Effect of daily avocado consumption for 6 mo compared with habitual diet on red blood cell fatty acid profiles and association with cardiometabolic risk factors in individuals with abdominal obesity: a randomized trial.

BACKGROUND: Avocado intake improves dietary fat quality, but the subsequent impact on red blood cell (RBC) saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and trans-fatty acid (TFA) composition and association with cardiometabolic health, has not been elucidated. OBJECTIVES: To compare the effect of consuming 1 avocado/d relative to habitual diet (HAB) on RBC-FA profiles, and their association with visceral adiposity and cardiometabolic risk factors (CMRFs) in individuals with abdominal obesity. METHODS: RBC-FA profiling at baseline, 3- and 6 mo was conducted in participants (n = 994) from the Habitual Diet and Avocado Trial (HAT). HAT was a multisite, free-living, parallel-arm intervention study in which participants were randomly assigned to either the avocado-supplemented group (AVO, usual diet with 1 avocado/d) or the HAB group (usual diet with limited avocado intake) for 6 mo. Changes in RBC-FA profiles, a secondary outcome measure, were determined within and between groups using linear regression and mixed effect models, adjusting for age, sex, BMI, clinical site, smoking status, and percentage of energy intake from fat at baseline. The association between changes in RBC-FAs with visceral adiposity measures and CMRFs was assessed after covariate and False Discovery Rate (FDR <0.05) adjustment. RESULTS: No major differences in RBC-FA profiles were observed between groups, with the exception of MUFA cis-vaccenic [18:1n-7c], which was significantly higher in AVO (ß: 0.11 [0.05, 0.17]) compared with the HAB (ß: 0.03 [-0.03, 0.08]) participants. In the HAB but not AVO group, increases in MUFA cis (18:1n-7c, oleic [18;1n-9c], erucic [22:1n-9c]) and MUFA trans (palmitelaidic [16:1n-7t], vaccenic [18:1n-7t], elaidic [18:1n-9t], and petroselaidic [18;1n-10-12t), as well as PUFA γ-linolenic [18:3n-6], dihomo-γ-linolenic [20:3n-6], arachidonic [20:4n-6], and α-linolenic [18:3n-3] were associated with unfavorable changes in visceral adiposity measures, lipid profiles, glucose, insulin and high sensitivity C-reactive protein concentrations. CONCLUSIONS: Daily avocado intake over 6-mo modified RBC-MUFA composition, notably 18:1n-7c, and potentially mitigated some of the unfavorable individual RBC-FA-CMRF associations observed over time in the HAB group. This trial was registered at https://clinicaltrials.gov/study as NCT03528031.

Effect of Intermittent vs. Continuous Energy Restriction on Visceral Fat: Protocol for The Healthy Diet and Lifestyle Study 2 (HDLS2).

Obesity in the United States and Western countries represents a major health challenge associated with an increased risk of metabolic diseases, including cardiovascular disease, hypertension, diabetes, and certain cancers. Our past work revealed a more pronounced obesity-cancer link in certain ethnic groups, motivating us to develop a tailored dietary intervention called the Healthy Diet and Lifestyle 2 (HDLS2). The study protocol is described herein for this randomized six-month trial examining the effects of intermittent energy restriction (5:2 Diet) plus the Mediterranean dietary pattern (IER + MED) on visceral adipose tissue (VAT), liver fat, and metabolic biomarkers, compared to a standard MED with daily energy restriction (DER + MED), in a diverse participant group. Using MRI and DXA scans for body composition analysis, as well as metabolic profiling, this research aims to contribute to nutritional guidelines and strategies for visceral obesity reduction. The potential benefits of IER + MED, particularly regarding VAT reduction and metabolic health improvement, could be pivotal in mitigating the obesity epidemic and its metabolic sequelae. The ongoing study will provide essential insights into the efficacy of these energy restriction approaches across varied racial/ethnic backgrounds, addressing an urgent need in nutrition and metabolic health research. Registered Trial, National Institutes of Health, ClinicalTrials.gov (NCT05132686).

