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United States Department of Agriculture

Agricultural Research Service

Research Project: PHYTOCHEMICALS AND HEALTHY AGING

Location: Human Nutrition Research Center on Aging

2013 Annual Report


1a.Objectives (from AD-416):
LAB: ANTIOXIDANTS Objective 1. Identify and quantify the phytochemical content of: blueberries, cranberries, and grapes; almonds, pistachios, and walnuts; whole grains; and cocoa-based foods; and contribute to future updates of the USDA Database for the Flavonoid Content of Selected Foods.

Objective 2. Determine the bioavailability, pharmacokinetics, metabolism and bioactivity of flavonoids and other phytochemicals from antioxidant-rich foods using in vitro experiments, animal models, and human studies..

Objective 3 Investigate the effect of age on quercetin bioavailability and metabolism due to changes in phase II enzyme activity.

Objective 4. Test whether exposure of rat dams to a “Western” diet during pregnancy and lactation will increase obese phenotypes in their pups and whether dietary flavonoids, particularly isoflavones, will decrease the obese phenotype.

LAB: CAROTENOIDS

Objective 1: Determine the ability of bioactive plant-based foods, including carotenoid-rich foods to exert biological functions and affect genomic stability. Objective 2: Determine the vitamin A requirement of healthy U.S. adults.


1b.Approach (from AD-416):
LAB: ANTIOXIDANTS Using advanced chromatographic methods, we will measure the flavonoid content and evaluate the total antioxidant capacity of selected plant foods and the influence of geographical regions, agricultural practices, and processing and storage. A rat model as well as microsomes from various rat tissues will be utilized to determine the effect of age on quercetin bioavailability and metabolism due to changes in phase II enzyme activity. We will explore the possible fetal origins of chronic disease by feeding obesigenic diets to rat dams during pregnancy and lactation and examine the change in obese phenotypes in their pups and test whether dietary flavonoids, particularly isoflavones, will decrease this phenotype. Using healthy older adults, we will determine the bioavailability and distribution of cranberry anthocyanins to blood, urine, and feces. Employing volunteers with coronary heart disease, we will test the effect of almond consumption on biomarkers of oxidative stress, inflammation, and vascular reactivity.

LAB: CAROTENOIDS By recruiting older adults (>60 yr, men and post-menopausal women) without and with metabolic syndrome to ingest bioactive plant foods or histidine dipeptide rich foods, we will measure plasma total antioxidant performance, plasma in vivo oxidative stress biomarkers, plasma water-soluble and fat-soluble antioxidants (carotenoids, tocopherol, ascorbic acid, and uric acid), plasma biomedical parameters to determine the ability of bioactive plant-based foods, including carotenoid-rich foods, to exert biological functions and affect genomic stability. Also, to explore a possible correlation between a change in serum apoE and a change in Macular Pigment (MP) density, we will measure HDL subpopulations by non-denaturing 2d gel electrophoresis, immuno-blotting, and image analysis. We will measure lipoproteins, antioxidative capacity, and markers of inflammation in order to better define the mechanism by which decreased body weight is associated with increased MP in humans. Using the stable isotope labeled vitamin A (labeled in three different levels, ^13 C_4 , ^13 C_8 , ^13 C_12 – retinyl acetate) and aphereses-autologues technique on human volunteers, we will measure the enrichment of these labeled retinols in human circulations and mathematical modeling to determine vitamin A bioavailability and the requirement of vitamin A through an intervention trial with various levels of vitamin A.


3.Progress Report:
This progress report includes the work of two subordinate projects at the HNRCA funded through a Specific Cooperative Agreeement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-073-01S(Antioxidants Research) and 1950-51000-073-02S (Carotenoids and Health).


