12 Antioxidants

8/10/2019 12 Antioxidants

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Antioxidants

Nutrition Concepts and

Controversies (FNH 250)


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I. Antioxidants, Oxidation, & Free Radicals1. WHAT ARE ANTIOXIDANTS?

b. Function

l reduce naturally-occurring reactive oxidizingspecies (ROS=oxidants) in the body, or damage

caused by ROS, which have one unpaired electronin their outer orbital

l antioxidants inhibit oxidant formation, intercept

oxidants once they are formed,

ROOH +

OH

O

OH

O

ROO+

OH

OOH

OH


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I. Antioxidants, Oxidation, & Free Radicals2. OXIDATION & FREE RADICALS

l during metabolic reactions, electrons can betransferred between atoms

l bonds between molecules can split in a way that

leaves atoms in the molecules with an unpaired,odd electron

l oxidation = loss of electron

l reduction = gain of electron

l sustained oxidation of CHO, PRO and FAT

necessary to


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I. Antioxidants, Oxidation, & Free Radicals

Oxidation = loss of electron

Reduction = gain of electron


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I. Antioxidants, Oxidation, & Free Radicals

2. OXIDATION & FREE RADICALS

l usually there is an even exchange of electrons in

metabolic exchange reactions, however,

occasionally an unpaired electron in the outermost

orbital does not get paired with another electron,

and remains unpaired; this destabilizes the atom

(or molecule) =


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l free radicals are highly reactive and can damage:cell membranes (lipids), cellular proteins, bloodLDL lipoproteins, and nuclear DNA (may initiate

cancer)

l examples of free radicals include: superoxideradical (O2), hydroxyl radical (OH), nitric oxide

(NO)

l many metabolic processes can produce free

radicals (e.g. immune responses,


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l also oxygen can accept an extra electron released in ametabolic reaction (e.g., in electron transport chain) toform a free radical

l free radicals are also produced by environmentalfactors: pollution, radiation exposure, exposure toultraviolet light, toxic substances, tobacco smoke

l free radicals gain stability by reacting with othercompounds (antioxidants) through a series of chain

reactions


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Lipid Oxidation

LH Free radicals (L + H)

Unsaturated lipidInitiator

INITIATION

L + O2 Peroxy radical (LOO)

PROPOGATION

LOO + LH LOOH + L


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Lipid OxidationAntioxidants (AH) can break this chain reaction by

reacting with LOO to form stable radicals (A) which

are either too unreactive or form non-radical products:

A + A

Non-radical products

A + LOO

LOO + AH LOOH + A

2A

LOOR

TERMINATION


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I. Antioxidants, Oxidation, & Free Radicals3. COMMON ANTIOXIDANT NUTRIENTS

l vitamin antioxidants (vitamins E, A, beta-carotene,and C) donate electrons to create paired electrons inthe outer orbital of the free radical thus quenching the

chain reaction and any damaging effect

l mineral antioxidants are required for antioxidantenzyme systems that destroy free radicals

l ex. superoxide dismutase (Cu, Zn, Mn), catalase(Fe), glutathione peroxidase (Se)


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FAT-SOLUBLE VITAMIN ANTIOXIDANTS

- Vitamins E, A and Beta-CaroteneAbsorption/Transportation/Storage of Fat-Soluble

Vitamins

l absorbed with dietary fat, incorporated intochylomicrons for transport into body

l liver = major site of storage for fat-soluble vitamins,except for vitamin E stored in fat cells

l due to storage, the risk for toxicity of fat-soluble

vitamins is greater than for water-soluble vitamins

l any fat malabsorption or intestinal disease (e.g.,

celiac, Crohns, AIDS) can lead to a deficiency of fat-soluble vitamins,


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II. VITAMIN E1. FORMS OF VITAMIN E

l TOCOPHEROL family of ~8 different compoundssynthesized by plants

l alpha-tocopherol active in human body

l fat-soluble vitamin found with fat in foods

absorption ranges from 20-70% of intake

l stored primarily in fat tissue (~90%);


