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Vitamins

Readings:– Chapters 9 & 10

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Outline- Overview- Bioavailability - minimizing losses- Classification

- Fat versus Water soluble

- Function, Recommendations, Sources, Deficiency, Toxicity- Fat Soluble - A,D,E and K- Water Soluble - B vitamins and C

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Overview

Characteristics of Vitamins: “vital to life”

• do not yield energy

• organic

• only required in small amount (mg or g)

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OverviewWhat to study…• know the characteristics and functions,

effects of deficiency and toxicity for each• be able to identify or list rich sources of each• need to know specific RDA for folate and

Vitamin C

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Understanding Vitamins

True or False?– if a little is good, then a lot is better– vitamins are energy boosters– vitamins work exclusively of one another

Vitamins in Foods– all food groups are natural sources of various

vitamins– also founds in enriched and fortified foods

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Bioavailability• the rate and extent to which a nutrient is

absorbed and used

Determinants• efficiency of digestion & time of transit through

the digestive tract• previous nutrient intake & nutrition status• other foods consumed at the same time• method of preparation• sources of the nutrient

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Minimizing Vitamin Losses• vitamins are organic therefore susceptible to

destruction by:

• prevent losses through:– refrigeration of fruits and vegetables– storing cut vegetables, fruits, and juice in airtight

containers to reduce oxidation– wash fruits and vegetables before cutting– steam vegetables in small amounts of water, avoid over

cooking

HEAT, UV LIGHT or OXIDATION

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Classifications of Vitamins

• classified according to solubility in fat versus water

Water Soluble = B Vitamins and Vitamin C

Fat Soluble = Vitamins A, D, E, and K

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Fat vs. Water SolubleWater Soluble Fat Soluble

Vitamins B Vitamins, C A, D, E, & K

Absorption directly into blood with lipids into lymph

Transport none required require protein carriers

Storage free in aqueous compartments

in cells associated with fat

Excretion readily via kidneys not readily

Toxicity only from supplements more likely

Requirement frequently (every 1- 3 days)

periodically (weeks to months)

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Vitamin Absorption

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Vitamin AVitamin A is found in two forms:• retinoids

– derived from animal sources– preformed Vitamin A (biologically active from)– includes retinal, retinol, and retinoic acid

• carotenoids– derived from plant sources– pro-vitamin form, converted to retinoid form by body as needed– examples: -carotene (pro-vitamin),– lycopene, lutein (nonprovitamin) may have other beneficial

roles (antioxidant, vision, cancer prevention)

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Vitamin A: Functions1. Vision• retinal forms part of molecule called rhodopsin

– compound found in cells of the retina– important for converting a light stimulus to an

electrical stimulus– allows brain to interpret visual information

• Fig 9-7

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Vitamin A: Functions

2. Protein Synthesis and Cell Division

• promotes differentiation of:

- epithelial cells

- goblet cells

- T lymphocytes

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Vitamin A: Functions

3. Reproduction and Growth• retinol important for sperm development in

men• required for normal fetal growth• important for bone remodeling and growth

– assists osteoclasts by helping enzymes that breakdown bone

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Vitamin A: Functions3. Antioxidant:• carotenoids only!!! • donates an electron to oxygen free

radicals to prevent OFR from stealing them from other molecules, halts the chain of free radical production

Definition of free radical…– unstable and highly reactive atoms or molecules

that have one or more unpaired electron– steal electrons from other molecules such as LDL,

membrane lipids, proteins and others

Antioxidant

Free Radicals

DNA

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Vitamin A: RecommendationsRecommendations• expressed as RE (retinol equivalents) or RAE

(retinol activity equivalents)• 1 RAE = 1 g of retinol

– Supplemental Betacarotene - 2ug = 1 RAE– Dietary Beta-carotene - 12ug = 1 RAE– Dietary Carotenoids - 24ug = 1 RAE

• Adult RDA = 700 – 900 RAE per day

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Vitamin A: Sources

1 cup sweet potatoes

½ cup pumpkin

½ cup carrots

100% of RDA =

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Vitamin A: Deficiency

• one of most common nutrient deficiencies worldwide

• leading cause of preventable blindness

• deficiency due to lack of intake requires one to two years to develop to develop adults, develops more quickly in children

