Brief Summary of Minutes of Annual Meeting

BRIEF SUMMARY OF THE ANNUAL MEETING Meeting was called to order June 3, 2013, at 9:00 a.m. CDST. Welcome and Introductions: Participants were welcomed by the Meeting Chair, Dr. Janos Zempleni, and University of Nebraska Administrators. Dr. Zempleni introduced Drs. David Jackson, Associate Dean and Associate Director, Agricultural Research Division, and Tim Carr, Department Chair, Nutrition and Health Sciences. Dr. Jackson provided a brief overview of multistate groups and the expectations in these groups. W2002 investigators introduced themselves and their programs. Dr. Carr provided an overview of current activities in the department, including recent and upcoming hires, and gave a tour of the department. Dr. Zempleni presented a brief overview of the W2002 project. The two scientists, who reviewed our proposal for re-authorization, requested only minimal edits. The proposal has been revised to address those changes and was uploaded by the administrative staff at Oregon State, Deanne Hudson. Following this, the election of the W3002 Chair was conducted. Dr. Connie Weaver was elected by the members present to be the chair for the next annual cycle. She will coordinate next year's W3002 meeting in Indiana. Objectives, timeline, and responsibilities were discussed. Dr. Weaver will consult with the group about an appropriate meeting date in the near future. Dr. Deirdra Chester, NIFA Program Leader, joined the meeting by phone and provided an update on the NIFA budget and current and future funding opportunities. Each W2002 investigator attending the meeting provided an oral progress report in the following order: 1) Emily Ho (via Skype): Benefits of Zinc and Dietary Factors in Cancer Prevention 2) Jairam Vanamala: Genetics of Carotenoid Bioavailability and Obesity in Children 3) Richard Bruno: Regulation of Vascular Endothelial Function by gamma-Tocopherol in Clinical Models of Oxidative Stress 4) Barbara Stoecker: Micronutrient Deficiencies in Ethiopia 5) Connie Weaver: Update on Work with Calcium Risk for CVD and Potassium in Bioavailability 6) Bin Yang: Enzymatic Enhancement of the Biological Activities of Flavonoids from Ganoderma 7) Janos Zempleni: Roles of Biotin and Holocarboxylase Synthetase in Disease Prevention. June 4, 2013 Invited speaker, Dr. Samodha Fernando, Assistant Professor in the Department of Animal Science, University of Nebraska-Lincoln, gave a talk on microbiome research and gene sequencing and bioinformatics expertise in his laboratory. Following this, additional discussion took place regarding building research collaboration. The meeting was adjourned at 1 p.m. CDST.

ACCOMPLISHMENTS The participants of this multi-state project have been highly productive during the past reporting period as evidenced by >100 peer-reviewed publications among participants and enhancement of collaborations between project members. Project objectives are listed below along with scholarly activities of the lead station. Objective 1): Determine the bioavailability (absorption, distribution, metabolism, elimination) of nutrients and other food components and their environmental and genetic determinants. Objective 2): Evaluate the bioactivity of nutrients and other food components in order to elucidate their underlying protective mechanisms. University of Arizona (Jennifer Teske): Establishing a rodent model to test the hypothesis that insufficient sleep increases risk for bacterial infection, obesity, and reduced quality of life. SUMMARY OF PROGRESS: Insufficient sleep may alter nutrient bioavailability through changes in the gut-brain bidirectional axis, which is integral to gastrointestinal functions such as motility, intestinal barrier function and mucosal immunity. We recently developed and validated a novel method of sleep interruption that is not confounded by increases in stress and thus developed a rodent model of insufficient sleep that mirrors the human condition whereby insufficient sleep with daily sleep opportunity results in hyperphagia, lower physical activity and body weight gain. Moreover, we showed that obese rodents were more sensitive to the deleterious effect of insufficient sleep relative to lean rats. These findings challenge the previous belief that sleep deprivation increases energy expenditure. We are currently testing the dose and duration of insufficient sleep that triggers hyperphagia and body weight gain and the relationship between feeding, physical activity and energy expenditure. To treat normalize abnormal sleep patterns in obese rats, we are testing compounds centrally to promote sleep during the resting phase, increase physical activity in the active phase