Human Bioavailability Trials with High Selenium Foods

Anna S. Keck1 and John W. Finley2

1 Dep. of Food Sciences & Human Nutrition, University of Illinois, Urbana IL2USDA/ARS, Grand Forks Human Nutrition Research Center, Grand Forks ND

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

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Keck et al., In Press

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 Se-accumulator 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 (plasma & Testis)

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Dietary Selenium (ug/g)

APlasma

Keck et al., In Progress

Selenate Broccoli Beef Wheat

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sma

Se (

ng/

mL

)

Accumulation:Se from beef >>Se from broccoli & wheat ~selenate

Accumulation of Selenium in Tissues

-Non-Plateauing (liver, prostate, muscle, kidney, spleen)

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CMuscle Selenate Broccoli Beef Wheat

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Accumulation:Se from beef >> Se from wheat & broccoli >> Selenate

Accumulation of Selenium in Tissues

-Linear

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Dietary Se (ug/g)

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in S

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g/g)

Selenate Broccoli Beef Wheat

Keck et al., In Progress

Accumulation in Brain:Se from beef >> Se from wheat & broccoli >> Selenate

Thioredoxin Reductase Activity

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Dietary Selenium (ug/g)

BColon

Selenate Broccoli Beef Wheat

Keck et al., In Progress

Activation of Selenoprotein activity:Se from broccoli & wheat >> Se from beef & Selenate

Selenium in Foods

NH3

COOH

WHEAT

CH-CH2-CH2-Se-CH3Selenomethionine

Transulfuration pathway

NH3

COOH

CH-CH2-SeHSelenocysteine

General proteins Lyase

SeH2SeO4 SeO3 GS-Se-SG

LyaseGSH GSH

NH3

COOHCH-CH2-Se-CH3

Se-methyl-selenocysteine

H-Se-CH3

Lyase

CH3-Se-CH3 BREATH

tRNA-C-C-COH

O tRNA-serine

tRNA-C-C-C-SeH

O

Lyase

CH3-Se-CH3

tRNA-selenocystein

Selenoprotein incorporation

CH3URINE

MEAT

MEAT

BROCCOLIGARLIC

SELENATE SELENITE

GSH-Px (5)deIodinase (3)Selenoprotein pSelenoprotein WTRSelenophosphate synthase 215kDa selenoprotein18kDa selenoprotein

Human Selenium-Foods Trials

1. Consumption of Se from Whole Wheat Cereal by Se-Adequate Men, Grand Forks Human Nutrition Center, USDA-ARS

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 Selenium-Adequate 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

12wk100 g cereal/day

whole wheat~56 or 306 g Se/d

4 wk100 g cereal/day refined wheat

~56 g Se/d

Design:

Plasma Selenium

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baseline post

Plas

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Se (n

g/m

l)

Se-Wheat Wheat

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Selenium fromwheat increasedplasma seleniumby 42%

Glutathione Peroxidase Activity in Red Blood Cells

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baseline post

GSH

-Px

(mU

nits

/min

)

Se-Wheat Wheat

Seleniumhad no effect

Non-Significant Data Collected C-reactive protein

VLDL Triglycerides Catalase SOD

Ongoing AnalysisDNA damage in WBCExercise –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)

9 g for 6weeks 90 g for 6weeks2 wk washout

Design:

-Self selected diet

Plasma Selenium

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Se-B B+Se B

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Selenium from broccoliincreased plasmaselenium by 12 %

Non-Significant Data Collected C-reactive protein VLDL Triglycerides ECSOD T3, free T3 T4, free T4

Ongoing AnalysisDNA damage in WBCPlasma 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

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Conc Change Conc Change Conc Change Conc Change

Broccoli Wheat Beef Control

Treatments

Se

(ng

/mL

)

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*Significantly differentfrom control (p = 0.001)

Mean +/- Std error

All foods were equallyeffective in increasingblood selenium concentrations

Total Daily Urine Excretion of Selenium

Different letters indicate significant differences (p<0.05)

Mean +/- Std error

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Broccoli Wheat Beef Control

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ne

Se

(g

/day

)

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bb

a

More selenium from broccoliand beef excretedinto urinethan from wheat

China study

Data collection is finishedAnalysis ongoingEndpoints:

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

AcknowledgementGrand Forks Human Nutrition Research Center:John W. Finley, PhD Brian Gregoire Taylor Jepson Korry Hinze, PhD Pete Leary Kevin Miller, PhD Karl Wald, PhD

Cindy Davis, PhD (at NCI)Bonnie Hoverson and Kitchen staffSandy Gallager & Clinical/nurse staffLuAnn JohnsonEmily Neilson

Fundings: IFAFS-USDA, General Mills

National Institute of Nutrition& Food Safety, Chinese CenterFor Disease Control & PreventionJunquan Gao, PhDX. Li

Oregon State University:Phil Whanger, PhD

University of Illinois:Elizabeth H. Jeffery, PhD