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Vitamin A: Deficiency

Symptoms & Consequences• first detectable sign =• increased incidence of infectious disease• xeropthalmia

– total blindness due to drying and hardening of the cornea

• keratinization– epithelial cells begin to secrete keratin

• hard inflexible protein in finger nails and hair

– decreased mucous production– skin becomes dry, rough and scaly

night blindness

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Vitamin A: Toxicity• vitamins A & D are the most toxic vitamins• only the retinoid form is toxic

– Upper Limit 3000 ug RAE as retinol– Over-consumption of carotenoids is not harmful because

conversion to retinoids is regulated• Carotenodermia - harmless orange coloration

Symptoms• nausea, vomiting, diarrhea• loss of appetite, fatigue, insomnia• headaches, blurred vision• dry itchy skin, rashes, nose bleeds• teratogenic: causes abnormal fetal development & birth defects -

stored for years limit intake during child bearing years– women need be careful if on Retin-A or Accutane for acne -

discontinue at least 2 yrs before becoming pregnant

On completion of your dietary analysis, you notice that your Vitamin A intake is 4x (400%) of the DRI.

- What are the potential health effects of this excess consumption?

- What other information do you need in order to justify your answer above?

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Vitamin D: Functions• also called calciferol or cholecalciferol• regulates the concentrations of calcium &

phosphate in the blood• promotes bone mineralization• supports immune system function• regulates cellular differentiation, proliferation,

and apoptosis (cell death)

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Vitamin D: Calcium Regulation

• works in conjunction with parathyroid hormone and calcitonin

• increases blood calcium (Ca2+) levels by three mechanisms:- stimulates Ca2+ absorption from the small

intestine- reduces Ca2+ excretion from kidney

- (by increasing re-absorption)

- mobilizes Ca2+ from bone

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Vitamin D: Recommendations & Sources

Recommendations• Adult = 5 g/day (200IU), requirements increase

after age 50 (10 g/day)– Current research suggests this should rise significantly

(25 g/day)

Sources• can be synthesized in the body from cholesterol

with exposure to UV light• rich food sources include dairy products, fatty fish,

fortified margarine, fortified soy and rice beverages, fortified cereals

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Vitamin D: Sources

UV Light

skin

fatty fish, dairy, fortified cereals

pre-vitamin D

liver

kidneys

active Vitamin D

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Vitamin D: Synthesis

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Vitamin D: Deficiency

• in children results in the disease rickets– bones fail to calcify– legs bend out because the bones are

softened and weak

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Vitamin D: Deficiency• in adults contributes to the development of

osteomalacia (soft bones)– occurs in conjunction with a low calcium intake– young women with repeated pregnancies at risk

• also increases risk of osteoporosis (decreased mineral density)– also occurs in conjunction with a low calcium

intake

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Vitamin D: Toxicity• Vitamin D and Vitamin A are the most toxic

vitamins• Toxicity usually only occurs with supplements• UL - 2000 IU (50g) / day (may be conservative)• leads to increased blood calcium =

hypercalcemia– tissues (kidney, heart, lungs, liver) become calcified– leads to death

• other symptoms include nausea, vomiting, loss of appetite, fatigue, kidney damage

• Sun exposure does not result in toxicity

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Vitamin D & Cancer?• Canadian Cancer Society recommends

Canadians consume a supplement of 1000 IU Vitamin D during fall & winter

• Epidemiology:– inverse correlation between colon cancer mortality

and UV exposure– mixed results from studies examining correlation

between dietary Vitamin D or serum Vitamin D and cancer incidence & mortality

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Vitamin D & Cancer• Is there biological evidence of a role of

Vitamin D in cancer protection?– experimental studies have found that that colon

cells express receptors for Vitamin D & calcitriol inhibits growth of cancer cells

• What are the mechanisms?– anti-proliferative effects– stimulates cellular differentiation– promotes apoptosis– reduces angiogenesis

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Vitamin E: Functions & Recommendations

