Brief Summary of Minutes of Annual Meeting

Tammy Bray (admin), Ann Bock (NM, by proxy), Richard Bruno (CT, application pending to group), Andy Clifford (UC-D), Emily Ho (OR), Barry Shane (UC-B), Barbara Stoecker (OK), Cyndi Thomson (AZ), Connie Weaver (IN), Joy Winzerling (AZ), Etta Saltos (USDA).

Short term outcomes and activities: University of California, Oregon State University, University of Arizona and Washington State University: Phytochemicals and chronic disease prevention: Studied performed in the Clifford lab (UC-Davis) have investigated the relationships between wine consumption, wine composition and cancer. They found that red wine (the residue from red wine remaining after removal of alcohol and water), delayed tumor onset in a mouse model in a positive, linear relationship when incorporated into the diet at levels of 0.5-4 mmol/kg diet. They also found that consumption the wine did alter distribution of PhlP in the rat tissues compared to control animals and animals fed other potential dietary chemopreventive agents, including phenylethyl isothiocyanate and sulforaphane. In order to improve measures of cruciferous vegetable exposure the Thomson lab (Arizona) developed and validated a cruciferous vegetable food frequency food questionnaire using urinary biomarkers of cruciferous vegetable exposure, dithiocarbamate, (JADA, 2007) and have recently described cruciferous vegetable intake in a large population of breast cancer survivors (Nutr and Cancer, in press, 2007). Along these lines we have assessed the effect of a plant-based diet on plasma carotenoid concentrations in breast cancer survivors (Ca Epidem Biomarkers Prev, 2006) and also explored measurement error associated with self-report instruments (Amer J Epi, 2006). They also have developed database programming to more fully describe citrus and d-limonene exposure in breast cancer survivors participating in the Womens Healthy Eating and Living study which will position us for assessing effects of citrus on recurrence in the near future. Further, assessment of dietary influences on breast mammographic density, a biomarker of breast cancer risk, suggests that greater vegetable and fruit intake is associated with reduced density in non-Hispanic whites, while in Hispanic women, dairy foods are associated with protection against high breast density (Menopause, 2006). The Ho laboratory (Oregon) recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells and prostate epithelial cells, namely the inhibition of histone deacetylase (HDAC). When SFN was consumed in the diet at an average daily dose of 7.5 umol per animal for 21 days, SFN suppressed the growth of human PC-3 prostate cancer cells by 40% in male nude mice. There was a significant decrease in HDAC activity in the xenografts, as well as in the prostates and mononuclear blood cells (MBC) of mice treated with SFN, compared to controls. There also was a trend towards increased global histone acetylation in the xenografts, prostates and MBC. In human subjects, a single dose of 68 g BroccoSprouts inhibited HDAC activity significantly in PBMC, 3 and 6 h following consumption. These findings provide evidence that one mechanism through which SFN acts as a cancer chemopreventive agent in vivo is through the inhibition of HDAC activity. Moreover, the data suggest that HDAC activity in PBMC may be used as a biomarker for assessing exposure to novel dietary HDAC inhibitors in human subjects. This work suggests that phytochemicals may have the ability to alter epigenetic events that lead to disease prevention. A recent collaboration between Oregon and Arizona has begun and a joint NIH grant on vegetable intake and breast cancer recurrence has been submitted by the Ho and Thomson laboratories. At UC-Berkeley, the Shane laboratory has continued studies on the metabolic and nutritional effects of common polymorphisms in human folate-related genes that have been shown to influence disease risk. They have identified a gene-gene interaction that influences the risk of heart disease and are developing cell culture models to mimic this interaction. They have continued to evaluate two new 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. These new animal models have gene interruptions that disturb mitochondrial folate metabolism and histone methylation, a process involved in regulation