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II. VITAMIN E2. FUNCTIONS OF VITAMIN E

a.Antioxidant Role in Maintaining Cell MembraneIntegrity

l vitamin E found in cell membranes where it

captures free radicals (often oxygen-based) thatdamage polyunsaturated fatty acids (PUFA)present in the phospholipids of the membrane

l special antioxidant role in the lung cellmembranes due to constant exposure to oxygen

l vitamin E also resides in mitochondrial and

nuclear membranes, protecting DNA and othercell compounds from oxidizing damage

l a lack of vitamin E may alter DNA and


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II. VITAMIN E2. FUNCTIONS OF VITAMIN E

b. Reduced Platelet Aggregation Protection AgainstHeart Disease

l inhibits enzyme (protein kinase C) needed for platelet

aggregationOther Functions

l protection of LDL from oxidation

l needed for iron metabolism in body (maintains RBCmembrane integrity)

l

proper immune functionl needed for maintenance of nerve and immune systems


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II. VITAMIN E3. SELENIUM A SPARING EFFECT ON VITAMIN E

l Selenium reduces the production of free radicalsthrough its antioxidant role, thus reducing thequantity of free radicals for vitamin E to neutralize

4. VITAMIN E DEFICIENCY

l in neutralizing the damaging free radicals, vitamin Ecan be broken down and lost from the body, needs

to be replaced

l clinical symptoms of deficiency not commonly seen,


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II. VITAMIN E4. VITAMIN E DEFICIENCY

l at greatest risk: preterm infants (esp. those with fatmalabsorption conditions e.g. Cystic Fibrosis)

l babies born before the transfer of vitamin E from

the mother has occurred during the last fewweeks of pregnancy

l loss of red blood cell (RBC) membrane integrity is

called ERYTHROCYTE HEMOLYSIS which canlead to HEMOLYTIC ANEMIA

l oral supplementation provided to preterm infants

l in adults see neuromuscular disorders, fibrocystic

breast disease


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II. VITAMIN E5. VITAMIN E TOXICITY

l relatively non-toxic (even as a fat-

soluble nutrient), wide safety range, %

absorption inverse to intakel vitamin E (usually supplemental levels)

can augment effects of anticoagulants

(e.g. aspirin, warfarin)


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II. VITAMIN E7. DRI-RDA

l all adults: 15 mg/day

l usual intakes insufficient to meet RDA

l new system = mg -old system = IU

l 1.5 IU = 1 mg active D--tocopherol = 1Tocopherol Equivalent (TE)

DRI-UL

l all adults 1000 mg/d


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III. VITAMIN C2. VITAMIN C FUNCTIONS

l vitamin C is needed for:

a. Collagen Synthesis

l vitamin C maintains Iron (Fe) in it's active form whichis required for the synthesis of collagen, a fibrous

structural protein that forms the base for all

connective tissues


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b. Antioxidant Property water-soluble antioxidant

l donates electron to damaging free radical to

inactivate damaging actionl acts in intracellular and extracellular fluid

compartments

l decreases formation of carcinogenic substances(nitrosamines) in the stomach

l keeps folate coenzyme (THF) intact

l restores vitamin E to active antioxidant form after


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c. Enhances Iron Absorption

l keeps iron in the Fe2+ (ferrous) form increasedabsorption at intestine

l vitamin C increases absorption


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Other Functions

l Synthesis and Functioning of Vital Cell Compounds

l vitamin C necessary for activation and function ofimmune cells

l vitamin C also necessary for synthesis of: thyroid

hormone, epinephrine, steroid hormones,


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III. VITAMIN C3. VITAMIN C DEFICIENCY what and who

l leads to widespread destruction of tissue due to it's

reducing properties and it's role in collagen

synthesis; wounds fail to heal

a.Scurvy symptoms: weakness, pinpoint

hemorrhages on arms and legs, bleeding gums,

loose teeth, impaired wound healing, painful joints

start after 30 days on vitamin C-free diet

l ~5 days @100mg/day


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III. VITAMIN C

Common symptoms include pinpoint bleeding aroundhair follicles, along the gums, and under the nails


