FAT SOLUBLE VITAMINS

VITAMIN A

Discovery• Ancient Greece

• Night blindness was cured by ingestion of cooked liver or topical application of juice from cooked liver to the eyes

• Vitamin A itself was not discover until the early part of twentieth century

• McCollum and Davis, Osborne and Mendel (1913)• Extracted accessory food factor from butterfat by the use of ether• Fat-soluble• Addition of butterfat to diet of animals ameliorated xeropthalmia

• An abnormal dryness of cornea and membrane of the eyes

• McCollum and Davis• Named it fat-soluble A

• C.E. Bloch• Addition of milk product to children’s diet could cure their

xeropthalmia

• Animal-feeding experiments• Only certain types of fats have this curative ability

• None in vegetable oil but present in butterfat, cod liver oil, and ether extract of egg yolk

• Fat-soluble A• Specific active principle in fats responsible for maintaining healthy

eyes

• Vitamin A• In 1920, fat-soluble was dropped and the factor was simply called

Vitamin A

• Plant pigment carotene• In 1920, its relationship to vitamin A was first demonstrated• In 1957, it was proved that carotene is a precursor of vitamin A and

converted in the body

• Vitamin A includes:• Retinol (vitamin A alcohol)• Retinal (vitamin A aldehyde)• Retinoic Acid (vitamin A acid)

Vitamin A• Pale yellow, almost colorless• Soluble in fat or fat solvents• Insoluble in water• High degree of unsaturation

• It can be destroyed by oxidation when fats or oils become rancid• Vitamin E or storage in cool, dry place will prevent oxidation and

rancidity

General Sources1. Preformed vitamin A found in animal foods

• Dairy foods and fish liver oils

2. Precursor carotene (provitamin A)• Plant foods with deep yellow or deep green pigment• The deeper the yellow or green, the more carotene• Chlorophyll (green pigment of plant) does not have any vitamin A

activity

2 Forms of Vitamin A• Vitamin A1

• Found in liver and body fat of fish and other foods of animal origin• Liver, milk, butter and egg yolk

• Vitamin A2• Found in fresh-water fish

Carotene• Found in orange-yellow and dark green fruits and

vegetables• Three types are known: alpha- , beta-, gamma-

• Beta-carotene is the most important• it has the highest vit. A activity and is the most plentiful

• The fourth is cryptoxanthin

Absorption of Vitamin A• Fat, bile salts and pancreatic juices – essential for

complete absorption of vitamin A• Sprue and celiac disease can cause vitamin A deficiency because it

interferes with fat metabolism• Diarrhea or excessive intake of mineral oil may interfere with absorption

Utilization of Vitamin A• Conversion of absorbed carotene to retinol

• Half of the biological activity is lost• Only 1/3 of carotene is available, therefore its utilization efficiency

is only 1/6 of vitamin A• Vitamin A equivalent of carotene

• Milligrams of carotene multiplied by 0.167 factor

Storage of Vitamin A• Stored in the liver

• Enough to meet vitamin A requirement for many months• Deficiency in vitamin A signs and symptoms develop very slowly• Cirrhosis of liver markedly reduces vitamin A storage

Functions• Formation of visual purple for maintenance of retina• Control of the differentiation of epithelium in mucus-

secreting structures• Promotion of bone remodeling• Promotion of normal reproduction in rats• Activation of cell membrane systems such as the E.R. and

plasma membrane• Promotion of health of the oral structures

Formation of Visual Purple• George Wald – Nobel Prize in medicine, 1967

• Discovered the biochemical role of vitamin A in the retina

• Human retina contains rods and cones• Photoreceptor systems

• Rods contain visual purple pigment rhodopsin• Sensitive to light of low intensity

• When light strikes retina, rhodopsin is split into• Opsin – protein component• Retinal – prosthetic group

• Visual purple becomes visual yellow in this process• This causes a nervous excitation to the optic nerve which

allows transmission of images to the brain

• Retinal is reduced to retinol in this process• Most of the retinol is oxidized back to retinal• In the dark, retinal combines with opsin to form rhodopsin

• Loss of degradation products will require new supplies of Vitamin A.

