Discovery of Vitamins
Vitamin
Year Discovered
Scientists
Vitamin A
1912-1914 (1913?)
Elmer V. McCollum and M. Davis
Vitamin D
1922
Edward Mellanby
Vitamin E
1922
Herbert Evans and Katherine Bishop
Vitamin K
1929
Henrik Dam
Thiamin (B1)
1912
Casimir Funk – coined term
“Vitamines” but e dropped off in 1920
because not all vitamins are composed
of amines
Riboflavin (B2)
1926
D. T. Smith, E. G. Hendrick
Niacin (B3)
1937
Conrad Elvehje
Pantothenic Acid (B5)
1933 but isolated in 1939
Richard Kuhn
Pyridoxine (B6)
1941
Paul Gyorgy
Biotin (B7)
1934
Paul Gyorgy
Folate (B9)
1933
Lucy Wills
Cyanocobalamin (B12)
1926, but isolated in 1948
Karl A. Folkers and Alexander R. Todd
Vitamin C
1912
A. Hoist and T. Froelich
Fat-soluble Vitamins
Overview of Vitamins
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Overview
 Are essential organic substances needed in small amounts in the diet for normal
function, growth, and maintenance of body tissues
 Vitamins A, D, E, and K dissolve in organic solvents whereas the B vitamins and
vitamin C dissolve in water
 Usually can’t be synthesized in sufficient quantities or synthesized at all
 Used in correcting deficiency diseases and some used to treat non-deficiency
diseases
 Found in plant and animal sources supply vitamins in the diet
 Little difference between “natural” vitamins isolated from foods versus
“synthesized”
Historical
 Scurvy in sailors cured by lime juice
 Correlation between chemicals factors and cures for deficiencies
 Many discovered during the late 19th, early 20th century
 As they were discovered were labeled using letters (A, B, C, D, E)
 Compounds continually identified as being essential and in the future may be
classified as vitamins
Storage
 Fat-soluble vitamins are not readily excreted and stored in fat cells
 Water-soluble vitamins are readily excreted from the body
Vitamin Toxicity
 Fat-soluble vitamins are not excreted readily and because they are stored in body
cells, accumulation may cause toxicity
 Vitamin A and D toxicities are observed more often than others
Inadequate absorption
Preservation of vitamins in food
 Vitamins can be lost as a result of: improper storage and excessive cooking
Absorption of fat-soluble vitamins
 Dependent on fat absorption efficiency – mediated by bile salts and lipase
 40-90% of fat-soluble vitamins are absorbed in the small intestine
 delivered using chylomicrons and lipoproteins
 individuals with cystic fibrosis, celiac disease, and Crohn’s disease have poor
ability to absorb fats and fat-soluble vitamins
Vitamin A
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Vitamin A is a generic term for a class of compounds called retinoids
Types of retinoids: retinol, retinal, and retinoic acid
Carotenoids: pigment in fruits and vegetables used in forming vitamin A
Alpha & Beta-carotene are examples of provitamins converted into vitamin A (retinol)
The release of vitamin A from food requires bile, digestive enzymes from the pancreas
and intestinal tract, and integration into micelles
90% of vitamin A absorbed in small intestine
Retinoids stored in liver and carotenoids stored in liver and adipose
Cellular Retinoid-Binding Proteins (CRBP or RBP) - needed for the transport of retinoids
into cell
Functions:
 Visual
 Retinal in retina of the eye turns visual light into nerve signals to the brain
 Cell differentiation – nuclear retinoid (RAR and RXR) receptors bind to DNA
and cause gene expression
 Used in growth and differentiation of epithelial, nervous, bone tissues
 Immunity – cell differentiation – produce cells involved in specific and
nonspecific immunologic defenses
Deficiency
 Hypovitaminosis
 Xerophthalmia
 Bitot’s spots (keratin deposited in conjunctiva; associated with night blindness)
 Follicular hyperkeratosis (keratin deposited around hair follicle)