of gene expression. They have continued to study one carbon metabolic fluxes and DNA methylation in these animals and in embryonic fibroblasts. The data indicate that disturbances in mitochondrial folate metabolism result in early embryonic lethality. They have investigated the influence of folate and vitamin B12 status in our experimental animals using cDNA array technology and have identified a number of genes that are responsive to vitamin status. They have continued to evaluate genetic risk factors for neural tube defects. This project aligns well with the study of epigenetic alterations and disease risk in the Ho lab and future work proposed by the Zempleni lab (Nebraska), a future participant in this multistate. At Washington State University, natural compounds and their effects on hypertension have been examined in the Shultz lab. Hypertension is a major controllable risk factor associated with cardiovascular disease events, such as myocardial infarction, stroke, and heart failure. Cleavage of angiotensinogen by rennin produces angiotensin I, which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). It has been reported that in vitro incubation of milk proteins with proteinase preparations can result in the release of ACE inhibitory peptides. We examined three commercial proteases, Validase BNP L, Validase FP II, and Multifect Neutral for digestion of 20% solutions of whey protein concentrate 80 (WPC80) for production of ACE inhibitory activity. Validase FP II produced 61% inhibition with an IC50 value of 4.1 mg/mL, Validase BNP L 46% inhibition with an IC50 value of 5.7 mg/mL, and Multifect Neutral 32% with an IC50 value of 8.1 mg/mL. Also at University of Arizona, the Winzerling laboratory has shown the first evidence that ferritin, the primary iron storage protein, decreases in lung cells exposed to cigarette smoke. This occurs at a time when individuals are exposed to iron in smoke and could promote oxidative stress and lung cell damage. Further, they have found that the expression of another protein involved in cell growth is altered by iron. This could have implications for the role of iron in growth, development and inflammation. University of Connecticut, University of Massachusetts, University of California, University of Nebraska: Bioavailability of nutrients. The Decker laboratory (U. Mass) continues work on omega-3 fatty acids. Numerous forms of omega-3 fatty acids are now commercially available. These include liquid oils, encapsulated powders and oil-in-water emulsions. In addition, many new technologies (e.g. nanotechnologies) are being proposed to deliver omega-3 fatty acids. The Decker lab has found that delivery of omega-3 fatty acids in the form of emulsions increases their bioavailability compared to oils in gelatin capsules (Garaiova, 2007). This data suggest that delivery systems could be used to increase omega-3 fatty acid bioavailability. However, very little is known about how these delivery systems will impact bioavailability once they are incorporated into foods. These studies were conducted in in situ digestions models and animal studies. The Driskell laboratory (Nebraska) has conducted studies examining vitamin status in Korean children. They found approximately 60% of vitamin A intakes of Korean young children came from provitamin A carotenoids. Plasma retinol concentrations of 2.4% of subjects were indicative of vitamin A deficiency; 42.3% had concentrations potentially indicative of marginal vitamin A status. Two-thirds of subjects had plasma ±-tocopherol concentrations indicative of inadequate vitamin E status. Many urban adult American Indians indicated having problems purchasing foods, with lack of money the primary reason. Many were overweight or obese, 32% had had nutrition education in the last 6-mo, and 39% indicated having a problem with alcoholism. Excessive intakes of cholesterol, saturated fats, sugars, and sodium were prevalent for those in all tribes. University of Connecticut-Storrs. Work done in the Koo laboratory (CT) provide evidence that: 1) the plasma level of lutein increases after egg consumption suggesting that egg can be a dietary vehicle of bioavailable carotenoids. This increase was associated with change in total cholesterol but diminishes with obesity. The plasma response to dietary lutein is related to lipoprotein size but