and normalize eating patterns to prevent eating during the resting phase. University of California, Berkeley (Barry Shane): OUTPUT: We have continued studies on the metabolic and nutritional effects of common polymorphisms in human folate-related genes that have been shown to influence disease risk. We have continued to evaluate the B12-dependent methionine synthase (MS) and methylene-tetrahydrofolate reductase (MTHFR) genetic mouse models to mimic the effects of these polymorphisms and to evaluate their effects on metabolism and how this is modified by nutritional status. We have developed a mouse model that mimics the clinical effects of human B12 and folate deficiency, and which will allow us to investigate potential adverse effects of high folate intake. We continue to evaluate genetic risk factors for neural tube defects and to identify putative modifier genes which influence folate status, homocysteine levels, and methylation potential using a number of mouse strains and a cohort of students at Trinity College, Dublin. University of California, Davis (Andrew Clifford): ABSTRACT: In a marker-trait association study we estimated the statistical significance of 65 single nucleotide polymorphisms (SNP) in 23 candidate genes on HDL levels of two independent Caucasian populations. Each population consisted of men and women and their HDL levels were adjusted for gender and body weight. We used a linear regression model. Selected genes corresponded to folate metabolism, vitamins B-12, A, and E, and cholesterol pathways or lipid metabolism. Extracted DNA from both the Sacramento and Beltsville populations was analyzed using an allele discrimination assay with a MALDI-TOF mass spectrometry platform. The adjusted phenotype, y, was HDL levels adjusted for gender and body weight only statistical analyses were performed using the genotype association and regression modules from the SNP Variation Suite v7. Statistically significant SNP (where P values were adjusted for false discovery rate) included: CETP (rs7499892 and rs5882); SLC46A1 (rs37514694; rs739439); SLC19A1 (rs3788199); CD36 (rs3211956); BCMO1 (rs6564851), APOA5 (rs662799), and ABCA1 (rs4149267). Many prior association trends of the SNP with HDL were replicated in our cross-validation study. Significantly, the association of SNP in folate transporters (SLC46A1 rs37514694 and rs739439; SLC19A1 rs3788199) with HDL was identified in our study. Given recent literature on the role of niacin in the biogenesis of HDL, focus on status and metabolism of B-vitamins and metabolites of eccentric cleavage of beta-carotene with lipid metabolism is exciting for future study. MID: 23656756 [PubMed - as supplied by publisher] CONCLUSIONS/IMPACTS: The strength of our study is the cross-validation between two independent populations (one on the West coast, from Sacramento, CA, and one from the East coast, from the Washington, D.C. area) with similar SNP associations identified in both populations. It would be of significant research interest to focus on the relation of B vitamins on HDL status. In this work, we have identified SNP in two folate transporters (SLC46A1 rs35714695 and rs739439; SLC19A1 rs3788199) having statistically significant ASE in relation to HDL status in both study populations. Cholesterol may be important for facilitating the import of folate across the cell membrane and higher serum folate concentrations have been associated with lower levels of LDL-C and higher levels of HDL-C [19]. Past work by Kitami et al. focused on the importance of the homeostatic role of cholesterol metabolism on folate retention in mouse strains, so there has been an established relationship between cholesterol and folate in the mouse [4]. Recent work by Zhang et al. identified the role of niacin (also known as vitamin B3) on early hepatic HDL formation through transcription of ABCA1. In that study, apoA1 lipidation Clifford et al. Lipids in Health and Disease 2013, 12:66 Page 5 of 10 http://www.lipidworld.com/content/12/1/66 and formation of nascent HDL was mediated and stabilized by niacin, which may prevent premature HDL catabolism [51]. Finally, the identification of the positive association of the BCMO1 SNP rs6564851 with HDL levels was of significance. This SNP has a high MAF in the two independent study populations of this work (Tables 1 and 2). Additionally, the presence of this SNP has been associated with a 48% reduction in activity of converting beta-carotene into vitamin A through central cleavage, resulting in higher circulating levels of plasma carotenoids [29]. These higher levels of carotenoids may be associated with higher levels of HDL and LDL [1]. The biological effects of the eccentric