Gallic acid mitigates intestinal inflammation and loss of tight junction protein expression using a 2D-Caco-2 and RAW 264.7 co-culture model.

A 2D-intestinal epithelial Caco-2/RAW 264.7 macrophage co-culture model was developed to demonstrate the relative efficacy of different phenolic acids to mitigate changes in Caco-2 epithelial cell redox state initiated both directly by autoxidation products, H2O2, and indirectly through cell communication events originating from cytokine stimulated macrophage. An inducer cocktail (lipopolysaccharide + interferon gamma) was used to activate RAW 264.7 cells in the 2D- Caco-2/RAW co-culture and intracellular changes in Caco-2 cell redox signaling occurred in response to positive changes (p < 0.05) in inflammatory biomarkers derived in macrophage that included IL-6, TNF-α, nitric oxide and peroxynitrite, respectively. Phenolic acids varied in relative capacity to reduce NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) in cocktail inflamed induced macrophage. This response in addition to the relative predisposition of gallic acid (GA) to undergo autoxidation to generate H2O2 activity (p < 0.05), culminated in downstream cell signaling in Caco-2 nuclear factor erythroid 2-related factor (Nrf2) activity (increase 26.9 %), altered monolayer integrity (increase 33.7 %), and release of interleukin 8 (IL-8) (decrease 80.5 %) (p < 0.05). It can be concluded that the co-culture model described herein was useful to assess the importance of communication between cytokine stimulated macrophage and intestinal cells. Moreover, the relative unique efficacy of GA, compared to other phenolic acids tested to protect against activated macrophage induced changes related to intestinal dysfunction were particularly relevant to epithelial redox signaling, intestinal permeability and regulation of tight junction proteins. This study concludes that phenolic acids are not equal in the capacity to protect against intestinal cell dysfunction despite some indication of biological activity.

Mangiferin: a review of dietary sources, absorption, metabolism, bioavailability, and safety.

Mangiferin is a potential candidate for use in nutraceutical and functional food applications due to its numerous bioactivities. However, the low bioavailability of mangiferin is a major limitation for establishing efficacy for use. This review describes current information on known food sources and factors that influence mangiferin contents, absorption, and metabolism features, and recent progress that has come from research efforts to increase the bioavailability of mangiferin. We also list patents that targeted to enhance mangiferin bioavailability. Mangifera indica L. is the major dietary source for mangiferin, a xanthone that varies widely in different parts of the plant and is influenced by many factors that involve plant propagation and post-harvest processing. Mangiferin absorption occurs mostly in the small intestine by passive diffusion with varying absorption capacities in different segments of the gastrointestinal tract. Recent research has led to the development of novel technologies to encapsulate mangiferin in nano/microparticle carrier systems as well as generate mangiferin derivatives to improve solubility and bioavailability. Preclinical studies reported that mangiferin < 2000 mg/kg is generally nontoxic. The safety and the increase in bioavailability are key limiting factors for developing successful applications for mangiferin as a nutritional dietary supplement or nutraceutical.Supplemental data for this article is available online at.

Emerging Protein Sources for Food Production and Human Nutrition.

It is estimated that by 2050, the world's population will be up to 9 billion [...].

Application of a HyPer-3 sensor to monitor intracellular H2O2 generation induced by phenolic acids in differentiated Caco-2 cells.

Intestinal epithelial cells (IECs) are an important point of contact between dietary food components consumed and subsequent whole-body utilization for body maintenance and growth. Selective bioactive phenolic acids, widely present in fruits, vegetables and beverages can generate hydrogen peroxide (H2O2) and contribute to the cellular redox balance, hence influencing well-known cellular antioxidant and pro-oxidant mechanisms. Our findings have showed that increasing extracellular H2O2 resulted in associated changes in intracellular H2O2 levels in Caco-2 cells (p < 0.05) which was facilitated by activity of a family of water channel membrane proteins, termed aquaporins (AQPs). To demonstrate this, a HyPer-3 genetically encoded fluorescent H2O2 sensitive indicator was used to enable fluorescent real-time imaging of intracellular H2O2 levels as a measure of changes occurring in extracellular H2O2 in differentiated Caco-2 cells exposed to different phenolic acids. The use of confocal microscopy and flow cytometry, respectively, captured visualization and quantification of H2O2 uptake in differentiated Caco-2 cells. DFP00173, an aquaporin 3 (AQP3) inhibitor was effective at inhibiting the intracellular uptake of H2O2 and was sensitive to varied levels of H2O2 generated when different phenolic acids were added to the culture media. In summary, HyPer-3 was shown to be an effective technique to demonstrate relative capabilities of structurally different dietary phenolic acids that have potential to alter intestinal redox balance by changing intracellular H2O2, and either antioxidant or pro-oxidant activity, respectively.

Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases.

Turmeric, the rhizome of Curcuma longa plant belonging to the ginger family Zingiberaceae, has a history in Ayurvedic and traditional Chinese medicine for treatment of chronic diseases, including metabolic and cardiovascular diseases (CVD). This parallels a prevalence of age- and lifestyle-related diseases, especially CVD and type 2 diabetes (T2D), and associated mortality which has occurred in recent decades. While the chemical composition of turmeric is complex, curcuminoids and essential oils are known as two major groups that display bioactive properties. Curcumin, the most predominant curcuminoid, can modulate several cell signaling pathways involved in the etiology and pathogenesis of CVD, T2D, and related morbidities. Lesser bioactivities have been reported from other curcuminoids and essential oils. This review examines the chemical compositions of turmeric, and related bioactive constituents. A focus was placed on the cellular and molecular mechanisms that underlie the protective effects of turmeric and turmeric-derived compounds against diabetes and CVD, compiled from the findings obtained with cell-based and animal models. Evidence from clinical trials is also presented to identify potential preventative and therapeutic efficacies. Clinical studies with longer intervention durations and specific endpoints for assessing health outcomes are warranted in order to fully evaluate the long-term protective efficacy of turmeric.

Knowledge and Perceptions of Carbohydrates among Nutrition-Major and Nutrition-Elective Undergraduate Students in Canada.

Objective: The purpose of the study was to assess knowledge and perceptions related to carbohydrates, including sugars, among Canadian nutrition-major undergraduates compared to those enrolled in elective nutrition courses (i.e., "nutrition-elective students").Methods: Cross-sectional surveys were distributed during class time at eight Canadian universities, which included 32 questions on demographics, knowledge and perceptions of carbohydrates and sugars. Descriptive analyses were performed. Differences between groups were tested by Chi-squared statistics.Results: A total of 1207 students (60% nutrition-majors) participated in the survey (January 2016-February 2017). Internet-based sources accounted for one-third of the sources where students obtained nutrition information. About 61% of internet-bases sources were "online" or "website" with no qualifiers, and about a quarter was from social media. A higher percentage of nutrition-majors correctly answered knowledge questions of carbohydrates compared with nutrition-elective students (p < 0.01); no difference was observed for sugars-related knowledge questions. The perceptions of sugars were generally negative and did not differ between groups.Conclusions: Several knowledge gaps and common perceptions on topics related to carbohydrates and sugars were identified; nutrition-major students performed better than nutrition-elective students on carbohydrate knowledge questions, but not sugars. These results highlight the importance of identifying methods to help students bridge knowledge gaps and develop skills to critically evaluate nutrition information from various resources and challenge personal biases.

Ginseng Prong Added to Broiler Diets Reduces Lipid Peroxidation in Refrigerated and Frozen Stored Poultry Meats.

Fatty acid content and lipid oxidation products were compared in chicken breast and leg meats derived from birds fed on animal-fat- and vegetable-oil-based diets, supplemented with ginseng prong powder. The first experiment examined polyunsaturated fatty acid (PUFA) content and the formation of primary and secondary lipid oxidation products in meats stored at refrigeration temperatures (4 °C) for up to 10 days, while the second experiment examined similar changes in the poultry meats when frozen stored at -18 °C, for up to six months. Results showed that initial lipid hydroperoxide concentrations increased in both breast and leg meat within the first week of refrigerated storage and also was ongoing during the first three to four months of frozen storage. A higher (p < 0.05) PUFA content in leg meat, especially in broilers fed a vegetable-oil-blended diet, corresponded to greater tendency for generation of primary lipid oxidation products after refrigerated and frozen storage (p < 0.05). The inclusion of powdered ginseng prong in broiler diets significantly inhibited (p < 0.05) secondary lipid oxidation products (e.g., malonaldehyde [MDA]) formation in both stored leg and breast meat, compared to controls. Significant interactions (p < 0.05) were obtained for storage time and inclusion of ginseng against production of primary and secondary lipid oxidation in broiler breast and leg meats from broilers fed PUFA-containing diets. We conclude that including ginseng prong in broiler growing diets represents a viable strategy to control lipid oxidation in refrigerated/cold-stored meat products.