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III. VITAMIN C3. VITAMIN C DEFICIENCY what and who

b. Alcoholics at risk, especially if consuming a

nutrient-poor diets

c. Smokers lower body levels of vitamin C, due tovitamin C being used to combat the oxidants

produced by cigarette smoking; RDA +35mg/day

over non-smoker RDA

d. Burn patients


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III. VITAMIN C4. VITAMIN C TOXICITY

l MEGADOSE = =10X DRI (90 or 75 mg/d >900or 750 mg/d)

a.Claims Attributed to Megadoses of Vitamin C

l common cold - no conclusive evidence for

reducing incidence of colds

l if taken before the cold takes hold, vitamin Cmay reduce the symptoms

l cancer -


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III. VITAMIN C4. VITAMIN C TOXICITY

b. Increased Susceptibility to Kidney Stone

Formation increased urine

concentration

c. Vitamin C and Iron vitamin C releases

Iron from its storage protein, free Iron can

act as a PRO-OXIDANT damaging to

the cell

d. Rebound Scurvy


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III. VITAMIN C5. VITAMIN C IN FOODS

l mostly vegetables and fruits (especially citrus)

l Losses in Food Preparation easily lost inprocessing & cooking, lost with excessive heat,

losses with prolonged exposure of cut surfaces toair, exposure to baking soda in cooking

6. DRI-RDA

l adults: males 90 mg/d females 75 mg/d

l active smokers: add 35 mg/d

l passive smokers: ensure getting RDA

l DRI-UL -all adults 2000 mg/d


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IV. BETA-CAROTENE1. FORMS OF VITAMIN A

a. RETINOIDS are PREFORMED vitamin A ready forimmediate use by the body

b. CAROTENOIDS are the PROVITAMIN A form that canbe converted into retinoids or used as is

l found in plant foods (the original source of all vitamin Ain nature)

l Carotenoids: >600 different pigments; ~50 in human diet

l examples: -carotene, -carotene, lutein, lycopene,cryptoxanthin, zeaxanthin

l carotenoids are absorbed as is and stored in adiposetissue or in the liver where they are converted to retinal,OR

l if retinol is needed in the body, -carotene can be split in


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IV. BETA-CAROTENE1. FORMS OF VITAMIN A

b. CAROTENOIDS are the PROVITAMIN A form that

can be carotenoids are transported to the liver in

chylomicrons and from the liver attached to retinol-binding protein (RBP) to target tissues


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IV. BETA-CAROTENE computing

Presentation copyright 2002 David A Bender and some images copyright 2002 Taylor & Francis Ltd

CH3

CH2OH

CH3 CH3CH3CH3

retinol

CH3

COOH

CH3 CH3CH3CH3

retinaldehyde

all-t rans-retinoic acid

CH3

CHO

CH3 CH3CH3CH3

CH3

CH3

H3C

COOH

CH3 CH3

9-c is-retinoic acid

CH3

CH3CH3CH3

CH3

CH2OH11-c is-retinol


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IV. BETA-CAROTENE2. FUNCTIONS OF -CAROTENE

a. Antioxidant

l carotenoids act as antioxidants to neutralize freeradicals, especially lipids in cell membranes and

