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Vitamins
HistoryPurified diets of carbohydrate, protein, fat, minerals and water were not capable of normal growth
“Accessory growth factors”
Casimir Funk, a Polish biochemist, isolated an antiberberi substance from rice polishings
Named it vitamineAn amineVital for life
Vitamins
Essential organic compounds required in very small amounts (micronutrients) involved in fundamental functions of the bodyUnrelated chemically
Not only amines so “e” was dropped
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VitaminsNot metabolic fuels (like glucose or fatty acids) or structural nutrients (like amino acids)Regulators (catalysts) of reactions, some of which are involved in energy metabolism
VitaminsOrganic molecules in foodRequired in small amountsClassified based on solubility
Fat solubleWater soluble
Fat-soluble Vitamins
RetinolErgocalciferolCholecalciferolTocopherolPhylloquinone
AD2
D3
EK
Chemical nameVitamin
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Water-soluble Vitamins
ThiaminRiboflavinNicotinamide (niacin)Pantothenic acidPyridoxineBiotinFolacin (folic acid)CholineCyanocobalaminAscorbic acid
B complexB1
B2
B3
B5
B6
B7
B12
C
Chemical nameVitamin
Vitamins
All vitamins are metabolically essential but not all required in the diet
Most mammals can synthesize vitamin C; not humans and primatesNo mammal can synthesize B vitamins but rumen bacteria do
Vitamins
Some function as vitamins after undergoing a chemical change
Provitamins (e.g., β-carotene to vitamin A)
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ClassificationBased on solubility in the laboratory, but solubility greatly influences how the body absorbs, transports and stores vitaminsFat-soluble
Vitamins A, D, E and KWater-soluble
B vitamins and vitamin C
The Basics of Water-Soluble Vitamins
Dissolve in waterB vitamins & vitamin CAbsorbed mostly in small intestine & stomachBioavailability
Nutritional status, other nutrients & substances in food, medications, age, illness
Circulated to liver in bloodNot stored in large quantities
The Basics of Water-Soluble Vitamins
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Naming the VitaminsFirst named vitamin A or BB-complex vitaminsGiven common names also
ThiaminRiboflavinNiacin
Chemical namesAscorbic acid
Memorizing B Vitamin Names & Numbers
Thiamin (Vitamin B1)Contains thiol & amine group
Thiamin pyrophosphate (TPP) or thiamin diphosphate
Thiamin triphosphate
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Bioavailability & Regulation of Thiamin in the Body
BioavailabilityIncreases when lowUses simple diffusion when high
Antithiamin factorsRaw fish, coffee, tea, berries, brussels sprouts, cabbage
Vitamin C prevents oxidationAlcohol inhibits thiaminExcess excreted in urine
Functions of ThiaminATP production
Synthesis of DNA & RNA
Noncoenzyme roles
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Thiamin Deficiency: Beriberi
“I can’t, I can’t”Prevalent in parts of the world that rely on unfortified, milled rice as stapleCauses weak & impaired immune functionTypes
Dry, wet, infantile, cerebral (Wernicke-Korsakoff syndrome)
Did you know…Riboflavin is easily destroyed by light so milk is packaged in cardboard or cloudy plastic containers so it is not destroyed.
