Discovery of Vitamins

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

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

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
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

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
Formationof calcitrioloccurs 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

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

Two forms: Vitamin K1Phyllaquinones (plant source) and vitamin K2menaquinone (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...

Understand the difference between water soluble and fat soluble vitamins
Understand the absorption of vitamins and differences in our ability to absorb each of them
Identify different forms of vitamins A D E K
Discuss the function(s) of vitamins A D E K
Describe signs and symptoms of deficiencies of vitamin A D E K
Identify sources of vitamin A D E K
List the RDAs or recommendations for vitamin A D E K
Describe signs and symptoms of toxicity of vitamin A D E K

U.S. Dietary Reference Intakes

VITAMIN A
RDA /

Males age 14 and older: 900 mcg/day
Females age 14 and older: 700 mcg/day
Men 3000 IU/day, women 2330 IU/day

/ PANTOTHENIC ACID (B5)
AI /

5 mg/day

VITAMIN D
AI /

5 ug/day (19-50yrs)
10 ug/day (51-70yrs)
15 ug/day (>70yrs)

/ BIOTIN (Vitamin H)
AI /

30 ug/day

VITAMIN E
RDA /

15mg/day

/ VITAMIN B6
RDA /

1.3 mg/day

VITAMIN K
RDA /

Men 120 ug/day
Women 90 ug/day

/ FOLATE
RDA /

400 ug/day

THIAMIN (B1)
RDA /

Men 1.2 mg/day and women 1.1 mg/day

/ VITAMIN B12
RDA /

2.4 ug/day

RIBOFLAVIN (B2)
RDA /

Men 1.3 mg/day and women 1.1 mg/day

/ VITAMIN C
RDA /

Men 90 mg/day and women 75 mg/day

NIACIN (B3)
RDA /

Men 16 mg/day and women 14 mg/day

/ CHOLINE
AI /

Men 550 mg/day and women 425 mg/day

Water Soluble Vitamins

B Vitamins

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)

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

Riboflavin (vitamin B2)

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)

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”
Pellagra – associated with consumption of unfortified maize (corn) as a dietary staple
Diets were low in the amino acid tryptophan, precursor of niacin and/or endogenous niacin was bound and non-bioavailable
Flour now is enriched with niacin
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:
Only observed in individuals who use supplements
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)

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)

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

Three forms (pyridoxine, pyridoxal, pyridoxamine) – all converted into the coenzyme PLP (pyridoxal phosphate)
PLP involved in more than 100 enzymatic reactions
Functions as a decarboxylase, an enzyme removing carbon dioxide from amino acids
Catalyzes the first step in synthesis of heme in red blood cells
Part of an enzyme that release glucose from glycogen during glycogenolysis
Catalyzes fatty acid synthesis
Catalyzes synthesis of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, and GABA)
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)

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

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
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)

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

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...

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