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United States Department of Agriculture

Agricultural Research Service

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Location: Jean Mayer Human Nutrition Research Center On Aging

2011 Annual Report

1a. Objectives (from AD-416)
LAB: ANTIOXIDANTS Objective 1. Identify and quantify the flavonoid content of: blueberries, cranberries, and grapes; almonds, pistachios, and walnuts; and cocoa-based foods and contribute to future updates of the USDA Database for the Flavonoid Content of Selected Foods. Objective 2. Investigate the effect of age on quercetin bioavailability and metabolism due to changes in phase II enzyme activity. Objective 3. 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. We will also investigate the bioavailability and chemopreventive properties of flavonoids, particularly anthocyanins, from berry fruit in a mouse model by examining their actions to reduce oxidative stress, modulate cell signaling pathways, decrease inflammation, and promote phase II detoxification. 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 Agreement with TUFTS UNIVERSITY. For further information and progress report, see 1950-51000-073-01S (Phytochemicals and Aging: Bioavailability, Metabolomics adn Bioactivity) and 1950-51000-073-02S (Dietary Carotenoids, Retinoids and Bioactivates on Healthy Aging).

4. Accomplishments
1. LAB: Antioxidants. Hibiscus tea lowers elevated blood pressure. High blood pressure is an established risk factor for heart disease and foods that contribute to reducing this condition present an important approach to this public health problem. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, investigated the antihypertensive effects of hibiscus tea (3 glasses daily) in a randomized, double-blind, placebo-controlled clinical trial of 65 pre- and mildly hypertensive adults not taking any blood pressure lowering medications. After 6 weeks, hibiscus tea significantly lowered systolic blood pressure compared to the placebo beverage. Diastolic blood pressure was also lowered, although this change did not differ statistically from the placebo. The change in mean arterial pressure was of borderline significance compared with placebo. Participants with a higher systolic blood pressure at baseline showed a greater response to hibiscus treatment. These results suggest daily consumption of hibiscus tea, in an amount readily incorporated into the diet, lowers blood pressure in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people with these conditions.

2. LAB: Antioxidants. Cranberry anthocyanins are absorbed in older adults. Research suggests that anthocyanins from berry fruit may affect a variety of physiological responses, including vascular functions, but little information is available regarding the pharmacokinetics of these flavonoids in humans. Characterizing the pharmacokinetics of phytochemicals is an essential step for informing the design of future human studies of plant compounds. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, studied the pharmacokinetics of anthocyanins from cranberry juice in 15 older adults with coronary artery disease. Marked inter-individual differences in plasma anthocyanin pharmacokinetics were observed with maximum concentrations detected between 1 and 3 hours. Cranberry anthocyanins were bioavailable but with notable differences in their maximum concentration and total absorption between individuals. The pattern of anthocyanin glucosides observed in plasma and urine generally reflected the relative concentration determined in the juice. Total recovery of urinary anthocyanin was less than 1% of the dose delivered. These data can now inform the rational design of clinical trials on the putative health benefits of cranberry juice.

3. LAB: Antioxidants. Age-related changes in the metabolism of flavonoids and other phytochemicals have not been studied. This lack of information represents an important gap in our knowledge about flavonoids as their metabolites appear to be the principal bioactive form of these phytochemicals. Since flavonoids are metabolized extensively by the enzyme UDP-glucuronosyltransferases (UGT), ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, hypothesized that UGT flavonoid conjugating activity changes with age. The effect of age on flavonoid glucuronidation toward the flavonol quercetin and the isoflavone genistein was determined using liver microsomes from rats of different ages (4-, 18- and 28-months). Significant changes were observed in the hepatic metabolite profile produced for both flavonoids with greater changes for genistein than quercetin. The capacity for flavonoid glucuronidation by rat liver microsomes appears dependent on age, UGT isoenzymes and flavonoid structure. Future research in humans is warranted to determine whether the putative health benefits of flavonoids are different between young and older adults. This study is the first demonstration of age-related changes in flavonoid metabolism.

4. LAB: Carotenoids and Health. Developed a Rapid Analysis Method Determining Phenolics in Plant Extract. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, developed a rapid analysis method determining phenolics in plant extract (Angelica keiskei and Glycine max) using a high resolution mass spectrometry coupled with informatics. This newly developed instrumentation method can further evaluate the phytonutrients in plant foods and benefit for agriculture plant choices. This accomplishment is significant because it provides a powerful and rapid new method to analyze bioactive components in plant foods.

