Controversies and Conundrums in Cardiac Cachexia: Key Questions About Wasting in Patients With HFrEF.

Cardiac cachexia is characterized by unintentional catabolic weight loss, decreased appetite, and inflammation and is common in patients with stage D (advanced) heart failure with reduced ejection fraction (HFrEF). Cardiac cachexia and related muscle-wasting syndromes are markers of, and a consequence of, the heart failure (HF) syndrome. Although many potential modalities for identifying cardiac cachexia exist, the optimal definition, diagnostic tools, and treatment options for cardiac cachexia remain unclear. Furthermore, it remains unclear whether attempts to reverse muscle wasting prior to advanced HF surgeries, such as left ventricular assist devices and heart transplantation, can improve outcomes. It is important that HF clinicians and dietitians are aware of the pathophysiology and mechanisms of muscle-wasting syndromes in patients with HF, to aid in the recognition and risk stratification of advanced HFrEF. Although the opportunities and rationale for attempting to address cardiac cachexia prior to advanced HF surgeries are uncertain, recent publications suggest that control of the neurohumoral syndrome of advanced HF may be important to permit the recovery of skeletal muscle mass.

Cardiac Cachexia in Left Ventricular Assist Device Recipients and the Implications of Weight Gain Early After Implantation.

Background Severe cardiac cachexia or malnutrition are commonly considered relative contraindications to left ventricular assist device (LVAD) implantation, but post-LVAD prognosis for patients with cachexia is uncertain. Methods and Results Intermacs (Interagency Registry for Mechanically Assisted Circulatory Support) 2006 to 2017 was queried for the preimplantation variable cachexia/malnutrition. Cox proportional hazards modeling examined the relationship between cachexia and LVAD outcomes. Of 20 332 primary LVAD recipients with available data, 516 (2.54%) were reported to have baseline cachexia and had higher risk baseline characteristics. Cachexia was associated with higher mortality during LVAD support (unadjusted hazard ratio [HR], 1.36 [95% CI, 1.18-1.56]; P<0.0001), persisting after adjustment for baseline characteristics (adjusted HR, 1.23 [95% CI, 1.0-1.42]; P=0.005). Mean weight change at 12 months was +3.9±9.4 kg. Across the cohort, weight gain ≥5% during the first 3 months of LVAD support was associated with lower mortality (unadjusted HR, 0.90 [95% CI, 0.84-0.98]; P=0.012; adjusted HR, 0.89 [95% CI, 0.82-0.97]; P=0.006). Conclusions The proportion of LVAD recipients recognized to have cachexia preimplantation was low at 2.5%. Recognized cachexia was independently associated with higher mortality during LVAD support. Early weight gain ≥5% was independently associated with lower mortality during subsequent LVAD support.

Randomized controlled trial of a novel lifestyle intervention used with or without meal replacements in work sites.

OBJECTIVE: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting. METHODS: Twelve work sites were randomized to an 18-month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6-month wait-listed control (n = 4). Participants were employees with overweight or obesity (N = 335; age = 48 [SD 10] years; BMI = 33 [6] kg/m2 ; 83% female). HWL was group-delivered in person or by videoconference. The primary outcome was 6-month weight change; secondary outcomes included weight and cardiometabolic risk factors measured at 6, 12, and 18 months in intervention groups. RESULTS: Mean 6-month weight change was -8.8% (95% CI: -11.2% to -6.4%) for enrollees in HWL and -8.0% (-10.4% to -5.5%) for HWL + MR (p < 0.001 for both groups vs. controls), with no difference between interventions (p = 0.40). Clinically meaningful weight loss (≥5%) was maintained at 18 months in both groups (p < 0.001). CONCLUSIONS: A new lifestyle intervention approach, deliverable by videoconference with or without MR, supported clinically impactful weight loss in employees.

Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation in Patients With Advanced Systolic Heart Failure.