 Xerosis
 Immune suppression
 Anemia
 Impaired tissue growth
Dietary Sources
o Liver, sweet potato, carrot, spinach, mango, acorn, squash, kale, broccoli,
margarine, peaches, apricots, cantaloupes, papaya
RDA
 RAE’s (retinol activity equivalents) versus IU’s
 Men 900 ug RAE/day, women 700 ug RAE/day
 Men 3000 IU/day, women 2330 IU/day
Toxicity
 Hypervitaminosis A
 Caused by excess dosages (100 times RDA)
 Can be fatal (13,000 times RDA)
 Chronic: liver damage, hair loss, bone/muscle pain, loss of appetite, dry skin and
mucous membranes, hemorrhages, coma
 Acute: gastrointestinal upsets/nausea, headaches, dizziness, muscle contraction
Vitamin D
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Two nutritionally important forms: vitamin D2 (ergocalciferol) which is found in plants
and vitamin D3 (cholecalciferol) which is synthesized in the body from cholesterol
Conversion in skin: provitamin D (a form of cholesterol) is converted to previtamin D3 is
converted to vitamin D3
D3 must be metabolized in the liver before becoming the active form of vitamin D
80% of vitamin D is absorbed in small intestine
Carried by proteins in blood stream
Formation of calcitriol occurs in the liver and kidneys
Functions of vitamin D:
 Maintains serum calcium and phosphorus concentrations within the range that
supports neuromuscular function and bone calcification
 Calcitriol causes calcium to be absorbed by kidneys and intestines and also causes
calcium to be released from bone
Deficiency
 Rickets and Osteomalacia
 Decreased calcium and phosphorus levels
Dietary sources
 Fortified milk, margarine, butter, cereals, egg yolks, live, fatty fish
AI (adequate intake)
 5 ug/day (19-50yrs)
 10 ug/day (51-70yrs)
 15 ug/day (>70yrs)
Toxicity
 Hypervitaminosis D
 5 times the AI is dangerous for infants, 10 times the AI for adults
 calcification of soft tissue, growth retardation, excess calcium excretion via the
kidneys (kidney stones), headaches, muscle weakness, fatigue, excessive thirst
Vitamin E
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Family of eight antioxidants, four tocopherols, alpha-, beta-, gamma- and delta-, and four
tocotrienols (also alpha-, beta-, gamma- and delta-)
Alpha-tocopherol is most active form
The release of vitamin E from food requires bile, digestive enzymes from the pancreas
and intestinal tract, and integration into micelles
Vitamin E is stored in liver and adipose tissue
Functions:
 Antioxidant
 Prevents propagation of free radicals
 Protects other substances from oxidation by being oxidized itsel
Dietary sources
 Polyunsaturated plant oils (margarine, salad dressings, shortenings), leafy green
vegetables, wheat germ, whole-grains, liver, egg yolks, nuts (esp. almonds),
seeds (esp. sunflower)
Deficiencies
 Hemolysis of red blood cells, anemia, degeneration of sensory neurons
RDA
 15mg/day
Toxicity
 Few symptoms (nausea, fatigue, blurred vision, augmentation of anti-clotting
medications)
Vitamin K
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Two forms: Vitamin K1 Phyllaquinones (plant source) and vitamin K2 menaquinone
(fish oils and meats)
80% of dietary vitamin K is absorbed
The release of vitamin K from food requires bile, digestive enzymes from the pancreas
and intestinal tract, and integration into micelles
Functions:
 Contributes to the synthesis of seven blood clotting factors
 Cofactor for enzymes
Dietary sources
 Liver, green and leafy vegetables, broccoli, peas, and green beans, milk
Deficiencies
 May occur as a result of inadequate fat absorption and/or antibiotic consumption
 Excessive bleeding may occur
RDA
 Men 120 ug/day
 Women 90 ug/day
Toxicity
 May interfere with anti-clotting medication
Chapter Objectives
After reading chapter nine - A student should be able to...
