Publications by authors named "Eunice Mah"

40 Publications

Effect of arabinogalactan on the gut microbiome: A randomized, double-blind, placebo-controlled, crossover trial in healthy adults.

Nutrition 2021 Apr 20;90:111273. Epub 2021 Apr 20.

Lonza Consumer Health Inc., Morristown, New Jersey, USA. Electronic address:

Objective: Promising evidence suggests beneficial health effects of arabinogalactan, but little is known about the effect of this non-digestible carbohydrate on the gut microbiota, a crucial mediator of human health. The objective of this study was to investigate the effect of an arabinogalactan product (ResistAid) on the fecal microbiome and short-chain fatty acids and gastrointestinal tolerance in healthy adults in a randomized, double-blind, crossover trial.

Methods: Thirty adults were randomly assigned to consume 15 g/d maltodextrin (control) or ResistAid for 6 wk.

Results: At week 6, compared to placebo, ResistAid supplementation led to a significant decrease in the ratio of fecal Firmicutes to Bacteroidetes, driven by an increase in Bacteroidetes and a decrease in Firmicutes. Moreover, the relative abundance of Bifidobacterium tended to increase with ResistAid supplementation. Additionally, ResistAid significantly decreased the α-diversity of the fecal microbiome. Predicted functional abundances based on 16S rRNA sequences showed that ResistAid supplementation increased the gene abundance of the gut microbiome for α-l-rhamnosidase, β-fructosidase, and levanase, as well as tricarboxylic acid and vitamin B biosynthesis pathways. Fecal isovaleric, valeric, and hexanoic acids were significantly lower after ResistAid consumption. There were no statistically significant changes in bowel habit, stool consistency, gastrointestinal tolerance symptoms, chemistry profile, metabolic panel, or vitals, suggesting that consumption of 15 g daily ResistAid over 6 wk is safe.

Conclusion: These results demonstrate that the gut microbiome composition and predicted functions can be modulated by ResistAid consumption, perhaps suggesting a mechanistic explanation on its reported benefits in metabolic parameters and the immune system.
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http://dx.doi.org/10.1016/j.nut.2021.111273DOI Listing
April 2021

Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

J Nutr 2021 May 12. Epub 2021 May 12.

Research & Innovation Center, Kyowa Hakko Bio Co., Ltd, Tsukuba, Ibaraki, 305-0841, Japan.

Background: Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations.

Objective: The objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI).

Methods: A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons.

Results: A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052).

Conclusions: Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. This trial was registered at clinicaltrials.gov as NCT03369925.
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http://dx.doi.org/10.1093/jn/nxab119DOI Listing
May 2021

The Role of Oat Nutrients in the Immune System: A Narrative Review.

Nutrients 2021 Mar 24;13(4). Epub 2021 Mar 24.

Quaker Oats Center of Excellence, PepsiCo Health & Nutrition Sciences, Barrington, IL 60010, USA.

Optimal nutrition is the foundation for the development and maintenance of a healthy immune system. An optimal supply of nutrients is required for biosynthesis of immune factors and immune cell proliferation. Nutrient deficiency/inadequacy and hidden hunger, which manifests as depleted nutrients reserves, increase the risk of infectious diseases and aggravate disease severity. Therefore, an adequate and balanced diet containing an abundant diversity of foods, nutrients, and non-nutrient chemicals is paramount for an optimal immune defense against infectious diseases, including cold/flu and non-communicable diseases. Some nutrients and foods play a larger role than others in the support of the immune system. Oats are a nutritious whole grain and contain several immunomodulating nutrients. In this narrative review, we discuss the contribution of oat nutrients, including dietary fiber (β-glucans), copper, iron, selenium, and zinc, polyphenolics (ferulic acid and avenanthramides), and proteins (glutamine) in optimizing the innate and adaptive immune system's response to infections directly by modulating the innate and adaptive immunity and indirectly by eliciting changes in the gut microbiota and related metabolites.
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http://dx.doi.org/10.3390/nu13041048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063794PMC
March 2021

Addition of Orange Pomace Attenuates the Acute Glycemic Response to Orange Juice in Healthy Adults.

J Nutr 2021 Jun;151(6):1436-1442

Center for Nutrition Research, Department of Food Sceince and Nutrition, Institute for Food Safety and Health, Illinois Institute of Technology, Chicago, IL, USA.

Background: Fiber is an important part of a healthy diet and is known to attenuate postprandial glycemia. Orange pomace (OP) is a by-product of orange juice (OJ) production and is a rich source of fiber.

Objective: Two separate studies determined the impact of added OP to 100% OJ on postprandial glycemic response compared with sugar-matched OJ or whole orange fruit (WOF).

Methods: Study 1 included 17 adults [65% female, age 39.3 ± 3.1 y, and BMI (in kg/m2) 24.6 ± 0.7], and study 2 included 45 different adults (47% female, age 25.1 ± 4.3 y, and BMI 22.5 ± 1.6). Studies were conducted at separate locations using a randomized, 3-arm, crossover design to test the glycemic response to sugar-matched OJ, OJ with 5 g fiber from OP (OPF), or WOF. The primary outcomes were 2-h glucose incremental area under the curve (iAUC) in study 1, analyzed by repeated measures ANOVA, and maximum glucose concentration (Cmax) in study 2, analyzed using PROC MIXED (ANCOVA). Glucose and insulin concentrations were measured at fasting and multiple time points over 2 h after test product consumption (study 1, serum; study 2, plasma).

Results: In study 1, glucose iAUC was not significantly lower in OPF compared to the OJ or WOF (825 ± 132 compared with 920 ± 132 and 760 ± 132 mg · min · dL-1, respectively, P = 0.57 for both). In study 2, glucose iAUC was significantly lower in WOF compared with OPF and OJ (689 ± 70.7 compared with 892 ± 70.7 and 974 ± 70.7 mg · min · dL-1, P = 0.02 and 0.001, respectively). Data from both studies indicated OPF reduced Cmax compared with OJ and that the reductions were comparable to WOF (study 1: OPF, 115 ± 4.06 compared with OJ, 124 ± 4.06 and WOF, 114 ± 4.06 mg · dL-¹, P = 0.002 and 0.75, respectively; study 2: OPF, 128 ± 1.92 compared with OJ, 136 ± 1.92 and WOF, 125 ± 1.92 mg · dL-¹, P = 0.001 and 0.28, respectively).