LDL may reduce risk for cancer andatherosclerosis


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IV. BETA-CAROTENE2. FUNCTIONS OF -CAROTENE

b. Immune Function

l -carotene needed for immune system to fightagainst infections

c. Skin Health

l -carotene thought to protect skin against sun

damage

d. Vision

l -carotene protects eyes against


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IV. BETA-CAROTENE5. -CAROTENE IN FOODS

l plant foods only

l dark green and orange vegetables: ex. broccoli,spinach, kale, squash, yams, pumpkin, carrots

l orange and red fruit: ex. mango, papaya, apricots,

cantaloupe, tomatoes, red bell peppers

l Food Preparation moderate cooking can enhanceavailability of -carotene

6. -CAROTENE RECOMMENDATIONS

l no DRI due to lack of conclusive evidence for


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V. VITAMIN A1. FORMS OF VITAMIN A

a. RETINOIDS are PREFORMED vitamin A ready for immediate use by the body

l retinol REPRODUCTION (retinyl esters found in

foods); mostly stored in liver

l retinal VISION

l retinoic acid GROWTH & DEVELOPMENT

l found in animal foods and supplements

l high absorption can be toxic,


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V. VITAMIN A2. FUNCTIONS OF VITAMIN A

a. Antioxidant

l retinol quenches (neutralizes) free radicals

l protects LDL from oxidation may reduce risk for

cancer and atherosclerosis

b. Vision

l rods and cones in retina at back of eye require

vitamin A

l cornea at front of eye requires vitamin A


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V. VITAMIN A

Rod and cone photoreceptor cells are the principal light

detecting cells in the retina.Rods: long, thin, & more numerous than the cone cells, more

important for night & peripheral vision

Cones: conical, critical role in detailed vision & central vision.


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In the presence of light the retinal changes from a cis form

to a trans form (also referred to as "bleached"). Thishappens very quickly as the rhodopsin dissociates into it's

components in the presence of light. The reassembly of

the opsin and retinal is relatively slow.

Rhodopsin

Retinal Opsin

Sensitiveto colourSensitiveto light


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V. VITAMIN A2. FUNCTIONS OF VITAMIN A

c. Growth, Development and Reproduction

l cell differentiation needed to code for specificproteins

l bone vitamin A needed to break down old bone(osteoclasts) to permit bone turnover

d. Health of Mucous Membranes in Epithelial Tissue

l protects against infection in eyes, urinary tract, skin,lungs, etc.

e. Immune Function

l needed for production of immune cells (e.g. T-cells)


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V. VITAMIN A

vitamin A

(retinal)

opsin

(protein in eye)

Rhodopsin

(in rods)

+ some retinal

opsin

additional

vitamin A

because

some is lost

signal

to brain

+

3. VITAMIN A DEFICIENCY

it takes 1-2 years of not consuming vitamin A-rich foods to

see deficiency symptoms in adults

a. Vision (night blindness, Xerophthalmia)

i) NIGHT BLINDNESS retina


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V. VITAMIN A3. VITAMIN A DEFICIENCY

a. Vision

l clear sight will not resume until rhodopsin isregenerated with new retinal supply from blood

l low intakes slow recovery from flashes of lightunder dim conditions

l can progress to


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b. Growth, Development & Reproduction

l animals with vitamin A deficiency cannot reproduce

l children fail to grow properly

l a deficiency early in life can cause abnormal jaw

bone growth resulting in crooked teeth and poor

dental health


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c. Health of Mucous Membranes in Epithelial Tissue

l a lack of vitamin A can lead to a reduced mucousproduction and KERATINIZATION of cells hard,

cracked skin & increased infection risk anddecreased absorption at intestinal cells

d. Immune Function

l children in developing countries have a high

incidence of measles

l the severity of their illness corresponds with theirdeficiency of


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V. VITAMIN A4. VITAMIN A TOXICITY

a. Causes

l medical treatment for serious acne with Retin-A (topical) orAccutane (oral)

l very high risk for fetal malformation if taken duringpregnancy TERATOGENIC; Since the introduction of

Accutane in1982, ~ 160,000 women of child bearing age

have ingested the drug. Between 1982 and 1987, ~ 900-1300 malformed children, 700-1000 spontaneousabortions and 5000-7000 elective abortions were due to

Accutane exposure.

hydrocephaly, ear malformations, cardiovasculardefects and IQ

Accutane carries a pregnancy category X warning,.


