Background:We observed significant gains in appendicular lean mass (ALM) over the first 6 months of left ventricular assist device (LVAD) support for patients with heart failure with reduced ejection fraction (HFrEF). We sought to determine whether improved HF neurohumoral stability, inflammation, physical activity, or nutrition, are most closely related to this muscle mass recovery. Methods:We prospectively recruited 30 adults with HFrEF ±21 days from LVAD implantation. Dual X-ray absorptiometry (DXA) measured ALM at baseline and at 3- and 6-months post-LVAD implantation (n = 22 with ALM at baseline and 3 months). Markers of neurohumoral HF stability (NT-proBNP, growth differentiation factor-15), inflammation [high sensitivity C-reactive protein (hsCRP)], habitual physical activity (24-hour average steps), and nutritional intake (24-hour average dietary protein) were also recorded. Mixed effects models separately evaluated the change in each parameter over time and relationships with the change in ALM. Results:At baseline, participants (87% male, mean age 56 ± 12 years) showed a significant negative association between ALM and log N-terminal-pro B natriuretic peptide (NT-proBNP) (r = -0.38, 95% CI -0.66, -0.001, p = 0.050) and log growth differentiation factor-15 (GDF-15) (r = -0.42, 95% CI -0.69, -0.05, p = 0.027). Over the 6-month study period, NT-proBNP and hsCRP decreased, 24-hour steps increased, whereas GDF-15 and 24-hour dietary protein were unchanged. There was an increase in ALM across study timepoints, which was significantly associated only with reductions in log NT-proBNP and hsCRP on mixed effects models. Conclusions:The recovery in ALM over the first 6 months of LVAD support was most closely associated with improved HF neurohumoral stability and inflammation, rather than activity or nutritional changes.

Background Higher malnutrition risk is associated with mortality among patients with heart failure and heart transplantation (HT). We investigated which malnutrition risk scores – geriatric nutrition risk index (GNRI), prognostic nutritional index (PNI), or controlling nutritional status (CONUT) – have the strongest mortality association for HT candidates, and whether they are prognostic at the time of HT listing or HT operation. Methods We reviewed adults listed for primary HT at a single center 1987–March 2022, with survival follow-up to November 2022. We constructed Cox proportional hazards models and restricted cubic spline curves for each risk score at both HT listing and HT operation and inputted HT operation as a time-varying covariate for models commencing at listing. Risk scores were assessed as continuous and binary variables. Weight change between listing and HT was evaluated similarly. Results The 1,024 patients [76% male; median age 55 (46–61) years; HT operation n = 656] had median follow-up of 4.6 (interquartile range 1.6–8.7) years. As a continuous variable, lower GNRI at HT listing (greater malnutrition risk) was independently associated with higher mortality. As binary variables, higher risk GNRI, PNI or CONUT scores at listing were all associated with higher mortality. Conversely, risk scores at time of HT operation were not associated with subsequent mortality. There was a non-significant trend towards higher mortality with greater weight loss between listing and HT operation. Conclusion Malnutrition risk scores showed prognostic utility only at time of HT listing. As a continuous variable, GNRI at HT listing was independently associated with subsequent mortality.

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 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.

ObjectiveLifestyle 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. MethodsTwelve 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/m(2); 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. ResultsMean 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). ConclusionsA new lifestyle intervention approach, deliverable by videoconference with or without MR, supported clinically impactful weight loss in employees.

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.

Introduction: Patients with advanced systolic heart failure (HF) 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 or fat mass gains. Hypothesis: We hypothesized that LVAD recipients would gain skeletal muscle mass during the first 6 months of LVAD support. Methods: We prospectively recruited 28 adults with systolic HF ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry (DXA) to calculate fat free mass (FFM, representing all lean mass), appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass (FM). DXA was repeated at 3 and 6 months after LVAD implantation (±14 days), with study participation ending after either the 6 month visit or heart transplantation, whichever occurred first. Paired t-testing and mixed effects models were used to evaluate changes over time each for FFM, ALM and FM. Results: The cohort was 86% (24/28) male, with mean age 56 ±12 years and mean BMI 26.6 ±5.5 kg/m 2 at baseline. The median Intermacs class was 2 and duration of HF 50 months. Per European Working Group on Sarcopenia in Older People (EWGSOP) criteria, 41% of participants had muscle wasting at baseline. There was a significant increase from baseline to 3 months and then 6 months of LVAD support for FFM (Fig 1A; baseline: 56.6 ±11.8 kg, n=27; 3 months: 57.9 ±11.3 kg, n=23; 6 months: 62.7 ±11.1 kg, n=17; p-value for change=0.025) and for ALM (Fig 1B; 22.2 ±5.6 kg; 23.2 ±5.0 kg; 25.4 ± 4.5 kg; p<0.001). There was no increase in FM over the same period (p=0.36). Amongst 22 participants with comparison DXAs, 81% had a ≥5% ALM gain by either 3 or 6 months. Conclusions: Among patients with advanced systolic HF and a high baseline prevalence of muscle wasting, there was a significant gain in skeletal muscle mass, as represented by both FFM and ALM, over the first 6 months of LVAD support.

