future studies in this area, particularly those in which short-term measurements of energy expenditure are combined with a nutrient balance study to determine the composition of weight gain, because even small errors in the estimate of total energy expenditure can lead to unacceptably large errors in calculated energy deposition.

The effect of ambient temperature on the energy requirements of the lactating rat was investigated. Ambient temperature was maintained at 13, 20 or 25°C during lactation, and digestible energy (DE) intake, milk output and energy balance were measured between 4 and 12 d post partum. Ambient temperature did not significantly affect DE intake. Milk output was highest in the rats housed at 13°C and lowest in those kept at 25°C, although the rate of body fat mobilization was lowest in the rats kept at 20°C and highest in the rats kept at 25°C. Energy expenditure on activity and maintenance, determined from the difference between DE intake and body nutrient mobilization plus the energy used for milk production, was significantly higher in the rats housed at 25°C than in those kept at 13°C. This is an opposite trend to that which occurs in nonlactating rats. The results indicate that the gross efficiency of energy utilization during lactation is higher at 13°C than it is at 25°C in the rat.

We investigated the importance of adaptive variations in energy expenditure in the regulation of energy balance in young and elderly men of normal body weight leading unrestricted lives. Changes were measured in total and resting energy expenditure and body composition in response to overeating by approximately 4.2 MJ/d or undereating by 3.3 MJ/d for 21 d in 39 young and elderly men consuming a typical diet. In the young men, an average of 85–90% of the excess energy intake during overeating was deposited. During underfeeding, mobilization of body energy compensated for an average of 65% of the energy deficit in these subjects. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (+0.63 ± 0.20 MJ/d, P< 0.01) and decreased during underfeeding (-0.42 ± 0.12 MJ/d), but at least some of these changes were due to the obligatory expenditure associated with nutrient assimilation. There was no significant change in energy expenditure for physical activity or thermoregulation from overfeeding or underfeeding. Preliminary results indicate that aging had no effect on responses to overfeeding or underfeeding. These findings suggest that adaptive variations in energy expenditure are not the major determinant of energy regulation in young adults of normal body weight and that, instead, energy balance is maintained on a day-to-day basis through the control of nutrient intakes.

The possibility that lactation increases the efficiency of energy use was investigated by comparing energy expenditure on activity and maintenance in virgin and lactating rats fed either ad libitum or restricted amounts of food. Energy expenditure was determined, by difference, in a nutrient balance study. Lactating rats fed ad libitum expended 34.9% less energy on activity and maintenance than did control animals. Of this change, 82% was specifically associated with lactation, but the remaining 18% was associated with the negative energy balance that occurred during lactation. Lactating rats fed restricted amounts of food expended less energy on activity and maintenance than did virgin rats fed at the same level of restriction, but this change was associated with increased negative energy balance and not specifically with lactation. These results indicate that the efficiency of energy use is increased substantially during lactation in the rat, regardless of the level of energy intake, and that mechanisms associated with negative energy balance play an important role in the change.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

ObjectiveTo assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition.DesignRandomized controlled trial.Setting10 villages in Guinea-Bissau.Participants1059 children aged 15 months to 7 years; children younger than 4 were the primary population.InterventionsSupervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast).Main outcome measurementsThe primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models.ResultsAmong children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (−0.23, −0.43 to −0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (−5.82 cm2, −11.28 to −0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFicompared with the control meal and FBF in both age groups combined (1.14 mm2/s×10−8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03).ConclusionsChildhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups.Trial registrationClinicalTrials.gov NCT03017209.