Regulation & Bioavailability of Riboflavin
Types:Free form
Can be absorbedBound to proteinCoenzyme (FMN or FAD)
Absorption through simple diffusion when intake high
Active transport when intake lowAnimal foods more bioavailableAlcohol inhibits absorptionExcess excreted in urine
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Coenzyme Functions of Riboflavin
Energy metabolismRedox reactionsFormation of ATP, water, carbon dioxideβ-oxidationConverts vitamin A & folate to active forms, tryptophan to niacinForms vitamin B6 & K
Riboflavin DeficiencyAriboflavinosis
Weakness, cheilosis, stomatitis, glossitis, anemia, confusion
AlcoholicsDiseases that interfere w/ riboflavin utilization
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Niacin (Vitamin B3)Forms
Nicotinic acidNicotinamide
Body uses both forms to make:NAD+
NADP
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Dietary Sources of Niacin1 mg niacin = 60 mg tryptophanNiacin equivalent
Combined amounts of niacin & tryptophan in foods
Bioavailability of NiacinAnimal products more bioavailable than plantIncreasing bioavailability
Treating grain products with alkaline substances cleaves protein from niacin
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Regulation of Niacin in Body
Small intestinal absorptionSimple diffusion when intake is highActive transport when intake is low
Circulated to liverAttached to transport proteins
Converted to NAD+ or NADP
Liver converts tryptophan to niacin when needed
Functions of NiacinCoenzymes catalyze redox reactions related to energy metabolismSynthesizes fatty acids, cholesterol, steroid hormones, & DNAMetabolizes vitamin C & folateNAD+
Protein synthesisMaintenance, replication & repair of DNAGlucose homeostasisCholesterol metabolism
Lower LDL & increase HDL
Niacin Deficiency: Pellagra“Rough skin”Four Ds
DermatitisDementiaDiarrheaDeath
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Tryptophan, Niacin, & Pellagra
Used to be thought of as infectious diseaseJoseph Goldberger
Studies done adding protein sources to diet
Prevented & treated disease through dietEnrichment programs developedRare in U.S.
Niacin ToxicityNicotinic acid (1 g/day)
Skin inflammationItchinessFlushingHeartburnNauseaIncreased plasma glucoseLiver damage
Regulation of Pantothenic Acid in the Body
BioavailabilityIncreases via active transport when intake is lowCirculated to liver via bloodNot stored in bodyCoenzyme form high in liver, kidney, heart, adrenal glands, & brain
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Functions of Pantothenic Acid in the Body
Use of glucose, amino acids, & fatty acids for ATP productionSynthesizes:
HemeCholesterolBile saltsPhospholipidsFatty acidsSteroid hormones
Pantothenic Acid Deficiency & Toxicity
DeficiencyRare“Burning feet syndrome”
ToxicityRareNausea & diarrhea
Vitamin B6
FormsPyridoxinePyridoxalPyridoxamine
Similar biological activities
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Regulation of Vitamin B6 in the Body
Absorbed in small intestine Circulated in blood to liver
Forms pyridoxal phosphate (PLP)Coenzyme form of B6
Stored in muscle & liver
Functions of Vitamin B6 in the Body
PLP coenzyme to metabolismProteins & amino acids via transamination
Synthesizes nonessential amino acidsProduces nonprotein substances
Converts tryptophan to niacin
Vitamin B6 Deficiency: Microcytic Hypochromic Anemia
Results in inadequate heme productionDecreases oxygen availability in tissuesImpairs ability to produce ATP via aerobic metabolism
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Vitamin B6 ToxicityExcess supplement use
Severe neurological problemsDifficulty walkingNumbness in hands & feet
Bioavailability of BiotinReduced by:
AvidinEgg whites
Alcohol
Extreme heat destroys biotin
Regulation of Biotin Enzymes cleave to protein-biotin complexes in small intestineProduced by large intestine bacteriaCirculates to liver via bloodSmall amounts stored in
MuscleLiverBrain
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Functions of BiotinCatalyzes carboxylation reactionsUse of amino acids & fatty acids in citric acid cycle for synthesis of fatty acidsGene expression
Biotin DeficiencyUncommonSeen in:
Individuals who eat large quantities of raw egg whitesConditions impairing intestinal absorptionGenetic disorders
