Fat soluble Vitamins - By Dr. P. Ravisankar.

05/01/2023 Vignan Pharmacy College, Vadlamudi, Guntur

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FAT SOLUBLE VITAMINS

B.VIJAY KUMAR

Dr. PANCHUMARTHY RAVI SANKAR M. pharm., Ph.D.

VIGNAN PHARMACY COLLAGEVADLAMUDI, GUNTUR (DT) A.P

VITAMINS

INTRODUCTION A vitamin is an organic compound required as a nutrient in tiny amounts

for the maintenance and growth of an living organism. Vitamins deficiency may lead to certain specific diseases or symptoms

which can be cured by the administration of that specific vitamin only. The term vitamin was first discovered by Funk. Funk coined the term "vitamine" a combination word from vita and

amine, meaning amine of life. At the time they were considered to be amines that are vital for the life. After researchers began to suspect that not all "vitamines" had an amine

component (particularly vitamine A). How ever it was later found that not all vitamins contains “nitrogen” or

amines. In 1920, Drummond proposed that the final "e" be dropped. That’s why

in the word Vitamines “e” is removed and called vitamins.

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CLASSIFICATION VITAMINS

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Based on solubility in oil Based on solubility in water

Fat soluble vitamins Water soluble vitamins

Vitamin -A Vitamin-D Vitamin-E Vitamin-K

Vitamin-D2 Vitamin-D3 Vitamin-K1 Vitamin-K3

B-complex vitamins Non B-complex vitamine Ex: Vitamin-C

Based on type of source

Thermo labile Thermostable

Vitamin-B2 Vitamin-B3 Vitamin-B6 Vitamin-B12 Niacin Folic acid Biotin

Based on Stability

Ex:Vitamin-B1

Retinol Tocopherol

Ergocalciferol Cholecalciferol

Ascorbic acid

Thiamine

Riboflavin Pantothenic acid Pyridoxine Cyanacobalamine Vit-H

Nicotinamide Nicotinic acidVitamin-K1 - (Phytonadione) Folic acid -(Pteroylglutamic acid) Vitamin-K3 - (Menadione) (Niacinamide)-

BASIC STRUCTURAL MOIETY OF FAT SOLUBLE VITAMINS

FAT SOLUBLE VITAMINS BASIC STRUCTURAL MOIETY

Vitamin - A Diterpenoid

Vitamin – D Steroidal moiety

Vitamin - E Chromane ring system with isoprenoid side chain.

Vitamin- K Napthaquinone derivative.

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VITAMIN



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CHEMICAL NATURE AND PROPERTIES OF VITAMIN-A

Natural formA1 （ Retinol）

A2 （ 3-dehydro-retinol ）Active form Retinol, Retinal, Retinoic acid

Pro-vitamin A β-carotene

Storage Liver, Adipose tissue of the body


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CH2OH

CHO

COOH

RETINOL

RETINAL(Vitamin A aldehyde)

RETINOIC ACID

STRUCTURES OF VITAMIN-A


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Vitamin A, D, E, K

FAT SOLUBLE VITAMINS


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Fat soluble vitamins1. Vitamins A, D, E and K are the fat-soluble vitamins.2. These vitamins are soluble mainly in lipids or oil. So called

as fat soluble vitamins.3. Excessive use of fat soluble vitamins may lead to their accumulation in the body (hypervitaminosis) due to delayed elimination rate. This accumulation of vitamins results in toxic effects.4. Fat soluble vitamin tend to be stored in fatty tissues

(adipose tissue) of the body and in the liver.5. They are eliminated slowly from the body because of their

lipophilic character.


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Vitamin-A Vitamin-A is a family of fat-soluble Retinoids:

Retinol, Retinal, Retinoic Acid

Retinol Retinal Retinoic Acid

Animal foods Stored in Body Function:

Reproduction

Found in plants Retinal = Vision Retinoic = Regulates growth


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Beta-caroteneDark leafy green vegetables,

spinach, broccoli.

Deep orange veggiesCarrots, pumpkin, squash,

sweet potato.

Deep orange fruitsApricots, cantaloupe.

VITAMIN-A SOURCES


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SOURCE OF VITAMIN-A Beta-carotene

Dark leafy green vegetables, spinach, broccoli

Deep orange veggies Carrots, pumpkin, squash, sweet potato

Deep orange fruits, Apricots, cantalo

Milk, butter, cheese, cream, eggs, liver

Lycopene

Tomatoes, papaya, water melon.