Altered proteome profiles related to visceral adiposity may mediate the favorable effect of green Mediterranean diet: the DIRECT-PLUS trial.

OBJECTIVE: The objective of this study was to explore the effects of a green Mediterranean (green-MED) diet, which is high in dietary polyphenols and green plant-based protein and low in red/processed meat, on cardiovascular disease and inflammation-related circulating proteins and their associations with cardiometabolic risk parameters. METHODS: In the 18-month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green-MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green-MED diet group also consumed green tea (3-4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat. Proteome panels were measured at three time points using Olink CVDII. RESULTS: At baseline, a dominant protein cluster was significantly related to higher phenotypic cardiometabolic risk parameters, with the strongest associations attributed to magnetic resonance imaging-assessed visceral adiposity (false discovery rate of 5%). Overall, after 6 months of intervention, both the MED and green-MED diets induced improvements in cardiovascular disease and proinflammatory risk proteins (p < 0.05, vs. healthy dietary guidelines), with the green-MED diet leading to more pronounced beneficial changes, largely driven by dominant proinflammatory proteins (IL-1 receptor antagonist protein, IL-16, IL-18, thrombospondin-2, leptin, prostasin, galectin-9, and fibroblast growth factor 21; adjusted for age, sex, and weight loss; p < 0.05). After 18 months, proteomics cluster changes presented the strongest correlations with visceral adiposity reduction. CONCLUSIONS: Proteomics clusters may enhance our understanding of the favorable effect of a green-MED diet that is enriched with polyphenols and low in red/processed meat on visceral adiposity and cardiometabolic risk.

Lifestyle Intervention in Reducing Cardiometabolic Risk Factors in Students with Dyslipidemia and Abdominal Obesity: A Randomized Study

Abstract Background The long incubation periods of cardiovascular diseases offer opportunities for controlling risk factors. In addition, preventive interventions in childhood are more likely to succeed because lifestyle habits become ingrained as they are repeated. Objective To investigate the effects of recreational physical activities, in combination or not with a qualitative nutritional counseling, in cardiometabolic risk factors of students with dyslipidemia and abdominal obesity. Methods Students (8-14 years old) were randomly divided into three groups (n=23 each): i ) Control; ii ) PANC, students undergoing Physical Activity and Nutritional Counseling, and iii ) PA, students submitted to Physical Activity, only. Blood samples (12-h fasting) were collected for biochemical analysis and anthropometric markers were also assessed. Two-Way RM-ANOVA and Holm-Sidak's test, and Friedman ANOVA on Ranks and Dunn's test were applied. P ≤ 0.05 was considered significant. Effect sizes were evaluated by Hedges' g and Cliff's δ for normal and non-Gaussian data, respectively. Results Compared to the control group and to baseline values, both interventions caused significant average reductions in total cholesterol (11%; p <0.001), LDL-c (19%; p=0.002), and non-HDL-c (19%; p=0.003). Furthermore, students in the PANC group also experienced a significant decrease in body fat compared to baseline (p=0.005) and to control (5.2%; g=0.541). Conclusions The proposed strategies were effective to reduce cardiometabolic risk factors in children and adolescents. The low cost of these interventions allows the implementation of health care programs in schools to improve the students' quality of life.

The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial.

Purpose: Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes. Methods: In a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5-10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen. Results: WP reduced PPG area under the curve [AUC0-60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects. Conclusion: Pre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual's insulin resistance, their obese state, or other obesity-related ailments needs further investigation. Clinical Trial Registration: ISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.

Diagnosis and management of secondary causes of steatohepatitis.

The term non-alcoholic fatty liver disease (NAFLD) was originally coined to describe hepatic fat deposition as part of the metabolic syndrome. However, a variety of rare hereditary liver and metabolic diseases, intestinal diseases, endocrine disorders and drugs may underlie, mimic, or aggravate NAFLD. In contrast to primary NAFLD, therapeutic interventions are available for many secondary causes of NAFLD. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of patients with fatty liver disease, and treatment of the underlying disease should be started to halt disease progression. Common genetic variants in several genes involved in lipid handling and metabolism modulate the risk of progression from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma development in NAFLD, alcohol-related liver disease and viral hepatitis. Hence, we speculate that genotyping of common risk variants for liver disease progression may be equally useful to gauge the likelihood of developing advanced liver disease in patients with secondary fatty liver disease.

Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention.

Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (-43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.

Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. METHODS: Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. RESULTS: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 µmol/L, P = 0.001). CONCLUSIONS: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production.

Is Abdominal Fat Distribution Associated with Chronotype in Adults Independently of Lifestyle Factors?

Both abdominal obesity and its visceral component are independently associated with cardiometabolic diseases. Among the non-modifiable and modifiable determinants, lifestyle plays a central role, while chronotype is an emerging factor. Evening type (E-Type), more active and efficient in the last part of the day, has been associated with a health-impairing style, resulting in a higher risk of obesity and cardiometabolic diseases than morning type (M-Type). However, no study has examined the contribution of chronotype to abdominal fat distribution, even considering adherence to the Mediterranean diet (MD). We conducted a cross-sectional study on 416 adults (69.5% females, 50 ± 13 years). Waist circumference (WC), visceral fat (VAT) using ultrasonography, chronotype through the reduced Morningness-Eveningness Questionnaire (rMEQ), and adherence to MD were studied. Our results showed no differences in WC and VAT between chronotypes. However, adherence to MD resulted significantly lower in the E-Types compared to M-Types. WC decreased with increasing Mediterranean score and rMEQ score, and VAT decreased with increasing rMEQ score, indicating that E-Types have +2 cm of WC and +0.5 cm of VAT compared to M-Types. In conclusion, these results showed that chronotype is independently associated with abdominal obesity and visceral fat, underlining the potential implications of the individual circadian typology on abdominal obesity.

Effects of diet-induced weight loss on postprandial vascular function after consumption of a mixed meal: Results of a randomized controlled trial with abdominally obese men.

BACKGROUND: Effects of weight loss on postprandial vascular function have not been studied so far. We therefore examined (i) effects of diet-induced weight loss on postprandial changes in various vascular function markers after consumption of a mixed meal and (ii) differences between normal-weight and abdominally obese men of comparable age at baseline and after weight loss. METHODS: Fifty-four apparently healthy abdominally obese (waist circumference: 102-110 cm) and 25 normal-weight men (waist circumference: <94 cm) participated. The abdominally obese men were randomly allocated to a diet-induced weight-loss program or a no-weight loss control group. Men assigned to the weight-loss program followed a calorie-restricted diet for six weeks targeting a waist circumference of less than 102 cm, followed by a weight-maintenance period for two weeks. The control group maintained their habitual diet and physical activity levels. Measurements were performed before and two hours after consumption of the test meal consisting of two muffins (containing 56.6 g fat) and 300 mL low-fat milk. RESULTS: The mean weight loss was 10.3 kg in the weight-loss compared with the control group. The postprandial change in flow-mediated vasodilation of the brachial artery (FMD) was significantly higher at baseline in normal-weight as compared with the postprandial change in abdominally obese men (1.89 ± 2.52 versus 0.48 ± 2.50 percentage points; P = 0.027). However, no differences in postprandial changes were observed in the abdominally obese men after weight loss compared with the control treatment. Also, weight reduction did not affect postprandial changes in carotid-to-femoral pulse wave velocity, retinal microvascular caliber properties, or plasma markers of microvascular endothelial function. Even though postprandial increases in triacylglycerol (P = 0.028), insulin (P = 0.029) and C-peptide concentrations (P < 0.001) were reduced in the abdominally obese men following weight loss, postprandial changes in FMD at the end of the weight-loss treatment were still more unfavorable as compared with those observed in normal-weight individuals. CONCLUSION: In this trial with abdominally obese men, we did not find effects of diet-induced weight loss on postprandial changes in vascular endothelial function, arterial stiffness and markers of microvascular function. This trial was registered on ClinicalTrials.gov under study number NCT01675401.

Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study.

BACKGROUND & AIMS: Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms. METHODS: This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35-75 y), following 4-wk IER (48 h 600 kcal/d followed by 5-day healthy eating advice) or CER diets (-500 kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation. RESULTS: Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%) -2.6; 95% CI -3.3, -1.9 and -2.9; -3.6, -2.1 for CER and IER, respectively, P = 0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER-IER - 4.8% (0.7, 8.9), P < 0.05) and fasting plasma non-esterified fatty acid concentrations were lower after IER compared to CER (mean difference CER-IER 0.15 mmol/L (0.06, 0.24), P < 0.005). There were no differences in lipids, adipokine/inflammatory markers, ABP or HRV between diets. CONCLUSIONS: Short-term CER or IER diets are comparable in their effects on most markers of cardiometabolic risk, although adaptive changes in glucose and fatty acid metabolism occur. This study is registered at clinicaltrials.gov as NCT02679989.

The Effect of Habitual Fat Intake, IL6 Polymorphism, and Different Diet Strategies on Inflammation in Postmenopausal Women with Central Obesity.

The hypothesis that habitual fat intake, the IL6 genotype, the Mediterranean diet or the central European diet for 16 weeks affect biomarkers of inflammation in centrally obese postmenopausal women, was tested in a randomized controlled trial. Dietary intake was assessed using a three-day food diary. Lipid parameters were measured using a Beckman Coulter AU analyzer. Transcription of TNF and IL6 genes was analyzed in peripheral blood mononuclear cells using real-time PCR. Concentrations of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6) were measured with ELISA. rs1800795 polymorphism of IL6 was analyzed using hydrolyzing probes. Higher energy intake from fat was associated with higher IL6 levels (p < 0.05). Significantly (p < 0.01) lower total cholesterol (T-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were observed in the GG IL6 rs1800795 genotype group. Both diets significantly (p < 0.001) decreased TNFα concentrations. Neither IL6 gene transcription levels nor blood IL6 concentrations were affected by them. Our findings confirm that habitual fat intake may affect inflammation. The rs1800795 IL6 polymorphism alone did not significantly affect body weight or body composition in aimed group, but C-allele carriers had higher levels of T-C and LDL-C. This polymorphism did not affect inflammation. Both diets may lead to a decrease in TNFα concentration.

The Effect of Wolffia globosa Mankai, a Green Aquatic Plant, on Postprandial Glycemic Response: A Randomized Crossover Controlled Trial.

OBJECTIVE: To compare the postprandial and overnight glycemic response using a novel green aquatic plant thought to provide a dietary source for high-quality protein, with an iso-carbohydrate/protein/caloric dairy shake. RESEARCH DESIGN AND METHODS: This is a randomized controlled crossover trial among 20 abdominally obese participants (age 51.4 years; fasting plasma glucose 110.9 mg/dL), who were allocated to replace dinner with either, first, a green shake containing Wolffia globosa duckweed (Mankai: specific-strain) or an iso-carbohydrate/protein/calorie yogurt shake. A 2-week flash glucose-monitoring system was used to assess postmeal glucose dynamics (6 net administration days; 97 observation days in total). We further obtained from each participant dietary/daily activity/satiety scale/sleep logs. Participants were recruited from the green-Mediterranean diet arm of the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols Unprocessed (DIRECT-PLUS) study. RESULTS: Wolffia globosa Mankai elicited a lower postprandial glucose peak compared with yogurt (∆peak = 13.4 ± 9.2 vs. 19.3 ± 15.1 mg/dL; P = 0.044), which occurred later (77.5 ± 29.2 vs. 59.2 ± 28.4 min; P = 0.037) and returned faster to baseline glucose levels (135.8 ± 53.1 vs. 197.5 ± 70.2 min; P = 0.012). The mean post-net incremental area under the curve (netAUC) was lower with Wolffia globosa up to 60 and 180 min (netAUC 60 min: 185.1 ± 340.1 vs. 441.4 ± 336.5 mg/dL/min, P = 0.005; netAUC 180 min: 707.9 ± 1,428.5 vs. 1,576.6 ± 1,810.1 mg/dL/min, P = 0.037). A Wolffia globosa-based shake replacing dinner resulted in lower next-morning fasting glucose levels (83.2 ± 0.8 vs. 86.6 ± 13 mg/dL; P = 0.041). Overall, postprandial glucose levels from the shake administration until the next morning were lower in the Wolffia globosa Mankai green shake compared with the yogurt shake (P < 0.001). Overnight sleep duration was similar (378.2 ± 22.4 vs. 375.9 ± 28.4 min; P = 0.72), and satiety rank was slightly higher for the Wolffia globosa shake compared with the yogurt shake (7.5 vs. 6.5; P = 0.035). CONCLUSIONS: Wolffia globosa Mankai duckweed may serve as an emerging alternative plant protein source with potential beneficial postprandial glycemic effects.