Conclusion: Data from both studies demonstrated no significant effect of OPF on postprandial iAUC compared with OJ. However, adding OP into OJ attenuates the postprandial glucose Cmax, and the responses were comparable to WOF in healthy adults.
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http://dx.doi.org/10.1093/jn/nxab017DOI Listing
June 2021

Vitamin A and D Absorption in Adults with Metabolic Syndrome versus Healthy Controls: A Pilot Study Utilizing Targeted and Untargeted LC-MS Lipidomics.

Mol Nutr Food Res 2021 01 7;65(2):e2000413. Epub 2020 Dec 7.

Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA.

Scope: Persons with metabolic syndrome (MetS) absorb less vitamin E than healthy controls. It is hypothesized that absorption of fat-soluble vitamins (FSV) A and D would also decrease with MetS status and that trends would be reflected in lipidomic responses between groups.

Methods And Results: Following soymilk consumption (501 IU vitamin A, 119 IU vitamin D ), the triglyceride-rich lipoprotein fractions (TRL) from MetS and healthy subjects (n = 10 age- and gender-matched subjects/group) are assessed using LC-MS/MS. Absorption is calculated using area under the time-concentration curves (AUC) from samples collected at 0, 3, and 6 h post-ingestion. MetS subjects have ≈6.4-fold higher median vitamin A AUC (retinyl palmitate) versus healthy controls (P = 0.07). Vitamin D AUC is unaffected by MetS status (P = 0.48). Untargeted LC-MS lipidomics reveals six phospholipids and one cholesterol ester with concentrations correlating (r = 0.53-0.68; P < 0.001) with vitamin A concentration.

Conclusions: The vitamin A-phospholipid association suggests increased hydrolysis by PLB, PLRP2, and/or PLA IB may be involved in the trend in higher vitamin A bioavailability in MetS subjects. Previously observed differences in circulating levels of these vitamins are likely not due to absorption. Alternate strategies should be investigated to improve FSV status in MetS.
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http://dx.doi.org/10.1002/mnfr.202000413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902427PMC
January 2021

A Randomized, Double-Blind, Crossover Study to Determine the Available Energy from Soluble Fiber.

J Am Coll Nutr 2020 Jul 30:1-7. Epub 2020 Jul 30.

Biofortis, Merieux NutriSciences, Addison, Illinois, USA.

Objective: Determining the available energy (caloric value) of dietary non-digestible fibers that are fermented to varying degrees by intestinal microbes and metabolized to short chain fatty acids is important for provision of accurate information to food and beverage manufacturers for reformulation and labeling purposes. The objective of this human study was to determine the available energy of soluble fiber products by measuring post consumption breath hydrogen, with inulin as a control.

Methods: PROMITOR Soluble Corn Fiber 70 (SCF70) and PROMITOR Soluble Corn Fiber 85B (SCF85B) are Tate & Lyle dietary fiber products with 70% and 85% fiber, respectively. The fiber portion of these products is structurally representative of the fiber portion of all PROMITOR SCF products. The study conducted was a randomized, double-blind, crossover design. Breath hydrogen was quantified following consumption of beverages consisting of 8 oz. of water and: inulin (control), SCF70, or SCF85B at 5, 10, or 15 g (total ingredient weight, "as is"). Subjects were generally healthy men and women (N = 19), age 18 to 34 years, with body mass index (BMI) 19.3 to 24.8 kg/m. The primary outcome was incremental area under the curve over 10 h (iAUC0-10 h) for inulin, SCF70, and SCF85B at each dose. The available energy (kcal/g ingredient and kcal/g fiber) from SCF70 and SCF85B at each dose was then calculated using inulin as the reference.

Results: Results demonstrated that breath hydrogen production was significantly lower following consumption of SCF70 and SCF85B compared to inulin at all consumption amounts. There were no significant differences in breath hydrogen production following consumption of SCF70 compared to SCF85B.

Conclusion: The available energy per gram of fiber was not significantly different between the SCF70 and SCF85B PROMITOR products. The available energy of the fiber portion of PROMITOR SCF products was determined to be 0.2 kcal/gram.
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http://dx.doi.org/10.1080/07315724.2020.1790440DOI Listing
July 2020

The effect of egg consumption on cardiometabolic health outcomes: an umbrella review.

Public Health Nutr 2020 04 10;23(5):935-955. Epub 2019 Oct 10.

Biofortis, Mérieux NutriSciences, Addison, IL, USA.

Objective: This umbrella review provides an overview of the consistency and gaps in the evidence base on eggs and cardiometabolic health.

Design: PubMed, Web of Science, Cochrane Library, the Nutrition Evidence Systematic Review and Agency for Healthcare Research and Quality databases were screened for evidence-based reviews in English that assessed human studies on egg consumption and cardiometabolic outcomes.

Results: Seven systematic reviews and fifteen meta-analyses were identified, with eighteen of these published since 2015. Overall, the systematic reviews were of low quality, while meta-analyses were of moderate- to high-quality. No association of increased egg intake and risks of heart disease or stroke in the general population were found in the meta-analyses. Increased risk of heart failure was noted in two meta-analyses that analysed the same three cohort studies. Five recent meta-analyses reported no increased risk of type 2 diabetes mellitus (T2DM) in the general population, although increased risk in US-based populations only has been reported. Older (<2013) meta-analyses reported increased risks of cardiovascular disease (CVD) or heart disease in T2DM populations, and no recent evidence-based reviews were identified. Finally, only one meta-analysis reported intervention studies specifically on eggs and biomarkers (i.e. lipids), and the results contradicted those from observation studies.

Conclusions: Recent evidence-based reviews conclude that increased egg consumption is not associated with CVD risk in the general population. More research is needed on the positive associations between egg consumption and heart failure and T2DM risk, as well as CVD risk in diabetics, before firm conclusions can be made.
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http://dx.doi.org/10.1017/S1368980019002441DOI Listing
April 2020

Soluble and Insoluble Yeast -Glucan Differentially Affect Upper Respiratory Tract Infection in Marathon Runners: A Double-Blind, Randomized Placebo-Controlled Trial.

J Med Food 2020 Apr 1;23(4):416-419. Epub 2019 Oct 1.

Biofortis, Mérieux NutriSciences, Addison, Illinois, USA.