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.

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.

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/m(2)) 272 +/- 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 -70 +/- 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.

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.

AbstractObjectiveTo 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 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).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.

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-1β) 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.

IntroductionMacro- and micronutrient insufficiencies are common in patients with ambulatory systolic heart failure (HF) and are associated with adverse clinical outcomes. Less is known about dietary quality in advanced systolic HF, particularly the adequacy of protein intake. It is also unknown if dietary quality improves during mechanical support and so we sought to determine nutrient intake changes early after left ventricular assist device (LVAD) implantation.MethodsWe recruited adults with advanced systolic HF ±21 days from LVAD implantation. Weight and appendicular lean mass (ALM) were assessed by whole-body dual X-ray absorptiometry (DXA). Food intake was assessed with 3-day facilitated food records and entered into the Food Processor Nutrition Analysis Software. Study procedures were repeated after 3 months ±14 days of LVAD support. The Institute of Medicine's Estimated Average Requirement values (EARs, age and sex-specific ranges) were tabulated beside the median (quartile 1-3) results from the baseline and 3-month food records.Comparisons were made between baseline and 3-month intakes using Wilcoxon matched-pairs signed rank tests.ResultsThe cohort (n=18) was 78% male, with median age 60 years, weight 77.5 kg, BMI 25.2 kg/m2 and serum albumin 3.4 g/dL. Baseline dietary quality was poor as compared to general population EARs (Table 1), with a high prevalence of vitamin A, B1, B6, D, E, folate, calcium, magnesium, zinc and selenium insufficiencies. Protein supplementation products were used by 78% at baseline and 39% at 3 months. Despite no changes in average daily calorie or carbohydrate intake from baseline to 3 months, and only a non-significant upward trend in protein and fat intake, there was an increase in total body weight and appendicular lean mass (Table). Micronutrient intakes did not significantly improve at 3 months, and intake of calcium and vitamin D decreased.ConclusionsBaseline micronutrient dietary quality was poor amongst patients with systolic HF undergoing LVAD implantation. Micronutrient changes at 3 months were variable, with some intakes including calcium and vitamin D decreasing, possibly secondary to reduced use of supplementation products after the LVAD implantation hospitalization. Protein intake was sufficient per estimated average requirements and non-significantly trended upwards during the first 3 months of LVAD support.

Undernutrition is prevalent among young children worldwide and is associated with impaired cognition and reduced educational attainment. We conducted a randomized controlled trial to test the effect of a novel supplementary food (regenerative nutrition for enhanced wellness-cognition; RENEW-C) compared to traditional feeding practices on cognitive function, cerebral blood flow and oxygen metabolism in rural Guinea-Bissau. Children aged 15 months to 7 years (n = 1059) were randomized to receive isocaloric quantities of RENEW-C (a highly-fortified cocoa-based bar), a USAID fortified blended food (FBF) or a Control food (rice cooked with oil, replicating a traditional breakfast). The primary outcome was executive function. Secondary outcomes included a cerebral blood flow index (CBFi) and cerebral metabolic rate of oxygen (CMRO2) measured by Frequency-Domain Near-Infrared Spectroscopy and Diffusion Correlation Spectroscopy (FDNIRS-DCS, MetaOx, ISS Inc.). Six-month changes for RENEW-C and FBF versus Controls were assessed by multivariable linear mixed models adjusted for age, sex, baseline measurement, and study cohort. Improvements in executive function (0.38; 95% CI: 0.10, 0.71; P = 0.02) were observed for RENEW-C compared to Controls in the predefined study focus (children < 4 years consuming >75% their supplement). There was no significant effect of RENEW-C in children ≥ 4 years. No benefit of the FBF was observed in either age group. In addition, changes in CBFi and CMRO2 in RENEW-C children were greater than in Controls in both ventrolateral prefrontal cortical regions (P = 0.03 and P = 0.04 for left and right, respectively) and greater than FBF in the left ventrolateral (P = 0.05) and left dorsolateral (P = 0.03) prefrontal cortices. Compared with traditional feeding practices, the RENEW-C supplement consumption was correlated with a marked improvement in executive function among children < 4 years and large increases in vascular perfusion and oxygen metabolism in a region where undernutrition is prevalent. These results indicate that new approaches to formulating supplementary foods for children at risk of undernutrition can potentially yield substantial improvements in brain health and cognition. Boston Foundation.