1. Understand the difference between water soluble and fat soluble vitamins
2. Understand the absorption of vitamins and differences in our ability to absorb each of
them
3. Identify different forms of vitamins A D E K
4. Discuss the function(s) of vitamins A D E K
5. Describe signs and symptoms of deficiencies of vitamin A D E K
6. Identify sources of vitamin A D E K
7. List the RDAs or recommendations for vitamin A D E K
8. Describe signs and symptoms of toxicity of vitamin A D E K
U.S. Dietary Reference Intakes
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VITAMIN A
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RDA
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VITAMIN D
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Males age 14 and older: 900
mcg/day
Females age 14 and older: 700
mcg/day
Men 3000 IU/day, women 2330
IU/day
5 ug/day (19-50yrs)
10 ug/day (51-70yrs)
15 ug/day (>70yrs)
AI
VITAMIN E
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15mg/day
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Men 120 ug/day
Women 90 ug/day
RDA
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30 ug/day
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1.3 mg/day
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400 ug/day
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2.4 ug/day
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Men 90
mg/day and
women 75
mg/day
AI
BIOTIN (Vitamin
H)
VITAMIN B6
FOLATE
RDA
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Men 1.2 mg/day and women 1.1
mg/day
VITAMIN B12
RDA
RDA
RIBOFLAVIN
(B2)
5 mg/day
RDA
RDA
THIAMIN
(B1)
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AI
RDA
VITAMIN K
PANTOTHENIC
ACID (B5)
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Men 1.3 mg/day and women 1.1
mg/day
VITAMIN C
RDA
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NIACIN (B3)
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Men 16 mg/day and women 14
mg/day
RDA
CHOLINE
AI
Men 550
mg/day and
women 425
mg/day
Water Soluble Vitamins
B Vitamins
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Do not provide energy directly
Help the body metabolize the nutrients that yield energy (carbohydrates, fat, protein)
Some B vitamins are components of coenzymes
B vitamins include: thiamin, riboflavin, niacin, pantothenic acid, biotin, vitamin B6,
folate, vitamin B12
Thiamin (vitamin B1)
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Absorbed in jejunum by a carrier-mediated system and passive diffusion
Transported in the blood and by red blood cells
Part of coenzyme thiamin pyrophosphate (TPP) used in energy metabolism of
 Carbohydrates (pyruvate  acetyl CoA)
 Branched-chain amino acids (alpha-ketogluterate  succinyla-CoA)
Thiamin deficiencies: Beriberi and Wernicke-Korsakoff Syndrome
 Beriberi
 1897, Dr. Christiaan Eijkmann, Indonesian island of Java
 Natives suffering from beri beri
 Symptoms included muscle weakness, weight loss, nervous disorders and
ultimately paralysis and death
 Dr. Eijkmann noticed chickens exhibiting some of the same symptoms as
the beri beri victims
 Natives (victims) ate white rice while (healthy) chickens were fed brown
rice but chickens with similar symptoms to natives were fed white rice
 Conclusion: something on the brown coat of rice prevented beri beri
 Types:
 Dry beriberi – peripheral neuropathy, “burning feet syndrome”,
abnormal reflexes, and diminished sensation and weakness in the
legs
Wet beriberi – cardiac manifestations such as rapid heart rate,
enlargement of the heart, edema, difficulty breathing, and
congestive heart failure
 Cerebral beriberi – Wernicke-Korsakoff syndrome
 Wernicke-Korsakoff Syndrome
 Result of habitual use of alcohol
 Wernicke’s disease – damage to multiple nerves in the central and
peripheral nervous system
 Korsakoff syndrome – impairment of memory and intellect/cognitive
skills; confabulation (fabrication) occurs to make up for gaps in memory
 Other factors causing thiamine deficiency:
 Hemodialysis, diuretics, alcoholism – increases flow of urine and loss of
thiamin
 Anti-thiamin factors – chemicals found in plants that bind to and/or react
with thiamin to render it in a form oxidized in the body; tea and coffee
may cause thiamin depletion
 Thiaminase – enzyme found in raw shellfish and raw freshwater fish;
enzyme breaks down thiamin in food
Dietary sources: whole-grain, fortified, or enriched grain products, pork, soy milk,
ham, and bacon
RDA: men 1.2 mg/day and women 1.1 mg/day
Toxicity: none reported but anaphylactic shock can occur in dosages lager than 3 grams
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Riboflavin (vitamin B2)
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In stomach, HCl releases riboflavin from its bound from
Absorbed actively or passively
Transported in the blood via protein carriers
Part of coenzyme Flavin adenine dinucleotide (FAD) used in energy metabolism
High amounts excreted turn urine the bright yellow color
Riboflavin deficiencies: ariboflavinosis
 Cracks at the corners of the mouth (cheilosis), painful, redness of tongue
(glossitis), skin rash, photophobia (sensitivity to light).