Vitamin A Deficiency: Vision• Ability to reproduce rhodopsin is reduced• Faulty adaptation of eyes to the dark or night blindness

Vitamin A Deficiency and Cancer• Deficiency of vitamin A may lead to cellular changes

which is similar to those that occur when a normal cell is transformed into a precancerous cell

Maintenance of Epithelial Cells and Tissues

• Presence of vitamin A allows certain cells of the epithelium that resemble a cube to form mucus-secreting cells

• Absence of vitamin A will cause the mucus-secreting cell to degenerate• Produces keratin instead of mucus

• Vitamin A produces glycoprotein• Substance from which mucus is made

• Without vitamin A:• Scleral and corneal epithelia of the eye becomes keratinized• Normal mucosal surfaces of the conjunctiva become dry and

granular• Severe secondary infection may occur

• Pus is exuded and the eye will hemorrhage

• Bitot’s spots – keratin debris accumulated in whitish plaques

• Keratinization and thickening of corneal epithelium causes xeropthalmia

• Impairs vision

• Keratomalacia – softening of cornea leading to deformation and destruction

• In the absence of vitamin A:• Ciliated columnar epithelium of the respiratory tract is replaced by

non-ciliated stratified squamous epithelium• Impairment of normal defensive function of the mucosa• Keratin formation may act as a foreign body

• Produces irritation and infection

• Follicular hyperkeratosis – rough sandpaper like skin and numerous papules caused by the plugging of hair shafts and sebaceous gland ducts

Promotion of Bone Remodeling• Vitamin A deficiency is accompanied by cessation of bone

growth• Intramembranous bone formation is normal but bone

remodeling sequences become abnormal and stop• Failure of conversion of osteoblasts to osteoclasts

• Thickening of the bone is present when there is vitamin A deficiency

• Thickening of the skull or vertebral column may cause compression of nerve tissue resulting to nerve lesion

• Excess of vitamin A causes resorption of cartilage and old bone

Promotion of Normal Reproduction in Rats

• In the absence of vitamin A:• Failure in spermatogenesis occurs in the male• Fetal resorption occurs in the female

Activation of Cell Membranes• Vitamin A ensures the normal structure and function of the

cell membranes• Severe vitamin A deficiency can cause abnormalities in

RNA metabolism and protein synthesis

Vitamin A Deficiency: Oral Structures• Periodontium

• Produces hyperkeratosis and hyperplasia of gingival tissue• Tendency of periodontal pocket formation due to proliferation of basal

cells of gingival epithelium and decreased cellular infiltrate of the lamina propria

• Teeth• In rodents,

• Growth of incisor teeth is slowed down or completely stopped• Enamel formation is affected due to disturbance in differentiation and

function of ameloblasts• Hypoplastic (incompletely developed) chalky white incisors plus a loss of

the usual orange pigment• Disorders of the labial and lingual odontoblasts produce regular labial

dentin with interglobular spaces and thin, atubular lingual dentin• Crowding of teeth, stunting and thickening of tooth roots can also be

present

• In humans,• Teeth are less sensitive to deficiencies• No absolute correlation between vitamin A deficiency and dental caries

or enamel hypoplasia• Deficiency in vitamin A should probably be very severe which is rare

• Salivary glands• Atrophy of salivary glands• Reduced salivary flow• Increases caries

• Oral Mucous Membranes• Epithelial metaplasia – reversible change wherein one cell type is

replaced by another• Hyperkeratinization• Leukoplakia – thickened white patches on mucous membranes

• Cleft Lip and Palate• Deficiency or high doses of vitamin A induces cleft lip and palate

Recommended Dietary Allowance• 1 retinol equivalent = 1 µg of retinol or 0.6 µg of beta-

carotene• 1 international unit (IU) = 0.3 µg of retinol or 0.6 µg of

beta-carotene• Adult man => 1000 RE or 5000 IU• Adult woman => 800 RE or 4000 IU

Food Sources• Preformed Vitamin A (available only in animal products)