cleavage products of beta-carotene (the apo-beta-carotenoids), especially on lipid metabolism and oxidative stress, are an exciting area of future study. University of California, Davis (Andrew Clifford): ABSTRACT: Kinetic models enable nutrient needs and kinetic behaviors to be quantified and provide mechanistic insights into metabolism. Therefore, we modeled and quantified the kinetics, bioavailability, and metabolism of RRR-alpha-tocopherol in 12 healthy adults. Six men and 6 women, aged 27 ± 6 y, each ingested 1.81 nmol of [5(-14)CH(3)]-(2R, 4'R, 8'R)-alpha-tocopherol; each dose had 3.70 kBq of (14)C. Complete collections of urine and feces were made over the first 21 d from dosing. Serial blood samples were drawn over the first 70 d from dosing. All specimens were analyzed for RRR-alpha-tocopherol. Specimens were also analyzed for (14)C using accelerator MS. From these data, we modeled and quantified the kinetics of RRR-alpha-tocopherol in vivo in humans. The model had 11 compartments, 3 delay compartments, and reservoirs for urine and feces. Bioavailability of RRR-alpha-tocopherol was 81 ± 1%. The model estimated residence time and half-life of the slowest turning-over compartment of alpha-tocopherol (adipose tissue) at 499 ± 702 d and 184 ± 48 d, respectively. The total body store of RRR-alpha-tocopherol was 25,900 ± 6=220 µmol (11 ± 3 g) and we calculated the adipose tissue level to be 1.53 µmol/g (657 µg/g). We found that a daily intake of 9.2 µmol (4 mg) of RRR-alpha-tocopherol maintained plasma RRR-alpha-tocopherol concentrations at 23 µmol/L. These findings suggest that the dietary requirement for vitamin E may be less than that currently recommended and these results will be important for future updates of intake recommendations. PMID: 23077194 [PubMed - indexed for MEDLINE] PMCID: PMC3497961 [Available on 2013/12/1] University of California, Davis (Andrew Clifford): ABSTRACT: Using linear regression models, we studied the main and 2-way interaction effects of the predictor variables gender, age, BMI, and 64 folate/vitamin B-12/homocysteine (Hcy)/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma Hcy normalized by RBC folate measurements (nHcy) in 373 healthy Caucasian adults (50% women). Variable selection was conducted by stepwise Akaike information criterion or least angle regression and both methods led to the same final model. Significant predictors (where P values were adjusted for false discovery rate) included type of blood sample [whole blood (WB) vs. plasma-depleted WB; P < 0.001] used for folate analysis, gender (P < 0.001), and SNP in genes SPTLC1 (rs11790991; P = 0.040), CRBP2 (rs2118981; P < 0.001), BHMT (rs3733890; P = 0.019), and CETP (rs5882; P = 0.017). Significant 2-way interaction effects included gender × MTHFR (rs1801131; P = 0.012), gender × CRBP2 (rs2118981; P = 0.011), and gender × SCARB1 (rs83882; P = 0.003). The relation of nHcy concentrations with the significant SNP (SPTLC1, BHMT, CETP, CRBP2, MTHFR, and SCARB1) is of interest, especially because we surveyed the main and interaction effects in healthy adults, but it is an important area for future study. As discussed, understanding Hcy and genetic regulation is important, because Hcy may be related to inflammation, obesity, cardiovascular disease, and diabetes mellitus. We conclude that gender and SNP significantly affect nHcy. PMID: 22833659 [PubMed - indexed for MEDLINE] Colorado State University (Jairam Vanamala): Purple-fleshed potato prevents and reverses high-fat diet elevated oxidative/inflammatory markers in distal colon, mesenteric fat and systemic circulation. SUMMARY OF PROGRESS: Purple-fleshed potatoes (PP) are rich in anti-inflammatory bioactive compounds such as anthocyanins and carotenoids. However, potatoes are typically processed before consumption. This year we focused on anti-oxidant and anti-inflammatory properties of raw vs. processed PP in vivo compared to WP - white-fleshed potato. We hypothesized that processed PP will not only prevent HFD elevated oxidative stress/inflammation biomarkers (prevention) in young pigs, but also suppress these biomarkers in a pig with established obesity (reversal). To test our hypothesis, in the prevention study, we utilized 56 pigs, 3 weeks post-weaning, consuming one of the seven diets: HFD and HFD supplemented with WP or PP (raw/baked/chips; 10% w/w) for 13 weeks. We also had 8 animals consuming standard low-fat diet (LFD) to establish baseline levels of oxidative stress and inflammation. In the protection study, pigs initially consumed HFD for 12 weeks before being assigned for an additional 5 weeks to one of the 5 diets; HFD and HFD containing 10/20% processed PP or WP (chips, N=8). In