4.Accomplishments
1. ANTIOXIDANTS LAB: Post-harvest bleaching of pistachios reduces their nutritional quality. Pistachio consumption is associated with reductions in blood cholesterol and antioxidant defenses because they are rich in unsaturated fats, phytosterols, fiber, and antioxidants. Post-harvest bleaching is typically done to whiten nut shells in order to kill fungi and improve the look of the product. However, the impact of bleaching on nutritional quality and the overall safety of pistachios remains to be examined. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts investigated whether bleaching would increase rancidity of fats and oxidation of phytosterols in pistachio oil, as well as whether bleached oil would be toxic to liver cells. We found that bleaching increased lipid rancidity, with the largest increase noted with a type of bleach containing hydrogen peroxide and iron. Bleached pistachio oil also contained less phytosterols than untreated pistachio oil. In a test tube, liver cells treated with bleached oil did not survive as well as those treated with untreated oil. These results show that the bleaching has detrimental effects on nutritional quality and possibly the associated health benefits of pistachios by increasing rancidity, decreasing phytosterol content, and inducing cell toxicity.

2. ANTIOXIDANTS LAB: Dietary fat and sugar can modify the metabolism of the flavonoid quercetin. Consumption of flavonoids from plant foods has been associated with a reduced risk of certain cancers, heart disease, and neurodegenerative disorders. The absorption and metabolism of flavonoids have been partly characterized and reveal a marked variation between individuals. Using rats, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts investigated the effect of dietary modifications on the metabolism of quercetin, a ubiquitous dietary flavonoid. We fed parents a diet high in saturated fat and fructose a month before conception and through lactation and examined the metabolism of quercetin by the liver in both parent and their offspring. After weaning, the rat pups were fed the control diet for an additional three months. Compared to rats fed a standard chow, females fed a diet high in saturated fat and fructose showed a decreased capacity to metabolize quercetin and in utero exposure to the diet decreased the capacity of their pups to do the same. Thus, unhealthy diets consumed by parents may affect the way some healthful plant nutrients are metabolized in the body of their children.

3. CAROTENOIDS LAB: Germinated brown rice is rich in phytochemicals. Germinated brown rice is rich in phytochemicals such as gamma-oryzanols (ferulic acid ester of phytosterols), alphatocopherol, alpha-tocotrienols and polyphenols. It has been reported that gammaoryzanols are not only potent antioxidants but also suppress hyperlipidemic and hyperinsulinemic responses in experimental animals such as diabetic rats and rabbits. Phenolics, in particular y-oryzanol analogues in the germinated brown rice were identified by ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts using LC-MS/MS and an informatics approach. In addition, stability of bioactive compounds in the germinated brown rice were evaluated and the essential information will provide fundamental bases for developing dietary strategies in reducing the prevalence of chronic diseases such as diabetes and cardiovascular disease.

4. CAROTENOIDS LAB: Significant association between retinal lutein/zeaxanthin and brain. Lutein/Zeaxanthin. Age-related cognitive decline is expected to rise due to the increase in the aging population. Based on previous work which showed that lutein levels in the brain are significantly related to pre-mortem measures of cognition, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts tried to define the relationship between retinal and brain lutein. We revealed that there is significant association between retinal lutein/zeaxanthin and brain lutein/zeaxanthin in humans; that is similar to findings in these associations in non-human primates. Macular pigment density could therefore be used as a biomarker to assess brain lutein/zeaxanthin status. Macular pigment assessment may be an important tool to confirm the effect of a dietary intervention containing lutein on cognitive function in the elderly and thus possible to evaluate dietary lutein in combating age-related cognitive decline.

5. CAROTENOIDS LAB: Vitamin A requirements in Chinese adults. Vitamin A is needed for healthy vision and immune function. Vitamin A requirements have been estimated but not determined through direct measures. A study trial on vitamin A requirements in Chinese adults using an isotope dilution technique and vitamin A intervention has been conducted successfully by ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts. The goal of this study is to determine the dietary vitamin A requirement for keeping a constant vitamin A pool in the body in a Chinese population (116 healthy adult volunteers). The linear regression analysis on the data showed that the predicted values of dietary vitamin A intake for maintaining total body vitamin A storage (vitamin A status is unchanged during 4-month intervention) was about 748 ug Retinol Equivalents (RE) or 561 ug Retinol Active Equivalents (RAE) for males and 600 ug RE or 472 ug RAE for females. The values could be used as Estimated Average Requirement (EAR) of vitamin A for an adult Chinese population. These values may be used as practical reference values for adult Americans (current vitamin A EAR are 625 and 500 RAE for males and females, respectively).