In a previous study, consumption of a dairy beverage incorporating insoluble -glucan decreased upper respiratory tract infection (URTI) symptomatic days and severity in marathon runners. In this report, we extended our previous findings by presenting data on a dairy beverage containing soluble -glucan and URTI in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed dairy beverages (250 mL/day) containing 250 mg of insoluble ( = 69) or soluble ( = 76) baker's yeast -glucan (Wellmune) or placebo ( = 133) for the 45 days before, day of, and 45 days after the marathon (91 days total). Participants completed a daily online survey assessing compliance and URTI symptoms, which were evaluated using the Jackson Index and confirmed by the study physician. Total severity of URTI was significantly lower in the insoluble yeast -glucan group compared to the placebo group, but was not different between the soluble yeast -glucan group and placebo group. Severity ratings for nasal discharge were significantly lower in both the insoluble and soluble yeast -glucan groups compared to the placebo group. Additionally, severity rating for sore throat was lower in the insoluble, but not the soluble yeast -glucan group compared to the placebo group. The insoluble yeast -glucan group, but not the soluble yeast -glucan group also reported fewer URTI symptomatic days compared to the placebo group. The results suggest that soluble and insoluble yeast -glucan, incorporated into a food matrix, differentially affected exercise-induced URTI in marathon runners.
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http://dx.doi.org/10.1089/jmf.2019.0076DOI Listing
April 2020

100% Fruit Juice and Dental Health: A Systematic Review of the Literature.

Front Public Health 2019 12;7:190. Epub 2019 Jul 12.

Biofortis, Mérieux NutriSciences, Addison, IL, United States.

The objective of this systematic review was to assess the scope and breadth of publicly available prospective cohort and randomized controlled trial (RCT) literature on 100% fruit juice and dental caries or tooth erosion in humans. We performed a systematic search in MEDLINE/PubMed, EMBASE, and Web of Science for studies published from inception through May 2018, and the Cochrane Library databases for reports published through January 2018. Prospective cohort studies or RCTs conducted on dental health and 100% fruit juice, and published in English were selected. No restrictions were set for age, sex, geographic location, or socioeconomic status. Eight publications representing five independent prospective cohort studies and nine publications on nine RCTs were included. All prospective cohort studies were in children or adolescents, and all RCTs were in adults. Prospective cohort studies on tooth erosion found no association between juice intake and tooth erosion, while those on dental caries incidence reported either no association or an inverse association between 100% fruit juice intakes and dental caries incidence. RCTs on tooth erosion showed decreased microhardness, increased surface enamel loss, increased erosion depth, greater enamel softening, and/or increased pellicle layer with 100% fruit juice, and those on dental caries showed increased demineralization of enamel slabs with 100% fruit juice. The existing evidence on 100% fruit juice intake and caries and tooth erosion are not conclusive. Overall, prospective cohort studies in children and adolescents found no association between 100% fruit juice intake and tooth erosion or dental caries, but, RCT data in adults suggests that 100% fruit juice could contribute to tooth erosion and dental caries. The RCT data, however, were from small, short-term studies that utilized intra-oral devices generally devoid of normal plaque or saliva action, and generally employed conditions that are not reflective of normal juice consumption.
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http://dx.doi.org/10.3389/fpubh.2019.00190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640211PMC
July 2019

Narrative Review of Hydration and Selected Health Outcomes in the General Population.

Nutrients 2019 Jan 1;11(1). Epub 2019 Jan 1.

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W, Canada.

Although adequate hydration is essential for health, little attention has been paid to the effects of hydration among the generally healthy population. This narrative review presents the state of the science on the role of hydration in health in the general population, specifically in skin health, neurological function (i.e., cognition, mood, and headache), gastrointestinal and renal functions, and body weight and composition. There is a growing body of evidence that supports the importance of adequate hydration in maintaining proper health, especially with regard to cognition, kidney stone risk, and weight management. However, the evidence is largely associative and lacks consistency, and the number of randomized trials is limited. Additionally, there are major gaps in knowledge related to health outcomes due to small variations in hydration status, the influence of sex and sex hormones, and age, especially in older adults and children.
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http://dx.doi.org/10.3390/nu11010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356561PMC
January 2019

Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability.

J Nutr Biochem 2019 01 25;63:165-176. Epub 2018 Sep 25.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Postprandial hyperglycemia (PPH) transiently impairs vascular endothelial function (VEF) in an oxidative stress-dependent manner by decreasing nitric oxide (NO) bioavailability. Dairy milk and its proteins attenuate PPH, but whether this improves VEF is unknown. We hypothesized that dairy milk, mediated by its whey and/or casein proteins, improves VEF by attenuating PPH-induced oxidative stress that otherwise decreases NO bioavailability. A randomized, cross-over trial was conducted in adults with prediabetes (n=23) who ingested glucose (75 g, GLU) alone or with 473 mL of non-fat dairy milk (MILK) or isonitrogenous (16.5 g) amounts of whey (WHEY) or casein (CASEIN) in 473 mL of water. Prior to and at 30 min intervals for 180 min postprandially, we assessed brachial artery flow-mediated dilation (FMD) and measured biomarkers of glycemic control, oxidative stress, and NO homeostasis. FMD decreased to the greatest extent during GLU, which was similarly improved in dairy trials. Compared with GLU, AUCs for glucose, malondialdehyde, F-isoprostanes, methylglyoxal, and endothelin-1 were similarly lower in dairy trials. Plasma arginine and NO metabolites were greater but methylated arginine metabolites were lower in dairy trials compared with GLU. Postprandial insulin, lipids, and tetrahydrobiopterin redox status did not differ among trials. Thus, dairy milk, mediated by its whey and casein proteins, attenuates PPH-mediated impairments in VEF by limiting oxidative stress. This improves NO bioavailability to the vascular endothelium by increasing arginine availability and limiting competitive inhibition on NO biosynthesis by asymmetric dimethylarginine. These findings support observational studies that dairy milk lowers cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.jnutbio.2018.09.018DOI Listing
January 2019

Beverage Containing Dispersible Yeast β-Glucan Decreases Cold/Flu Symptomatic Days After Intense Exercise: A Randomized Controlled Trial.

J Diet Suppl 2020 31;17(2):200-210. Epub 2018 Oct 31.

Biofortis, Mérieux NutriSciences, Addison, IL, USA.

In this double-blind, randomized, placebo-controlled parallel study, we examined the effect of dairy-based beverages (250 mL/day) containing 250 mg of dispersible baker's yeast β-glucan (Wellmune) compared to a macronutrient- and calorie-matched control on upper respiratory tract infection (URTI) in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed either β-glucan ( = 132) or control ( = 225) for the 45 days prior to, day of, and 45 days after the marathon (91 days total). Participants completed a daily online survey assessing compliance, training status, and URTI symptoms. URTI occurrence and severity were evaluated using the Jackson Index and confirmed by the study physician. No significant differences in average duration and number of URTI episodes were found between β-glucan and control. However, those who completed the study per protocol on the β-glucan beverage reported significantly fewer URTI symptomatic days (3.43 ± 6.44 days, max 27 days) compared to those on control beverage (3.84 ± 6.84 days, max 49 days). Total URTI severity was significantly lower for β-glucan (4.52 ± 1.61) compared to control (5.60 ± 2.23). Specifically, lower ( < .05) severity ratings for nasal discharge and sore throat were reported for β-glucan compared to control. Average missed postmarathon workout days due to URTI were significantly less for β-glucan (0.09 ± 0.38 days, max 2 days) compared to control (0.36 ± 1.40 days, max 10 days). Overall, consumption of dairy-based beverages containing dispersible yeast β-glucan decreased URTI symptomatic days, severity of specific URTI symptoms, and missed postmarathon workout days due to URTI, without affecting duration and number of URTI episodes.
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http://dx.doi.org/10.1080/19390211.2018.1495676DOI Listing
September 2020

Dairy milk, regardless of fat content, protects against postprandial hyperglycemia-mediated impairments in vascular endothelial function in adults with prediabetes by limiting oxidative stress responses that reduce nitric oxide bioavailability.

J Nutr Biochem 2019 01 16;63:129-139. Epub 2018 Oct 16.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Postprandial hyperglycemia (PPH) transiently impairs vascular endothelial function (VEF) in an oxidative-stress-dependent manner by decreasing nitric oxide (NO) bioavailability. Dairy milk, regardless of fat content, attenuates PPH, but whether this improves VEF by limiting oxidative stress responses that otherwise decrease NO bioavailability is not known. We hypothesized that nonfat and full-fat dairy milk would similarly improve VEF by attenuating PPH-induced oxidative stress that otherwise decreases NO biosynthesis and bioavailability. A randomized, crossover trial was conducted in adults with prediabetes (n=22) who ingested glucose (75 g) dissolved in 473 ml of water (GLU), or glucose with an equal volume of nonfat dairy milk (NFM) or full-fat dairy milk (FFM). Prior to and at 30-min intervals for 180 min postprandially, we assessed brachial artery flow-mediated dilation (FMD) and measured circulating biomarkers of glycemic control, oxidative stress and NO homeostasis. AUC for FMD and NO metabolites was lowest in GLU but relatively greater in NFM and FFM. Compared with GLU, AUCs for glucose, malondialdehyde, F-isoprostanes and endothelin-1 were similarly lower in dairy trials. Milk-mediated vasoprotection was accompanied by greater levels of plasma arginine and lower levels of asymmetric dimethylarginine and symmetric dimethylarginine. Postprandial insulin, lipids and tetrahydrobiopterin redox status did not differ among trials. Thus, dairy milk, regardless of its fat content, attenuates PPH-mediated impairments in VEF by limiting oxidative stress. This improves NO bioavailability to the vascular endothelium by increasing arginine availability and limiting competitive inhibition on NO biosynthesis by asymmetric dimethylarginine.
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http://dx.doi.org/10.1016/j.jnutbio.2018.10.002DOI Listing
January 2019

Substitution of Corn Starch with Resistant Starch Type 4 in a Breakfast Bar Decreases Postprandial Glucose and Insulin Responses: A Randomized, Controlled, Crossover Study.

Curr Dev Nutr 2018 Oct 9;2(10):nzy066. Epub 2018 Aug 9.

Biofortis, Mérieux NutriSciences, Addison, IL.

Background: Resistant starches type 4 (RS4) are chemically modified starches that are resistant to digestion by human enzymes.

Objective: We aimed to test our hypothesis that replacement of standard starch with RS4 in a baked breakfast bar would decrease postprandial glycemic and insulinemic responses in healthy adults.

Methods: In this double-blind, randomized crossover study, 21 healthy adults [10 men; 20-45 y old; BMI (kg/m): 19.3-27.0] consumed a baked breakfast bar containing tapioca-based RS4 (Actistar 75330; Cargill, Inc.) or a macronutrient-matched control bar, delivering 32 g and 4 g of dietary fiber, respectively. Primary outcome was the incremental area under the curve (iAUC) for postprandial capillary glucose. Other outcomes included postprandial serum insulin iAUC, glucose and insulin maximum concentration (C), and time to C (T).

Results: Median glucose iAUC was 22% lower ( < 0.05) and median insulin iAUC was 37% lower ( < 0.05) after consumption of the RS4 food compared with the control food. Glucose and insulin C and T were not significantly different ( > 0.05) between foods.

Conclusion: The results suggest that replacement of standard starch with tapioca-based RS4 is a practical approach for reducing available carbohydrate in products and achieving postprandial blood glucose management. This trial was registered at clinicaltrials.gov as NCT03239288.
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http://dx.doi.org/10.1093/cdn/nzy066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186909PMC
October 2018

Co-ingestion of whole eggs or egg whites with glucose protects against postprandial hyperglycaemia-induced oxidative stress and dysregulated arginine metabolism in association with improved vascular endothelial function in prediabetic men.

Br J Nutr 2018 10 30;120(8):901-913. Epub 2018 Aug 30.

1Human Nutrition Program, Department of Human Sciences,The Ohio State University,Columbus, OH 43210,USA.

Replacing a portion of a glucose challenge with whole eggs (EGG) or egg whites (WHITE) was shown to protect against glucose-induced impairments in vascular function. We hypothesised in the present study that previously observed vasoprotection following co-ingestion of EGG or WHITE with glucose was attributed to limiting postprandial hyperglycaemia-induced oxidative stress that improves NO∙ bioavailability. Prediabetic men completed a randomised, cross-over study in which they ingested isoenergetic meals containing 100 g glucose (GLU), or 75 g glucose with 1·5 EGG, seven WHITE or two egg yolks (YOLK). At 30 min intervals for 3 h, we assessed plasma NO∙ metabolites, the lipid peroxidation biomarker malondialdehyde, antioxidants, arginine and its methylated metabolites (asymmetric dimethylarginine and symmetric dimethylarginine), tetrahydrobiopterin redox status, vasoconstrictors and inflammatory markers. Compared with GLU, malondialdehyde was lower and NO∙ metabolites were greater in EGG and WHITE, but YOLK was not different from GLU. Malondialdehyde was inversely correlated with NO∙ metabolites and vascular function, whereas NO∙ metabolites were positively correlated with vascular function. Compared with GLU, arginine was greater, but asymmetric and symmetric dimethylarginine and angiotensin-II were lower in all egg-based meals. Antioxidants, tetrahydrobiopterin redox status and inflammatory markers did not differ among treatments. Thus, while each egg-based meal improved arginine metabolism, only EGG and WHITE limited lipid peroxidation. This suggests that vasoprotection mediated by EGG and WHITE likely occurs in an NO∙-dependent manner by improving arginine metabolism and attenuating oxidative stress that otherwise limit NO∙ biosynthesis and bioavailability to the vascular endothelium.
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http://dx.doi.org/10.1017/S0007114518002192DOI Listing
October 2018

Replacing carbohydrate during a glucose challenge with the egg white portion or whole eggs protects against postprandial impairments in vascular endothelial function in prediabetic men by limiting increases in glycaemia and lipid peroxidation.