A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats.

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.

Changes in Sedentary and Active Lifestyle, Diet Quality and Body Composition Nine Months after an Education Program in Polish Students Aged 11⁻12 Years: Report from the ABC of Healthy Eating Study.

The sustainability of education focused on improving the dietary and lifestyle behaviours of teenagers has not been extensively studied. The aim of this study was to determine the sustainability of diet-related and lifestyle-related school-based education on sedentary and active lifestyle, diet quality and body composition of Polish pre-teenagers in a medium-term follow-up study. An education-based intervention study was carried out on 464 students aged 11⁻12 years (educated/control group: 319/145). Anthropometric measurements were taken and body mass index (BMI) and waist-to-height ratios (WHtR) were calculated, both at the baseline and after nine months. Dietary data from a short-form food frequency questionnaire (SF-FFQ4PolishChildren) were collected. Two measures of lifestyle (screen time, physical activity) and two diet quality scores (pro-healthy, pHDI, and non-healthy, nHDI) were established. After nine months, in the educated group (vs. control) a significantly higher increase was found in nutrition knowledge score (mean difference of the change: 1.8 points) with a significantly higher decrease in physical activity (mean difference of the change: -0.20 points), nHDI (-2.3% points), the z-WHtR (-0.18 SD), and the z-waist circumference (-0.13 SD). Logistic regression modelling with an adjustment for confounders revealed that after nine months in the educated group (referent: control), the chance of adherence to a nutrition knowledge score of at least the median was over 2 times higher, and that of the nHDI category of at least the median was significantly lower (by 35%). In conclusion, diet-related and lifestyle-related school-based education from an almost one-year perspective can reduce central adiposity in pre-teenagers, despite a decrease in physical activity and the tendency to increase screen time. Central adiposity reduction can be attributed to the improvement of nutrition knowledge in pre-teenagers subjected to the provided education and to stopping the increase in unhealthy dietary habits.

The Combination of Whey Protein and Dietary Fiber Does Not Alter Low-Grade Inflammation or Adipose Tissue Gene Expression in Adults with Abdominal Obesity.

BACKGROUND: Abdominal obesity is characterized by low-grade inflammation and plays a central role in the development of type 2 diabetes and cardiovascular diseases. Dietary factors can influence low-grade inflammation and affect adipose tissue function. AIM: To investigate the separate and combined effects of whey protein and cereal fiber on inflammatory markers and adipose tissue gene expression in abdominal obesity. METHODS: We performed a 12-week, double-blind, randomized controlled dietary intervention in 65 adults with abdominal obesity. The participants were randomized to 4 groups using a 2 × 2 factorial design; they received either 60 g/day of whey protein or maltodextrin in combination with high-fiber wheat bran products (30 g fiber/day) or low-fiber refined wheat products (10 g fiber/day). Plasma concentrations of tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), interleukin 1 receptor antagonist (IL-1Ra), and adiponectin were measured before and after intervention. Changes in gene expression related to inflammation, insulin signaling, and lipid metabolism were measured in abdominal subcutaneous adipose tissue. RESULTS: After intervention, TNF-α was reduced for both high-fiber groups compared with baseline, but did not significantly differ from the low-fiber groups. There were no differences in fasting or postprandial inflammatory markers between the groups. The relative gene expression of ribosomal protein S6 kinase B1 (S6K1) was increased after whey protein compared with maltodextrin consumption. CONCLUSION: Intake of whey protein in combination with high cereal fiber content did not differentially affect low-grade inflammation or adipose tissue gene expression compared with maltodextrin and low fiber content in individuals with abdominal obesity.