Review Publications
Berryman, C.E., Grieger, J.A., West, S.G., Chen, C., Blumberg, J.B., Rothblat, G.H., Sankaranarayanan, S., Kris-Etherton, P.M. 2013. Acute Consumption of Walnuts and Walnut Components Differentially Affect Postprandial Lipemia, Endothelial Function, Oxidative Stress, and Cholesterol Efflux in Humans with Mild Hypercholesterolemia.. Journal of Nutrition. 143:788-794.

Serra, A., Bryant, N., Motiva, M., Blumberg, J.B., Chen, C. 2012. The fetal programming of dietary fructose and saturated fat on hepatic quercetin glucuronidation in rats. Nutrition. 28:1165-1171.

Liu, J., Liu, Y., Chen, C., Chang, W., Chen, C. 2013. The effect of almonds on inflammation and oxidative stress in Chinese patients with type 2 diabetes mellitus: a randomized crossover controlled feeding trial. European Journal of Nutrition. 52:927-935.

Vishwanathan, R., Johnson, E.J. 2013. Nutrition and age-related eye diseases. In: David Heber, M.D.,PhD. Handbook of Nutrition and Food. 3rd Edition. Boca Raton, FL: CRC Press. p.1023-1036.

Marklund, M., Mckeown, N.M., Blumberg, J.B., Chen, C. 2013. Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and beta-oxidation: a proof of concept study. Food Chemistry. 139:925-930.

Maki, K.C., Gibson, G.R., Dickmann, R.S., Kendall, C.C., Chen, C., Costabile, A., Almeida, N.G., Jenkins, D., Zello, G.A., Blumberg, J.B. 2012. Digestive and physiological effects of a wheat bran extract, arabino-xylan-oligosaccharide, in breakfast cereal. Nutrition. 28:1115-1121.

Rasmussen, H.M., Muzhingi, T., Eggert, E.R., Johnson, E.J. 2012. Lutein, zeaxanthin, meso-zeaxanthin content in egg yolk and their absence in fish and seafood. Journal of Food Composition and Analysis. 27(2):139-144.

Vishwanathan, R., Chung, M., Johnson, E.J. 2013. A systematic review on zinc for the prevention and treatment of age-related macular degeneration. Investigative Ophthalmology and Visual Science. 54(6):3985-3998.

Shim, E., Yeum, K., Tang, G., Ahn, S., Hwang, J., Lee-Kim, Y. 2012. Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients. Nutrition and Cancer. 64(7):956-963.

Johnson, E.J., Vishwanathan, R., Johnson, M., Hausman, D.B., Davey, A., Scott, T.M., Green, R.C., Miller, L., Gearing, M., Woodward, J., Nelson, P.T., Chung, H., Schalch, W., Wittwer, J., Poon, L.W. 2013. Relationship between serum and brain carotenoids, a-tocopherol and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. Journal of Aging Research. DOI:10.1155/2013/951786.

Johnson, E.J. 2012. A possible role for lutein and zeaxanthin in cognitive function in the elderly. American Journal of Clinical Nutrition. 96(5):1161S-1165S.

Racicot, K., Craven, A., Chen, C. 2012. Bleaching augments lipid peroxidation products in pistachio oil and its cytotoxicity. European Journal of Lipid Science and Technology. 114:1362-1372.

Rasmussen, H.M., Johnson, E.J. 2013. Nutrients for the aging eye. Clinical Interventions in Aging. 8:741-748.

Joo, N., Dawson-Hughes, B., Kim, Y., Oh, K., Yeum, K. 2013. Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: analysis of the 4th & 5th Korean National Health and Nutrition Examination Survey. Journal of Bone and Mineral Research. 28(4):764-770.

Dohadwala, M.M., Holbrook, M., Hamburg, N.M., Shenouda, S.M., Chung, W.B., Titas, M., Kluge, M.A., Wang, N., Palmisano, J., Milbury, P.E., Blumberg, J.B., Vita, J.A. 2011. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease. American Journal of Clinical Nutrition. 93(5):934-940.

Li, L., Zhao, X., Wang, J., Muzhingi, T., Suter, P.M., Tang, G., Yin, S. 2012. Spirulina can increase total-body vitamin A stores of Chinese school-age children determined by a paired isotope dilution technique. Journal of Nutritional Science. doi:10.1017/jns.2012.21.

Last Modified: 10/1/2014
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