both prevention and reversal studies there were no significant differences in feed intake or weight gain between treatment groups. In the prevention study, animals consuming HFD had greater levels of oxidative stress and inflammatory markers in the colon, mesenteric fat and systemic circulation compared to LFD. Both PP and WP diets (raw/baked/chips) numerically elevated colonic mucosal glutathione ratio (GSH: GSSG), however, only the values in raw PP consuming pigs were significantly higher compared to HFD control. In addition, potato diets suppressed expression of pro-inflammatory markers (TNF-alpha, NFkB and TLR-4) in the colonic mucosa and mesenteric fat compared to HFD control. All the potato diets suppressed urinary oxidative stress markers; 8-isoprostane (8IP) and DNA adduct 8-OHDG; and serum levels of pro-inflammatory cytokine TNF-alpha; compared to HFD control, to levels similar to LFD animals. However, in the reversal study only the consumption of processed PP but not WP elevated colon mucosal and mesenteric fat GSH: GSSG ratio compared to HFD control. Similarly, colon mucosal and mesenteric fat expression of TNF-alpha, NFkB and TLR-4, and systemic levels of 8IP and TNF-alpha; were suppressed by processed PP diets compared to HFD control. These findings indicate that PP, even after processing, prevents and protects against HFD elevated colonic, mesenteric and systemic oxidative stress/inflammation in HFD consuming pigs. Potato products are not only rich in bioactive phenolics but also contain toxic compounds such as glycoalkaloids (GA) and acrylamide (AL). However limited information is available on how storage and processing alter GA and AL. GA and AL content measured by UPLC- PDA differed among the cultivars and ranged from 33 to 114 microg/gfw and 330 to 1533 ppb, respectively. Depending on the cultivar storage either elevated or did not affect the GA content, however, processing (baking and chipping) reduced the GA levels. Though 3 months of storage and processing did not increase the GA content above the safety limit, chipping and frying resulted in AL formation. University of Connecticut (Sung Koo and Ji-Young Lee): Lowering plasma total and low-density lipoprotein (LDL) cholesterol concentrations by dietary factors has proven its effectiveness to reduce coronary heart disease (CHD) risk. Studies have almost exclusively focused on the liver but contribution of intestine to the hypocholesterolemic effect of dietary factors has been largely neglected. Recently, significance of transintestinal cholesterol efflux (TICE) in removing excess cholesterol from the body has emerged. We found that EGCG and blackcurrent polyphenol-rich extract altered the expression of genes involved in cholesterol absorption, chylomicron assembly, and apical as well as basolateral cholesterol efflux in Caco-2 cells. Our results suggest that the polyphenols may be able to increase apical efflux of LDL-derived cholesterol in the intestine, an event known as TICE. This raises the possibility that cholesterol-lowering effects of the polyphenols could be attributed partly to TICE stimulation. OUTPUTS: The results from this project were disseminated by oral or poster presentation at the Experimental Biology in April 2013. University of Massachusetts (Eric Decker and Yeonhwa Park): Delivery Systems for Bioactive Components. Nanotechnological principles are being used to design effective delivery systems for lipophilic bioactive food components (nutraceuticals). We have developed a variety of different structured delivery systems from food-grade ingredients, such as nanoemulsions, microemulsions, solid lipid nanoparticles and nanolaminated droplets. These delivery systems can be encapsulated within a wide range of different functional food and beverage products without adversely affecting their desirable properties. We have shown that the dimensions (particle size), composition (fatty acid chain length) and interfacial properties (composition, charge, interactions) influence the biological fate of these structured delivery systems, and the bioaccessibility of encapsulated components. For example, we have shown that the bioaccessibility of beta-carotene encapsulated within nanoemulsion-based delivery systems increases with decreasing particle size, and is higher when the hydrophobic core consists of long chain fatty acids than medium chain fatty acids or indigestible oils. Results with standardized in vitro digestion models have been correlated to animal feeding studies. University of Nebraska, Lincoln (Janos Zempleni): SUMMARY OF PROGRESS: My laboratory has expanded our research activities beyond epigenetic mechanisms through which biotin and chromatin