• Liver• Kidney• Cream• Butter• Egg yolk

• Major Dietary Plant Source• Carrots• Sweet potatoes• Squash• Apricots• Spinach• Collards• Brocolli• Cabbage• Dark leafy greens

• Processing and cooking cause little loss of vitamin A because of water insolubility

• Pureeing, mashing or cutting increases availability of carotenes due to rupture of cell walls

Therapy• Mild Vitamin A deficiency

• Oral administration of 30,000 IU of vitamin A daily• Toxic if taken for more than a month

• Advanced cases of epithelial metaplasia in adults with xeropthalmia and skin disorders such as keratomalacia

• Initial dose 500,000 IU in the first few days• Reduced to half by the next few days and reduced to ¼ by the middle of

second week• Third week, dosage = 30,000 IU

• Parenteral (by injection) aqueous dispersion of vitamin A can be used when initially combined with a fatty acid. Oral administration of cod liver oil (30 ml = 25,000 IU) may then be used.

• Supportive therapy consisting of high-protein and high-calorie diet rich in sources of vitamin A and carotene is recommended

Toxicity: Hypervitaminosis• Vitamin A has a potential for toxicity because it is stored in

the body• Chronic hypervitaminosis in adults has occurred when

they are given 100,000 to 150,000 IU (20 to 30 times the RDA)

• Misinformed people• “IF SOME IS GOOD, MORE IS BETTER”

• Causes anorexia, irritability, loss of weight, tenderness over long bones, enlarged spleen and liver

• Vitamin A concentration in serum = 0.1mg/ml• Effective therapy: stop administration of Vitamin A

Hypercarotenemia• Serum carotene level = 250 µg/ml• Produces yellow orange discoloration of skin and oral

mucosa but not jaundiced eyes• Caused by excessive ingestion of carrots in various forms,

especially in juices• Not harmful• Therapy: stop carotene ingestion

VITAMIN D

Vitamin D(Discovery)

• Sir Edward Mellanby (1918)• Rickets(softening of bones in children) in puppies is a nutritional

deficiency that was curable by the administration of cod liver oil(contains Vit. A and Vit D).

• (1922) researchers found that heated and aereated cod liver oil would not cure xerophthalmia(medical condition in which the eye fails to produce tears) in experimental animals.• Vitamin A is destroyed

Vitamin D(Discovery)

• Animals are cured when they were fed with diets containing abnormal calcium to phosphorus ratio(Vitamin D).

• It is called vitamin D because it is the fourth vitamin to be discovered.• After discovering vitamin D, many researchers studied the relationship

of ultraviolet light to the formation of vit. D in animals and food.

Vitamin D(Chemistry)• There are 3 types

• Only 2 are of nutritional importance (Vit. D2 and D3)• Fat soluble and stable to cooking, processing, storage, and acids but

sensitive to light.

Vitamin D(Chemistry)• Vit. D2

• Ergocalciferol• From provitamin ergosterol

• Present in plants, especially in fungi and yeast.

• Synthetic form produced by irradiating ergosterol with UV light.• 1 mg=40,000 IU (internation unit)

Vitamin D(Chemistry)• Vit. D3

• Cholecalciferol• Naturally occurring form of viamin D in animal tissues

• Produced in the skin

• Precursor-7-dehydrocalciferol• Occurs naturally but in small amounts in egg yolk, liver, fish,

fortified milk(pasteurized milk enriched with one or more nutrients, usually vitamins A and D, that has been standardized at 400 International Units per quart (fortified vitamin D milk).)

Vitamin D(Chemistry)• People derive most of their vit. D from the irradiation

activity of the sunlight on oils in the skin.• D2 and D3 are equally potent as dietary supplement.

Vitamin D(Absorption)• Absorbed in the intestinal tract

• By the presence of bile salts and fats.• Transported into the lymph circulation via chylomicrons(particles of

emulsified fat fount in the blood).• The ff can aversely affect vit. D absorption.

• Pancreatitis, sprue (A chronic, chiefly tropical disease characterized by diarrhea, emaciation, and anemia, caused by defective absorption of nutrients from the intestinal tract), and malabsorption disorders.