not number and 2) the plasma triglyceride-lowering effect of green tea is mediated partly via its inhibitory effect on liver synthesis and release of fat by suppressing the expression of SREBP1c and its responsive genes. The Clifford laboratory (UC-Davis) also conducted a feasibility study which determined the fate of a true tracer dose of 14C-RRR-alpha-tocopherol and of 14C-all-rac-alpha-tocopherol in a crossover design. Mass balances, and kinetic modeling of the dataset revealed that fractional absorption of 14C-RRR-alpha-tocopherol and 14C-all-rac-alpha-tocopherol were each the same at 0.775 (as expected) while vitamin E catabolism and elimination involved -CPHC), transferring to alpha-CEHC (and some returning to liver, being converted to plasma, and being rapidly eliminated in urine, rather than in enterohepatic circulation as occurs for reverse cholesterol transfer. Kansas State University, Purdue Univesity, Oklahoma State University: Nutrient influences on bone health. The Medeiros (Kansas), Weaver (Purdue) and Stoecker (Oklahoma) labs have continued collaborations on studies investigating specific nutrients and their effects on bone health. At Kansas State University, work in the Medeiros lab previously reported that severe iron deficiency negatively impacts bone microarchitecture. Here they determined whether marginal iron restriction that reflects some human consumption patterns could have similar consequences. Thirty-two weanling female, rats were randomly divided into four groups and fed the following diets for 10 weeks: 1) iron adequate, calcium adequate (FeA:CaA), 2) calcium restricted (FeA:CaR), 3) iron restricted (FeR:CaA), and 4) both calcium and iron restricted (FeD:CaR). DEXA analysis revealed that CaR decreased bone mineral density (BMD), and FeR decreased whole body bone mineral content (BMC). Iron restricted and calcium restricted groups had lower BMD than their adequate counterparts. All treatment restricted groups had lower BMD in the 4th lumbar (L-4) vertebrae than the FeA:CaA group. Vertebrae BMD was lower in all treatment groups compared to the control group and for BMC, the CaR groups were lower than the CaA groups and the FeR groups were lower that the FeA groups.and BMC were lower in iron and calcium restricted groups. The microarchitecture of the L-4 vertebrae was compromised in FeA:CaR, FeR:CaA, and FeR:CaR: 1) the connectivity density was reduced by FeR and by CaR; and 2) trabecular number was decreased and trabecular separation was increased by FeR ; Cortical thickness of the femur was reduced by both FeR and CaR. The microarchitecture work by microCT, was performed in collaboration with the Stoecker laboratories (Oklahoma). Finite element analysis revealed that L-4 vertebrae from the FeR:CaA group had greater internal stress with an applied force than the FeA:CaA group, thus would be more likely to break. Chelation of iron in cultured osteoblast cells impaired mineralization, but had no impact upon Type I collagen deposition. Iron depletion, similar to that occurring among some human populations reduced bone strength and microarchitecture based on in vivo and in vitro results reported here. Impaired mineralization with iron depletion appears to be a possible mechanism for the observed bone abnormalities. Suppression of bone resorption in postmenopausal women by various commercial preparations of isoflavones was tested in the Weaver laboratory (Purdue) with a novel method using calcium-41. Phytoestrogens are being marketed as an alternative to estrogen therapy for preventing bone loss in postmenopausal women without sufficient evidence of efficacy. Isoflavone preparations from soy cotyledon, soy germ, kudzu, and red clover were compared to estradiol and bisphosphonate for suppressing bone resorption. The soy cotyledon preparation suppressed bone resorption by 18% compared to approximately 25% suppression by estradiol and the bisphosphonate. No other product was effective at reducing bone loss. Outputs- Major outputs are book chapters and peer-reviewed publications. Website has also been maintained by Ann Bock at New Mexico State University. New collaborative projects have also been established with joint papers and joint grants. Milestones- Prepare renewal of multi-state project by Fall 2007. Continue with collaborative studies and submit joint grants Fall 2007.