Signs & SymptomsDepression, hallucinations, skin irritations, infections, hair loss, poor muscle control, seizures, developmental delays in infants
Folate (Folacin)
Consists of:Nitrogen-containing double ring structureNitrogen-containing single ring structureGlutamic acid
Folic acidSynthetic formFortified foods & supplements
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Dietary Sources of FolateSince 1998All cereal products in U.S. fortified with folic acidHeat, light, & oxygen destroy folate
Bioavailability of Folate Depends on formInfluences
Genetic factorsDrugs
Absorption higher with:Fortified foodsSupplements
Dietary folate equivalents (DFE)
Regulation of Folate in Body
Glutamate units must be cleaved before absorbed
Converted to tetrahydrofolate (THF)Results in 5-methyl tetrahydrofolate
Circulated to liver via bloodLittle is stored
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Function of Folate: Single-Carbon Transfers
Coenzyme involved in transfer of single-carbon groups to form organic substances
Homocysteine to methioninePurines & pyrimidinesNormal growth & development
Focus on Life Cycle Nutrition: Folate, Neural Tube Defects, & Spina Bifida
Neural tube Spinal cord & brain
Defects result when:Closure of neural tube is incomplete
Spina bifida20 out of 100,000 babies
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Folate, Neural Tube Defects, & Spina Bifida
Folate supplementation decreases risk in some women
IOM recommends:That women capable of becoming pregnant take folic acid supplements and/or consume folic acid-fortified foods in addition to a varied diet
Folate Deficiency: Macrocytic Anemia
Red blood cells (RBC) remain immatureCells are large & contain organelles not found in mature RBC
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Folate DeficiencyAlcoholicsPeople w/ intestinal diseasesPeople taking certain medicationsElderlyGenetic variations
Regulation of Vitamin B12 in the Body
Must be cleaved before absorptionBound to R protein & intrinsic factorOnce absorbed, binds to transcobalaminCirculates to liver via bloodStored in liver
Functions of Vitamin B12
Coenzyme that catalyzes:Production of succinyl CoA
Uses amino acids & fatty acids for ATP production
Key for ruminants!!
Conversion of homocysteine to methionine
Allows use of folate
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Vitamin B12 Deficiency & Pernicious Anemia
VegansBreastfed infants of B12-deficient mothersElderly
Pernicious anemiaGastric cells stop intrinsic factor secretionInjections of B12 given
Signs & symptomsMacrocytic anemia, fatigue, difficulty sleeping, numbness, memory loss, severe neurological disturbances
Folate, Vitamin B12, & Anemia
B12 DeficiencyCaused by secondary folate deficiency
Folate “masks” B12 deficiency
Regulation of Vitamin C in the Body
Absorption in small intestine via active transportUses glucose transport proteinHigh intakes
Absorbed by simple diffusion in stomach & small intestine
Circulates to liver via bloodExcess excreted in urine
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Functions of Vitamin CAntioxidant
Accepts & donates electrons
Involved in a variety of redox reactions
The “Recharging” of Enzymes
ExamplesCollagen
Synthesis of carnitine
Synthesis of hormonesCholecystokinin Gastrin
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BioavailabilityEnhances absorption of:
IronCopperChromium
Consuming vitamin C sources with these minerals increases their bioavailabilityExample
Orange juice + iron-enriched cereal
Vitamin C & Protection from Free Radical Damage
Free radicalsCharged substances that have unpaired electrons in their outer shells Break DNA & oxidize fatty acids found in cell membranes
Vitamin CDestroys free radicals
Vitamin C & Protection from Free Radical Damage
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Vitamin C, the Common Cold, & Other Diseases
Suggested that large vitamin C doses benefit immune systemMore research needed:
Common coldCancerHeart diseaseCataracts
Vitamin C Deficiency & Toxicity
DeficiencyScurvy
Signs & symptomsBleeding gumsSkin irritationsBruisingPoor wound healing
ToxicityNauseaDiarrheaCrampingKidney stones
Choline: A “New” Essential Vitamin?