• also called -tocopherol

• acts as an antioxidant– prevents oxidation

of polyunsaturated fatty acids and other lipids and Vitamin A

– may reduce the oxidation of LDL and help lower risk of cardiovascular disease

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Vitamin E:

vegetable oils(canola, safflower,

corn, olive)

sunflower seeds

sweet potatoes

prawns& shrimp

Others: salmon, almonds, pistachios, soy beans, enriched cereals

Recommendations•Adults = 15 mg TE/day (tocopherol equivalents)

•Sources

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Vitamin E: Deficiency• rare in healthy adults

– Though smoking destroys vitamin E– Also destroyed by oxygen, metals, light and repeated frying

• in premature infants results in erythrocyte hemolysis (rupture of cell membrane)– leads to hemolytic anemia– red blood cells burst open– corrected with Vitamin E treatment

• prolonged deficiency causes neuromuscular dysfunction– poor muscle coordination, impaired reflexes– impaired vision and speech

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Vitamin E: Toxicity

• rare, effects less severe than Vitamin A or D toxicity

• usually occurs with supplements• upper limit is 65x greater that RDA• very high doses may interfere with the blood

clotting actions of Vitamin K or enhance actions of anti-clotting medications

• More damage if individual has a vit K deficiency as well as very high vit E intake– Risk of hemorrhage

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Vitamin K: Functions

• necessary for blood clotting– ‘koagulation’

– activates prothrombin, the precursor to thrombin

– thrombin is an enzyme required for synthesis of blood clots

– also important for other reactions in formation of a blood clot

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Vitamin K: Functions

• important for the synthesis of bone proteins– lack of Vitamin K

results in abnormal protein production which bone minerals cannot bind to

– adequate intakes may reduce risk of hip fractures

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Vitamin K: Recommendations & Sources

Recommendation• Adult RDA = 90 - 120 g/day

Sources• made by intestinal bacteria

– this meets about ½ of body’s needs

• significant food sources include dark green leafy vegetables (kale, spinach, turnip greens, broccoli, romaine lettuce) cauliflower, cabbage, and soybean products

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Vitamin K Sources

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Vitamin K: Deficiency• primary deficiencies rare as average intake is

sufficient and it is resistant to cooking• secondary deficiency may result from:

– conditions that disrupt fat absorption– antibiotics that destroy colonic bacteria that

synthesize Vitamin K– new born infants have a sterile gut and are usually

given a single dose of Vitamin K at birth to prevent hemorrhagic disease

• results in hemorrhagic disease (unchecked bleeding), may be fatal

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Vitamin K: Toxicity• rare, though may occur with

supplements• reduces the effectiveness of anti-

coagulant drugs used to prevent blood clotting

• symptoms include:– jaundice, red blood cell hemolysis, and

brain damage

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The B Vitamins

• act primarily as coenzymes

• work as catalysts• required for many

energy-producing metabolic reactions

• Often found together in foods, a lack of one may indicate others are low– Poor, elderly and

alcoholics at risk for deficiency

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Vitamin B6

Niacin

Riboflavin

BiotinFolate

Thiamin

Vitamin B12

PantothenicAcid

B vitamins in concert…

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Thiamin (Vitamin B1): Functions

• part of coenzyme TPP(thiamin pyrophosphate)– important for de-carboxylation reactions (removal of

CO2)– needed to convert pyruvate to acetyl CoA

• found on nerve cell membranes, important for nerve cell function

• RDA is roughly 1 mg per day, slightly higher during pregnancy and lactation

• average intake of Canadians meets or exceeds recommendation

glucose pyruvate acetyl CoA + CO2 TPP

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Thiamin (Vitamin B1): Sources

• found in small amounts in many foods, DRI easily met with a well-balanced diet

• destroyed by heat

1 slice of watermelon or ½ cup cooked peas provides

about ¼ of RDA

pork and pork products are exceptionally rich sources

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Thiamin (Vitamin B1): Deficiency

• deficiency results in Beri Beri (Sinhalese for “I can’t, I can’t”)

Symptoms

• can be characterized by edema (called wet Beriberi) or by muscle wasting (called dry Beriberi)

• no toxicity symptoms have been reported for thiamin

q weakness and fatigueq enlarged heartq cardiac failureq apathy

q poor short term memoryq confusion, irritabilityq muscle paralysisq nerve degeneration

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Riboflavin (Vitamin B2): Functions

• forms part of coenzymes FAD and FMN• participates in oxidation / reduction and de-

amination reactions• associated with antioxidant performance of

enzyme glutathione peroxidase• required (with iron & Vitamin B6) to convert the

amino acid tryptophan to the B vitamin niacin• required to convert Vitamin B6 to its coenzyme

form• RDA about 1 mg, most Canadians meet or

exceed.