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.

To evaluate the effectiveness of a novel low-burden behavioral intervention (BI) for weight loss on changes in body weight and cardiometabolic risk factors when implemented with or without meal replacements (MR). Twelve worksites (≥300 employees each) in the Greater Boston area participated in a cluster-randomized controlled trial, with 8 worksites (n = 259 participants) allocated to the intervention group (IG) and 4 worksites (n = 76) to a wait-listed control group (CG). IG participants were further randomized to receive the BI, which emphasizes hunger and craving management via diet composition, for 18 months without or with MR (BI + MR). Weight and cardiometabolic variables were measured at baseline and 6 months for all groups, and also at 12 and 18 months in the IGs. Linear mixed models compared 6-month changes in % weight loss, body mass index (BMI), body fat, and cardiometabolic risk factors for all groups. Similar analyses were conducted for the BI and BI + MR groups at 12 and 18 months. Estimated means and standard deviations were calculated. Statistical models were adjusted for age, sex, baseline measurement, and worksite. The study population was 83% female. The Mean ± SD for age and BMI were 47.9 ± 10.4 years and 32.9 ± 5.5 kg/m2, respectively. At 6 months, average weight loss was 9.2 ± 7.2% for BI and 8.3 ± 7.0% for BI + MR. Weight loss was significantly greater in both IGs than the CG (both P < 0.001), but not significant between IGs (P = 0.35). Similar results were observed for BMI and % body fat (both P < 0.01). BI and BI + MR had significant reductions in glucose and triglycerides (P < 0.05) compared to the CG. Changes in total cholesterol and LDL were significantly greater in BI + MR compared to BI alone (P < 0.05). Clinically significant reductions in weight and cardiometabolic risk factors were sustained in the IGs at 12 and 18 months. To our knowledge, weight loss in this study was greater than previous scalable worksite-based interventions. Weight loss did not significantly differ between the BI and BI + MR groups, and MR use was associated with additional reductions in total and LDL cholesterol. These results demonstrate the feasibility of novel approaches to achieve clinically impactful weight management in worksite settings. Nutrient Foods LLC.