Dietary sources: milk products, beef liver, steamed oysters, enriched or whole grains
RDA: men 1.3 mg/day and women 1.1 mg/day
Toxicity: none reported
Niacin (nicotinic acid, nicotinamide, niacinamide, B3)
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Readily absorbed in the stomach and intestine by active and passive transport
Transported to liver to be converted to coenzyme forms, NAD and NADP
Nicotinamide adenine dinucleotide (NAD) used in energy metabolism
Niacin Deficiencies: Pellagra also “smooth swollen red tongue”
o Pellagra – associated with consumption of unfortified maize (corn) as a dietary
staple
o Diets were low in the amino acid tryptophan, precursor of niacin and/or
endogenous niacin was bound and non-bioavailable
o Flour now is enriched with niacin
o Cultures still relying on maize as a staple presoak maize in alkaline lime prior to
cooking to liberate bound niacin
Dietary sources: milk, eggs, meat, poultry, fish, whole grain and enriched breads and
cereals, nuts
RDA: men 16 mg/day and women 14 mg/day
Toxicity:
o Only observed in individuals who use supplements
o Supermegadose levels of nicotinic acid (2000 to 4000 mg). Some patients report
“niacin flush” (red skin), itching skin (urticaria), heartburn, nausea, etc.
Pantothenic Acid (B5)
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Part of coenzyme A (CoA) which is used in metabolism of carbohydrate, protein,
alcohol, and fat
Pantothenic acid deficiencies: none reported
Dietary sources: organ meats, mushrooms, broccoli, avocados, whole grains, sunflower
seeds, peanuts
Adequate Intake (AI): 5 mg/day
Toxicity: none reported
Biotin (B7)
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Found in two forms: free vitamin and the protein bound coenzyme form (boicytin)
Used in fat synthesis, amino acid metabolism, and glycogen synthesis
Biotin deficiencies: biotinidase in small intestine cleaves the bond between biotin and a
protein, releasing the free biotin vitamin – if infants lack the enzyme then levels of free
biotin vitamin decrease; may lead to skin rash, hair loss, convulsions, impaired growth
Dietary sources: widespread in foods; organ meats, egg yolks, soybeans, fish, whole
grains
Adequate Intake (AI): 30 ug/day
Toxicity: none reported
Vitamin B6
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Three forms (pyridoxine, pyridoxal, pyridoxamine) – all converted into the coenzyme
PLP (pyridoxal phosphate)
PLP involved in more than 100 enzymatic reactions
o Functions as a decarboxylase, an enzyme removing carbon dioxide from amino
acids
o Catalyzes the first step in synthesis of heme in red blood cells
o Part of an enzyme that release glucose from glycogen during glycogenolysis
o Catalyzes fatty acid synthesis
o Catalyzes synthesis of neurotransmitters (serotonin, dopamine, norepinephrine,
histamine, and GABA)
o Converts the amino acid tryptophan into the B vitamin niacin
Vitamin B6 deficiencies: seborrheic dermatitis, microcytic hypochromic anemia,
convulsion, depression, and confusion
Dietary sources: meats, fish, poultry, potato, liver, soy products
RDA: 1.3 mg/day
Toxicity: nerve damage, depression, fatigue, headaches
Folate/Folic acid (B9)
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In body target cells, all forms of folate are converted into the coenzyme form, called
tetrahydrofolic acid (THFA or THF)
THFA involved in the synthesis of DNA bases’ adenine and guanine
Folate deficiencies: megoblastic anemia, smooth red tongue, mental confusion,