Anguera, M. C., Field, M. S., Perry, C., Ghandour, H., Chiang, E.-P., Selhub, J., Shane, B. and Stover, P. J. (2006). Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase. J. Biol. Chem. 281:18335-18342. Braun M.M., Martin, B.R., Kern, M., McCabe, G.P., Peacock, M., Jiang, Z., Weaver C.M. Calcium Retention in Adolescent Boys on a Range of Controlled Calcium Intakes, Am. J. Clin. Nutr. 84:414-418, 2006. Braun, M. and Weaver, C.M. A call to evaluate the impact of calcium-fortified foods and beverages. Nutr. Today 41:40-47, 2006. Cheong, J.M.K., Martin, B.R., Jackson, G.S., Elmore, D., McCabe, G.P., Nolan, J.R., Barnes, S., Peacock, M., Weaver, C.M. Soy isoflavones do not affect bone resorption in postmenopausal women: A dose response study using a novel approach with 41Ca. J. Clin. Endocrin. Metab. 92:577-585, 2007. Clark, R.M., Balakrishnan, A., Waters, D., Aggarwal D., Owen, K.Q., Koo, S.I. L-Carnitine increases liver ±-tocopherol and lowers liver and plasma triglycerides in aging ovariectomized rats. J. Nutr. Biochem. [Epub ahead of print] March 16, 2007. Daphne Q.-D. Pham, Peter J. Kos, Jonathan J. Mayo and Joy J. Winzerling. (2006) Regulation of the ribonucleotide reductase small subunit (R2) in the yellow fever mosquito, Aedes aegypti. Gene. 372:182-90. Dashwood, RH, Myzak, MC and Ho, E. (2006) Dietary HDAC inhibitors: Time to rethink weak ligands for cancer prevention. Carcinogenesis, Feb;27(2):344-9. Davy SR, Benes BA, Driskell JA. Sex differences in dieting trends, eating habits, and nutrition beliefs of a group of Midwestern college students. J Am Diet Assoc 2006;106:1673-7. Dawn L. Geiser, Dianzheng Zhang and Joy J. Winzerling. (2006) Ferritin secretion: Mosquito cell respond to an iron load. Insect Biochemistry and Molecular Biology. 36(3):177-87 de Moura FF, Burri BJ, and Clifford AJ, 2006. Accelerator mass spectrometry in the study of vitamins and mineral metabolism in humans. Handbook of Vitamins. Eds McCormick DB, Rucker RB, Suttie JW, Zempleni J; Marcel Dekker, NY. Drewel BT, Giraud DW, Davy SR, Driskell JA. Less than adequate vitamin E status observed in a group of preschool boys and girls living in the United States. J Nutr Biochem 2006;17:132-8. Driskell JA and Wolinsky I, Ed. Sports Nutrition: Vitamins and Trace Elements, 2nd ed. Boca Raton, FL: CRC Press, 2006. Driskell JA, Nunn,MN, Giraud DW, Hamouz FL. Effects of induction, conventional, and microwave cooking on sensory qualities and carotenoid retention in selected vegetables. J Am Diet Assoc 2006;106(8):A-42. Driskell JA. Summary - Vitamins and trace elements in sports nutrition. In: Driskell JA, Wolinsky I, ed. Sports Nutrition: Vitamins and Trace Elements, 2nd ed. Boca Raton, FL: CRC Press, 2006. Ebeler SE, Dingley KH, Ubick E, Abel S, Mitchell AE, Burns SA, Steinberg FM, and Clifford AJ, 2005. Animal models and analytical approaches for understanding the relationships between wine and cancer. Drugs Exp Clin Res;31:19-27. Gabriela Ramos-Clarmont M., Evelia Acedo-Felix, Joy Winzerling and Luz Vazquez-Moreno (2007) Escherichia coli K88 Interaction with IgA Oligosaccharides. EXCLI Journal, 6:10  22. Garaiova I, Guschina IA, Plummer SF, Tang J, Wang D, Plummer NT. A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification. Nutr J. 2007 25;6:4. Getachew G, Burri BJ, Kelly P, Haack KW, Ognebene TJ, Buchholz BA, Vogel JS, and Clifford AJ, 2006. How to convert biological and environmental carbon to graphite for AMS. Radiocarbon;48:325-336. Hennig, B., Ettinger, A., Jandacek, R.J., Koo, S.I., McClain, C., Seifried, H., Silverstone, A., Watkins, B., and Suk, W.A. Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases. Environ. Health. Perspect. 493-495, 2007. Joy J. Winzerling and Daphne Q.-D. Pham (2006) Iron Metabolism in Mosquitos: Mining the Anopheles gambiae database. Insect Biochemistry and Molecular Biology. 