IOMDesignated choline as essential in some situations
Certain populations at risk? conditionally essentialSome do not consider it a vitamin
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Dietary Sources of CholinePlant & animal foods
Eggs, liver, legumes, pork
LecithinMayonnaise & salad dressings
Regulation of Choline in the Body
Unbound choline absorbed in small intestineCirculates to liver via bloodLecithin
Cleaved from glycerol backbone by pancreatic enzymesTaken up by intestinal cells & reconstituted into lecithin moleculesReleased into lymphBecomes LDL
Made in body by methionine
Functions of Choline in Body
Synthesizes phospholipids & acetylcholineComponent of cell membranes & lipoproteinsMuscle controlStructural roleMetabolic reactions
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Choline Deficiency & ToxicityDeficiency
? liver damage in adult menToxicity
Fishy body odor, perspiration, salivation, low blood glucose, liver damage
Carnitine
Conditionally essential for infants
Classification being debated
Animal sourcesMeat, milk, & human milk
Regulation & Functions of Carnitine in the body
Absorbed in small intestineProduced from methionine & lysineAssists fatty acids to cross membranes
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Carnitine Deficiency & Toxicity
DeficiencyRare Genetic conditions
Muscle weakness, hypoglycemia, heart irregularities
ToxicityNone known
Summary
Summary
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Fat-Soluble VitaminsOrganic substances that dissolve in lipids & are vital to healthMicronutrientsVitamins A, D, E, & KKey players in:
Cell growthMaturationGene regulation
Basics of Fat-Soluble Vitamins
Absorbed in small intestineRequires lipids & bileCirculated in lymph via chylomicronsBecome part of lipoproteins or bound to transport proteinsAntioxidant propertiesStored in body
Vitamin A & the Carotenoids
RetinoidsRetinol (preformed vitamin A)
Most potent formCan be synthesized from retinal
RetinalCan be converted to retinoic acid
Retinoic acid
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CarotenoidsTypes
Provitamin A carotenoidsBeta-caroteneCan be converted to vitamin A
Nonprovitamin A carotenoidsCannot be converted to vitamin ALycopene, astaxianthin, zeaxanthin, luteinConsidered phytochemicals
Dietary Sources of Vitamin A & Provitamin A Carotenoids
Retinol activity equivalent (RAE)1 RAE = 12 micrograms beta-carotene & 1 microgram retinol
Preformed vitamin AOrgan meats, liver, fatty fish, dairy products
Provitamin AYellow, orange, red fruits/veg, leafy greens
Regulation of Vitamin A & Carotenoids in Body
Contained in chylomicronsEnter lymphJoin blood at thoracic ductDelivered to adipose tissue, muscle, & eyeWhat is not used, taken back to liver
Carotenoids packaged into VLDLsVitamin A attached to retinol binding proteins & transthyretin
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Vitamin A Synthesis and Storage
β-carotene is converted to vitamin A in the intestinal mucosa90% is stored in liver, mainly as the ester, retinyl palmitateCarotenoids can be stored in adipose tissue
Functions of Vitamin ACell differentiation
Maintaining healthy immune system
Building strong bones
Vision
Vitamin A & Vision
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Night BlindnessInadequate amounts of retinal to re-form rhodopsin
Compound in retina that consists of the protein opsin & vitamin cis-retinal that is needed for night vision
Night vision becomes difficult
Vitamin A & Cell Differentiation
Vitamin A, Growth & Reproduction
Regulates cell differentiationExample
During embryonic growth, vitamin A assists in differentiation & maturation of tissues & organs
Needed for successful reproduction
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Vitamin A & the Immune Function
Maintains protective barriersEpithelial tissues
Helps produces lymphocytes & antibodies
Deficiencies – increased rate of infectious disease & illness
Vitamin A, the Carotenoids, & Cancer
Epidemiological studiesDiets rich in vitamin A or carotenoids associated with lower risk of some types of cancersLong-term, high-dose supplementation of beta-carotene in combination with other dietary factors increases incidence of lung & colorectal cancer
RecommendationDo not take vitamin A &/or beta-carotene supplements to reduce cancer risk
Vitamin A & Bone HealthRequired for processes with osteoclasts & osteoblasts
Favors bone formation
High preformed vitamin A intakeMay lead to greater risk of bone fractures in older people
Research needed?
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Functions of CarotenoidsInfluences immune system
Antioxidant functionRegulation of gene expressionMaintenance of normal cell turnoverDecreases risk for certain diseases
Focus on Foods: Fruits, Vegetables, Carotenoids, & Health
LuteinMay decrease growth of breast tumors
LycopeneRelated to lower risk of prostate cancer
Lutein & zeaxanthinRelated to decreased risk of macular degeneration
Make your plate colorful!Beta-carotene
Carrots, sweet potatoes
LycopeneTomatoes, pink grapefruit, apricots, watermelon
LuteinDark green leafy vegetables
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Vitamin A DeficiencyUncommon in industrialized countries
Secondary vitamin A deficiency
Cystic fibrosisAlcoholics
Vitamin A Deficiency Disorder (VADD)
Increased risk of infection
Night blindness
XerophthalmiaDry eyes & scarringBitot’s spotsBlindness
HyperkeratosisSkin is rough, bumpy, irritated
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Focus on Diet & Health: Vitamin A & International Child Health
100-400 million children have VADDNonindustrialized countriesVitamin A supplementation decreases morbidity & mortality
WHO Recommends supplementation after 6 months in needed regions
Biotechnology
Biotechnology: Golden Rice
Vitamin A & Carotenoid ToxicityUpper safe levels are 4-10x requirements in nonruminants and 30x in ruminantsHypervitaminosis A in humans
Polar explorers eating polar bear or seal liverSelf-medication and overprescription
Blurred visionLiver abnormalitiesReduced bone strengthBirth defectsIncrease risk of lung cancerHypercarotenemia
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Vitamin D
Conditionally essential
FormsErgocalciferol (D2)
Plant sources & supplements
Cholecalciferol (D3)Animal foods & made by body
Regulation, Metabolism, & Synthesis of Vitamin D
Packaged into micellesAbsorbed into enterocyteIncorporated into chylomicronsLymph, then bloodRemnants taken to liver“Sunshine vitamin”
Synthesis of Vitamin D
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Influences on Vitamin D Synthesis
Areas with smog, overcast weather, very short daysDarker skinSunscreenAge-related changes
Activation of Vitamin D
Functions of Vitamin DRegulation of:
Blood calcium concentration
Gene expression
Cell differentiation
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Vitamin D & Calcium Homeostasis
Vitamin D, Cell Differentiation, & Cancer
Movement of vitamin D into nucleusStimulation of genes coding for specific proteinsExamples
Bone health GI function? prevention of colon, breast, skin, prostate cancers
Vitamin D DeficiencyRicketsOsteomalaciaOsteoporosisPeople over 50:
Get > 15 minutes sun exposure/dayIncrease vitamin D intake
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Vitamin D ToxicityHypercalcemia
OversupplementationDeposits of calcium in soft tissuesAffects function of nervous systemPromotes bone lossDeath
Vitamin E
8 different compounds
alpha-tocopherolMost biologically active
Regulation of Vitamin E in Body
Requires bile & synthesis of micellesCirculated in chylomicrons via lymph & bloodLiver
Repackaged into VLDLs
ExcessStored in adipose tissue
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Cell Membrane Structure
Vitamin E & CancerAntioxidants protect DNA from free radical damage? if vitamin E might prevent or cure cancerDiets high in vitamin E
Associated with decreased cancer riskLittle experimental evidence
Vitamin E & CataractsCloudy growths that develop on the lens of the eyeCauses vision to become cloudyCan lead to blindnessEvidence suggests:
Older people who take vitamin E supplements are at lower risk for developing cataracts
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Vitamin E & Heart DiseaseSlows rate of plaque formationSupplementation
400 mg/dayCauses overall increased risk of mortality