Br J Nutr 2018 02 16;119(3):259-270. Epub 2018 Jan 16.

1Human Nutrition Program, Department of Human Sciences,The Ohio State University,Columbus,OH 43210,USA.

Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs vascular endothelial function (VEF). We hypothesised that co-ingestion of a glucose challenge with egg-based meals would protect against glucose-induced impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross-over study was conducted in prediabetic men (n 20) who ingested isoenegertic meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with 1·5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2-isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were assessed. In GLU, FMD decreased at 30-60 min and returned to baseline levels by 90 min. GLU-mediated decreases in FMD were attenuated at 30-60 min in EGG and WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to baseline, glucose increased at 30-120 min in GLU and YOLK but only at 30-90 min in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK. Postprandial lipids and methylglyoxal did not differ between treatments. Thus, replacing a portion of a glucose challenge with whole eggs or egg whites, but not yolks, limits postprandial impairments in VEF by attenuating increases in glycaemia and lipid peroxidation.
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http://dx.doi.org/10.1017/S0007114517003610DOI Listing
February 2018

Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial.

Am J Clin Nutr 2017 05 29;105(5):1070-1078. Epub 2017 Mar 29.

Biofortis Inc., Addison, IL; and

Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited. We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol. In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period. Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all < 0.05) in total cholesterol [-3.9% (95% CI: -9.3%, 1.7%) compared with 0.8% (95% CI: -1.5%, 4.5%), respectively], LDL cholesterol [-4.8% (95% CI: -12.6%, 3.1%) compared with 1.2% (95% CI: -2.3%, 7.8%), respectively], non-HDL cholesterol [-5.3% (95% CI: -8.6%, 2.1%) compared with 1.7% (95% CI: -0.9%, 5.6%), respectively], and the total-cholesterol:HDL-cholesterol ratio [-0.0% (95% CI: -4.3%, 4.8%) compared with 3.4% (95% CI: 0.6%, 5.2%), respectively]. There were no significant differences between diets for HDL cholesterol and triglyceride. In comparison with a control diet, the incorporation of cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741.
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http://dx.doi.org/10.3945/ajcn.116.150037DOI Listing
May 2017

Increased static and decreased capacity oxidation-reduction potentials in plasma are predictive of metabolic syndrome.

Redox Biol 2017 08 14;12:121-128. Epub 2017 Feb 14.

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, United States. Electronic address:

Electric conductivity in plasma is the balance between oxidized and reduced molecules (static Oxidation-Reduction Potential, sORP) and the amount of readily oxidizable molecules (capacity ORP, cORP). Adults with metabolic syndrome (MetS) have increased inflammation, dyslipidemia and oxidative stress; therefore, participants with MetS were hypothesized to have higher plasma sORP and lower cORP than those measures in healthy adults. Heparin-anticoagulated plasma from healthy and age- and gender-matched individuals with MetS (BMI: 22.6±0.7 vs. 37.7±3.0kg/m, respectively) was collected in the fasting state at 0, 24, 48, and 72h during each of four separate interventions in a clinical trial. At baseline, plasma sORP was 12.4% higher (P=0.007), while cORP values were less than half (41.1%, P=0.001) in those with MetS compared with healthy participants. An sORP >140mV detected MetS with 90% sensitivity and 80% specificity, while a cORP <0.50μC detected MetS with 80% sensitivity and 100% specificity. sORP and cORP values in participants with MetS compared with healthy adults were linked to differences in waist circumference and BMI; in plasma markers of dyslipidemia (triglycerides, HDL-cholesterol, and oxidized LDL-cholesterol) and inflammation (C-reactive protein, IL-10); as well as with urinary markers of lipid peroxidation (e.g., 2,3-dinor-5,6-dihydro-8-iso-PGF; 2,3-dinor-8-iso-PGF). Higher sORP values are a robust indicator of metabolic stress, while lower cORP values act as an indicator of decreased metabolic resilience.
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http://dx.doi.org/10.1016/j.redox.2017.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318349PMC
August 2017

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.

Am J Clin Nutr 2017 03 11;105(3):571-579. Epub 2017 Jan 11.

Human Nutrition Program, The Ohio State University, Columbus, OH.

Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements. We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status. Adults (healthy or with MetS; = 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeled -α-tocopherol (d-α-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured α-CEHC and α-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma α-tocopherol, α-CEHC, and α-CMBHC concentrations at various times ≤72 h. During the first 24 h, participants with MetS compared with healthy adults excreted 41% less α-CEHC (all values are least-squares means ± SEMs: 0.6 ± 0.1 compared with 1.0 ± 0.1 μmol/g creatinine, respectively; = 0.002), 63% less hexadeuterium-labeled (d)-α-CEHC (0.04 ± 0.02 compared with 0.13 ± 0.02 μmol/g creatinine, respectively; = 0.002), and 58% less d-α-CMBHC (0.017 ± 0.004 compared with 0.041 ± 0.004 μmol/g creatinine, respectively; = 0.0009) and had 52% lower plasma d-α-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC): 27.7 ± 7.9 compared with 58.4 ± 7.9 nmol/L × h, respectively; = 0.01]. d-α-CEHC peaked before d-α-T in 77 of 80 paired plasma concentration curves. Urinary d-α-CEHC 24-h concentrations were associated with the plasma AUC of d-α-T ( = 0.53, = 0.02) and d-α-CEHC ( = 0.72, = 0.0003), and with urinary d-α-CMBHC ( = 0.88, < 0.0001), and inversely with the plasma inflammation biomarkers C-reactive protein ( = -0.70, = 0.0006), interleukin-10 ( = -0.59, = 0.007), and interleukin-6 ( = -0.54, = 0.01). Urinary α-CEHC and α-CMBHC are useful biomarkers to noninvasively assess α-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs α-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.
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http://dx.doi.org/10.3945/ajcn.116.138495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320409PMC
March 2017

Green tea extract treatment reduces NFκB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability.

J Nutr Biochem 2017 03 21;41:34-41. Epub 2016 Dec 21.

Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

NFκB-mediated inflammation contributes to liver injury during nonalcoholic steatohepatitis (NASH). We hypothesized that antiinflammatory activities of green tea extract (GTE) during NASH would lower tumor necrosis factor receptor-1 (TNFR1)- and Toll-like receptor-4 (TLR4)-mediated NFκB activation. Male C57BL6/J mice (6 weeks old) were fed a low-fat (LF) or high-fat (HF) diet for 12 weeks to induce NASH. They were then randomized to continue on these diets supplemented with 0 or 2% GTE (n=10/group) for an additional 8 weeks prior to evaluating NASH, NFκB inflammation and TNFR1 and TLR4 receptor complexes and their respective ligands, TNFα and endotoxin. HF feeding increased (P<.05) serum alanine aminotransferase (ALT) activity and histological evidence of NASH compared with LF controls. HF-mediated increases in NFκB p65 phosphorylation were also accompanied by increased serum TNFα and endotoxin concentrations, mRNA expression of hepatic TNFR1 and TLR4 and MyD88 protein levels. GTE in LF mice had no effect (P>.05) on liver histology or inflammatory responses. However, GTE in HF mice decreased biochemical and histological parameters of NASH and lowered hepatic p65 phosphorylation in association with decreased serum TNFα, mRNA expression of TNFR1 and TLR4 and MyD88 protein. GTE in HF-fed mice also lowered serum endotoxin and up-regulated mRNA expression of duodenal occludin and zonula occluden-1 and ileal occludin and claudin-1 that were otherwise lowered in expression by HF feeding. These data suggest that dietary GTE treatment reduces hepatic inflammation in NASH by decreasing proinflammatory signaling through TNFR1 and TLR4 that otherwise increases NFκB activation and liver injury.
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http://dx.doi.org/10.1016/j.jnutbio.2016.12.007DOI Listing
March 2017

A green tea-containing starch confection increases plasma catechins without protecting against postprandial impairments in vascular function in normoglycemic adults.

Food Funct 2016 Sep 5;7(9):3843-53. Epub 2016 Aug 5.

Human Nutrition Program, The Ohio State University, Columbus, Ohio 43210, USA.

Postprandial hyperglycemia (PPH) increases cardiovascular disease risk regardless of glucose intolerance by transiently impairing vascular endothelial function (VEF) by limiting nitric oxide bioavailability in an oxidative stress-dependent manner. Preclinical studies show that green tea catechins attenuate PPH by inhibiting starch digestion. We hypothesized that a starch-based confection containing catechin-rich green tea extract (GTE) would limit PPH-mediated impairments in VEF in normoglycemic adults. We formulated a unique GTE confection and then conducted a double-blind, randomized, controlled, crossover study in healthy men (n = 15; 25.3 ± 1.0 years; 22.4 ± 1.8 kg m(-2)) in which they ingested starch confections (50 g carbohydrate) formulated with or without GTE (1 g) prior to evaluating sensory characteristics of confections and plasma glucose, biomarkers of lipid peroxidation and nitric oxide homeostasis, and brachial artery flow-mediated dilation (FMD) at 30 min intervals for 3 h. Sensory evaluation of confections indicated acceptable consumer appeal and an inability to distinguish between confections regardless of GTE. Plasma catechins concentrations increased following ingestion of the GTE confection. However, plasma glucose peaked at 60 min (P < 0.05) following confection ingestion and was unaffected throughout the postprandial period by the GTE confection (P > 0.05). FMD was significantly decreased only at 60 min regardless of confections containing GTE. Also at 60 min, both confections similarly increased plasma malondialdehyde while decreasing arginine and increasing asymmetric dimethylarginine/arginine. The successfully formulated GTE-containing confection effectively delivered catechins, but without mitigating PPH-mediated impairments in VEF in association with oxidative stress that likely limits nitric oxide bioavailability.
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http://dx.doi.org/10.1039/c6fo00639fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378873PMC
September 2016

Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients.

Int J Vasc Med 2016 22;2016:4613202. Epub 2016 Feb 22.

Division of Cardiology, Hartford Hospital, Hartford, CT 06102, USA.

Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- and γ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y). Results. Relative to Pre, total cholesterol (7.8 ± 1.5 mmol/L) and LDL-cholesterol (6.2 ± 1.2 mmol/L) were 61% and 70% lower (P < 0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52-69% lower at Post (P < 0.01), and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.
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http://dx.doi.org/10.1155/2016/4613202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779839PMC
March 2016

Green tea extract provides extensive Nrf2-independent protection against lipid accumulation and NFκB pro- inflammatory responses during nonalcoholic steatohepatitis in mice fed a high-fat diet.

Mol Nutr Food Res 2016 Apr 18;60(4):858-70. Epub 2016 Feb 18.

Human Nutrition Program, The Ohio State University, Columbus, OH, USA.

Scope: Green tea extract (GTE) reduces liver steatosis and inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized GTE would mitigate NASH in a nuclear factor erythroid-2-related-factor-2 (Nrf2)-dependent manner in a high fat (HF) induced model.

Methods And Results: Nrf2-null and wild-type (WT) mice were fed an HF diet containing 0 or 2% GTE for eight weeks prior to assessing parameters of NASH. Compared to WT mice, Nrf2-null mice had increased serum alanine aminotransferase, hepatic triglyceride, expression of free fatty acid uptake and lipogenic genes, malondialdehyde and NFκB phosphorylation and expression of pro-inflammatory genes. In WT mice, GTE increased Nrf2 and NADPH:quinone oxidoreductase-1 mRNA, and lowered hepatic steatosis, lipid uptake and lipogenic gene expression, malondialdehyde, and NFκB-dependent inflammation. In Nrf2-null mice, GTE lowered NFκB phosphorylation and TNF-α and MCP1 mRNA to levels observed in WT mice fed GTE whereas hepatic triglyceride and lipogenic genes were lowered only to those of WT mice fed no GTE. Malondialdehyde was lowered in Nrf2-null mice fed GTE, but not to levels of WT mice, and without improving the hepatic antioxidants α-tocopherol, ascorbic acid and uric acid.

Conclusion: Nrf2 deficiency exacerbates NASH whereas anti-inflammatory and hypolipidemic activities of GTE likely occur largely independent of Nrf2 signaling.
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http://dx.doi.org/10.1002/mnfr.201500814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828297PMC
April 2016

α-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial.

Am J Clin Nutr 2015 Nov 7;102(5):1070-80. Epub 2015 Oct 7.

Human Nutrition Program, Department of Human Sciences and

Background: Increasing dietary fat intake is expected to improve α-tocopherol bioavailability, which could be beneficial for improving α-tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary α-tocopherol requirements.

Objective: Our objective was to assess dose-dependent effects of dairy fat and metabolic syndrome (MetS) health status on α-tocopherol pharmacokinetics in plasma and lipoproteins.