36:310-321. Kim Y-N, Driskell JA. Anthropometric measurements, selected nutrient intakes, and hemoglobin, hematocrit, and serum cholesterol values of 2-6 y old children in Republic of Korea. FASEB J 2006;20(5):A1051-2. Kim Y-N, Lora KR, Giraud DW, Driskell JA. Nonsupplemented children of Latino immigrants have low vitamin E intakes and plasma concentrations and normal vitamin C, selenium, and carotenoid intakes and plasma concentrations. J Am Diet Assoc 2006;106:385-91. Koo, S.I. and Noh, S.K. Green tea as inhibitor of the intestinal absorption of lipids: Potential mechanism for its lipid-lowering effect. J. Nutr. Biochem. 18:179-183, 2007. Lora KR, Giraud DW, Davy SR, Driskell JA. Children of Latino immigrants, 4-8 years, in rural Nebraska are adequate in vitamin B-6. Int J Vit Nutr Res 2006;76(2):47-56. Lora KR, Giraud DW, Morse KL, Driskell JA. Anthropometric characteristics and selected nutrient intakes of Latino immigrant children, 4-8 y, in rural Nebraska. FASEB J 2006;20(4):A621. Myzak, MC, Hardin, K. Dashwood, RH and Ho, E. (2006) Sulforaphane Inhibits Histone Deacetylase Activity in BPH-1, LnCaP, and PC-3 Prostate Epithelial Cells. Carcinogenesis, 27 (4): 811-819. Nijhout, H. F., Reed, M. C., Lam, S.-L., Shane, B., Gregory, J. F. III and Ulrich, C. M. (2006). In silico experimentation with a model of hepatic mitochondrial folate metabolism. Theoret. Biol. Med. Mod. 3:40-50. Pierce JP, Natarajan L, Sun S, Al-Delaimy W, Flatt SW, Kealey S, Rock CL, Thomson CA, Newman VA, Ritenbaugh C, Gold E and Caan BJ.for the Womens Healthy Eating and Living (WHEL) Study Group*. Increase in Plasma Carotenoid Concentrations in Response to a Major Dietary Change in the Women's Healthy Eating and Living (WHEL) study. Cancer Epi Biomarkers Prev 15;1886-92, 2006. Reed, M. C., Nijhout, H. F., Neuhouser, M. L., Gregory III, J. F., Shane, B., James, S. J., Boynton, A. and Ulrich, C. M. (2006). A mathematical model gives insights into nutritional and genetic aspects of folate-mediated one-carbon metabolism. J. Nutr. 136:2653-2661. Reinwald, S. and Weaver, C.M. Soy isoflavones and bone health: a double-edged sword? J. Natural Products. 69:450-459, 2006. Ritzenthaler, K.L., McGuire, M.K., Shultz, T.D., McGuire, M.A., Koepp, A.E., Luedecke, L.O., Hanson, T.W., Dasgupta, N. & Chew, B.P. (2005) Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J.Nutr. 135:422-430. Shane, B. Folate, vitamin B12 and vitamin B6. (2006) In Biochemical, Physiological, Molecular Aspects of Human Nutrition, Stipanuk, M. H., ed., second edition, pp. 693-732, Saunders, New York. Thomson CA, Newton TR, Graver EJ, Jackson K, Reid PM, Hartz VL, Cussler EC, Hakim IA. Cruciferous Vegetable Intake Questionnaire Improves Cruciferous Vegetable Intake Estimates. Journal of the American Dietetic Association. (April, 2007). Thomson CA, Rock CL, Caan BJ, Flatt SW, Al-Delaimy WA, Newman VA, Hajek RA, Chilton RJ, Pierce JP. Increase in Cruciferous Vegetable Intake in Women Previously Treated for Breast Cancer Participating in a Dietary Intervention Trial. Nutrition and Cancer 2006 (Accepted). Wang, S., Noh, S.K. and Koo, S.I. Epigallocatechin gallate and caffeine differentially inhibit the intestinal absorption of cholesterol and fat in ovariectomized rats. J. Nutr. 136: 2791-2796, 2006. Wang, S., Noh, S.K. and Koo, S.I. Green tea catechins inhibit pancreatic phospholipase A2 and intestinal absorption of lipids in ovariectomized rats. J. Nutr. Biochem. 17: 492-498, 2006. Weaver, C.M. Ch. 29 Calcium. In: Present Knowledge in Nutrition. 9th Ed, ILSI, Washington, DC 2006. Weaver, C.M., Rothwell, A.P., Wood, K.V. Measuring calcium absorption and utilization in humans. Current Opinion in Clinical Nutrition and Metabolic Care 9:568-574, 2006.