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

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

HDL cholesterol efflux capacity and cholesteryl ester transfer are associated with body mass, but are not changed by diet-induced weight loss: A randomized trial in abdominally obese men.

BACKGROUND AND AIMS: Obesity is associated with a lower HDL-mediated cholesterol efflux from macrophages and a higher CETP (cholesteryl ester transfer protein) activity, but effects of weight loss are not clear. In addition, associations with visceral and subcutaneous adipose tissue are not known. We therefore investigated effects of diet-induced weight loss on HDL-mediated cholesterol efflux and cholesterol ester (CE) transfer in abdominally obese men. Differences between normal-weight and abdominally obese men were also examined. METHODS: Twenty-five apparently healthy, normal-weight men (waist circumference: <94 cm) and 52 abdominally obese men (waist circumference: 102-110 cm) were included. Abdominally obese subjects were randomly allocated to a dietary weight-loss intervention group or a no-weight loss control group. Individuals from the intervention group followed a very-low-calorie diet for 6 weeks to obtain a waist circumference below 102 cm, followed by a 2-week weight-stable period. Cholesterol efflux was measured in BODIPY-labeled murine J774 macrophages. CE transfer was measured by quantifying the transfer of CE from radiolabeled exogenous HDL to apoB-containing lipoproteins. RESULTS: Cholesterol efflux capacity was 9 percentage point (pp) lower in abdominally obese than in normal-weight men (p≤0.001), while CE transfer was 5 pp higher (p≤0.01). Diet-induced weight-loss of 10.3 kg did not change cholesterol efflux and CE transfer. In addition, stepwise regression analysis did not suggest that the different fat depots are differently related to efflux capacity and CE transfer. CONCLUSIONS: After a 2-week weight-stable period, dietary weight loss of 10 kg did not improve ABCA1-mediated cholesterol efflux and CE transfer in abdominally obese men.

A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.

Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans (Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-ß) were significantly greater than after the control diet (p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk.

Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity.

Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol. To this aim, obese women were evaluated at time 0 and after 4, 6, and 12 months of individualized prescribed physical activity and hypocaloric diet. Dual-energy-X-ray absorptiometry measurements were performed at each time point, as well as blood was collected at the same points. Cells were incubated with sera of subjects before and after physical activity as described: obese at baseline and after for 4, 6, and 12 months of physical activity and nutritional protocol intervention. Osteoblasts exposed to sera of patients, who displayed increased lean and decreased fat mass (from 55.5 ± 6.5 to 57.1 ± 5.6% p ≤ 0.05; from 44.5 ± 1.1 to 40.9 ± 2.6% p ≤ 0.01 respectively), showed a time-dependent increase of Wnt/ß-catenin signaling, versus cells exposed to sera of obese patients before intervention protocol, suggesting recovery of osteoblast homeostasis upon improvement of body composition. An increase in ß-catenin nuclear accumulation and nuclear translocation was also observed, accompanied by an increase in Adiponectin receptor 1 protein expression, suggesting positive effect on cell differentiation program. Furthermore, a decrease in sclerostin amount and an increase of type 1 procollagen amino-terminal-propeptide were depicted as compared to baseline, proportionally to the time of physical activity, suggesting a recovery of bone remodeling modulation and an increase of osteoblast activity induced by improvement of body composition. In conclusion, our results show for the first time that sera of obese sedentary women who increased lean mass and decreased fat mass, by physical activity and hypocaloric diet, rescue osteoblasts differentiation and activity likely due to a reactivation of Wnt/ß-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity.