bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of metabolic syndrome and associated factors in children and adolescents with obesity, in Mexico
Authors: Romero‐Velarde Enrique , Aguirre‐Salas Liuba , Alvarez‐Román Yussani , Vásquez‐Garibay Edgar , Casillas‐Toral Erika , Fonseca‐Reyes Salvador
Published: June 2021

Objective. To estimate the prevalence of metabolic syndrome (MS) in obese children and adolescents attending a Hospital Clinic and identify associated factors.

Material and methods. Cross sectional design with 120 children and adolescents with obesity (BMI> 2.0 SD). Personal and family history was collected, blood pressure was measured and determination of serum glucose, insulin, lipoprotein HDL cholesterol and triglycerides were performed. The presence of MS with the International Diabetes Federation criteria was identified. The association of MS with different variables was identified with chi square test and calculation of odds ratio.

Results. Mean age 10.6 ± 2.7 years; 60% of subjects were male.The prevalence of MS was 36.7%; it was higher in females (41.7 vs 33.3%).The presence of MS was more frequent in those with a history of large birth weight, and associated with insulin resistance (p< 0.001). Systolic and diastolic blood pressure was higher and HDL lower in subjects older than twelve years (p< 0.05); insulin serum levels and HOMA index were higher in this age group (p< 0.05).
Conclusions. The prevalence of MS is high in this group of children and adolescents with obesity. The history of large birth weight and the presence of insulin resistance should alert us to the presence of the disease.
Effects of Extra‐Virgin Olive Oil and Fish Oil on Lipid Profile and Oxidative Stress in Patients with Metabolic Syndrome
Authors: Dichi Isaias , Venturini Danielle , Urbano Mariana , Simão Andréa
Published: June 2021

The aim of this study was to verify if extra‐virgin olive oil and fish oil would have a synergistic effect on lipid and oxidative stress parameters in patients with metabolic syndrome (MetS). One hundred and two patients (81 female and 21 male) with MetS (aged 51.45 years) from the ambulatory of the University Hospital of Londrina, Paraná, Brazil participated in this intervention study. A control group (CG) maintained their usual diet; the fish oil group (FO) received 3 g/d of fish oil n‐3 fatty acids; the olive oil group (OO) received 10mL/d of extra‐virgin olive oil, and the fish and olive oil group (FOO) received 3 g/d of fish oil and 10mL/d of extra‐virgin olive oil. Assessments were performed at baseline and after 90 days. Differencesacrosstreatmentgroupsshowedastatisticallysignificantdecrease (p<0.05) in TC and LDL‐C when FOO was compared with CG and OO, respectively. Hydroperoxides showedasignificantdecrease (p<0.05) when FOO was compared with CG, whereas there was an increase in TRAP/AOPP (p<0.05) in FOO when compared to FO. The present study provides evidence that increased dietary n‐3 PUFA and extra‐virgin olive oil have beneficial synergistic effects on lipid metabolism and oxidative stress in MetS patients.
Increasing plasma antioxidant performance after lifestyle modification is impaired by the presence metabolic syndrome and its pro‐oxidant status
Authors: Moreto Fernando , Kano Hugo , Torezan Gabriel , Teixeira Okesley , Correa Camila , Burini Roberto
Published: June 2021

Metabolic syndrome (MetS) is often accompanied by pro‐oxidative processes and lifestyle modifications (LisM) as treatment can provide better antioxidant defense through exercise and diet. We aimed to elucidate influencing factors on plasma total antioxidant performance (TAP) in subjects with or without MetS. Sixty subjects were clinically enrolled in a LisM program with exercise and nutritional guidance. They were divided in two groups: with MetS (n=27) and without MetS (n=33). Both groups performed LisM protocol and clinical (with cardiorespiratory fitness, CRF), nutritional, anthropometrical and biochemical (with TAP and pro‐oxidative markers) assessments. Statistical significances were set at p<0.05. All the subjects responded to LisM reducing MetS prevalence, BMI, body fat and waist circumference (WC) and increasing healthy eating index, CRF and plasma reduced glutathione, HDL‐C and TAP (49.5±8.4 to 51.6±9.0%). Those with MetS showed no changes in TAP (46.5±7.9 to 47.1±7.5%) whereas those without MetS showed increased TAP (48.4±7.4 to 53.7±8.1%) after LisM. We observed that changes (Δ) in TAP in those with MetS were inversely and significantly related to changes in systolic BP (r=‐0.49), fasting blood glucose (r=‐0.48), WC (r=‐0.45), plasma oxidized glutathione (r=‐0.43) and malondialdehyde (r=‐0.39); however, in those without MetS, changes in TAP were directly and significantly related to changes in plasma reduced glutathione (r=0.46) and HDL‐C (r=0.38). We concluded that plasma antioxidant restoration after lifestyle modification is impaired by the presence of MetS components and their oxidative imbalance. Supported by CAPES and CNPq
Proteomic Analysis of the Low Molecular Weight Peptide Fraction in Serum of Obese Zucker Rat
Authors: Hakkak Reza , Post Steven , Mackintosh Samuel , West Kirk , Tackett Alan
Published: June 2021

Obesity is a major risk factor for the development of cardiovascular disease, diabetes and certain types of cancer. Analysis of serum components represents a minimally invasive method for detecting biomarkers of obesity‐associated risk. Analysis of potential serum biomarkers is either focused on the levels of serum proteins or on the abundance of low molecular weight peptides that constitute the serum peptidome. In this study, we used quantitative tandem mass spectrometry to measure differences in the serum peptidome of obese Zucker rats. Lean and obese female Zucker rats (n=16) were assigned to AIN‐93‐G diet for 8 weeks, serum samples were collected and kept at ‐20 C until analysis. As expected, obese rats gained significantly (P<0.001) more weight than lean rats. Using Tandem Mass Tags (TMTs), we were able to identify and quantify a set of peptides that were elevated in the serum of obese Zucker rats. Peptides derived from apoE and the coordinately regulated apoA1, apoCIII,and apoA1 were all significantly higher in the obese rats suggesting an increase in lipoprotein metabolism. In addition, we found that fibrinogen‐derived peptides were higher in obese rats indicating enhanced inflammation. Together our results suggest that obesity induced metabolic and inflammatory changes are reflected in the serum peptidome. Supported by R01GM106024 to AJT and ABI to RH.
The Effect of Diet and Exercise in Women with Polycystic Ovary Syndrome
Authors: Sweatt Kat , Ovalle Fernando , Azziz Ricardo , Gower Barbara
Published: June 2021

In addition to hyperandrogenism and ovulatory dysfunction, two thirds of women with PCOS exhibit insulin resistance, hyperinsulinism, and metabolic dysfunction that produce many characteristics of PCOS. The purpose of this study was to determine the effects of exercise alone and exercise combine with a standard (STD) or reduced carbohydrate (RED) weight‐loss diet in women with polycystic ovary syndrome (PCOS). Overweight and obese (BMI 26‐40 kg/m2) women with PCOS age 21‐45 years underwent a 12 week aerobic exercise intervention. After 4 weeks of exercise, participants were randomized to either a STD (55:18:27 % energy from carbohydrate: fat: protein) or RED (41:19:40) diet for 8 weeks while continuing to exercise. Testing was done at baseline, after 4 weeks of exercise, and after 8 weeks of combined diet + exercise. Results indicate that diet + exercise resulted in weight loss (p<0.05), decreased body fat (p<0.05), and increased insulin sensitivity (32% increase, p<0.05). Reproductive measures showed improved estradiol and LH:FSH ratio. The RED diet resulted in greater weight loss, decreased testosterone (‐10.3% change) and reduced fasting glucose and insulin (‐6.4% and ‐25%) compared to the STD diet. We demonstrate that diet + exercise is beneficial because of improvements in insulin sensitivity, weight, body composition, and reproductive measures. A reduced carbohydrate diet may be more beneficial compared to a standard weight loss diet by eliciting increased weight loss and reduced insulin and serum testosterone.
Effect of Eating Speed at Breakfast on Gut Appetite Hormone Responses and Daily Energy Intake
Authors: Crisp Kelli , Phillips Melody , Adams‐Huet Beverley , Dart Lyn , Bouza Brooke , Franklin Brian , Shah Meena
Published: June 2021

The influence of eating speed on postprandial appetite gut hormone responses and daily energy intake is unclear. Twenty‐five subjects (68% male; age: 25.9±8.1 years; BMI: 25.0±3.2 kg/m2) were recruited to examine this. Subjects ate the same breakfast (a mixed meal) at a slow (30 min) and fast (10 min) speed, on two separate days, in a random order. Ghrelin, glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) concentrations were determined from blood samples collected in the fasting state and at 30, 60, 120, and 180 min after breakfast began. Appetite was evaluated in the fasting and postprandial states using visual analogue scales. Daily food intake after breakfast was assessed by food recall. Mixed model repeated measures analysis revealed no main effect for eating condition or eating condition by time interaction effect on ghrelin (p=0.66 and p=0.44, respectively), GLP‐1 (p=0.87 and p=0.32, respectively), PYY (p=0.49 and p=0.21, respectively), hunger (p=0.31 and p=0.69, respectively), or fullness (p=0.34 and p=0.12, respectively). Daily energy and macronutrient intakes after breakfast were not affected by eating speed. In conclusion, eating speed at breakfast did not affect the postprandial appetite hormone responses, hunger and fullness levels, or daily energy and macronutrient intake. This study was funded by TCU.
A Higher Number of Eating Episodes is Associated with Lower Dietary Energy Density and Better Diet Quality in American Adults
Authors: Hollis James , Zhu Yong
Published: June 2021

To investigate the association between the number of eating episodes and energy intake, energy density, diet quality, and body weight status in American adults, data from the 2011‐2012 National Health and Nutrition Examination Survey were used in this study. Eligible participants (N=4731) were classified into tertiles by the number of eating episodes (either 1‐4, 5‐6, or 蠅7 eating episodes) reported from the first 24‐hour dietary recall. Adjusting for covariates, a higher number of eating episodes was significantly associated with increased energy intake (P<0.001), however, it was not associated with body weight or waist circumference (P>0.05). A higher number of eating episodes was also significantly associated with lower dietary energy density (P<0.01) and this was independent on whether beverage or water intake was included in the calculation of energy density. Compared to participants in the lower tertile of the number of eating episodes, those from the middle and upper tertiles had a significantly higher score of the Healthy Eating Index 2010 (P<0.001), suggesting participants with 5 or more eating episodes had better diet quality. Results from this study revealed that the number of eating episodes was not associated with body weight status in American adults although people with a higher number of eating episodes had a healthier diet.
High Oleic Sunflower Oil Alters the Proportions of n‐6 and n‐3 Polyunsaturated Fatty Acids in Young and Aging C57BL/6 Heart Tissue
Authors: Zhang Ji Yao , Kim Ellen , Lawrence Peter , Kothapalli Kumar , Brenna J Thomas
Published: June 2021

Introduction

Oils high in linoleic acid (LA) widely available in the U.S. food supply suppress accumulation of n‐3 polyunsaturated fatty acids (PUFA). The increasing availability of high oleic oils will shift tissue PUFA away from n‐6. Little is known about the shift in highly unsaturated fatty acids in heart. Here we report the fatty acid composition in heart of neonate, juvenile and aged mice fed with high oleic (HO) fat to establish the effects on heart PUFA.

Methods

A mouse diet with HO sunflower was fed to one group of mice, and the mouse facility house diet rich in LA was fed to controls. Female mice were fed ad libitum for one month before breeding through pregnancy and pups were weaned to the diets of the dams. Heart was harvested on postnatal day 1, 7, 13, 21 and 1 year. Heart fatty acids were extracted using one‐step method and quantified by gas chromatography.

Results

No differences in food intake or body weight were observed. Arachidonic acid did not change between groups. Other n‐6 PUFA were significantly lower in HO than control group at all ages. Eicosapentaenoic acid, docosahexaenoic acid and total n‐3 PUFA were several fold higher in HO than controls.

Conclution

Substitution of linoleic acid with oleic acid could reduce the n‐6 PUFA but increase n‐3 PUFA in mouse heart during development and aging.

Funding Source

NIH R01 AT007003
Plasma Elaidic Acid Level as Biomarker of Industrial trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study
Authors: Chajes Veronique , Biessy Carine , Ferrari Pietro , Romieu Isabelle , Slimani Nadia
Published: June 2021

Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarkers of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow‐up, age, energy, alcohol, smoking status, physical activity, and region.

In women only, a trend was observed between doubling elaidic acid level and an increased risk of weight gain (odds ratio (OR)=1.23, 95% confidence interval (CI)=0.97‐1.56, p=0.082), and with a decreased risk of weight loss (OR=0.69, 95% CI=0.55‐0.88, p=0.002) (p‐trend<.0001). No association was found for saturated and cis‐monounsaturated fatty acids.

These data suggest that a high intake of industrial trans fatty acids may increase the risk of weight gain and decrease the risk of weight loss in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially‐produced trans fatty acids.
A dual functioning extensively hydrolyzed casein modulates cytokine secretion by immune cells and insulin responses from beta cells in vitro
Authors: Brennan L , Ben Larbi N , Aarbiou J , Gross G , Lambers T. , van Tol E. , Collins L , Fischer F , Loscher C
Published: June 2021

Objectives

Type 1 Diabetes is characterized by progressive autoimmune destruction of pancreatic β‐cells. The aim of this study was to assess whether extensively hydrolyzed casein might interfere with the release of pro‐inflammatory cytokines by immune cells and whether it might preserve β‐cell function in vitro.

Methods

Murine and human immune cells were pre‐incubated with specific hydrolyzed casein and fractions thereof for 1‐hour followed by activation of the cells with LPS or CD40. Cytokine secretion was measured after 24 hours. Furthermore, effects of the hydrolysate on insulin secretion by β‐cells were assessed.

Results

Pro‐inflammatory cytokine secretion from murine macrophages was decreased by the hydrolysate and fractions thereof. Similarly, dose‐dependent inhibition of pro‐inflammatory cytokine responses was confirmed using human primary dendritic cells and macrophages. Finally, specific hydrolysate fractions that exerted anti‐inflammatory effects also significantly promoted insulin secretion from β‐cells following exposure to IL‐1β, IFN‐γ or IL‐23. Not all hydrolysate fractions showed these activities, highlighting the potential specificity of certain hydrolysate preparations.

Conclusion

Extensively hydrolyzed casein and some specific fractions display dual functionality; they can exert anti‐inflammatory effects on cells of the immune system and rescue insulin secretion impaired by inflammatory activity. These mechanisms may contribute to a potential preventive effect in the development of inflammatory diseases.
Body weight status are associated with biomarkers of inflammation and bone turnover in former smokers
Authors: Lee Sang Gil , Vance Terrence , Hurbert Patrice , Xie Liyang , Kim Bohkyung , Lee Jiyoung , Boling Bradley , Lee Sun‐Kyeong , Chun Ock K.
Published: June 2021

Smoking, aging and obesity are associated with oxidative stress, inflammation, and chronic diseases. Former and current smokers have greater oxidative stress and inflammation compared with non‐smokers. However, there is limited evidence on how this is affected by demographic, lifestyle, and clinical risk factors. Thus, we investigated the relationship between age, BMI and pack‐year, and biomarkers of oxidative stress, inflammation, cardiovascular disease, and bone disorder in 49 healthy former smokers aged 25 to 60 years. In the multiple linear regression analysis, a 1 unit increase in BMI was associated with a change in fasting plasma IL‐6 of ‐6.3% ( 95% CI ‐9.12, ‐0.56), CRP of 6.1% (95% CI 0.56, 11.83), IL‐1β of ‐ 9.1% (95% CI ‐13.63, ‐4.40), adiponectin of ‐4.7% (95% CI ‐8.91, ‐0.27), bone‐specific alkaline phosphatase (BSAP) of ‐6.5% (95% CI ‐11.15, ‐1.52), and urinary N‐telopeptide of type I collagen (NTX1) of ‐6.1% (95% CI ‐10.93, ‐1.09). However, pack‐year and age did not alter these biomarkers in our study. Our findings indicate that BMI is associated with the inflammation and bone turnover of former smokers. IL‐6 and IL‐1β were negatively correlated with BMI. The association between BMI and bone turnover was less clear, with both BSAP and NTX1 inversely associated with BMI. Therefore, further research is warranted to investigate the relationship between BMI and inflammation and bone turnover in former smokers. Funding: the Nutricia Research Foundation and CT Department of Public Health Biomedical Research Program
Consumption of Acai Beverage (Euterpe oleracea Mart.) in Cardio‐metabolic Syndrome
Authors: Simbo Sunday , Kim Hyemee , Chrown Justin , Roque Andrea , Banerjee Nivedita , Talcott Steve , Kreider Richard , Mertens‐Talcott Susanne
Published: June 2021

Açaí fruit (Euterpe oleraceaMart.) is rich in anthocyanins where cardiovascular benefits have been demonstrated in previous studies. In contrast, few human clinical assessments have previously been conducted. This study examined the beneficial activities of acai beverage on body composition and cardiovascular disease markers in 37 volunteers (BMI= 33.56±1.4) diagnosed with the metabolic syndrome. Volunteers consumed 2 x 10 oz/day acai beverage (n=18) or placebo (n=19) for 12 weeks. Body composition, dietary intake, blood and urine were obtained at 0, 4, 8, and 12 weeks. Data revealed that there was no significant time (Wilks' Lamda p=0.3271) and time by body composition effects (Wilks' Lamda p=0.9999). Selected biochemical lipid and glucose metabolism parameters analyzed by ANCOVA with body composition and nutritional intake as covariates revealed changes: Insulin (‐14.4559 ± 7.6974 ulU/ml, p=0.0758) and C‐peptide (‐1650.78 ± 762.19 pg/ml, p=0.0458) were decreased, and resistin (2280.06 ± 1059.18 pg/ml, p=0.0479) was increased. Results indicate that the consumption of acai may have a potential in improving markers of glucose metabolism in metabolically challenged individuals.
Development of a “Super‐Kid” Model Based on Plasma [13c10]‐Retinol Kinetics in Well‐Nourished Mexican Infants
Authors: Lopez Teros Veronica , Green Michael , Ford Jennifer , Astiazaran‐Garcia Humberto , Tang Guangwen
Published: June 2021

To study vitamin A (VA) metabolism in infants, a tracer dose of [13C10]‐retinyl acetate was given orally to 15 subjects (15‐34 months), 2 samples were drawn/child to build a 10 time‐point kinetic curve from 7.5 h to 35 d after dosing; mean fraction of dose in plasma was calculated at each sampling time. Model‐based compartmental analysis using WinSAAM was used to develop a composite 'super‐kid’ model of plasma [13C10]‐retinol kinetics. Data fit a 5 compartment model which includes a delay element representing VA digestion and absorption plus chylomicron formation and metabolism; a compartment for uptake and metabolism of newly absorbed VA in liver; the plasma retinol pool; and two extravascular VA storage pools: a fast‐ and a slower turning‐over compartment. Irreversible loss was modeled from the slower turning‐over pool, at a rate of 2.6% per day, which is the system fractional catabolic rate (FCR). Our modeling results indicate early and rapid VA absorption, followed by significant retinol recycling among plasma and tissues and high retinol turnover, plus a low system FCR reflecting the relatively high VA stores in these well‐nourished infants who received a 60 mg retinyl acetate dose as part of a National Program in Mexico, 3 mo prior to this study. The 'super kid’ approach facilitates model development in infants for whom blood collections need to be minimized or when access to subjects is limited in the field.

IAEA 16880
Profile of Gallic Acid Metabolites in Urine After the Intake of Mango (Mangifera indica, L.) cv. Keitt in Humans.
Authors: Barnes Ryan , Krenek Kimberly , Talcott Susanne , Talcott Stephen
Published: June 2021

The polyphenolic profile of mango is mainly based on gallic acid derivatives. The biological activity of gallic acid is well established, however effects of absorption and metabolism are widely under investigated. Chemical characterization and assessment of biological activities of gallic acid metabolites will provide the basis to conduct clinical trials with a high relevance for public health. This study investigated gallic acid metabolites after consumption of 400 grams of mango cv. Keitt in 10 healthy volunteers over 12 h. For the first time, 6 urinary, gallic acid metabolites were identified indicating the absorption of gallic acid derived from gallic acid glycosides. O­‐methylgallic acid‐O‐sulfate was identified as the major metabolite 0‐6 hours post consumption at an average concentration of 0.396 mg/ 10mg urinary creatinine, followed by O­‐methylgallic acid at 0.012 mg/ 10mg urinary creatinine. Colonic metabolites (pyrogalloyl derivatives) were detected in urine after 3‐6 h. Results indicate absorption and metabolism of gallic acid derivatives in humans where colonic metabolites are absorbed via enterohepatic circulation.
Safety evaluation of Long‐term Feeding of D‐psicose‐carrier‐complex for Rats
Authors: Shirai Yoko , Kamimura Wataru
Published: June 2021

It is known that intake of D‐psicose induces the decrease of body fat accumulation, the decline in serum glucose level, and the elevation of serum insulin level. The availability of rare sugars, however, is limited due to the low digestion ratio and the different way of disposition from glucose. In this study, we attempted to elevate the blood threshold level of rare sugars by means of drug‐delivery techniques. In order to apply for functional foods, we chose several kinds of safe, easily available, inexpensive carriers, and prepared the complexes of these carriers with rare sugars. We assessed the effects of chronic feeding of the D‐psicose‐carrier‐complexes for rats to obtain the basic data on the safety of the D‐psicose‐carrier‐complexes as nutritional substrates. Rats were fed diets containing 0.4 % complex for 9 weeks. No difference was found between the control group and the complex‐fed groups in body weight gain, food efficiency, and most serum chemical levels. These results suggest that the D‐psicose‐carrier‐complexes have no dietary toxicity for rats.
Bioavailability of furocoumarins after ingestion of grapefruit or grapefruit juice
Authors: Lee Sang Gil , Kim Kijoon , Vance Terrence , Perkins Christopher , Provatas Anthony , Qureshi Abrar , Cho Eunyoung , Chun Ock K.
Published: June 2021

Furocoumarins are photoactive compounds that may cause phytophotodermatitis and are abundant in grapefruit. However, little is known about the distribution of furocoumarins in fresh grapefruit and commercial grapefruit juices. Furthermore, the fate of grapefruit furocoumarins in humans is largely unknown. Thus, seven furocoumarins: bergaptol, psoralen, 8‐methoxypsoralen (8‐MOP), bergapten, 6′,7′‐dihydroxybergamottin (6′,7′‐DHB), epoxybergamottin, and bergamottin in grapefruit (whole, flesh, and peel) and grapefruit juice were measured using UPLC‐MS/MS. We also measured the concentration of furocoumarins from the plasma of 6 healthy young‐adult subjects before and at 90 and 180 min after consumption of grapefruit (600 g, n=3) or grapefruit juice (474 ml, n=3). Six compounds in grapefruit or juice were detected but 8‐MOP was not detectable. Peel contained more furocoumarins than flesh in grapefruit. Bergamottin and 6′,7′‐DHB were predominant compounds in flesh and juice. In plasma, bergamottin and 6′,7′‐DHB were found after grapefruit and grapefruit juice ingestion and absorbed with different rates. The findings indicate that furocoumarins from grapefruit can be absorbed, metabolized and reliably measured in plasma. Since bergamottin derivatives are well‐known UVA‐induced photosensitizer, further research is warranted to examine the association between furocoumarin bioavailability and disease risk. This study was funded by the Warren Alpert Medical School of Brown University.
Tracking Isoflavones in Whole Soy Flour, Soy Muffins and Plasma after Consumption of Muffins by Healthy Adults
Authors: Padhi Emily , Hawke Aileen , Liu Ronghua , Zhu Honghui , Duncan Alison , Tsao Rong , Ramdath Dan
Published: June 2021

The cardio‐protective effect of soy may be related to isoflavones. Research is needed to determine how isoflavones change during processing and digestion from a raw food ingredient to the biological fluid in order to better understand the relationship between isoflavone form, the food matrix, and the health effects conferred. This study tracked the abundance and transformation of soy isoflavones in: de‐fatted whole soy flour; a baked soy muffin; and plasma after regular consumption of soy muffins in a human clinical trial. Isoflavones were identified and quantified in soy flour and muffins by HPLC, and in plasma by LC‐MS/MS after participants (n=162) consumed soy muffins at doses of either 12.5g or 25g soy protein daily for 6 weeks. Soy muffins were sampled from 7 different production days (n=14) and analyzed for individual isoflavone isoforms and total isoflavone. Mean (±SEM) isoflavone content was 4.14±1.29 mg/g (DW) in soy flour and 1.10±0.04 mg/g (DW) in soy muffins. Soy flour and muffins contained similar proportions of isoflavone isoforms, but soy muffins contained overall lower absolute isoflavone content. Median total plasma isoflavone concentrations at week 6 for the low dose soy and the high dose soy groups were 91.0 and 333.7 ng/mL, respectively. Baking soy flour does not result in major changes in the relative proportion of isoflavones isoforms. Regular consumption of soy results in a dose‐related increase in plasma isoflavones with an approximate 4‐fold increase with a doubling of the dose. Funded through the Government of Canada Growing Forward I Science substantiation Program (RBPI#1746).
Understanding Quercetin Kinetic Profile in Human Plasma From Multiple Clinical Studies Using Mixed Effects Modeling
Authors: Marsteller Douglas , St. Peter John , Pirner Mark
Published: June 2021

Scientific literature extensively suggests positive health benefits associated with the dietary ingestion of plant‐derived polyphenolic flavonoids. One such flavonol is quercetin, a molecule that occurs naturally in many fruits and vegetables. The objectives of this research effort were to define a population kinetic model for quercetin in human plasma and determine if demographics, anthropometrics, and oral formulations influence model parameters. The data consisted of information from 9 clinical studies employing 7 different daily oral doses and 5 different formulations. A total of 121 different subjects and 1932 observations were included in the final dataset. Impact of oral formulation on total bioavailability (F) was quantified. A parsimonious 2‐compartmental model indicated an absorption rate (Ka, 2.91 hr‐1), central clearance (CL/F, 252 L/h) and volume of distribution (Vc/F, 2730 L), intercompartmental clearance (Q3/F, 56 L/h), peripheral compartment volume (Vp/F, 863 L), and a proportional residual error structure (40%). Basal concentrations were assessed as a steady state rate. Intersubject variability was identifiable for Ka (52%), CL/F (64%), and Vc/F (56%). Body weight was a covariate on CL/F. Simulations were used to inform product‐exposure equivalencies and assess future trial design. This knowledge about population variability has a high probability of facilitating reduced development time while providing a robust assessment of plasma exposure profile.
An Open‐label Study to Evaluate the Effect of 5,000 IU of Vitamin D3 Softgel on Serum 25‐hydroxyvitamin D Levels among Healthy Adults
Authors: Hirsh Steven , Huber Luke , Schmid Kira , Woolger Judith , Joyal Steven
Published: June 2021

Background

There has been little research performed to determine the most effective vehicle, from a bioavailability perspective, for vitamin D supplementation. It has been observed that further studies are needed to compare the bioavailability from the use of different vehicles (eg, powders, oils, and ethanol).

Objective

To assess the effect of a 5,000 IU vitamin D3 lipid‐based softgel formulation on serum 25‐hydroxyvitamin D levels in healthy male and female subjects already taking a daily 5,000 IU vitamin D3 encapsulated powder formulation for at least 3 months.

Methods

After discontinuing their vitamin D3 capsules, 16 qualified participants were dispensed and instructed to take a lipid‐based softgel formulation containing 5,000 IU vitamin D3 for 60 days. Assessments of 25‐hydroxyvitamin D level were conducted at baseline (prior to vitamin D3 softgel ingestion), Day 30, and Day 60.

Results

Fifteen participants completed the study with no serious adverse events reported. 25‐hydroxyvitamin D levels increased an average of 7.34 ng/mL (16%) by day 30 and 13.1 ng/mL (28.5%) by day 60 compared to baseline. The mean changes from baseline to days 30 and 60 were statistically significant.

Conclusion

The lipid‐based softgel formulation containing 5,000 IU of vitamin D3 taken daily for 60 days was associated with a statistically significant increase in 25‐hydroxyvitamin D levels among healthy adults subsequent to use of 5,000 IU vitamin D3 capsules for 3 months or more. Hence, our findings provide a rationale for further studies investigating the most effective vehicle for vitamin D3 supplementation.
Bradford Hill Criteria and the Case for γ‐Tocopherol as an Essential Dietary Nutrient in the Prevention of Nitrogen Oxide‐mediated Cellular Damage and Associated Chronic Diseases of Aging.
Authors: Cooney Robert , Schuller Kristyn
Published: June 2021

The nutrition field is awash with recommendations for the benefits of “antioxidants” for the prevention of chronic diseases of aging, e.g. cancer, yet evidence of efficacy in humans for individual antioxidants is limited to cell culture, animal studies, or to epidemiologic associations. Indeed, large clinical trials with relatively high doses of the most promising antioxidant agents, β‐carotene and α‐tocopherol, have paradoxically demonstrated pro‐carcinogenic effects in humans. γ‐Tocopherol is an ubiquitous dietary antioxidant which is typically found at micromolar levels in humans. It possesses unique antioxidant properties that specifically target nitrogen oxide species capable of damaging DNA in cells. Data from published studies of the chemistry of γ‐tocopherol, its biology, its epidemiology, its effects on animal models of disease and clinical effects of decreased levels in humans are assessed in light of the Bradford Hill criteria for causality in order to establish a prima facie case for the essentiallity of γ‐tocopherol in human nutrition. While the epidemiology of γ‐tocopherol is uniquely complex, its coherence with fundamental studies of γ‐tocopherol and the plausibility provided by our understanding of its chemical mechanism of action and unique biological effects add considerable weight to epidemiological and clinical observations of its associations with chronic diseases of aging. Taken together, the evidence supports a beneficial effect of and possible requirement for moderate intake of γ‐tocopherol in the diet, however, it is unlikely that significantly higher intake beyond levels found in the typical American diet would offer additional benefit.
Bitter Melon Improves Glycemic Control and Inflammation in Adipose Tissue of Obese and Diabetic Rats
Authors: Chang Eugene , Choi Jung Mook , Kim Lisa , Park Cheol‐Young
Published: June 2021

Momordica charantia, known as bitter melon has been used for the prevention and treatment of obesity and diabetes, but the mechanisms have not been fully determined. In the present study, we investigated the effects of bitter melon on glycemic control using a rat model representing late onset of hyperglycemia, a chronic course of disease, mild obesity and clinical onset of diabetes mellitus. Male OLETF rats were fed 45% high fat (HF) diet supplemented with either 1% bitter melon or 3% BM for 6 weeks. Without significant changes of body weight and food intake, bitter melon supplementation significantly improved glycemic control during oral glucose tolerance test. Moreover, 3% bitter melon supplementation in high fat diet significantly decreased serum concentrations of insulin and triglycerides, compared to high fat diet. mRNA expression of genes involved in inflammation such as TNFα and 11β‐Hydroxysteroid dehydrogenase1 were significantly reduced in 3% bitter melon group. In addition, bitter melon‐contained diet significantly decreased GRP78, IRE1, XBP1, and ATF4 mRNA levels related to ER stress in adipose tissue. In conclusion, bitter melon may be useful in the prevention/treatment of hyperglycemia by decreasing adipose tissue inflammation.
t,t‐Farnesol As A Mevalonate‐Derived Inducer of Murine 3T3‐F442A Preadipocyte Differentiation
Authors: Torabi Sheida , Mo Huanbiao
Published: June 2021

We previously reported that lovastatin, a competitive inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, dose‐dependently inhibited the differentiation of murine 3T3‐F442A preadipocytes with concomitant downregulation of peroxisome proliferator‐activated receptor γ (PPARγ), leptin, fatty acid binding protein 4 (αP2), adiponectin and CCAAT/enhancer binding protein α. d‐δ‐Tocotrienol, a vitamin E molecule and a downregulator of HMG CoA reductase, mimics lovastatin‐mediated mevalonate deprivation in inhibiting glucose uptake by 3T3‐F442A cells and the expression of GLUT4 and pAKT; the tocotrienol effect was reversed by rosiglitazone, a PPARγ agonist. We now show that t,t‐farnesol, a mevalonate‐derived sesquiterpene, dose‐dependently (25 ‐ 75 μmol/L) increased glucose uptake and intracellular triglyceride content of 3T3‐F442A cells. Real‐time qPCR and western‐blot showed that t,t‐farnesol increased the mRNA and protein levels of GLUT4 and PPARγ. The mRNA levels for αP2, lipoprotein lipase, and adiponectin were also upregulated, indicating the essential role of mevalonate pathway in adipocyte differentiation and upregulation of PPARγ, PI3K and adipogenic genes. GW9662 (10 µmol/L), an antagonist of PPARγ, and Ly294002 (10 µmol/L), a phosphatidyl‐inositol 3 kinase (PI3K) inhibitor, reversed the effects of t,t‐farnesol on cellular lipid content. t,t‐Farnesol at these concentrations did not affect the expression of HMG CoA reductase or cell viability. The mevalonate pathway may offer a novel target for modulating adipogenesis.
The combination of docosahexaenoic acid (DHA) and regorafenib synergistically inhibits colon cancer cell growth.
Authors: Cai Xiaokun , Zhang Guodong , Xiao Hang
Published: June 2021

Utilization of different anticancer agents in combination to produce enhanced inhibitory effects on carcinogenesis is a promising approach to improve anticancer efficacy and reduce potential side‐effects. In this study, we investigated the combination effects between DHA and regorafenib, a potent chemotherapeutic drug for advanced colorectal cancer, on human colon cancer cells. Cell viability assay and colony formation assay demonstrated that the combination of DHA and regorafenib had much stronger inhibitory effects on the cancer cells in comparison to the treatments with DHA or regorafenib alone. These enhanced effects were confirmed to be synergistic by isobologram analysis. Cell cycle and apoptosis assay showed significant G1 phase cell cycle arrest and extensive apoptosis induced by the combination treatment. Results from Western blotting indicated that the inhibitory effects of the combination treatment was associated with increased levels of cleaved caspase 3, cleaved PARP and P21. Overall, our results provide a basis for using DHA and regorafenib in combination for the inhibition of colon cancer. The enhanced anticancer effects by the combination may reduce the required dose of regorafenib for efficacy, which may lower the unwanted side‐effects of regorafenib such as hypertension.

This study was supported in part by the Armstrong Fund for Science from University of Massachusetts Amherst.
Effect of Caseolamina (Cassia nomame) associated with Phaseolamine (Phaseolus vulgaris) supplementation in glicemia and body weight in Wistar rats
Authors: Figueiredo Amanda , Vulcano Daniela , Rafacho Bruna Paola
Published: June 2021

Increased body weight is a problem with great relevance(1). The use of phaseolamine and caseolamine supplementation has recently emerged, with the function of inhibiting the absorption of carbohydrates and lipids(2). However, their effects still remain to be proven. In this study was evaluate the effect of faseolamine and caseolamine extract supplementation in weight gain of rats, as well as glycemic profile and possible effects. Wistar rats were allocated in 2 groups: 1) control group (GC, n=10, 5 females and 5 males); and 2) supplemented group (GS, n=10, 5 females and 5 males). The supplementation in the first 20 days was GS drunk extracts of caseolamine diluated in water (2,5mg/kg/dia). In the last 20 days, phaseolamine (5mg/kg/dia) was added to the GS group. GC drunk only water. Data were analyzed by t‐test. Results show that GS presented lower glycemic profile than GC throughout all the study period (p= 0,010), independently of the supplementation. In relation to weight gain, there was no difference between the GC and GS groups (p= 0,623; p= 0,970), as well as chow ingestion (p= 0,436; p= 0,607). Diarrhea was not detected during the experiment. The study demonstrated that caseolamine and phaseolamine extracts produced significant effect on glycemic profile, but not on the body weight gain of the rats. 1. Birari RB, Bhutani KK. Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug discovery today. 2007;12(19‐20):879‐89. 2. Mosca M, Boniglia C, Carratu B, Giammarioli S, Nera V, Sanzini E. Determination of alpha‐amylase inhibitor activity of phaseolamin from kidney bean (Phaseolus vulgaris) in dietary supplements by HPAEC‐PAD. Analytica chimica acta. 2008;617(1‐2):192‐5.
The Soy Tofu By‐product, Biji, Ameliorates High Fat Diet‐induced Obesity in C57BL/6J Mice
Authors: Kim Hyun Suk , Yu Ok Kyeong , Byun Moon Sun , Cha Youn Soo
Published: June 2021

Biji is a soybean by‐product left over after straining soy milk when making tofu; it has a high water content making it vulnerable to spoilage. However, Biji contains significant amount of dietary fiber and protein as well as considerable amounts of isoflavones and mineral elements, making it a suitable functional ingredient with health promoting attributes. Therefore, this study aimed to validate the anti‐obesity effect of biji in diet induced obese mice. Thirty two C57BL/6J male 4 week old mice were divided into four groups (n=8) and were fed for 12 weeks with normal diet (ND), high‐fat diet (HD), HD with 10% Biji (BL), or HD with 20% Biji (BH). After sacrifice, blood and liver samples were collected for analyses of hepatic and serum lipid profiles, along with serum insulin and leptin. The results showed that the food intake was not significantly different among the four groups, but the food efficiency ratios (FER) of BH and ND were significantly lower than HD and BL. Body weight gain and body fat mass were lower in ND and BH compared to HD. Furthermore, a significantly lower level of serum TG and TC was noted in BH and ND which were more pronounced than HD. Serum insulin levels of BH and ND were also significantly lower than HD. Similarly, the leptin level of BH, BL, and ND were significantly lower than HD. In conclusion, Biji appears to contribute beneficial effects on ameliorating anthropometric attribute as well as biomarkers related to obesity, however this study did not elucidate the changes in the expression of hepatic lipid metabolic genes, therefore further studies evaluating its effects on gene expression will be conducted.
D‐Xylose suppresses adipogenesis and lipid abnormalities in high‐fat diet‐induced obese mice
Authors: Lim Eunjin , Lim Ji Ye , Jeong Seung A , Shin Jae‐Ho , Seok Pu Reum , Jung Sangwon , Yoo Sang‐Ho , Kim Yuri
Published: June 2021