A Rapid Gas-Chromatography/Mass-Spectrometry Technique for Determining Odour Activity Values of Volatile Compounds in Plant Proteins: Soy, and Allergen-Free Pea and Brown Rice Protein.

Plant-based protein sources have a characteristic aroma that limits their usage in various meat-alternative formulations. Despite being the most popular plant-based protein, the allergenicity of soy protein severely restricts the potential adoption of soy protein as an animal substitute. Thereby, allergen-free plant-protein sources need to be characterized. Herein, we demonstrate a rapid solid-phase-microextraction gas-chromatography/mass-spectrometry (SPME-GC/MS) technique for comparing the volatile aroma profile concentration of two different allergen-free plant-protein sources (brown rice and pea) and comparing them with soy protein. The extraction procedure consisted of making a 1:7 w/v aqueous plant protein slurry, and then absorbing the volatile compounds on an SPME fibre under agitation for 10 min at 40 °C, which was subsequently injected onto a GC column coupled to an MS system. Observed volatile concentrations were used in conjunction with odour threshold values to generate a Total Volatile Aroma Score for each protein sample. A total of 76 volatile compounds were identified. Aldehydes and furans were determined to be the most dominant volatiles present in the plant proteins. Both brown rice protein and pea protein contained 64% aldehydes and 18% furans, with minor contents of alcohols, ketones and other compounds. On the other hand, soy protein consisted of fewer aldehydes (46%), but a more significant proportion of furans (42%). However, in terms of total concentration, brown rice protein contained the highest intensity and number of volatile compounds. Based on the calculated odour activity values of the detected compounds, our study concludes that pea proteins could be used as a suitable alternative to soy proteins in applications for allergen-free vegan protein products without interfering with the taste or flavour of the product.

Whey Proteins as a Potential Co-Surfactant with Aesculus hippocastanum L. as a Stabilizer in Nanoemulsions Derived from Hempseed Oil.

The use of natural surfactants including plant extracts, plant hydrocolloids and proteins in nanoemulsion systems has received commercial interest due to demonstrated safety of use and potential health benefits of plant products. In this study, a whey protein isolate (WPI) from a byproduct of cheese production was used to stabilize a nanoemulsion formulation that contained hempseed oil and the Aesculus hippocastanum L. extract (AHE). A Box-Behnken experimental design was used to set the formulation criteria and the optimal nanoemulsion conditions, used subsequently in follow-up experiments that measured specifically emulsion droplet size distribution, stability tests and visual quality. Regression analysis showed that the concentration of HSO and the interaction between HSO and the WPI were the most significant factors affecting the emulsion polydispersity index and droplet size (nm) (p < 0.05). Rheological tests, Fourier transform infrared spectroscopy (FTIR) analysis and L*a*b* color parameters were also taken to characterize the physicochemical properties of the emulsions. Emulsion systems with a higher concentration of the AHE had a potential metabolic activity up to 84% in a microbiological assay. It can be concluded from our results that the nanoemulsion system described herein is a safe and stable formulation with potential biological activity and health benefits that complement its use in the food industry.

Lysine Bioavailability in School-Age Children Consuming Rice Is Reduced by Starch Retrogradation.