proteins maintain genome stability and participate in gene regulation, and now include the roles of biotin-related enzymes and bioactive compounds in foods and their roles as checkpoints in adipocyte differentiation and fatty acid oxidation: 1) Epigenetics: Holocarboxylase synthetase (HLCS) is the sole protein biotin ligase in the human proteome. HLCS interacts physically with chromatin proteins known to mediate gene repression, including euchromatic H3K9 methyltransferase EHMT-1, the maintenance DNA methyltransferase DNMT1, the methyl-CpG-binding domain protein MeCP2, histone deacetylase (HDAC) 1, and the nuclear co-repressor N-CoR. Studies with synthetic inhibitors and transgenic models suggest that DNA methylation is a primary loading factor, followed by docking of HLCS, followed by docking of EHMT-1 and/or HDACs. Importantly, we discovered a novel biotinylation site in EHMT-1, namely K161, which might be essential for chromatin positioning of EHMT-1 and the subsequent methylation of K9 in histone H3. Biotin synergizes with folate in the repression of pro-inflammatory cytokines. 2) Adipocyte differentiation and fatty acid oxidation: We have generated preliminary evidence suggesting that the biotin-dependent acetyl-CoA carboxylase 2 (ACC2) is a checkpoint in adipocyte differentiation, and also plays a critical role in inhibiting the mitochondrial uptake of fatty acids. Inhibition of ACC2 by bioactive food compounds impairs adipocyte differentiation by >80% and causes a 50% body fat loss in Drosophila melanogaster mutants genetically predisposed to storing excess body fat. We have devised an innovative, high-throughput screen for identifying synthetic and natural compounds that increase mitochondrial uptake and oxidation of fatty acids. Ohio State University (Richard Bruno): Epidemiological observations suggest that the presence of nonalcoholic fatty liver disease (NAFLD) dramatically increases the risk for cardiovascular disease (CVD). Thus, we have conducted studies to examine the extent to which phytonutrients regulate oxidative stress and inflammatory responses in experimental and clinical models of NAFLD and CVD. In a high-fat feeding model of NAFLD, we examined the extent to which green tea extract (GTE) protects against liver injury by regulating hepatic and adipose inflammatory responses under the transcriptional control of nuclear factor kappa B (NFkB). Wistar rats were fed a low-fat (LF; 10% kcal) diet containing no GTE or a high-fat (HF; 60% kcal) diet containing 0, 1, or 2% GTE for 8 wks. We then examined whether GTE reduced NFkB activation and expression levels of inflammatory mediators that are regulated in a NFkB-dependent manner. In a separate clinical study, a randomized cross-over trial was conducted in healthy men to examine the extent to which gamma-tocopherol (g-T) supplementation protects against vascular dysfunction otherwise induced by acute hyperglycemia by regulating lipid peroxidation and the ratio of asymmetric dimethylarginine relative to arginine (ADMA/Arg), an index of nitric oxide bioavailability. SUMMARY: Validated dietary approaches are needed to prevent and treat obesity-related disorders, especially cardiovascular disease and nonalcoholic fatty liver disease (NAFLD) that continue to be problematic at the state, national, and global levels. SITUATION: Weight management is well-recognized to reduce the risk of obesity and related disorders, but weight loss has a poor long-term success rate as evidenced by the frequent occurrence of weight regain. This indicates a critical need to develop complementary dietary strategies that regulate body weight and/or its associated inflammatory responses leading to chronic disease. RESPONSE: OARDC/OSU scientists demonstrated that the regular consumption of green tea reduces obesity, fat infiltration to the liver, and inflammation in laboratory animals with NAFLD whereas dietary supplementation of gamma-tocopherol (a unique form of vitamin E) to humans reduces blood vessel dysfunction otherwise induced by elevations in blood sugar. These studies provide the foundational basis for larger scale clinical studies in effort to validate these novel health-promoting dietary approaches. Ohio State University (Mark Failla): Our program is focused on the absorption, metabolism and efficacy of health promoting dietary compounds. During the past year we have used Caco-2 human intestinal cells, mice and human subjects to address questions about carotenoids, isoflavonoids, xanthones, and anthocyanins. A summary of recent findings follows. Absorption, metabolism and bioactivity of mangosteen xanthones. There are numerous, largely unsubstantiated, health claims for commercially