Obesity is one of the global epidemic problems and major risk factors for many metabolic diseases. D‐Xylose has been used as an alternative sweetener due to its low absorption rate in the gut. The present study investigated the effect of D‐xylose on adipogenesis and lipid abnormalities in high‐fat diet (HFD)‐induced obese mice. Male C57BL/6 mice were fed a HFD for 4 months with or without 5% D‐xylose (Xylo 5) or 10% D‐xylose (Xylo 10) mixed with sucrose. Although there were no significant difference in body and liver weight among the groups, fasting blood glucose level, subcutaneous and visceral adipose tissue weight, and serum blood markers, including total cholesterol and LDL cholesterol levels were significantly decreased in both of D‐xylose supplemented groups. Furthermore, D‐xylose supplementation down‐regulated expression of adipogenesis‐related genes, such as C/EBPα, FAS, and SREBP‐1C in visceral adipose tissues. Histopathologically, Supplementation withXylo 5 or Xylo 10 resulted in improvement of HFD‐induced fat accumulation in the liver. In conclusion, these results suggested that D‐xylose is beneficial for the alleviation of adipogenesis and dyslipidemia in obese mice.
Dairy‐derived bioactive fatty acids improve pancreatic ß‐cell function
Authors: Kraft Jana , Jetton Thomas , Satish Basanthi , Gupta Dhananjay
Published: June 2021

Recent studies suggest that diets rich in dairy products protect against type 2 diabetes. The principal constituents responsible are thought to be bioactive lipids, in particular trans‐palmitoleic acid (trans‐9 16:1; TPA), although the nature of this protection is unknown. We have recently identified another milk‐derived fatty acid (FA) that may be, in part, responsible for these effects: 15‐methyl‐hexadecanoic acid, a branched‐chain FA (iso 17:0; MHA). Using the INS‐1 ß‐cell line to examine chronic effects of hyperglycemia, we characterized these two FAs with respect to altering levels of the key ß‐cell transcription factor, Pdx1. INS‐1 cells subjected to chronic high glucose (20 mM) for 24‐72 h exhibited ~50% reduced Pdx1 levels. At 24 h, neither MHA, TPA, or MHA+TPA (each at 10 μm) affected Pdx1; however, under basal (5.5 mM) glucose conditions, both TPA and MHA+TPA increased Pdx1. By 48 h, MHA supplementation markedly increased Pdx1 levels in high glucose cultures (2.6‐fold). Accordingly, 72 h cultures with 20 mM glucose + MHA maintained modestly elevated Pdx1 levels (1.25‐fold). We have previously shown that ß‐cell PPARγ regulates pdx1 expression. Positive MHA‐specific effects on Pdx1 protein levels under hyperglycemic conditions are transcriptionally conferred as demonstrated by a 2‐fold enhancement of activity in a pdx1 reporter assay. Similarly, both MHA and TPA elicited ~2‐fold increases in pparγ activity. Collectively, these data demonstrate distinct and potentially complementary bioactivities of dairy‐derived MHA and TPA. We postulate that a key target of these bioactive FAs responsible for modulating diabetes risk is the pancreatic ß‐cell.
In Vivo Neuroprotective Effects of Cinnamon Bioactive Compounds in C. elegans and D. melanogaster
Authors: Stavinoha Rebecca , Gomada Yuki , Jamison Brandon , Vattem Dhiraj
Published: June 2021

We previously reported that polar fractions of cinnamon may have therapeutic potential in Alzheimer's disease (AD) and Parkinson's disease (PD). The objective here was to evaluate the in vivo neuroprotective effects of polar bioactive compounds (10‐25 mg/ml of Sodium Benzoate, Cinnamic Acid, Cinnamaldehyde, Cinnamyl Acetate, Ethyl Cinnamate and Procyanidin B1) on experimentally induced neurodegeneration in C. elegans and D. melanogaster. For AD, time to thermally induced Aβ1–42 aggregation mediated paralysis was evaluated in transgenic C. elegans (CL4176). For PD, MPP+ induced neurodegeneration was qualtified by loss in motility and degradation of GFP signal in wild type and transgenic C. elegans. In drosophila, neurodegeneration was induced via the UAS/GAL4 tissue‐specific expression system and neurotoxicity was induced via exposure to rotenone (0.5 M ) and scored for locomotion, and geotaxis. Results suggest that treatment with bioactive compounds caused statistically significant (p < 0.05) amelioration (12‐30%) in markers of neurodegeneration and neurotoxicity both C. elegans and D. melanogaster.

Grant Funding Source: VRDÜR Foundation
Plant‐Derived Bioactive Lipids Impact Glucose Homeostasis and Energy Metabolism in Mice
Authors: Jetton Thomas , Peshavaria Mina , Bay Pamela , Rowlandson Shae , Kraft Jana
Published: June 2021

Echium oil (EO) contains stearidonic (18:4 n3) and γ‐linolenic acid (18:3 n6); bioactive lipids with potential positive metabolic effects similar to fish oil (FO) derived bioactive components. Accordingly, we examined the metabolic impact of an obesogenic diet (HF; 60% kcal total fat) vs. a low‐fat diet (LF; 10% kcal total fat), each supplemented with 20% of total fat content of eitherEO, or FO, or no supplement (CON) for 12 weeks in B6NTac mice. While daily weight gain, energy intake, blood glucose, plasma insulin concentrations, and insulin resistance were all significantly higher in the HF vs. LF groups, there were no oil‐specific differences in these parameters among the groups. However, the EO‐enriched HF group exhibited improved glucose tolerance by week 12. EO supplementation in HF, but not FO, also led to reduced visceral fat accrual without affecting body mass. Although HF‐FO and HF‐EO groups displayed increased skeletal muscle insulin sensitivity, endoplasmic reticulum (ER) stress was reduced only in the HF‐EO group, shown by expression of BiP, a marker of ER stress. Hepatic steatosis was markedly reduced in both HF‐FO and HF‐EO groups. These distinct metabolic improvements in the HF‐EO group is likely attributable to 18:3 n6, as this fatty acid was incorporated into both adipose and muscle tissue at higher levels when compared to the FO or CON groups. Our study suggests that EO improves energy metabolism in HF‐fed mice in part due to enhanced skeletal muscle physiology and reduced visceral fat and hepatic lipid accumulation.