BACKGROUND: Patients with advanced systolic heart failure are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle mass gains. We aimed to determine whether skeletal muscle mass increases early during LVAD support. METHODS: We prospectively recruited 30 adults with systolic heart failure ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry to measure fat free mass, appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass. Dual X-ray absorptiometry imaging was repeated at 3 and 6 months after LVAD implantation, with participation ending after the 6-month visit or heart transplantation, whichever occurred first. Changes in body composition were evaluated using mixed effects linear regression models. RESULTS: The cohort was 87% male, with mean age 56±12 (SD) years, and mean body mass index 26.4±5.4 kg/m2. Per sarcopenia ALM criteria, 52% of participants had muscle wasting at baseline. At baseline, mean fat free mass and ALM were 56.4±11.7 and 21.0±5.3 kg, respectively. Both measures increased significantly (P<0.001) over 6 months of LVAD support: mean fat free mass change at 3 and 6 months: 2.3 kg (95% CI, 1.0-3.5) and 4.2 kg (95% CI, 2.2-6.1); mean ALM change at 3 and 6 months: 1.5 kg (95% CI, 0.7-2.3) and 2.3 kg (95% CI, 0.9-3.6). CONCLUSIONS: Among LVAD recipients with advanced systolic heart failure and high baseline prevalence of muscle wasting, there were significant gains in skeletal muscle mass, as represented by dual X-ray absorptiometry fat free mass and ALM, over the first 6 months of LVAD support.

Randomized trial of a novel lifestyle intervention compared with the Diabetes Prevention Program for weight loss in adult dependents of military service members.

BACKGROUND: Lifestyle interventions are the first-line treatment for obesity, but participant weight loss is typically low. OBJECTIVES: We evaluated the efficacy of an alternative lifestyle intervention [Healthy Weight for Living (HWL)] compared with a modified Diabetes Prevention Program (m-DPP). HWL was based on a revised health behavior change model emphasizing hunger management and the development of healthy food preferences. m-DPP was a standard Diabetes Prevention Program implemented with counselor time matched to HWL. Participants were adult dependents of military personnel and had overweight or obesity. METHODS: Participants were randomly assigned to HWL (n = 121) or m-DPP (n = 117), delivered primarily by group videoconference with additional midweek emails. The primary outcome was 12-mo weight change. Secondary outcomes included 6-mo changes in cardiometabolic risk factors and diet. Intention-to-treat (ITT) and complete case (CC) analyses were performed using linear mixed models. RESULTS: Retention did not differ between groups (72% and 66% for HWL and m-DPP at 12 mo, respectively; P = 0.30). Mean ± SE adjusted 12-mo weight loss in the ITT cohort was 7.46 ± 0.85 kg for HWL and 7.32 ± 0.87 kg for m-DPP (P = 0.91); in the CC cohort, it was 7.83 ± 0.82 kg for HWL and 6.86 ± 0.88 kg for m-DPP (P = 0.43). Thirty-eight percent of HWL and 30% of m-DPP completers achieved ≥10% weight loss (P = 0.32). Improvements in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, general health, sleep, and mood were similar across groups; improvements in diastolic blood pressure were greater in m-DPP. Adjusted group mean reductions in energy intake were not significantly different between groups, but HWL participants were more adherent to their dietary prescription for lower glycemic index and high fiber and protein (P = 0.05 to <0.001 for ITT). CONCLUSIONS: HWL and m-DPP showed equivalent and clinically impactful mean weight loss with cardiometabolic benefits. These results identify an alternative approach for behavioral treatment of overweight and obesity.This trial was registered at clinicaltrials.gov as NCT02348853.

Whole- and Refined-Grain Consumption and Longitudinal Changes in Cardiometabolic Risk Factors in the Framingham Offspring Cohort.

BACKGROUND: Greater whole grain (WG) consumption is associated with reduced risk of cardiovascular disease (CVD); however, few prospective studies have examined WG or refined grain (RG) intake and intermediate cardiometabolic risk factors. OBJECTIVES: We examined the longitudinal association between WG and RG intake on changes in waist circumference (WC); fasting HDL cholesterol, triglyceride, and glucose concentrations; and blood pressure. METHODS: Subjects were participants in the Framingham Offspring cohort study [n = 3121; mean ± SD baseline age: 54.9 ± 0.2 y; BMI (kg/m2) 27.2 ± 0.1]. FFQ, health, and lifestyle data were collected approximately every 4 y over a median 18-y follow-up. Repeated measure mixed models were used to estimate adjusted mean changes per 4-y interval in risk factors across increasing categories of WG or RG intake. RESULTS: Greater WG intake was associated with smaller increases in WC (1.4 ± 0.2 compared with 3.0 ± 0.1 cm in the highest compared with the lowest category, respectively; P-trend < 0.001), fasting glucose concentration (0.7 ± 0.4 compared with 2.6 ± 0.2 mg/dL; P-trend < 0.001), and systolic blood pressure (SBP; 0.2 ± 0.5 compared with 1.4 ± 0.3 mm Hg; P-trend < 0.001) per 4-y interval. When stratified by sex, a stronger association with WC was observed among females than males. Higher intake of WG was associated with greater increases in HDL cholesterol and declines in triglyceride concentrations; however, these differences did not remain significant after adjustment for change in WC. Conversely, greater RG intake was associated with greater increases in WC (2.7 ± 0.2 compared with 1.8 ± 0.1 cm, P-trend < 0.001) and less decline in triglyceride concentration (-0.3 ± 1.3 compared with -7.0 ± 0.7 mg/dL, P-trend < 0.001). CONCLUSIONS: Among middle- to older-age adults, replacing RG with WG may be an effective dietary modification to attenuate abdominal adiposity, dyslipidemia, and hyperglycemia over time, thereby reducing the risk of cardiometabolic diseases.