5. LAB: Carotenoids and Health. Lutein and Zeaxanthin Intake are related to Eye Health. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, found accurate assessment of intake of lutein and zeaxanthin that are selectively taken up into the macula of the eye may protect against the development of age-related macular degeneration. This is important in understanding of their individual roles in eye health. We analyzed the top major food sources for lutein and zeaxanthin intake in NHANES (National Health and Nutrition Examination Survey) 2003-2004 by high-performance liquid chromatography. The results were applied to dietary data from 8,525 participants in NHANES 2003-2004. Our findings suggest that the relative intake of lutein and zeaxanthin may be important to age-related macular degeneration risk and the individual intake of lutein or zeaxanthin may be associated with eye health. These data provide the basis for defining the adequate intake of lutein and zeaxanthan for optimal eye health.

6. LAB: Carotenoids and Health. High Beta Carotene Maize Effectively Converts to Vitamin A in Zimbabwean Men. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, reported that biofortified high beta carotene maize and its conversion to vitamin A were studied in Zimbabwean men. The volunteers consumed intrinsically labeled high betacarotene yellow maize. The results showed a very effective conversion of maize beta carotene to vitamin A (3.2 unit of beta carotene provided 1 unit of vitamin A by weight). The results provided a strong evidence that high beta carotene yellow maize is very effective dietary source for vitamin A and thus to help combat vitamin A deficiency in maize eating populations around the world.

Review Publications
Li, S., Liu, Y., Chang, W., Chen, C., Chen, C., Liu, J. 2011. Almond consumption improved glycemic control and lipid profiles in patients with type 2 diabetes mellitus. Metabolism. 60:474-479.

Shih, C., Chen, C., Liu, J., Chen, C., Lin, H., Chou, H., Li, S. 2010. Riboflavin protects mice against liposaccharide-induced shock through expression of heat shock protein 25. Food and Chemical Toxicology. 48:1913-1918.

Sandberg, M.A., Johnson, E., Berson, E.L. 2010. Macular pigment optical density is related to serum lutein in retinitis pigmentosa. Investigative Ophthalmology and Visual Science. 51(2):1086-1091.

Mckay, D.L., Chen, C., Saltzman, E., Blumberg, J.B. 2010. Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults: a randomized, placebo-controlled clinical trial. American Journal of Clinical Nutrition. 140(2):298-303.

Chen, C.E., Crott, J., Liu, Z., Smith, D. 2010. Fructose and saturated fats predispose hyperinsulinemia in lean male rat offspring. European Journal of Nutrition. 49(6):337-343.

Tang, G. 2010. Bioconversion of dietary provitamin A carotenoids to vitamin A in humans. American Journal of Clinical Nutrition. 91(5):1466S-1473S.

Milbury, P.E., Kalt, W. 2010. Xenobiotic metabolism and berry flavonoid transport across the blood brain barrier. Journal of Agriculture and Food Chemistry. 59(7):3950-3956.

Milbury, P.E., Vita, J.A., Blumberg, J.B. 2010. Anthocyanins are bioavailable in humans following an acute dose of cranberry juice. Journal of Nutrition. 140(6):1099-1104.

Correa, C.R., Li, L., Aldini, G., Carini, M., Chen, O., Chun, H., Cho, S., Park, K., Russell, R.M., Blumberg, J.B., Yeum, K. 2010. Composition and stability of phytochemicals in five varieties of black soybeans (glycine max). Food Chemistry. 123:1176-1184.

Aldini, G., Regazzoni, L., Pedretti, A., Carini, M., Cho, S., Park, K., Yeum, K. 2011. An integrated high resolution mass spectrometric and informatics approach for the rapid identification of phenolics in plant extract. Journal of Chromatography A. DOI: 10.1016/j.chroma.2011.02.065.

Muzhingi, T., Gadaga, T., Siwela, A., Grusak, M., Russell, R., Tang, G. 2011. Yellow maize with high (beta)-carotene is an effective source of vitamin A in healthy Zimbabwean men. American Journal of Clinical Nutrition. 94(2):510-519.

Last Modified: 06/22/2017
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