weakness, fatigue, headache, elevated homocysteine levels (which may increase risk of
blood vessel injury and thus heart attack)
Dietary sources: fortified grains, asparagus, lentils, orange juice, leafy green vegetables,
legumes, seeds, liver
RDA: 400 ug/day
Toxicity: may mask vitamin B12 deficiency symptoms
Vitamin B12
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Also called cobalamin
Contains the mineral cobalt and is synthesized exclusively by bacteria, fungi, and algae
B12 in food is released from proteins by action of HCL and pepsin in gastric juice
The free B12 binds to a protein (R-protein) and travels to the small intestines where a
protease cleaves the protein from the vitamin
Free B12 then is bound to an intrinsic factor and travels to the ileum where B12 is
absorbed
50% of B12 absorbed in healthy adult
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Disruption of absorption can occur as a result of
 Absence or defective synthesis of R-protein
 Defective binding of intrinsic factor/B12 complex to cells of ileum
 Absence of much of the ileum and stomach
 Absence or defective synthesis of the intrinsic factor
 Bacterial overgrowth of the small intestines
 Use of anti-ulcer medications
 Chronic mal-absorption syndromes
B12 deficiencies: achlorhydria and/or atrophic gastritis causes stomach cells to be
damaged and impairs the production of HCL and intrinsic factor – without HCL and the
intrinsic factor, B12 cannot be absorbed and may lead to pernicious anemia
Dietary sources: meat, poultry, seafood, eggs, milk, and fortified cereals
RDA: 2.4 ug/day
Toxicity: none reported
Vitamin C (ascorbic acid)
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Found in all living tissues
Most animals (except humans and other primates) can be synthesize it from glucose
Absorption occurs in the small intestine by active and passive transport
70-90% is absorbed at daily intakes between 30-180 mg – 50% or less at higher dosages
Acts as a reducing agent
Functions as an antioxidant
Involved in connective tissue biosynthesis
Protects white blood cells against oxidative damage
Vitamin C deficiencies: Scurvy, fatigue, pinpoint hemorrhages, bleeding gums and joints,
impaired wound healing, bone pain, fractures, and diarrhea
Dietary sources: orange juice and other citrus fruits, brussels sprouts, bell peppers,
broccoli, tomatoes, potatoes, papaya, strawberries
RDA: men 90 mg/day and women 75 mg/day
Toxicity: nausea, abdominal cramps, diarrhea, fatigue, headache
Vitamin-like Compound
Choline
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Absorbed in the small intestines
Found in all tissues
Precursor of acetylcholine (a neurotransmitter) and phosphatidylcholine (lecithin)
Choline deficiencies: liver damage
Dietary sources: milk, liver, eggs, peanuts
Adequate Intake (AI): men 550 mg/day and women 425 mg/day
Toxicity: body odor, low blood pressure, reduced growth rate, liver damage
Chapter Objectives
After reading chapter ten - A student should be able to...
1.
2.
3.
4.
5.
6.
Discuss the function(s) of the B vitamins and vitamin C
Describe signs and symptoms of deficiencies of the B vitamins and vitamin C
Identify sources of the B vitamins and vitamin C
List the RDAs or recommendations for the B vitamins and vitamin C
Describe signs and symptoms of toxicity of the B vitamins and vitamin C
List the various “vitamin-like” compounds and discuss their role in the human body