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Riboflavin (Vitamin B2): Sources

• small amounts in many foods, easy to meet DRI with a well-balanced diet

• destroyed by UV light

3 oz liver exceeds RDA

1 cup yogurt ½ RDA

½ cup cooked mushrooms

¼ RDA

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Riboflavin (Vitamin B2): Deficiency

• deficiency is rare, but usually occurs in combination with other nutrient deficiencies, called ariboflavinosis

• causes inflammation of membranes of mouth, skin, eyes, and digestive tract– inflamed eyelids, sensitivity to light– sore throat, cracks in upper lips and at corners of

mouth– Glossitis (swollen tongue) and dermatitis

• no toxicity symptoms have been reported for riboflavin

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Niacin (Vitamin B3): Functions• other names include nicotinamide & nicotinic acid• part of coenzyme NAD required for many reactions of energy

metabolism, especially metabolism of glucose, fat, and alcohol

RDA 12-16 mg NE /dayCC C C C

Glucose2 Pyruvate

2 ATP

NAD+ NADH + H+

CC C C

C C C

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Niacin (Vitamin B3): Sources

• can be synthesized from amino acid tryptophan– 60 mg tryptophan = 1 mg niacin– requires Riboflavin, Iron, and Vitamin B6

• diets rich in high quality protein never lack niacin

Best sources per kcal:• spinach• mushrooms• chicken breast• liver• fish (cod, halibut, tuna…)

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Niacin (Vitamin B3): Deficiency

• results in pellagra, “mal de la rosa”

Symptoms (4 “D’s”)Dermatitis

Diarrhea

Dementia

Death

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Niacin (Vitamin B3): DeficiencyPopulations at risk:

– alcoholics

– protein poor diets centered on corn• 70% of niacin in corn unavailable for

digestion and absorption• high leucine interferes with conversion of

tryptophan to niacin

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Niacin (Vitamin B3): Toxicity

• non-toxic if from Niacin naturally occurring in FOOD

• large doses (1,300 - 3,000 mg/day) used pharmacologically to treat high cholesterol

• dose of 250 mg/day can produced side effects, including:– niacin flush– headaches, nausea, glucose intolerance, blurred

vision, liver damage, and peptic ulcers

• upper limit of 35 mg/day

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Pantothenic Acid: Functions & Sources

Functions• forms part of CoEnzyme A• involved in over 100 metabolic reactions

including synthesis of lipids, neurotransmitters, steroid hormones, and hemoglobin

Sources• “pantos” = everywhere

Both deficiency and toxicity are rare.

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Biotin: Functions

Functions

• forms part of a coenzyme responsible for replenishing oxaloacetate in the TCA cycle (metabolism of carbs and fat)

• important for gluconeogenesis, fatty acid synthesis, and breakdown of certain fatty acids and amino acids

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Biotin: Sources

Sources• widespread in many foods:

– liver, egg yolks, soy beans, fish, whole grains

• protein avidin in raw egg white prevents absorption

• synthesized by colonic bacteria, but not absorbed

Both deficiency and toxicity are rare.

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Vitamin B6: Functions• part of coenzyme PLP which is required for

protein metabolism:– Transamination of amino acids– synthesis of niacin from tryptophan– synthesis of neurotransmitters, hemoglobin, & DNA

• required for the synthesis of white blood cells• important for steroid hormone activity and

cognitive function• converts homocysteine to cysteine

– High homocysteine correlated with heart disease risk

• RDA 1.0 - 1.5 mg / day

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Vitamin B6: Sources• ample amounts provided by protein rich

foods

• easily destroyed by heat

1 medium banana

½ RDA

1 medium potato or 3 oz chicken ¼ RDA

Best sources per kcal:• spinach• broccoli• carrots• tomato juice• squash

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Vitamin B6: Deficiency

• rare, alcoholics and the elderly most at risk

• drugs may interfere with Vitamin B6 (e.g. INH used to treat tuberculosis)

Symptoms• nerve damage, depression, confusion• impaired immune function• microcytic anemia (“micro” = small, “cytic” =

cell)

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Vitamin B6: Toxicity

• stored in muscle thus can accumulate (unlike other water soluble vitamins)

• only occurs with supplements– Sometimes abused by bodybuilders– taken to treat PMS, carpal tunnel syndrome or

sleep disorders– no scientific evidence to support use!