Healthy Aging-Nutrition Matters: Start Early and Screen Often.

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.

Comparison of Indices of Carbohydrate Quality and Food Sources of Dietary Fiber on Longitudinal Changes in Waist Circumference in the Framingham Offspring Cohort.

The long-term impact of carbohydrate quality on abdominal weight gain is not fully understood. We aimed to examine the prospective relation of a carbohydrate quality index (CQI; defined by four criteria: dietary fiber, glycemic index, whole grain-to-total grain ratio, and solid-to-total carbohydrate ratio), total, cereal grain, vegetable, and fruit fiber, carbohydrate-to-total fiber ratio, and carbohydrate-to-cereal fiber ratio with changes in waist circumference (WC). Subjects were middle-aged to older, mostly white, participants in the Framingham Offspring cohort (n = 3101 subjects), with mean baseline age 54.9 ± 0.2 years (mean ± SE) and body mass index (BMI) 27.2 ± 0.1 kg/m2. Food frequency questionnaire (FFQ), health, and lifestyle data were collected approximately every four years over a median total follow-up of 18 years. Repeated measure mixed models were used to estimate adjusted mean change in WC per four-year interval across quartiles of carbohydrate variables. In the most adjusted model, a higher CQI was marginally associated with a smaller increase in WC (2.0 ± 0.1 vs. 2.4 ± 0.1 cm in highest vs. lowest quartile, p-trend = 0.04). Higher ratios of carbohydrate-to-fiber and carbohydrate-to-cereal fiber were associated with greater increases in WC per four-year interval (2.6 ± 0.1 vs. 2.0 ± 0.1 cm, p-trend < 0.001, and 2.5 ± 0.1 vs. 2.1 ± 0.1 cm in highest versus lowest categories, p-trend = 0.007, respectively); whereas higher intake of total fiber (1.8 ± 0.1 vs. 2.7 ± 0.1 cm, p-trend < 0.001), cereal fiber (2.0 ± 0.1 vs. 2.5 ± 0.1 cm, p-trend = 0.001), and fruit fiber (2.0 ± 0.1 vs. 2.7 ± 0.1 cm, p-trend < 0.001) were associated with smaller increases in WC compared to lower intakes. There was a significant interaction between total fiber and total carbohydrate (as % of total energy intake). After stratification, the association between fiber intake and change in WC was not maintained in the context of a high carbohydrate diet. Better carbohydrate quality, primarily higher fiber intake and lower carbohydrate-to-fiber ratios, may help attenuate increases in abdominal adiposity over time.

Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial.

OBJECTIVE: To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition. DESIGN: Randomized controlled trial. SETTING: 10 villages in Guinea-Bissau. PARTICIPANTS: 1059 children aged 15 months to 7 years; children younger than 4 were the primary population. INTERVENTIONS: Supervised 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 MEASUREMENTS: The 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. RESULTS: Among 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 CBFi compared 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). CONCLUSIONS: Childhood 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 REGISTRATION: ClinicalTrials.gov NCT03017209.

Lack of Differences in Inflammation and T Cell-Mediated Function between Young and Older Women with Obesity.

Both obesity and aging are associated with dysregulated immune and inflammatory responses. There is limited knowledge, however, on differences in the immune system between young and older adults with obesity. The goal of this study was to compare circulating inflammatory cytokines and T cell-mediated immune response between young and older women with obesity. Twenty-three young (23-43 years) and 21 older (60-83 years) women with obesity were recruited at the Weight and Wellness Center at Tufts Medical Center. Circulating inflammatory cytokines (CRP, IL-6, and IL-1ß) and ex vivo indicators of T cell-mediated immune function were compared between the groups. Older women with obesity had significantly fewer circulating CD3+, CD8+, CD19+, and natural killer T (NKT) cells compared to young women with obesity (p = 0.016, p < 0.0001, p = 0.0003, and p < 0.0001, respectively). However, with few exceptions, there was no significant difference in inflammation markers or stimulated lymphocyte proliferation and cytokine production by peripheral blood mononuclear cells between young and older participants. These findings are in contrast to those previously reported in young and old subjects with healthy weight and call for further investigation into the impact of obesity on premature aging of the immune system.