sold juices and products prepared from tropical fruits and botanicals. One such fruit juice product is prepared from mangosteen for which sales of beverages in the US exceeded $200 million in 2008. To date, the majority of the health claims for mangosteen have been based on cellular studies, limited studies with rodents and two reported human intervention studies with healthy individuals. Slight reductions in a plasma marker of inflammation were noted in the chronic human intervention trial. The primary bioactive component in mangosteen juice products is a family of polyphenolic compounds referred to as xanthones. In order for this compound to promote systemic health, they and/or their bioactive metabolites must be absorbed and delivered to target tissues. As no information is available in the literature on the absorption and metabolism of xanthones, we examined the tissues of mice fed diet with 0.1% alpha-mangostin, the most abundant xanthone in mangosteen pericarp. Chronic consumption of this diet reduced the growth of a HT-29 xenograft by 40%. We also examined plasma and urine from healthy human subjects fed two ounces of mangosteen juice as part of a typical fast food breakfast. We also have found that human cell lines of intestinal, hepatic and immunological origin take up alpha-mangostin and transform it to phase II metabolites and other xanthones. Pre-treatment of these cells with the xanthone decreased secretion of proinflammatory cytokines in response to inflammatory insults. Influence of type and amount of dietary fat on the bioaccessibility and bioavailability of bioactive compounds from foods. We have found that fats rich in unsaturated long-chain fatty acids promote the solubilization of carotenoids, isoflavonoids and xanthones in mixed micelles during digestion and in turn enhance uptake by Caco-2 cells. A single meal trial with human subjects examined the effect of 3 types of dietary fat at 3 levels of intake on carotenoid absorption. Both bioaccessibility and bioavailability of hydrocarbon carotenoids was enhanced by co-ingestion of fats rich in long chain, unsaturated fatty acids. The bioaccessibility of isoflavonoids in a soft soy pretzel was not increased by the adding either additional lard or canola oil to the standard formulation. Thus, the soy-based product can serve as a healthy snack food. Retention during cooking and bioaccessibility of provitamin A carotenoids in biofortified cassava. The amount of beta-carotene delivered to the plate after processing cassava according to cultural styles of cooking and ²beta-carotene bioaccessibility increased in proportion to provitamin A content in transgenic high beta-carotene cultivars, as we previously reported for accessions with high provitamin A that were generated by traditional breeding practices. The bioavailability of carotenoids from a vegetable salad was increased in response to the amount of co-consumed fat with a trend towards increased carotenoid absorption when the relative amount of unsaturated fat was elevated. Effect of structure on anthocyanin stability in the oral cavity. Anthocyanin-rich fruits have exhibited chemopreventive and therapeutic properties in the oral cavity of animal models and humans. Confectionaries and oral gels are being developed to increase retention of dried berries and extracts in the mouth as a means of increasing retention of the compounds in the oral cavity. Information regarding the stability of various anthocyanins from fruit sources in the oral cavity and the comparative bioactivity of the natural compounds vs. spontaneously and enzymatically generated metabolites is very limited. Such information is needed for the strategic development of health-promoting oral delivery devices. We have found that delphindin and petunidin anthocyanins are less stable in saliva and in the human oral cavity than other anthocyanidins. We have also found that mixtures of anthocyanins from different fruits have anti-inflammatory activity in cultures of activated human oral cell lines. This activity for some mixtures was not lost when the majority of the anthocyanins had spontaneously degraded in cell culture medium prior to its addition to the cell lines. This supports the possibility that the phenolics produced during the degradation of the anthocyanins possess anti-inflammatory activity. Oklahoma State University (Edralin Lucas): Effects of mango supplementation on body weight and composition and clinical parameters of obese individuals. Previously, mango fruit (Mangifera indica L.) has been shown to improve body composition and blood glucose in an animal model of diet-induced obesity. The objective of this pilot clinical study was to examine the