Design: A randomized, crossover, double-blind study was conducted in healthy and MetS adults (n = 10/group) who ingested encapsulated hexadeuterium-labeled (d6)-RRR-α-tocopherol (15 mg) with 240 mL nonfat (0.2 g fat), reduced-fat (4.8 g fat), or whole (7.9 g fat) milk before blood collection at regular intervals for 72 h.

Results: Compared with healthy participants, those with MetS had lower (P < 0.05) baseline plasma α-tocopherol (μmol/mmol lipid) and greater oxidized low-density lipoprotein (LDL), interleukin (IL)-6, IL-10, and C-reactive protein. Regardless of health status, d6-α-tocopherol bioavailability was unaffected by increasing amounts of dairy fat provided by milk beverages, but MetS participants had lower estimated d6-α-tocopherol absorption (±SEM) than did healthy participants (26.1% ± 1.0% compared with 29.5% ± 1.1%). They also had lower plasma d6-α-tocopherol AUC from 0 to 72 h, as well as maximal concentrations (Cmax: 2.04 ± 0.14 compared with 2.73 ± 0.18 μmol/L) and slower rates of plasma disappearance but similar times to Cmax. MetS participants had lower d6-α-tocopherol AUC from t = 0-12 h (AUC0- t final) in lipoprotein fractions [chylomicron, very-low-density lipoprotein (VLDL), LDL, high-density lipoprotein]. Percentages of d6-α-tocopherol AUC0- t final in both the chylomicron (r = -0.46 to -0.52) and VLDL (r = -0.49 to -0.68) fractions were inversely correlated with oxidized LDL, IL-10, IL-6, and C-reactive protein.

Conclusions: At dietary intakes equivalent to the Recommended Dietary Allowance, α-tocopherol bioavailability is unaffected by dairy fat quantity but is lower in MetS adults, potentially because of greater inflammation and oxidative stress that limits small intestinal α-tocopherol absorption and/or impairs hepatic α-tocopherol trafficking. These findings support higher dietary α-tocopherol requirements for MetS adults. This trial was registered at www.clinicaltrials.gov as NCT01787591.
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http://dx.doi.org/10.3945/ajcn.115.118570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625597PMC
November 2015

α-Tocopherol supplementation reduces 5-nitro-γ-tocopherol accumulation by decreasing γ-tocopherol in young adult smokers.

Free Radic Res 2015 12;49(9):1114-1121. Epub 2015 May 12.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210.

γ-Tocopherol (γ-T) scavenges reactive nitrogen species (RNS) to form 5-NO2-γ-T (NGT). However, α-T supplementation decreases circulating γ-T, which could limit its RNS scavenging activities. We hypothesized that α-T supplementation would mitigate NGT accumulation by impairing γ-T status. Healthy smokers (21 ± 1 y, n = 11) and non-smokers (21 ± 2 y, n = 10) ingested 75 mg/d each of RRR- and all-rac-α-tocopheryl acetate for 6 d. Plasma α-T, γ-T, γ-carboxyethyl hydroxychromanol (CEHC), NGT, and nitrate/nitrite were measured prior to supplementation (Pre), the morning after 6 consecutive evenings of supplementation (Post 1), and on the mornings of d 6 (Post 6) and d 14 (Post 14) during the post-supplementation period. α-T supplementation increased plasma α-T, and decreased γ-T, in both groups and these returned to Pre concentrations on Post 6 regardless of smoking status. Plasma γ-CEHC increased after the first dose of supplementation in both groups, suggesting that α-T supplementation decreased plasma γ-T in part by increasing its metabolism. Plasma NGT and nitrate/nitrite concentrations at Pre were greater in smokers, indicating greater nitrative stress due to cigarette smoking. Plasma NGT concentration was lowered only in smokers on Post 1 and Post 6 and was restored to Pre levels on Post 14. Plasma nitrate/nitrite tended (P = 0.07) to increase post-supplementation only in smokers, supporting decreases in RNS scavenging by γ-T. Plasma NGT concentration was more strongly correlated (P < 0.05) with γ-T in smokers (R = 0.83) compared with non-smokers (R = 0.50), supporting that α-T-mediated decreases in γ-T reduces NGT formation. These data indicate that α-T supplementation limits γ-T scavenging of RNS in smokers by decreasing γ-T availability.
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http://dx.doi.org/10.3109/10715762.2015.1040788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892894PMC
May 2016

Green Tea Lowers Hepatic COX-2 and Prostaglandin E2 in Rats with Dietary Fat-Induced Nonalcoholic Steatohepatitis.

J Med Food 2015 Jun 2;18(6):648-55. Epub 2014 Dec 2.

1Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA.

Green tea extract (GTE) protects against nonalcoholic steatohepatitis (NASH) by decreasing hepatic steatosis and nuclear factor kappa B (NFκB) activation. We hypothesized that hypolipidemic and anti-inflammatory activities of GTE would protect against NASH by reducing cyclooxygenase-2 (COX-2), an NFκB-dependent enzyme, and prostaglandin E2 (PGE2) in a dietary fat-induced obese model. Male Wistar rats were fed a low-fat diet containing no GTE or a high-fat (HF) diet containing GTE at 0%, 1%, or 2% for 8 weeks. Insulin resistance and total hepatic fatty acids increased following HF feeding (P<.05) and these were normalized by GTE at 1-2%. GTE (1-2%) normalized hepatic malondialdehyde without affecting cytochrome P450 2E1 mRNA expression, which was otherwise increased by HF feeding. HF-mediated increases in hepatic COX-2 protein and activity as well as PGE2 concentrations were normalized by GTE (1-2%). COX-2 activity and PGE2 were correlated to each other, and to serum alanine aminotransferase (ALT) and hepatic NFκB-binding activity (P<.05; r=0.28-0.49). GTE attenuated HF-mediated increases in total hepatic n-6 and n-3, without affecting the n-6/n-3 ratio. GTE did not affect HF-mediated increases in n-6 in nonesterified fatty acid (NEFA) and phospholipid pools, whereas n-3 and n-6/n-3 in both pools were unaffected by GTE and HF feeding. GTE decreased total hepatic arachidonic acid without affecting HF-mediated increases in arachidonic acid in NEFA or phospholipid pools. Thus, GTE attenuates lipid peroxidation and PGE2 accumulation by decreasing COX-2 activity independent of arachidonic acid availability and supports an additional mechanism by which GTE protects against liver injury during NASH in an HF-feeding model.
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http://dx.doi.org/10.1089/jmf.2014.0048DOI Listing
June 2015

Greater γ-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2α.