BACKGROUND: Rice is one of the most commonly consumed cereal grains and is part of staple diets in the majority of the world. However, it is regarded as an incomplete protein, with lysine being a limiting amino acid. OBJECTIVES: Our objectives were to determine the bioavailability of lysine in school-age children consuming cooked white rice and to assess the effect of rice starch retrogradation. METHODS: Bioavailability or metabolic availability (MA) of lysine was determined using the indicator amino acid oxidation (IAAO) method in a repeated-measures design. Six healthy school-age children (3 boys, 3 girls) with a mean ± SD age of 6.8 ± 0.98 y randomly received 4 crystalline l-lysine intakes (2, 6, 10, 14 mg · kg-1 · d-1), and 5 rice intakes to provide lysine at 8, 11, or 14 mg · kg-1 · d-1. The 14 mg · kg-1 · d-1 intakes were measured twice as warm rice and once as cold rice (to assess the impact of starch retrogradation on MA). Diets provided protein at 1.5 g · kg-1 · d-1 and calories at 1.7 times the participant's measured resting energy requirement, and were isonitrogenous. Breath samples were collected at baseline and during an isotopic steady state for 13C enrichment measurement. The MA of lysine from rice was determined by comparing the IAAO response of rice with l-lysine using the slope-ratio and single intake methods. Starch retrogradation was characterized using differential scanning calorimetry. RESULTS: MA of lysine in warm rice measured in school-age children was 97.5% and was similar to a repeated rice study (97.1%) within the same study population. MA of lysine was reduced significantly (P < 0.05) to 86.1% when the cooked rice was consumed cold, which corresponded to detectable starch retrogradation. CONCLUSIONS: To our knowledge, this is the first study to measure the MA of lysine from rice in school-age children. Although the bioavailability of lysine from rice is high, it can be reduced by retrogradation of its starch component.This trial was registered at clinicaltrials.gov as NCT04135040.

Bacteriophage-Insensitive Mutants of Antimicrobial-Resistant Salmonella Enterica are Altered in their Tetracycline Resistance and Virulence in Caco-2 Intestinal Cells.

Bacteriophages have shown promise as therapeutic alternatives to antibiotics for the control of infectious bacteria, including the human pathogen Salmonella. However, the development of effective phage-based applications requires the elucidation of key interactions between phages and target hosts, particularly since host resistance to phage is inevitable. Little is known about the alteration of host phenotypes following the development of resistance to phage. The aim of this study is to evaluate the antibiotic susceptibility and virulence of a Salmonella isolate following the development of resistance to bacteriophage SI1. We observed enhanced susceptibility to tetracycline and decreased invasion capacity in a differentiated Caco-2 intestinal cell line. Whole genome sequence analysis revealed an array of mutations, most notably, truncations in vgrG1_2, a core gene involved in Type VI secretion and mutations in the lipopolysaccharide, thereby indicating the plausible attachment site of phage SI1. These findings shed light on understanding the underlying mechanism for phage immunity within the host. Importantly, we reveal an associated genetic cost to the bacterial host with developing resistance to phages. Taken together, these results will aid in advancing strategies to delay or eliminate the development of host resistance when designing informed phage-based antimicrobials.

Benefits of Anthocyanin-Rich Black Rice Fraction and Wood Sterols to Control Plasma and Tissue Lipid Concentrations in Wistar Kyoto Rats Fed an Atherogenic Diet.

Background: This study reports on the relative effects of administrating a cyanidin-3-O-glucoside-rich black rice fraction (BRF), a standardized wood sterol mixture (WS), and a combination of both to lower plasma and target tissue lipid concentrations in Wistar Kyoto (WKY) rats fed atherogenic diets. Methods: Male WKY (n = 40) rats were randomly divided into five groups, which included a nonatherogenic control diet and atherogenic diets that included a positive control and atherogenic diets supplemented with BRF or WS, respectively, and a combination of both BRF + WS. Plasma and target tissue liver, heart and aorta cholesterol, and triacylglycerides (TAG) content were also measured. Results: Rats fed atherogenic diets exhibited elevated hyperlipidemia compared to counterparts fed nonatherogenic diets (p < 0.001); this effect was mitigated by supplementing the atherogenic diets with BRF and WS, respectively (p < 0.05). Combining BRF with WS to enrich the supplement lowered cholesterol similar to the WS effect (p < 0.05) and lowered TAG characteristic to the BRF effect (p < 0.05). Conclusions: Rats fed diets containing BRF or WS effectively mitigate the hypercholesterolemia and elevated TAG induced by feeding an atherogenic diet. The benefit of adding BRF + WS together is relevant to the lipid parameter measured and is target tissue-specific.