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b. Symptoms

l loss of appetite

l headaches

l dry skin

l nausea

l blurred vision

l bone defects

l

enlarged liver/spleen


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c. Types

l ACUTE toxicity single large dose (e.g. =200,000g RAE)

l CHRONIC toxicity ~10X DRI (retinoids only)

l TERATOGENIC toxicity associated with

increased vitamin A intake during pregnancy


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V. VITAMIN A5. VITAMIN A IN FOODS

dark green vegetables

spinach, broccoli

dark orange vegetables yams,carrots

fruits apricots, papaya,

cantaloupe, mango

breakfast cereal fortified

liver (pt)

fish oils

fortified milk

Eggs

margarine fortified

Cheese, Butter

~ 50% vitamin A in diet Non-toxic

~ 50% vitamin A in diet Can be toxic

PLANT FOODS (Carotenoids)ANIMAL FOODS (Retinoids)

Food Preparation moderate cooking


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V. VITAMIN A6. VITAMIN A RECOMMENDATIONS

l DRI-RDA (Dietary Reference Intake Recommended Dietary Allowance t)

l adults males: 900 g/d

females: 700 g/d

l narrow safety range for RETINOIDS, choose

foods over supplements

l DRI-UL (Dietary Reference Intake TolerableUpper Limit)

l all adults 3000 g/d (preformed Vitamin Aonly


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EWCFG: Choose at least one dark green and oneorange vegetable each day


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RETINOL ACTIVITY EQUIVALENTS (RAE)

l new system for measuring vitamin A activity in different

carotenoids equal to that provided by 1 g retinol

l 1 g RAE = 1 g retinol = 2 g -carotene (supplemental) =12 g -carotene (dietary) = 24 g other carotenes

l old system of measuring vitamin A activity used IU

(International Units), still used on labels of vitaminsupplement containers

l 1 g retinol = 3.3 IU of retinol or 6.6 IU of -carotene

(supplemental) or 20 IU of -carotene (dietary)

l 1 IU retinol = 0.3 g RAE; 1 IU -carotene (supplemental)= 0.15 g RAE; 1 IU -carotene (dietary) = 0.05 g RAE


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TRACE MINERAL ANTIOXIDANTS

Selenium, Copper, Zinc, Manganese, IronTrace Minerals

l needed in quantities of


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VI. SELENIUM1. INTRODUCTION

l absorption doesn't seem to be physiologicallycontrolled, but homeostasis in the body is controlledby the kidneys increased potential for toxicity,

especially if taking supplementsl found mostly associated with amino acids:

selenomethionine (storage Se) and selenocysteine


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VI. SELENIUM2. FUNCTIONS OF SELENIUM

a. Antioxidant Role

l Selenium is a cofactor for the glutathioneperoxidase (GPx) enzyme system that protects

against cell membranes destruction by freeradicals (riboflavin is a coenzyme for GPx)

l Selenium reduces the production of free radicals;

vitamin E neutralizes free radicals, therefore,Selenium has a


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VI. SELENIUM computing

Presentation copyright 2002 David A Bender and some images copyright 2002 Taylor & Francis Ltd

HS CH2 CH

C

NH

O

NH CH2 COOH

C

O

CH2 CH2 CH

COOH

NH2

CH2 CH

COOH

NH2

CH2HOOC

C

N

HC CH2

O

CH2 C

HN

O

C

NH

HC CH2 S

CH2

O

C

COOHCH2NH

O

NH

C

CHCH2S

H2

HOO

glutathione peroxidase

NADPH

NADP+

glutathione reductase

2 x reduced glutathione (GSH)

oxidised glutathione (GSSG)

lipid peroxide

fatty acid

reduction of lipid peroxides by glutathione peroxidase

a selenium-dependent enzyme

The antioxidant role of selenium


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VI. SELENIUM2. FUNCTIONS OF SELENIUM