Exp Biol Med (Maywood) 2015 Apr 30;240(4):527-33. Epub 2014 Oct 30.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA

Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = -0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence.
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http://dx.doi.org/10.1177/1535370214556948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935369PMC
April 2015

Quercetin bioavailability is associated with inadequate plasma vitamin C status and greater plasma endotoxin in adults.

Nutrition 2014 Nov-Dec;30(11-12):1279-86. Epub 2014 Jun 11.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA; Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA. Electronic address:

Objective: Quercetin bioavailability exhibits high interindividual variation for reasons that remain unclear. We conducted a 24-h pharmacokinetic study to investigate whether individual differences in circulating antioxidants, oxidative stress and inflammation, and intestinal permeability affect quercetin bioavailability.

Methods: Healthy adults (n = 9 M/7 F; 34.3 ± 4.5 y; 27.0 ± 1.7 kg/m(2)) ingested 1095 mg quercetin aglycone with a standardized meal. Plasma antioxidants, biomarkers of oxidative stress and inflammation, and endotoxin were measured at baseline (0 h), and quercetin and its methylated metabolites isorhamnetin and tamarixetin were measured at timed intervals for 24 h.

Results: Plasma pharmacokinetics of quercetin, isorhamnetin and tamarixetin were highly variable between participants (CVinter = 37-96%). Plasma vitamin C concentrations (34.6 ± 2.5 μmol/L), but no other antioxidants, were inversely correlated to the Cmax and AUC0 to 24 h of total quercetin (Qtotal; sum of quercetin, isorhamnetin and tamarixetin; r = -0.52 to -0.53; P < 0.05). Plasma endotoxin (0.13 ± 0.01 EU/mL), a surrogate marker of intestinal permeability, was correlated to Qtotal Cmax (r = 0.45; P < 0.05) and tended to be correlated to Qtotal AUC0 to 24 h (r = 0.38; P = 0.07). Additionally, vitamin C was inversely related to C-reactive protein, myeloperoxidase, and endotoxin (r = -0.46 to -0.55; P < 0.05), whereas endotoxin was positively correlated to C-reactive protein (r = 0.73; P < 0.05).

Conclusions: These findings suggest that vitamin C status and plasma endotoxin may be associated with interindividual variations in quercetin bioavailability. Greater quercetin absorption and bioavailability may be associated with poor vitamin C status and increased intestinal permeability in healthy adults.
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http://dx.doi.org/10.1016/j.nut.2014.03.032DOI Listing
June 2015

γ-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation.

Free Radic Biol Med 2013 Dec 27;65:1291-1299. Epub 2013 Sep 27.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Oxidative stress and inflammation persist years after smoking cessation thereby limiting the restoration of vascular endothelial function (VEF). Although short-term smoking cessation improves VEF, no studies have examined co-therapy of antioxidants in combination with smoking cessation to improve VEF. We hypothesized that improvements in γ-tocopherol (γ-T) status during smoking cessation would improve VEF beyond that from smoking cessation alone by decreasing oxidative stress and proinflammatory responses. A randomized, double-blind, placebo-controlled study was conducted in otherwise healthy smokers (22 ± 1 years; mean ± SEM) who quit smoking for 7 days with placebo (n=14) or γ-T-rich supplementation (n=16; 500 mg γ-T/day). Brachial artery flow-mediated dilation (FMD), cotinine, and biomarkers of antioxidant status, oxidative stress, and inflammation were measured before and after 7 days of smoking cessation. Smoking cessation regardless of supplementation similarly decreased plasma cotinine, whereas γ-T-rich supplementation increased plasma γ-T by seven times and its urinary metabolite γ-carboxyethyl hydroxychroman by nine times (P<0.05). Smoking cessation with γ-T-rich supplementation increased FMD responses by 1.3% (P<0.05) beyond smoking cessation alone (4.1 ± 0.6% vs 2.8 ± 0.3%; mean ± SEM). Although plasma malondialdehyde decreased similarly in both groups (P<0.05), plasma oxidized LDL and urinary F2-isoprostanes were unaffected by smoking cessation or γ-T-rich supplementation. Plasma TNF-α and myeloperoxidase decreased (P<0.05) only in those receiving γ-T-rich supplements and these were inversely related to FMD (P<0.05; R=-0.46 and -0.37, respectively). These findings demonstrate that short-term γ-T-rich supplementation in combination with smoking cessation improved VEF beyond that from smoking cessation alone in young smokers, probably by decreasing the proinflammatory mediators TNF-α and myeloperoxidase.
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http://dx.doi.org/10.1016/j.freeradbiomed.2013.09.016DOI Listing
December 2013

Low-fat milk ingestion prevents postprandial hyperglycemia-mediated impairments in vascular endothelial function in obese individuals with metabolic syndrome.

J Nutr 2013 Oct 21;143(10):1602-10. Epub 2013 Aug 21.

Departments of Nutritional Sciences, and.

Greater intakes of low-fat dairy foods are associated with a lower risk of cardiovascular disease. The objective of this study was to examine whether acute low-fat milk ingestion would limit postprandial impairments in vascular endothelial function by limiting oxidative stress responses that decrease nitric oxide (NO) bioavailability. A randomized, double-blind, cross-over study was conducted in adults with metabolic syndrome (MetS) who ingested low-fat milk (475 mL) or an isocaloric volume of rice milk after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose, malondialdehyde (MDA), arginine (ARG), and asymmetric dimethylarginine (ADMA) were assessed at 30-min intervals during the 3-h postprandial period. Participants' (n = 19) postprandial FMD responses were unaffected by low-fat milk but transiently decreased (P < 0.01) from 6.2 ± 0.8% (mean ± SEM) at baseline to 3.3 ± 0.7% at 30 min and 3.9 ± 0.6% at 60 min following rice milk consumption. Glucose and MDA increased to a greater extent in the rice milk trial (P < 0.001). The MDA area under the 3 h postprandial curve (AUC0-3 h) was correlated with glucose AUC0-3 h (r = 0.75; P < 0.01) and inversely related to FMD AUC0-3 h (r = -0.59; P < 0.01). ARG decreased following rice milk and increased with low-fat milk, whereas only rice milk increased ADMA:ARG. The ADMA:ARG AUC0-3 h was correlated with MDA AUC0-3 h (r = 0.55) and was inversely related to FMD AUC0-3 h (r = -0.52) (P < 0.05). These findings suggest that low-fat milk maintains vascular endothelial function in individuals with MetS by limiting postprandial hyperglycemia that otherwise increases lipid peroxidation and reduces NO bioavailability. This trial was registered at clinicaltrials.gov as NCT01411293.
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http://dx.doi.org/10.3945/jn.113.179465DOI Listing
October 2013