RecommendationTaking vitamin E supplements to decrease risk of heart disease is discouraged
Vitamin E DeficiencyUncommonReports in:
Infants fed formulas with inadequate vitamin EGenetic abnormalitiesFat malabsorption
SymptomsNeuromuscular problems, loss of coordination, muscular painHemolytic anemia
Vitamin E ToxicityRare
Very high doses:Hemorrhages
Genetic differences
Caution:Vitamin E supplements
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Vitamin K
Refers to 3 compounds:Phylloquinone (K1)
Food & supplementsMenaquinone (K2)
Produced by bacteria in large intestine
Menadione (K3)Produced commercially
Regulation of Vitamin K in the Body
Absorbed via micellesIncorporated into chylomicronsEnters lymph & then blood
Vitamin K produced in large intestineEnters epithelial cells by simple diffusion
LiverPackages dietary & bacterially produced forms into lipoproteins
Functions of Vitamin K: Coagulation
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Did you know…Vitamin K also catalyzes carboxylation of other proteins for bone & tooth development
Binds calcium
If you take a calcium supplement, take a look at the label. More than likely, vitamin K is an ingredient!
Nutrient-Drug Interactions & Vitamin K
Long-term antibiotic useKills intestinal bacteriaIncreases risk for deficiency
Coumadin (warfarin)“Thins the blood”Decreases activity of vitamin KEat a balanced dietLimit foods high in vitamin K to one serving each day
Dicoumarol found in moldy sweet cloverSweet clover disease
Vitamin K Deficiency & Toxicity
RareInfantsDiseases that cause lipid malabsorptionProlonged antibiotic use
Deficiency signsExcessive bleeding
Few toxic effects
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Vitamin K Injections During Infancy
Infants born with low storesLarge intestine lacks vitamin K-producing bacteriaHuman milk contains low levels
Vitamin K deficiency bleeding (VKDB)Mostly in breastfed infants5-10 babies/100,000 born
Vitamin C(ascorbic acid)
Energy releasing Hematopoietic Other
B-complex vitamins
Water-soluble vitamins
Thiamin (B1)Riboflavin (B2)Niacin (B3)Panthothenic acidBiotinVitamin B6
Folic acidVitamin B12Vitamin B6Pathothenic acid
Vitamin B6Thiamin (B1)Folic acidVitamin B12Niacin (B3)
Fat-soluble VitaminsAbsorbed with dietary fat in small intestine40-90% absorption efficiencyAbsorption typically regulated by need
↑need ↑absorptionTransported away from small intestine in chylomicra via blood and lymph (depending on size)
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Fat-soluble Vitamins, Cont.Liver either stores the vitamin or repackages it for delivery to other cells
Excess vitamin accumulates in liver and adiposeToxicities can occur; almost always associated with supplement use (not foods)
Water-soluble VitaminsAbsorbed at the small intestineAbsorption often highly regulated by either other vitamins or binding proteins in the small intestineTransported away from small intestine in bloodTypically not stored; instead, kidney filters excess into urine
Thus, more important to get these vitamins daily.Toxicities almost unheard of
Vitamin Supplements: Making Wise Choices
Dietary supplements not approved by FDA for safety & effectivenessResponsibility of:
Manufacturers Distributors
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Sorting Fact from FictionOffice of Dietary Supplementshttp://ods.od.nih.govRemember:
Safety firstThink twice about chasing the latest headlineLearn to spot false claimsMore may not be better“Natural” does not always mean safe
When Should You Consider Taking A Supplement?
Food availability limitedNot consuming certain foodsPeriods of rapid growth & developmentEconomic situations are difficultUse of low-calorie diet
Remember…Supplements should never replace medications or a variety of foods
Do not exceed ULs
Keep a record of all dietary supplements taken & share with healthcare provider