Plant Extracts Containing Saponins Affects the Stability and Biological Activity of Hempseed Oil Emulsion System.

In this study, two saponins-rich plant extracts, viz. Saponaria officinalis and Quillaja saponaria, were used as surfactants in an oil-in-water (O/W) emulsion based on hempseed oil (HSO). This study focused on a low oil phase content of 2% v/v HSO to investigate stable emulsion systems under minimum oil phase conditions. Emulsion stability was characterized by the emulsification index (EI), centrifugation tests, droplet size distribution as well as microscopic imaging. The smallest droplets recorded by dynamic light scattering (droplets size v. number), one day after the preparation of the emulsion, were around 50-120 nm depending the on use of Saponaria and Quillaja as a surfactant and corresponding to critical micelle concentration (CMC) in the range 0-2 g/L. The surface and interfacial tension of the emulsion components were studied as well. The effect of emulsions on environmental bacteria strains was also investigated. It was observed that emulsions with Saponaria officinalis extract exhibited slight toxic activity (the cell metabolic activity reduced to 80%), in contrast to Quillaja emulsion, which induced Pseudomonas fluorescens ATCC 17400 growth. The highest-stability samples were those with doubled CMC concentration. The presented results demonstrate a possible use of oil emulsions based on plant extract rich in saponins for the food industry, biomedical and cosmetics applications, and nanoemulsion preparations.

Chlorogenic acid isomers directly interact with Keap 1-Nrf2 signaling in Caco-2 cells.

Chlorogenic acid (CGA) exists as multiple isomers (e.g., 3-CQA, 4-CQA, 5-CQA, 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA) in foods such as coffee beverages, fruits and vegetables. This study aimed to investigate relative activities of these six different CGA isomers to modify redox biology in inflamed Caco-2 cells that involved Nrf2 signaling. Caco-2 cells were pre-treated with individual CGA isomers to assess the relative effectiveness to mitigate oxidative stress. Isomer-specific capacity of different CGA isomers for direct free radical scavenging activity and potential endogenous control of oxidative stress were determined using chemical assays and cell-based experiments, respectively. Molecular dynamics simulations of the CGA and Keap1-Nrf2 complex were performed to predict CGA structure-specific interactions. Results demonstrated that dicaffeoylquinic acid (diCQA including 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA) isomers had greater (p < 0.05) affinity to ameliorate oxidative stress through direct free radical scavenging activity. This observation corresponded to greater (p < 0.05) capacity to activate Nrf2 signaling compared to caffeoylquinic acid (CQA including 3-CQA, 4-CQA, and 5-CQA) isomers in inflamed differentiated Caco-2 cells. Simulations revealed that differences between the ability of CQA and diCQA to interact with the Keap1-Nrf2 complex may be due to differences in relative orientation within this complex. The observed CGA isomer-specific affinity for CQA to activate Nrf2 signaling was confirmed by nuclear translocation of Nrf2 induced by CGA and greater (p < 0.05) upregulation of genes related to Nrf2 expression.

Molecular Mechanisms That Define Redox Balance Function in Pathogen-Host Interactions-Is There a Role for Dietary Bioactive Polyphenols?

To ensure a functional immune system, the mammalian host must detect and respond to the presence of pathogenic bacteria during infection. This is accomplished in part by generating reactive oxygen species (ROS) that target invading bacteria; a process that is facilitated by NADPH oxidase upregulation. Thus, bacterial pathogens must overcome the oxidative burst produced by the host innate immune cells in order to survive and proliferate. In this way, pathogenic bacteria develop virulence, which is related to the affinity to secrete effector proteins against host ROS in order to facilitate microbial survival in the host cell. These effectors scavenge the host generated ROS directly, or alternatively, manipulate host cell signaling mechanisms designed to benefit pathogen survival. The redox-balance of the host is important for the regulation of cell signaling activities that include mitogen-activated protein kinase (MAPK), p21-activated kinase (PAK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor κB (NF-κB) pathways. An understanding of the function of pathogenic effectors to divert host cell signaling is important to ascertain the mechanisms underlying pathogen virulence and the eventual host-pathogen relationship. Herein, we examine the effectors produced by the microbial secretion system, placing emphasis on how they target molecular signaling mechanisms involved in a host immune response. Moreover, we discuss the potential impact of bioactive polyphenols in modulating these molecular interactions that will ultimately influence pathogen virulence.