effects of supplementation of freeze-dried mango fruit on body weight and composition and clinical parameters (i.e. glucose, lipid, liver function, and hematological parameters) in obese adults. Twenty adults (11 males and 9 females) with body mass index of 30-45 kg/m2 participated in the study and were given 10 g of freeze-dried mango daily for 12 weeks. Body composition, anthropometric and clinical parameters were measured at baseline and at the end of supplementation. There were no significant changes in body weight and composition, blood lipids, liver function, and hematological parameters after mango supplementation. However, similar to animal findings, mango significantly reduced blood glucose concentrations. Our findings indicate that regular consumption of mango does not increase body weight and blood glucose of obese individuals. Oklahoma State University (Barbara Stoecker): Relations between consumption of animal source foods and cognitive performance of primary school children in Ethiopia have been examined. Additionally, micronutrient status has been a major focus of completed work. Vitamin D status of rural women in southern Ethiopia was assessed by serum 25(OH)D concentrations, and biomarkers of iodine status in women not consuming iodized salt were measured. The work with iodine has been used to promote legislation in Ethiopia mandating iodization of salt for human consumption. To assess relations between consumption of animal source foods (ASF) and cognitive performance, primary school children were selected from five schools in Hawassa, Ethiopia, by two stage random sampling. The Raven's Colored Progressive Matrices (CPM board version) and selected tests from the Kaufman Assessment Battery for Children (KABC-II) were used to assess cognitive performance. Mean individual diet diversity scores were low 3.8 (1.1) and only 15% of children reported consumption of ASF, which included meat, poultry, fish or eggs. Stunted (height-for-age < -2 Z-score) children had lower cognitive test scores compared to children not stunted for several tests. Children who consumed meat, poultry, fish or eggs had higher scores for selected tests. Consumption of ASF and optimal anthropometric status support cognitive function in school children. Another study assessed vitamin D status of dark-skinned rural women living at 7 degree North latitude by measuring serum 25(OH)D concentrations. None of the women reported consuming vitamin D rich foods. Fewer than 16% of participants had 25(OH)D concentrations above 50 nmol/L despite extensive sunlight exposure. Furthermore, 15% of women had 25(OH)D < 30 nmol/L a marker for possible risk of deficiency. A cross-sectional survey in three rural communities of Sidama Zone, southern Ethiopia assessed urinary iodine concentration (UIC), goiter and dietary intake of iodine in a sample of 202 women. Median UIC was 37.2 µg/L which indicates a significant public health problem. None of the participants ever consumed iodized salt or had ever heard about use of iodized salt. Hence, there is a need to supply iodized salt and educational messages in order to achieve the goal of elimination of iodine deficiency disorders in the community. Oregon State University (Emily Ho): The lab has focused on the examination of the interaction of bioactive nutrients such as sulforaphane and zinc on mechanisms related to cancer and chronic disease development. ACCOMPLISHMENTS: Zinc and chronic disease: Recently we have found that zinc status is compromised with age. Zinc supplementation in older animals reverses age-related zinc deficiency and inhibits age-related immune defects and inflammatory processes. Age-related zinc deficiency may be related to methylation of the zinc transporter ZIP6. We also have preliminary data that suggests that zinc alters DNA methylation patterns and may be a novel mechanism by which zinc affects gene expression and the inflammatory response. We have also identified using untargeted metabolomics strategies that methyl-histidine may be a biomarker for human zinc deficiency. Plant-derived phytochemicals from tea and cruciferous vegetables: We have found that sulforaphane, a chemical found cruciferous vegetables is an inhibitor of histone deacetylases, increases acetylated histone levels and has anti-cancer properties in the prostate. We recently reported that SFN also causes decreases histone methylation, in particular H3K9me3. SFN does not affect H3K9 methyltransferase (SUVH3K9) expression, but alters cellular localization. Other phytochemicals derived from cruciferous vegetables, such as indole-3-carbinol may also have epigenetic targets and inhibit HDAC. This work suggests that phytochemical may have