Vitamin D(Transport and Storage)• Carried by the blood to the liver.• Converted to calcitrol (active form of vit. D).• Found in skin and brain, with smaller quantities in the

lungs, spleen, and bones.

Vitamin D(Metabolism)• Deluca (1969) showed that vit. D must first be converted

to atleast two biologically active metabolites before it can induce physiological changes.

Vitamin D(Metabolism)

1. Vit. D is hydroxylated in the liver and intestine to form 25-hydroxyvitamin D3(25-hydroxycholecalciferol [25-Oh-D])

2. Carried to the kidney for further hydroxylation to form 1,25-dihydroxyvitamin (1,25 dihydroxycholecalciferol or calcitrol)

• Regulated by circulating calcium, parathyroid hormone, and calcitonin.

Vitamin D(Metabolism)• Calcitrol enters epithelial cells of small intestine and acts

on nucleic acid.• Produces protein that binds calcium and promotes active transport

of calcium across the intestinal walls into the circulation(ensures sufficient supply of calcium to the bones).• Increased conc. of calcium promotes deposition.

Vitamin D(Function)• Functions both as a vitamin(present in food) and as a

hormone (formed in skin and acts on distant target organs, specially the instestines and bones).

• Promotes intestinal calcium and phosphate absorption.• Involved in formation and functioning of bones, teeth, nerves, and

muscle.

Vitamin D(Function)• In conjunction of the parathyroid gland. It maintains the

proper levels of serum calcium, and phosphorus, which promotes the formation, calcification and repair of bones.

• Stimulates renal tubular transport of calcium and phosphorus(Deluca).

• Aids in the treatment of serious bones disease.

Vitamin D(Recommended Dietary Allowance)• 400IU(10ug)/day

• Birth to 22 years of age• Due to bone formation and mineralization during active growth and

development• 500IU/day

• Pregnant and lactating• 300IU(7.5)/day

• 19-22-year-old female(not pregnant)• Allowance of 200 IU of vitamin D is recommended for adult men and

women• Maintain calcium• Reduce osteoporosis (past menopause)

Vitamin D(Sources)• Sunlight

• Major source• Depends on intensity and length of exposure• Color of skin

• Fatty fish, eggs, liver, butter• Small amount

• Fish liver oil fortified milk• Major food sources

• Milk and cheese products• Excellent supply of calcium and phosphorus in the ideal ratio of

1.2:1• Can help in the absorption of vit D and bone formation

Vitamin d(Indications for Vit D Supplementation)• Elderly (house-bound)• Lactose intolerant• infants

Vitamin D(Diseases)• Rickets

• Lack of orderly change from cartilaginous material to calcified bone during bone development.

• Mineralization of osteoid (young boen that has not undergone calcification) matrix does not occur.

• Overgrown and disorganized zone of cartilage, capillaries, and fibroblast at the end of long bone shafts where bone and cartilage join.

Vitamin D(Diseases)• Rickets

• Bone deformities occur• Example rickets rosary

• Radiograph• Outline of joins are blurred and hazy, and the epiphyseal line becomes

broadened.

• Treatment• 1000 to 5000 IU/day

• Depends on he severity

• 1ml halibut liver oil• 30-40 times more than cod liver oil• children

• 4 glasses of milk/day or 5g of calcium lactate

Vitamin D(Diseases)• Rickets

• Treatment• (Diet)- Egg, fortified butter, margarine, ascorbic acid, and iron• Vitamin D supplements should gradually reduced to prophylactic doses

of 400 IU daily after serum alkaline phosphatase decreases to normal levels.

• Prevention• Exposure to sunlight, diet rich in vitamin D.

Vitamin D(Diseases)• Osteomalacia

• Softening of bone due to failure of mineralization as they undergo remodeling

• Adult counterpart of rickets• Most often seen in women

• Repeated pregnancies• Who have little exposure to sunlight and who eats diet with low dairy

content.

• Experiences pain in ribs, spine, pelvis, and legs• leg bones may bend, leads to waddling gait

Vitamin D(Diseases)• Osteomalacia

• Treatment• 5000 to 20,000 IU of vitamin D accompanied by 5g of calcium gluconate

or calcium lactate three times a day.