The Role of Nitric Oxide in Regulating Intestinal Redox Status and Intestinal Epithelial Cell Functionality.

Important functions of intestinal epithelial cells (IECs) include enabling nutrient absorption to occur passively and acting as a defense barrier against potential xenobiotic components and pathogens. A compromise to IEC function can result in the translocation of bacteria, toxins, and allergens that lead to the onset of disease. Thus, the maintenance and optimal function of IECs are critically important to ensure health. Endogenous biosynthesis of nitric oxide (NO) regulates IEC functionality both directly, through free radical activity, and indirectly through cell signaling mechanisms that impact tight junction protein expression. In this paper, we review the current knowledge on factors that regulate inducible nitric oxide synthase (iNOS) and the subsequent roles that NO has on maintaining IECs' intestinal epithelial barrier structure, functions, and associated mechanisms of action. We also summarize important findings on the effects of bioactive dietary food components that interact with NO production and affect downstream intestinal epithelium integrity.

Pea Protein for Hempseed Oil Nanoemulsion Stabilization.

In this paper, we present the possibility of using pea protein isolates as a stabilizer for hempseed oil (HSO)-based water/oil emulsions in conjunction with lecithin as a co-surfactant. A Box-Behnken design was employed to build polynomial models for optimization of the ultrasonication process to prepare the emulsions. The stability of the system was verified by droplet size measurements using dynamic light scattering (DLS) as well as centrifugation and thermal challenge tests. The z-ave droplet diameters of optimized emulsion were 209 and 207 nm after preparation and 1 week storage, respectively. The concentration of free Linoleic acid (C18:2; n-6) was used for calculation of entrapment efficiency in prepared nanoemulsions. At optimum conditions of the process, up to 98.63% ± 1.95 of entrapment was achieved. FTIR analysis and rheological tests were also performed to evaluate the quality of oil and emulsion, and to verify the close-to-water like behavior of the prepared samples compared to the viscous nature of the original oil. Obtained results confirmed the high impact of lecithin and pea protein concentrations on the emulsion droplet size and homogeneity confirmed by microscopic imaging. The presented results are the first steps towards using hempseed oil-based emulsions as a potential food additive carrier, such as flavor. Furthermore, the good stability of the prepared nanoemulsion gives opportunities for potential use in biomedical and cosmetic applications.

l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women.

Background: Folic acid fortification of grains is mandated in many countries to prevent neural tube defects. Concerns regarding excessive intakes of folic acid have been raised. A synthetic analog of the circulating form of folate, l-5-methyltetrahydrofolate (l-5-MTHF), may be a potential alternative. Objective: The objective of this study was to determine the effects of folic acid or l-5-MTHF supplementation on blood folate concentrations, methyl nutrient metabolites, and DNA methylation in women living in Malaysia, where there is no mandatory fortification policy. Methods: In a 12-wk, randomized, placebo-controlled intervention trial, healthy Malaysian women (n = 142, aged 20-45 y) were randomly assigned to receive 1 of the following supplements daily: 1 mg (2.27 µmol) folic acid, 1.13 mg (2.27 µmol) l-5-MTHF, or a placebo. The primary outcomes were plasma and RBC folate and vitamin B-12 concentrations. Secondary outcomes included plasma total homocysteine, total cysteine, methionine, betaine, and choline concentrations and monocyte long interspersed nuclear element-1 (LINE-1) methylation. Results: The folic acid and l-5-MTHF groups had higher (P < 0.001) RBC folate (mean ± SD: 1498 ± 580 and 1951 ± 496 nmol/L, respectively) and plasma folate [median (25th, 75th percentiles): 40.1 nmol/L (24.9, 52.7 nmol/L) and 52.0 nmol/L (42.7, 73.1 nmol/L), respectively] concentrations compared with RBC folate (958 ± 345 nmol/L) and plasma folate [12.6 nmol/L (8.80, 17.0 nmol/L)] concentrations in the placebo group at 12 wk. The l-5-MTHF group had higher RBC folate (1951 ± 496 nmol/L; P = 0.003) and plasma folate [52.0 nmol/L (42.7, 73.1 nmol/L); P = 0.023] at 12 wk than did the folic acid group [RBC folate, 1498 ± 580 nmol/L; plasma folate, 40.1 nmol/L (24.9, 52.7 nmol/L)]. The folic acid and l-5-MTHF groups had 17% and 15%, respectively, lower (P < 0.001) plasma total homocysteine concentrations than did the placebo group at 12 wk; there were no differences between the folic acid and l-5-MTHF groups. No differences in plasma vitamin B-12, total cysteine, methionine, betaine, and choline and monocyte LINE-1 methylation were observed. Conclusion: These findings suggest differential effects of l-5-MTHF compared with folic acid supplementation on blood folate concentrations but no differences on plasma total homocysteine lowering in Malaysian women. This trial was registered at clinicaltrials.gov as NCT01584050.