Plasma Response to Deuterium-Labeled Vitamin K Intake Varies by TG Response, but Not Age or Vitamin K Status, in Older and Younger Adults.

Background: Phylloquinone is the primary form of vitamin K in the diet and circulation. Large intra- and interindividual variances in circulating phylloquinone have been partially attributed to age. However, little is known about the nondietary factors that influence phylloquinone absorption and metabolism. Similarly, it is not known if phylloquinone absorption is altered by the individual's existing vitamin K status. Objective: The purpose of this secondary substudy was to compare plasma response with deuterium-labeled phylloquinone intake in older and younger adults after dietary phylloquinone depletion and repletion. Methods: Forty-two older [mean ± SD age: 67.2 ± 8.0 y; body mass index (BMI; in kg/m2): 25.4 ± 4.6; n = 12 men, 9 women] and younger (mean ± SEM age: 31.8 ± 6.6 y; BMI: 25.5 ± 3.3; n = 9 men, 12 women) adults were maintained on sequential 28-d phylloquinone depletion (∼10 µg phylloquinone/d) and 28-d phylloquinone repletion (∼500 µg phylloquinone/d) diets. On the 23rd d of each diet phase, participants consumed deuterated phylloquinone-rich collard greens (2H-phylloquinone). Plasma and urinary outcome measures over 72 h were compared by age group, sex, and dietary phase via 2-factor repeated-measures ANOVA. Results: The plasma 2H-phylloquinone area under the curve (AUC) did not differ in response to phylloquinone depletion or repletion, but was 34% higher in older than in younger adults (P = 0.02). However, plasma 2H-phylloquinone AUC was highly correlated with the serum triglyceride (TG) AUC (r2 = 0.45). After adjustment for serum TG response, the age effect on the plasma 2H-phylloquinone AUC was no longer significant. Conclusions: Plasma 2H-phylloquinone response did not differ between phylloquinone depletion and repletion in older and younger adults. The age effect observed was explained by the serum TG response and was completely attenuated after adjustment. Plasma response to phylloquinone intake, therefore, seems to be a predominantly lipid-driven effect and not dependent on existing vitamin K status. More research is required to differentiate the effect of endogenous compared with exogenous lipids on phylloquinone absorption. This trial was registered at clinicaltrials.gov as NCT00336232.

Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update.

The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug-nutrient interactions is quite limited. A comprehensive, updated review of the potential drug-nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U.S. adult population is presented. For the majority of the interactions described in this paper, more high-quality intervention trials are needed to better understand their clinical importance and potential consequences. A number of these studies have identified potential risk factors that may make certain populations more susceptible, but guidelines on how to best manage and/or prevent drug-induced nutrient inadequacies are lacking. Although widespread supplementation is not currently recommended, it is important to ensure at-risk patients reach their recommended intakes for vitamins and minerals. In conjunction with an overall healthy diet, appropriate dietary supplementation may be a practical and efficacious way to maintain or improve micronutrient status in patients at risk of deficiencies, such as those taking medications known to compromise nutritional status. The summary evidence presented in this review will help inform future research efforts and, ultimately, guide recommendations for patient care.

Fecal concentrations of bacterially derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults.

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined.Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation.Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8.Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation.Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394.

A Randomized Controlled Trial of Two Ready-to-Use Supplementary Foods Demonstrates Benefit of the Higher Dairy Supplement for Reduced Wasting in Mothers, and Differential Impact in Infants and Children Associated With Maternal Supplement Response.

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 (ß = .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.

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.

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193.

Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women.