• symptoms include fatigue, depression, headache, numbness and muscle weakness, convulsions, and permanent nerve damage

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Folate: Functions• also called folacin or folic acid• part of coenzymes in energy metabolism • required for synthesis of DNA, important in cell

division– necessary for fetal development during pregnancy

• required for synthesis and development of red blood cells and other rapidly dividing cells

• activates Vitamin B12

• converts homoecystine to methionine with Vitamin B12,

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Folate: Recommendations & Sources

Recommendations• Adult: 400 g per day• During pregnancy: 600 g per day

Sources• abundant in legumes and many vegetables• destroyed by heat and oxygen• fortification of cereal grains required since

1998

Know these values for the exam!

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Folate: Sources 1 cup raw spinach ¼

RDA

½ cup navy beans 1/3

RDA

½ cup asparagus

1/3 RDA

Best sources per kcal:• black-eyed peas• lentils• okra• asparagus• kidney beans• tomato juice• broccoli• spinach

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Folate: Deficiency• one of most common nutrient deficiencies in

North America• may result from a variety of potential causes:

– inadequate intake– inadequate folate absorption– increased folate requirements– impaired folate utilization (associated with Vitamin

B6 deficiency)– altered folate metabolism (drug interactions)– excessive folate excretion (prolonged diarrhea)

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Folate: DeficiencySymptoms• megaloblastic anemia

– “mega” = large, “blast” = immature cell– also called macrocytic– red blood cells remain large and immature

because of impaired cell division– leads to weakness, fatigue, irritability and

headache

• other symptoms include glossitis and mental confusion

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Folate: Deficiency

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Folate: Deficiency during Pregnancy

• leads to neural tube defects in the developing fetus– abnormalities of the spine, brain, or skull

• e.g. spina bifida, anencephaly (part of brain missing)

• supplements generally recommended during pregnancy (under a physicians supervision)– synthetic form is better absorbed than food form

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Folate: Deficiency during Pregnancy

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Folate: Toxicity

• can MASK a Vitamin B12

deficiency

– early symptoms of a B12 deficiency

also include megaloblastic anemia

– too much folate prevents these

early symptoms from developing

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Vitamin B12: Functions

• absorption of Vitamin B12 requires a substance called intrinsic factor

• contains the mineral cobalt• forms part of coenzymes

– assists in break down of fatty acids and amino acids

• maintains myelin, a protective sheath around nerves– protects nerve fibers and promotes their normal

growth

• involved in bone cell activity & metabolism

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Vitamin B12: Functions

• activates folate

• works with folate to synthesize red blood cells

• important in synthesis of DNA and RNA

• with folate converts homocysteine to methionine

Folate (inactive) Folate (active)

homocysteine methionine

Vitamin B12

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Vitamin B12: Sources

Recommendations• RDA = 2.4 g per day• Daily Value = 6 g per day

Sources• only found in animal products

– e.g. meats, fish, poultry, dairy, eggs

• added to some fortified cereals • NOT available from fermented soy or sea algae or

yeast grown on a Vitamin B12 rich medium• destroyed by microwave cooking

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Vitamin B12: Deficiency

• average intake of Canadians > RDA• stored in liver and recycled

– may take several years for symptoms to develop

• concern for vegans: require supplements!• secondary deficiency due to lack of intrinsic

factor– called pernicious anemia– common in older individuals with atrophic gastritis

that have decreased production of stomach acid and intrinsic factor

More Information: http://www.cc.nih.gov/ccc/supplements/vitb12.html

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Vitamin B12: Deficiency

Symptoms• megaloblastic anemia (acute)