Chlorogenic Acid (CGA) Isomers Alleviate Interleukin 8 (IL-8) Production in Caco-2 Cells by Decreasing Phosphorylation of p38 and Increasing Cell Integrity.

The objective of this study was to determine the effect of six chlorogenic acid (CGA) isomers known to be present in coffee and other plant foods on modulating the inflammatory response induced by pro-inflammatory cytokines in the Caco-2 human intestinal epithelial cell line. Compared to caffeoylquinic acids (CQA), dicaffeoylquinic acids (DiCQA) had significantly stronger (p < 0.05) capacities to reduce phosphorylation of one of mitogen-activated protein kinases (MAPK) cascades, namely p38. Compared to the control, CQA isomers treatment resulted in around 50% reduction in an interleukin-8 (IL-8) secretion, whereas DiCQA, at the same concentration, resulted in a 90% reduction in IL-8 secretion, compared to the control cells. CGA isomer treatment also showed a significant effect (p < 0.05) on the up-regulation of NFκB subunit p65 nuclear translocation by more than 1.5 times, compared to the control. We concluded that CGA isomers exert anti-inflammatory activity in a mixture of interferon gamma (IFNγ) and phorbol myristate acetate (PMA)-challenged Caco-2 cells, by decreasing the phosphorylation of p38 cascade and up-regulating NFκB signaling.

Household Consumption of Thiamin-Fortified Fish Sauce Increases Erythrocyte Thiamin Concentrations among Rural Cambodian Women and Their Children Younger Than 5 Years of Age: A Randomized Controlled Efficacy Trial.

OBJECTIVES: To assess whether ad libitum consumption of thiamin-fortified fish sauce over 6 months yields higher erythrocyte thiamin diphosphate concentrations (eTDP) among women of childbearing age and their children aged 12-59 months compared with control sauce containing no thiamin. STUDY DESIGN: In this double-blind, randomized controlled efficacy trial, 276 nonpregnant, nonlactating women (18-45 years of age) and their families in Prey Veng, Cambodia, were randomized to receive 1 of 3 fish sauce formulations: low thiamin concentration (low, 2 g/L), high thiamin concentration (high, 8 g/L), or a control (no thiamin) fish sauce. Baseline (t = 0) and endline (t = 6 months) eTDP were measured with the use of high-performance liquid chromatography with a fluorescence detector. RESULTS: Fish sauce consumption did not differ between treatment groups (P = .19). In intent-to-treat analysis, women's baseline-adjusted endline eTDP (mean; 95% CI) was higher among women in the low (259; 245-274 nmol/L) and high (257; 237-276 nmol/L) groups compared with control (184; 169-198 nmol/L; P < .001); low and high groups did not differ (P = .83). Similarly, children's baseline-adjusted eTDP was higher in the low (259; 246-271 nmol/L) and high (257; 243-270 nmol/L) groups compared with control (213; 202-224 nmol/L; P < .001). CONCLUSION: Fortified fish sauce appears to be an efficacious means of improving biochemical thiamin status in nonpregnant, nonlactating women and their children (1-5 years of age) living in rural Cambodia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02221063.