b. Thyroid Hormone

l Selenium needed to convert T4 (thyroxine) to T3(triiodothyronine biologically active)

l thyroid hormones help regulate BMR, bodytemperature,


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VI. SELENIUM

O

C H2

C H

II

I

O H

I

C o o -+H3

N

O

C H2

C H

II

I

O H

C O O -+H3

N

Deiodinease is

Se-dependent

De-iodinase


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VI. SELENIUM3. SELENIUM DEFICIENCY

l deficiency seen in areas of the world where foodfrom other areas is often not transported in and thesoil is depleted of selenium

l Keshans disease (cardiomyopathy) damages heartmuscles.

l Kashin-Becks disease


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VI. SELENIUM4. SELENIUM TOXICITY

l =1 mg/day

l through the use of supplements

l symptoms: brittle nails and hairwith eventual loss, nervous system

abnormalities, distinct odour on

breath, fatigue, irritability


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VI. SELENIUM5. SELENIUM IN FOODS

l -Se is associated with PRO in foods

6. DRI-RDA

l adults: 55g/d

l typical intakes 2-5X RDA; no need for supplements

l DRI-UL

l all adults: 400 g/d

grains & seeds

grown in Se-rich soilsfresh produce grown

in Se-rich soils

meats (esp. organ meats)

Fish/shellfish

eggs

milk

Plant FoodsAnimal Foods


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OTHER TRACE MINERAL ANTIOXIDANTSl all of these trace minerals have multiple other roles

in the body

l food sources: plant and animal liver, meat, fish,poultry, legumes, nuts, seeds

VII. COPPER, ZINC, MANGANESEl required as cofactors by the SUPEROXIDE

DISMUTASE ENZYME system to protect against

oxidative damage in the cytoplasm (Cu, Zn) and inthe mitochondria (Mn) of cells

VIII. IRON (also see Blood Health notes)l integral component of CATALASE antioxidant

enzyme


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X. ANTIOXIDANTS & VISION IMPAIRMENTl antioxidants may assist in reducing our risk for age-

related macular degeneration and cataracts

l macular degeneration

l macula is in centre of retina and permits central

visionl adequate antioxidant nutrients to retina is one

factor that may help prevent or


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X. ANTIOXIDANTS & VISION IMPAIRMENTl cataracts

l cause cloudiness in the lens of the eye (focusingfunction)

l adequate antioxidant nutrient intake may reduce

free radical damage to the lens caused byexposure to UV light and oxygen

l current studies indicate inconclusive evidence for

antioxidant supplementation and reduced risk and/orprogression of


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XI. ANTIOXIDANTS & HEART DISEASEl Antioxidants (especially vitamin E and the

carotenoid, lycopene) may reduce our risk forcardiovascular disease typically by reducing

damage to our blood vessels, however, as withcancer,


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XI. ANTIOXIDANTS & HEART DISEASEl Potential antioxidant actions may include:

l Scavenging free radicals to prevent oxidativedamage to LDL, thus reducing risk for plaquebuild-up

l Enhancing immune function to reduce low gradeinflammation and potential breaking off of plaquefrom wall of blood vessel to form blood clot

l Inhibiting blood coagulation and reducing bloodclot formation

l Epidemiological studies indicate a lower risk for

CVD in men and women whose whole foodconsumption is high in fruits and vegetables effectof other substances


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XII. PHYTOCHEMICALSl some examples:l carotenoids

l lycopene: tomatoes, watermelon, papaya,apricots, pink grapefruit

l lutein: vegetables, fruit

l phytoestrogensl lignans & isoflavones: flaxseeds, soybeans

l phytosterols

l saponins & -sitosterol: soybeans, legumes,some margarines

l flavonoids

l anthocyanins: blueberries, other berries, fruits,citrus fruits, grapes (red wine), vegetables,onions, tea

12 Antioxidants

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