Background: The effect of whole grains on the regulation of energy balance remains controversial.Objective: We aimed to determine the effects of substituting whole grains for refined grains, independent of body weight changes, on energy-metabolism metrics and glycemic control.Design: The study was a randomized, controlled, parallel-arm controlled-feeding trial that was conducted in 81 men and postmenopausal women [49 men and 32 women; age range: 40-65 y; body mass index (in kg/m2): <35.0]. After a 2-wk run-in period, participants were randomly assigned to consume 1 of 2 weight-maintenance diets for 6 wk. Diets differed in whole-grain and fiber contents [mean ± SDs: whole grain-rich diet: 207 ± 39 g whole grains plus 40 ± 5 g dietary fiber/d; refined grain-based diet: 0 g whole grains plus 21 ± 3 g dietary fiber/d] but were otherwise similar. Energy metabolism and body-composition metrics, appetite, markers of glycemic control, and gut microbiota were measured at 2 and 8 wk.Results: By design, body weight was maintained in both groups. Plasma alkylresorcinols, which are biomarkers of whole-grain intake, increased in the whole grain-rich diet group (WG) but not in the refined grain-based diet group (RG) (P-diet-by-time interaction < 0.0001). Beta ± SE changes (ΔWG compared with ΔRG) in the resting metabolic rate (RMR) (43 ± 25 kcal/d; P = 0.04), stool weight (76 ± 12 g/d; P < 0.0001), and stool energy content (57 ± 17 kcal/d; P = 0.003), but not in stool energy density, were higher in the WG. When combined, the favorable energetic effects in the WG translated into a 92-kcal/d (95% CI: 28, 156-kcal/d) higher net daily energy loss compared with that of the RG (P = 0.005). Prospective consumption (P = 0.07) and glycemia after an oral-glucose-tolerance test (P = 0.10) trended toward being lower in the WG than in the RG. When nonadherent participants were excluded, between-group differences in stool energy content and glucose tolerance increased, and between-group differences in the RMR and prospective consumption were not statistically significant.Conclusion: These findings suggest positive effects of whole grains on the RMR and stool energy excretion that favorably influence energy balance and may help explain epidemiologic associations between whole-grain consumption and reduced body weight and adiposity. This trial was registered at clinicaltrials.gov as NCT01902394.

Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults.

Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity.Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights.Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk.Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations.Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394.

Weight Management: Perception, Interest, and Preferences in Adult Cancer Survivors.

BACKGROUND: Obesity in cancer survivors has been recognized as a growing crisis in cancer care, but cancer survivors may not perceive weight status as important and may not be motivated to manage weight. OBJECTIVES: This study aims to evaluate survivors' perception, interest, and preferences for weight management and to identify characteristics that may affect attitudes toward weight management. METHODS: This cross-sectional survey assessed cancer survivors' attitudes toward weight management with patients attending oncology outpatient clinics at Tufts Medical Center in Boston, Massachusetts. FINDINGS: Among 209 respondents who completed the survey, 35% were overweight and 27% were obese. Most participants indicated that they would like to lose weight or were interested or very interested in participating in weight management programs. The results reinforce the need for the oncology team to provide weight management support to cancer survivors.

A Pilot Randomized Controlled Trial of a New Supplementary Food Designed to Enhance Cognitive Performance during Prevention and Treatment of Malnutrition in Childhood.

BACKGROUND: Cognitive impairment associated with childhood malnutrition and stunting is generally considered irreversible. OBJECTIVE: The aim was to test a new nutritional supplement for the prevention and treatment of moderate-acute malnutrition (MAM) focused on enhancing cognitive performance. METHODS: An 11-wk, village-randomized, controlled pilot trial was conducted in 78 children aged 1-3 or 5-7 y living in villages in Guinea-Bissau. The supplement contained 291 kcal/d for young children and 350 kcal/d for older children and included 5 nutrients and 2 flavan-3-ol-rich ingredients not present in current food-based recommendations for MAM. Local bakers prepared the supplement from a combination of locally sourced items and an imported mix of ingredients, and it was administered by community health workers 5 d/wk. The primary outcome was executive function abilities at 11 wk. Secondary outcomes included additional cognitive measures and changes in z scores for weight (weight-for-age) and height (height-for-age) and hemoglobin concentrations at 11 wk. An index of cerebral blood flow (CBF) was also measured at 11 wk to explore the use of this measurement as a biological index of cognitive impairment. RESULTS: There were no significant differences in any outcome between groups at baseline. There was a beneficial effect of random assignment to the supplement group on working memory at 11 wk in children aged 1-3 y (P < 0.05). This difference contrasted with no effect in older children and was not associated with faster growth rate. In addition, CBF correlated with task-switching performance (P < 0.05). CONCLUSIONS: These preliminary data suggest that cognitive impairment can be monitored with measurement of CBF. In addition, the findings provide preliminary data that suggest that it may be possible to improve poor cognitive performance in young children through changes in the nutritional formulation of supplementary foods used to prevent and treat MAM. Powered studies of the new supplement formulation are needed. This trial was registered at clinicaltrials.gov as NCT03017209.