– as with a folate deficiency– leads to fatigue, irritability, etc…– masked by a high folate intake

• neurological symptoms (chronic)– creeping paralysis of nerves– begins at extremities and works up spine– may result in permanent nerve damage and paralysis

• no toxicity symptoms reported for Vit. B12

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Vitamin B6

Niacin

Riboflavin

BiotinFolate

Thiamin

Vitamin B12

PantothenicAcid

B vitamins in concert…

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Vitamin C: Functions• acts as a water based antioxidant

– re-activates Vitamin E (lipid based)– prevents oxidation of compounds in cells

and body fluids– neutralizes free radicals in polluted air and

cigarette smoke

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Vitamin C: Functions• acts as a cofactor in many reactions

– required for synthesis of collagen• structural protein of connective tissue

and forms matrix for bones and teeth– with iron, converts amino acids proline

and lysine to their hydroxy form– necessary for synthesis of carnitine,

serotonin, norepinephrine, and thyroid hormone (thyroxin)

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Vitamin C: Functions• other functions include:

– facilitates function of immune cells– deactivates histamine

• chemical compound of the immune system that mediates the allergy response

– enhances iron absorption• captures non-heme iron and keeps it in a

reduced form (ferrous iron) that is more easily absorbed

Recommendations (know for exam!)men = _________ women = _________ smokers = ______90 mg/day 75 mg/day + 30-35 mg

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Vitamin C: Sources• many animals can synthesize vit C, but NOT HUMANS

All of the following provide 100% of the RDA ¾ cup cooked broccoli ½ cup red bell pepper 1 kiwi 1 cup grapefruit juice 1 sweet potato 1 cup strawberries 1 large orange 1 cup Brussels sprouts

Best source per kcal!

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Vitamin C: Deficiency• results in scurvy

Symptoms– begin if intake drops to < 10 mg/day– bleeding gums, loss of teeth– pinpoint hemorrhages– muscles degenerate, bones soften, skin roughens– increased infections– hysteria and depression– microcytic anemia– sudden death due to massive internal bleeding

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Vitamin C: Deficiency

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Vitamin C: Toxicity

• 100 mg/day saturates tissues• minimal absorption or increase in blood

concentrations if intake > 200 mg/day• low risk of adverse effects if intake is below 2000

mg/day • greater than 2000 mg/day may lead to:

– nausea, abdominal cramps, diarrhea, nosebleeds– interference with anti-clotting medications– gout, kidney stones– pro-oxidative effect if iron intake is excessive

• Hemochromatosis - over storage of iron

– rebound scurvy?

supports metabolism

30 mg

75 mgRDA for women

RDA for men

90 mg

100 mgtissues saturate

female smokers110 mg

10 mg prevents scurvy

125 mgmale

smokers

limited absorption

200 mg

2000 mgadult UL

adverse effects

3000 mg

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Is Vitamin C a Cure for the Common Cold?

• proposed by Linus Pauling (Nobel prize winner in Physics)– claimed megadoses of Vitamin C prevented and cured

the cold– also proposed that Vitamin C could prolong life of cancer

patients

• does research support these claims? NO!– however, a Vitamin C intake > 1 g/day MAY decrease

the duration of a cold by one day

• mechanisms?– anti-histamine actions?– protect from immune cell Oxygen Free Radicals?

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Vitamin Supplements??• Supplements may be beneficial, and improve health of

population– Multivitamin has lowest risks for toxicity and good general benefits– While real food is better, population seems to be adverse to

increasing fruit and vegetable intake

• Most important – folate during child bearing years– B12 for vegans and those over 50

• Do not take more than recommended• Take with food, or just after a meal• Megadoses

– Vit E - shown to be have minimal impact– Vit C - may reduce symptoms for common colds– Vit D - could be very beneficial, more research required.

Vitamin C

Biotin

Vitamin A

Folate

Niacin

Riboflavin

protects against damage from oxygen free radicals

important for the differentiation of lymphocytes, goblet cells & epithelial cells

excess may mask a Vitamin B12 deficiency

can be synthesized from the amino acid tryptophan

enables amino acids to be used for energy

needed to replenish oxaloacetate in the citric acid cycle

Matching Exercise