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Human Bioavailability Trials with High Selenium Foods Anna S. Keck1 and John W. Finley2 Dep. of Food Sciences & Human Nutrition, University of Illinois, Urbana IL 2 USDA/ARS, Grand Forks Human Nutrition Research Center, Grand Forks ND 1 Grand Forks,ND November 4, 2004 Sources and Amounts of Selenium How much selenium is optimal? 50-100 g Se/d sufficient to prevent deficiencies (based on intake observations in areas where there are no signs of deficiency) Selenium may provide cancer protective effects at higher levels; ~150 -400 g Se/d Dietary sources of selenium: Meat, grains (wheat) & Brazil nuts 700 700
600 600 500 500 400 400 150 150 100 100 50 0 Keck et al., In Press 50
0 Selenium Toxicity High dosages of selenium can be toxic: a total intake of 1,000 g Se/d on a regular basis may lead to toxicity (as reported in 1 Chinese village) Typical signs of selenium toxicity hair and nail loss brittle nails or hooves and GI-tract disturbances In the northern Great Plains of the US has the highest selenium levels of the country: cattle and horses can develop "blind staggers," a debilitating hoof disease caused by eating high-Se grains and Seaccumulator plants such as locoweed (Astragalus) Selenium Accumulator Plants Crucifers that accumulate selenium include canola, Brussels sprouts, Indian mustard & broccoli Other selenium-accumulator plants: garlic & onion Much of the selenium in accumulator plants is in the form of selenium analogs of sulfur amino acids & methylated seleno amino acids
Irion (1999), Med Hypotheses 53, 232-5 Kotrebai et al (2000) Analyst 125, 71-8 Does the Chemical Form of Selenium Matter? Inorganic Salts Sodium selenite was used in the Keshan disease intervention study, given as a 500 or 1,000 g tablet /wk Used in most lab animal studies Selenomethionine (SeMet) -Commonly found Se in food The amino acid methionine with Se substituted for the S Dominant form of selenium in high-Se yeast -used in the cancer intervention studies Organic forms of selenium are less toxic than inorganic forms Different selenium forms have different degrees of bioavailability Accumulation of Selenium in Tissues -Plateauing 1.5 (plasma & Testis)
Plasma Se (ng/mL) A Plasma Selenate Broccoli Beef Wheat 1.0 0.5 0.0 0 0.5 1 1.5 2 Dietary Selenium (ug/g)
Accumulation: Se from beef >>Se from broccoli & wheat ~selenate Keck et al., In Progress Accumulation of Selenium in Tissues -Non-Plateauing 1.5 (liver, prostate, muscle, kidney, spleen) C Muscle Selenate Broccoli Beef Wheat 1.0 0.5 0.0 0
0.5 1 1.5 2 Dietary Selenium (ug/g) Accumulation: Se from beef >> Se from wheat & broccoli >> Selenate Keck et al., In Progress Accumulation of Selenium in Tissues -Linear Accumulation in Brain: Se from beef >> Se from wheat & broccoli >> Selenate 0.6 Brain Se (ug/g) 0.5 0.4 0.3
0.2 0.1 0 0 0.5 1 1.5 2 Selenate Broccoli Beef Wheat Dietary Se (ug/g) Keck et al., In Progress Thioredoxin Reductase Activity Selenate Broccoli Beef Wheat
Activation of Selenoprotein activity: Se from broccoli & wheat >> Se from beef & Selenate Keck et al., In Progress Selenium in Foods MEAT WHEAT NH3 COOH NH3 Transulfuration pathway CH-CH2-CH2-Se-CH3 Selenomethionine COOH General proteins Lyase SELENATE SELENITE SeO3
CH3-Se-CH3 O tRNA-selenocystein BREATH Lyase CH3-Se-CH3 CH3 tRNA-C-C-C-SeH URINE Selenoprotein incorporation GSH-Px (5) deIodinase (3) Selenoprotein p Selenoprotein W TR Selenophosphate synthase 2 15kDa selenoprotein 18kDa selenoprotein Human Selenium-Foods Trials
1. Consumption of Se from Whole Wheat Cereal by Se-Adequate Men, Grand Forks Human Nutrition Center, USDAARS 2. Consumption of Se from Broccoli by Se-Adequate Men, Grand Forks Human Nutrition Center, USDA-ARS 3. Consumption of Se from High-Se Foods by Se-Deficient Men, Xichang county, Sichuan province, China Criteria for Participating in the Human Selenium-Food Trials at the GFHNRC Male 18-45 years old Healthy Non-smoking No prescription drug or supplement use Willing to eat only food and drinks provided by GFHNRC for ~16 weeks (Wheat study only) Se-Wheat Trial:Consumption of Selenium