BackgroundLeft ventricular assist device (LVAD) candidates commonly experience unintentional weight loss (cardiac cachexia) pre-implantation. Cardiac cachexia is associated with mortality, but patients may regain lost weight once supported by an LVAD. We sought to characterize early post-LVAD weight changes, define the impact of early weight gain on survival, and identify pre-LVAD biomarkers of subsequent weight gain failure.MethodsWe reviewed single-center durable LVAD recipients 2010-2015, recording percent weight change (WC) from implantation to 3 and 6 months of LVAD support (±14 days). We constructed a Cox model, starting at 3 months, for the relationship between WC and mortality on LVAD support (censored on transplant). We used linear regression to identify pre-LVAD laboratory variables associated with positive WC at 3 months post-LVAD.ResultsOf 211 LVAD recipients, 166 survived on LVAD support >3 months and were eligible for analysis (21% female, mean age 55 y, BMI 27.9 kg/m2). Pre-LVAD BMI was not associated with subsequent mortality. The mean WC at 3 and 6 months was -2.97% (±std dev 8.66%) and +1.69% (±10.72%), respectively (Figure 1a), with 23% and 47% of patients achieving ≥+3% WC at 3 and 6 months. Patients with pre-LVAD BMI <25kg/m2 were more likely to gain ≥+3% weight than those with pre-LVAD BMI ≥25 kg/m2 at 3 months (44% vs 11%, p<0.001) and at 6 months (69% vs 33%, p<0.001). 21% of patients with <+3% WC at 6 months died on LVAD support, vs 11% of patients with ≥+3% WC at 6 months. Positive WC at 3 months was associated with lower mortality during subsequent LVAD support: hazard ratio, HR, 0.91 per 1% WC, 95% CI 0.87-0.95, p<0.001, n=166, adjusted for age and sex (Figure 1b). Positive WC at 6 months showed a similar association: adjusted HR 0.92, 95% CI 0.88-0.96, p<0.001, n=133). Achieving ≥+3% WC at 6 months was also associated with lower subsequent mortality (adjusted HR 0.32, 95% CI 0.13-0.80, p=0.015). Lower pre-LVAD neutrophil-lymphocyte ratio (NLR, inflammatory marker) and higher albumin were each associated with more positive WC by either 3 or 6 months post-LVAD.ConclusionMean weight declines early post-LVAD, followed by subsequent weight recovery at 6 months of LVAD support. A positive WC at 3 or 6 months is associated with greater future survival. Low albumin and high NLR at LVAD implantation may identify recipients at risk of weight gain failure, who could be targeted for an early nutritional intervention. Left ventricular assist device (LVAD) candidates commonly experience unintentional weight loss (cardiac cachexia) pre-implantation. Cardiac cachexia is associated with mortality, but patients may regain lost weight once supported by an LVAD. We sought to characterize early post-LVAD weight changes, define the impact of early weight gain on survival, and identify pre-LVAD biomarkers of subsequent weight gain failure. We reviewed single-center durable LVAD recipients 2010-2015, recording percent weight change (WC) from implantation to 3 and 6 months of LVAD support (±14 days). We constructed a Cox model, starting at 3 months, for the relationship between WC and mortality on LVAD support (censored on transplant). We used linear regression to identify pre-LVAD laboratory variables associated with positive WC at 3 months post-LVAD. Of 211 LVAD recipients, 166 survived on LVAD support >3 months and were eligible for analysis (21% female, mean age 55 y, BMI 27.9 kg/m2). Pre-LVAD BMI was not associated with subsequent mortality. The mean WC at 3 and 6 months was -2.97% (±std dev 8.66%) and +1.69% (±10.72%), respectively (Figure 1a), with 23% and 47% of patients achieving ≥+3% WC at 3 and 6 months. Patients with pre-LVAD BMI <25kg/m2 were more likely to gain ≥+3% weight than those with pre-LVAD BMI ≥25 kg/m2 at 3 months (44% vs 11%, p<0.001) and at 6 months (69% vs 33%, p<0.001). 21% of patients with <+3% WC at 6 months died on LVAD support, vs 11% of patients with ≥+3% WC at 6 months. Positive WC at 3 months was associated with lower mortality during subsequent LVAD support: hazard ratio, HR, 0.91 per 1% WC, 95% CI 0.87-0.95, p<0.001, n=166, adjusted for age and sex (Figure 1b). Positive WC at 6 months showed a similar association: adjusted HR 0.92, 95% CI 0.88-0.96, p<0.001, n=133). Achieving ≥+3% WC at 6 months was also associated with lower subsequent mortality (adjusted HR 0.32, 95% CI 0.13-0.80, p=0.015). Lower pre-LVAD neutrophil-lymphocyte ratio (NLR, inflammatory marker) and higher albumin were each associated with more positive WC by either 3 or 6 months post-LVAD. Mean weight declines early post-LVAD, followed by subsequent weight recovery at 6 months of LVAD support. A positive WC at 3 or 6 months is associated with greater future survival. Low albumin and high NLR at LVAD implantation may identify recipients at risk of weight gain failure, who could be targeted for an early nutritional intervention.

Sarcopenia is the age-related loss in fat-free mass (FFM) and deterioration in skeletal muscle function. FFM measurement is challenging in heart failure (HF) patients where a left ventricular assist device (LVAD) may affect dual energy X-ray absorptiometry (DXA) FFM values. In addition, increased extracellular water (ECW) volume can inflate FFM measurements by either the DXA or deuterium (DEU) dilution methods. We aimed to determine agreement between FFM measured by DXA vs DEU methods in advanced HF. We also assessed whether FFM changes at 3 months post-LVAD implantation.