Vitamin D(Diseases)• Enamel Hypoplasia

• Incomplete development of the enamel and dentin• Enamel calcifies poorly and in some areas fail to form.• Uncalcified dentin matrix• Earliest sign

• Calciotraumatic line in the dentin

Vitamin E

Vitamin E

• Fat soluble • Antioxidant

• Stop the free radical from forming in the first place

• Interrupt an oxidizing chain reaction to minimize the damage of free radicals

• Protects cell membranes and other fat-soluble parts of the body

• Promotes normal growth and development• Promotes normal red blood cell formation• Acts as anti-blood clotting agent

Vitamin E

Vitamin E

• Seed oils = major source• wheat germ oil• vegetable oils • nuts and seeds• whole grains• egg yolk• leafy green vegetables

Specific Food Sources

• vegetable oils • Corn, cottonseed, and peanut oil

• nuts and seeds• Almonds, hazelnuts, sunflower seeds,

walnuts, and margarine

• whole grains• whole-wheat flour, wheat germ

• Vegetables and fruits• Spinach, lettuce, onions, blackberries,

apples, and pears

Vitamin ERecommended Daily Allowances (RDA):

Males18+ 10 mg 30 IUFemales18+ 8 mg 24 IUpregnant 12 mglactating 11 mg

3-4 6-7 8

10

8 2 3

mg

mg

mg

mg

mg

mg

mg

Vitamin E

• Severe vitamin E deficiencies are rare• Lack of vitality • Lethargy • Apathy • Inability to concentrate• Muscle weakness

Vitamin E

• No harmful effects at 50 times RDA (1200 – 1500 IU)

• Vitamin E toxicity is rare

• Vitamin E requirement is proportional to the amount of unsaturation of polyunsaturated fatty acid in the diet.

• It helps fats not become rancid (antioxidant)

Additional Information:

Vitamin E

• Freezing may destroy Vitamin E• Extreme heat causes Vitamin E to break down• Avoid deep-fat frying foods that are natural

sources of Vitamin E

VITAMIN K

Vitamins Home Page

VITAMIN K’S METABOLIC/BIOCHEMICAL

FUNCTIONS

• Aids in blood clotting (primary function)• Prothrombin by the liver• Factor VII, IX, X

• In the process of blodclotting, prothrombin is converted to thrombin

• Thrombin will then convert Fibrinogen to Fibrin, the basis of blod clot

• Normal human blood when shed will clot within 5-8mins in room temp

AIDS IN BLOOD CLOTTING• Primary function of Vitamin K• Initiates the healing process by slowing and stopping the bleeding

• Given to patients before surgery to prevent excessive bleeding

VITAMIN K SYNOPSIS There are 3 forms of Vitamin K:• Vitamin K1

• principle natural dietary source of Vitamin K found in green leafy vegetables

• Vitamin K2 Produced in bacterial synthesis in the intestine

*both are unstable in ultravioletlight and destroyed by strong acids and alkalis

Vitamin K3

• Synthetic form of the vitamin K • also referred to as menadione

DIETARY SOURCES OF VITAMIN K

• Lentils• Egg Yolks• Whole wheat• Fruits• Cheese• Ham • Beef• Liver• Green tea • Tomatoes• yogurt

§ Freezing foods may destroy vitamin K, but heating has no effect

RECOMMENDATIONS FOR PREGNANT & LACTATING

WOMEN• < 18 years = 75 µg• 19-30 years= 90 µg• 31-50 years = 90 µg

• Brest fed infants may be at an increased risk for vitamin K deficiency because human milk is not a good source of this nutrient. To improve the amount of vitamin K in breast milk the mother should eat the recommended amount of green vegetables daily.

VITAMIN K DEFICIENCY• Since Vitamin K is obtained easily from the diet and synthesized in the body

*deficiencies are rare

• Antibiotics will interfere with the normal production of Vitamin K in the intestine

• Health problems that may lead to Vitamin K deficiency are:• Gallbladder or biliary disease• Liver disease• Ongoing diarrhea• Heavy menstrual bleeding