Enriched Whole Wheat Cereal by SeleniumAdequate Men Dietary Treatments: 1.High Se-Wheat Cereal (Se-W) Grown in South Dakota 2.Low Se-Wheat Cereal (W) Both wheat cereals made by a food company Design: 4 wk 100 g cereal/day refined wheat ~56 g Se/d 12wk 100 g cereal/day whole wheat ~56 or 306 g Se/d Plasma Selenium PlasmaSe(ng/ml) 200 *
150 Selenium from wheat increased plasma selenium by 42% 100 50 0 baseline Se-Wheat post Wheat GSH-Px (mUnits/min) Glutathione Peroxidase Activity in Red Blood Cells 60 50 40 30 Selenium
had no effect 20 10 0 baseline Se-Wheat post Wheat Non-Significant Data Collected C-reactive protein VLDL Triglycerides Catalase SOD Ongoing Analysis
DNA damage in WBC Exercise oxidative stress Se-Broccoli Trial: Consumption of Selenium Enriched Broccoli by Selenium-Adequate Men Dietary Treatments: High Se Broccoli (Se-B, 27 or 270 g/Se) Low Se broccoli + sodium selenate (B+Se, 27 or 270 g/Se) Low Se Broccoli (B, 0.27 or 2.7 g/Se) Design: 9 g for 6weeks -Self selected diet 2 wk washout 90 g for 6weeks Plasma Selenium 160 Plasma Se(ng/mL)
* 120 Selenium from broccoli increased plasma selenium by 12 % 80 9 Amount (g) Se-B B+Se 90 B Non-Significant Data Collected
C-reactive protein VLDL Triglycerides ECSOD T3, free T3 T4, free T4 Ongoing Analysis DNA damage in WBC Plasma Selenoprotein distribution China study: Consumption of Selenium-Foods by Selenium Deficient Men Dietary Treatments: 1.Low Se foods, 4.2 g Se/d (beef, wheat & broccoli) 2.High-Se broccoli,100 g Se/d (low beef & wheat) 3.High-Se wheat,100 g Se/d (low beef & broccoli) 4.High-Se beef,100 g Se/d (low broccoli & wheat) Location: Xichang county (Se-deficient region), Sichuan province, China 60 healthy men (19-45 old,15/ grp)
Consumed 1 food package (~25g dry) daily for 3 months Blood Selenium of Chinese Men Consuming 100 g Se/d as Broccoli, Wheat or Beef for 3 Months 160 * 120 * Se (ng/mL) * * 80 All foods were equally effective in increasing blood selenium concentrations *
Control Treatments *Significantly different from control (p = 0.001) Mean +/- Std error 60 Total Daily Urine Excretion of Selenium b b Urine Se (g/day) 50 a 40 30 a
20 10 More selenium from broccoli and beef excreted into urine than from wheat 0 Pre Post Broccoli Pre Post Wheat Different letters indicate significant differences (p<0.05) Pre
Post Beef Pre Post Control Mean +/- Std error China study Data collection is finished Analysis ongoing Endpoints: Retention of stable isotope intrinsically incorporated into food EEGs, (resting/evoked) cognitive testing Selenium status WBC COMET Summary Selenium from wheat and beef accumulate more in animal tissues than sodium selenate salt or selenium from broccoli Selenium from wheat accumulates more in
plasma than selenium from broccoli in selenium-adequate men (42% vs. 12%) In selenium-deficient humans, selenium from wheat, beef and broccoli were equally effective in accumulating in blood (2.1-2.5-fold) but more selenium from broccoli and beef was excreted in the urine than from selenium wheat Acknowledgement Grand Forks Human National Institute of Nutrition Nutrition Research Center: & Food Safety, Chinese Center John W. Finley, PhD For Disease Control & Prevention Brian Gregoire Taylor Jepson Korry Hinze, PhD Pete Leary Kevin Miller, PhD Karl Wald, PhD Junquan Gao, PhD X. Li Oregon State University: Phil Whanger, PhD
University of Illinois: Cindy Davis, PhD (at NCI) Bonnie Hoverson and Kitchen staff Elizabeth H. Jeffery, PhD Sandy Gallager & Clinical/nurse staff LuAnn Johnson Emily Neilson Fundings: IFAFS-USDA, General Mills
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