the ability to alter epigenetic events that lead to disease prevention. In human supplementation trials, we have directly compared the effects of the "whole food" (broccoli sprouts) to commercially available supplements. We have found a significant decrease in bioavailability and impact on HDACs with supplements compared to the whole food. Surprisingly, even when supplements are pre-treated with myrosinase, the release of sulforaphane from its glucosinolate precursors in the supplement is limited. Metabolomics in plasma samples from these studies also reveal that targets of SFN from supplements and food sources different significantly. OUTPUTS: 1) Test the effects of zinc status on epigenetics, oxidative stress, inflammation, DNA damage and cancer susceptibility in rodent models and humans. 2) Understand the determinants of bioavailability of phytochemicals derived from cruciferous vegetables. 3) Test the ability of sulforaphane supplementation from various sources (supplement vs. whole food) to reduce the incidence of prostate cancer via epigenetic modifications. OUTCOMES: 1) Identify new risk factors in prostate cancer and offer novel dietary modifications to reduce the incidence of prostate cancer. 2) Establish low dietary zinc as risk factor for inflammatory processes, DNA damage and cancer risk and identify new biomarkers for human zinc deficiency. 3) Establish low cruciferous vegetable intake as a risk factor for the development of prostate cancer by altering histone modifications and cell proliferation pathways. 4) Gain knowledge of the mechanisms behind the health benefits of micronutrients and phytochemicals such as zinc and compounds derived from cruciferous vegetables. Purdue University (Connie Weaver): The effect of high calcium intakes as dairy or calcium carbonate arterial calcification in the Ossabaw miniature pig model is being studied to address the controversy regarding the association of calcium supplementation and cardiovascular disease. Potassium is a shortfall nutrient. Our lab is studying the bioavailability and function of potassium from food and salts. Washington State University (Bin Yang): GOALS/OBJECTIVES/EXPECTED OUTPUTS: 1.Determine the bioavailability (absorption, distribution, metabolism, elimination) of nutrients and other food components and their environmental and genetic determinants. 2. Evaluate the bioactivity of nutrients and other food components in order to elucidate their underlying protective mechanisms. Flavonoids are widely distributed plant secondary metabolites, and they play important roles in preventing cardiovascular disease(Prahalathan, Saravanakumar et al. 2012) and cancer mainly due to its anti-oxidant activity(Spagnuolo, Russo et al. 2012), and even proved activity in promotion of bone health beyond calcium and vitamin D (Weaver, Alekel et al. 2012). Ginkgo leaves and its extracts have been well-known for its activity and used as capsule. Ganoderm lucid has been used to reduce the risk of numerous diseases and maintain good health in traditional Chinese medicine and nutrition since ancient times. Now there is considerable interest in altering the form of dietary flavones glycosides in order to positively affect their bioavailability and their biological activities in humans. GOALS AND OBJECTIVES: Objective 1. Bioavailability of flavonoids: Isolation and enzyme-catalyzed modification of flavonoids from G.lucid and Ginkgo. Objective 2. Evaluate the bioactivity of different flavones glycosides or aglycone in anti-oxidation. METHODS: Objective 1. Bioavailability of flavonoids: Isolation and enzyme-catalyzed alteration of flavonoids from G.lucid and Ginkgo. Flavonoids will be isolated and examined by chromatography and the particular structure will be elucidated by NMR and MS. The glycosides will be modified through glycosidase and glycosyltransferase catalyzed reactions. The absorption of modified glycosides and aglycone will be tested using a gastrointestinal tract simulating system. Objective 2. Evaluate the bioactivity of modified flavonoid glycosides or aglycone in anti-oxidation. Antioxidant activities of flavonoids and flavonoids with modified glycosides from G. lucid will be determined in vitro against different radical systems, such as DPPH (1, 1-diphenyl-2-picrylhydrazyl), ABTS [2,2'-azinobis (3-ethylenebenzothiazoline-6-sulphonic acid)] and hydroxyl radicals, in addition to ferric reducing antioxidant power assay. Anti-oxidant capacities of these flavonoids will be evaluated through cell-based anti-oxidant protection (CAP-e) assay and reactive oxygen species (ROS) formation in polymorphonuclear (PMN) cells (ROS PMN assay).

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