Retinol


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Retinol Fortified milk, butter cheese,

cream Fortified margarine Eggs Liver

Tomatoes Papaya Watermelon,

VITAMIN-A SOURCES

Lycopene


FUNCTIONS OF VITAMIN-A (RETINOIDS)

Growth and DevelopmentEmbryonic developmentEpithelial cells and mucus production in lungs,

trachea, skin, GI tractImmune Function

Maintains the epitheliumIncreased infections w/vitamin-A deficiency

DermatologyTopical and oral medications

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VITAMIN A DEFICIENCY - REPRODUCTION

1. In females: Increased abortions Neonates born dead/weak Deformed young: no eyeballs Hydrocephalus 2. In males: Keratinization of testicular epithelium


VITAMIN-A DISEASES

Deficiencies:

– Night blindness

– Xerophthalmia (permanent blindness)

– Follicular hyperkeratosis

– Impaired growth

– Increased infections

– Increased transmission of maternal/fetal HIV

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Vitamin A Toxicity

There are three syndromes of vitamin A toxicity:

• Acute Toxicity (very rare)– occurs in adults when >200 mg are ingested– symptoms include nausea, vomiting, vertigo, and blurry

vision. • Chronic Toxicity (rare)

– occurs with long-term ingestion of doses higher than 10 times the RDA.

– symptoms include problems talking, hair loss, hyperlipidemia, hepatotoxicity, bone and muscle pain, and vision problems.

– In postmenopausal women, it has been associated with increased fracture risk.

E.A. DENNIS 2010 ©


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Vitamin A Toxicity• Teratogenic Effects:

– Synthetic retinoids can be used to treat severe dermatological conditions including severe psoriasis and acne vulgaris.

– Synthetic retinoids, like acitretin, cause spontaneous abortions and severe life-threatening congenital malformations. • Women treated with retinoids must not get pregnant at

the time of treatment or become pregnant for up to 3 years after treatment.

• Patients receiving treatment with retinoids must not give blood for up to three years after treatment.– The presence of these drugs in plasma can be

demonstrated for up to several years after a person stops taking them. It could be disastrous if an unsuspecting pregnant woman received one in a transfusion, hence the ban.

E.A. DENNIS 2010 ©


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USES OF VITAMIN-A

1. Vitamin-A is mainly used in the treatment of treatment of deficiency of Vitamin-A.2. It is also used in the treatment of - Dermatological disease and lesions. - Xerophthalmia. - Cold, warts, corns and calluses( skin infections - Acne - Hyperkeratosis of arms.


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VITAMIN-D


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VITAMIN-D• Vitamin D = calciferol• Vitamin D2 = ergocalciferol

Completely synthetic form produced by the irradiation of the plant steroid ergosterol

Plant source – cannot be used by birds• Vitamin D3 = cholecalciferol

Produced photochemically by the action of sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterol

Animal source – required by birds


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• Infact Vitamin-D1 is containing molecular compound of lumisterol and D2 in 1:1 ratio.

Lumisterol

Vitamin-D1= Lumisterol + Vitamin D2 (calciferol)( 1 : 1 ) Ratio.

VITAMIN-D1

Important structures of vitamin D

Ergocalciferol

Cholecalciferol

Vitamin D5

C2H5

Sitocalciferol

Cisergocalciferol

Vitamin D - Cholecalciferol• Vitamin D is a cholesterol-like

molecule• Important to bone and calcium

regulation– Acts more like a steroid

hormone rather than a enzyme cofactor

H

H

HO

H

H

H

H

HO

H

H

H

H

HO

H

H

Cholecalciferol

Ergocalciferol

7-dehydrocholesterol

synthesis in skin

Diet

E.A. DENNIS 2010 ©7-dehydrocholesterol

• Cholecalciferol (D3) has two sources:– Diet

• plants have ergocalciferol (D2), which easily becomes D3

• animal flesh has ready-made D3

– Sunlight (UV)• Converts 7-dehydrocholesterol into

D3 in the skin

synthesis in skin

Cholecalciferol

Diet

Ergocalciferol

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Table 2: Recommended Dietary Allowances (RDAs) for Vitamin D [1]

Age Male Female Pregnancy Lactation0–12 months* 400 IU

(10 mcg)400 IU

(10 mcg)

1–13 years 600 IU(15 mcg)

600 IU(15 mcg)

14–18 years 600 IU(15 mcg)

600 IU(15 mcg)

600 IU(15 mcg)

600 IU(15 mcg)

19–50 years 600 IU(15 mcg)

600 IU(15 mcg)

600 IU(15 mcg)

600 IU(15 mcg)

51–70 years 600 IU(15 mcg)

600 IU(15 mcg)

>70 years 800 IU(20 mcg)

800 IU(20 mcg)

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• Fortified– Milk– Margarine– Butter– Cereal

• Veal, Beef• Egg yolk• Fatty fish (salmon, sardines, herring)

VITAMIN-D SOURCES


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• The Sunshine Vitamin– Approximately 90% of

Vitamin D requirement obtained from sun

– UV light from sun hits skin, triggers synthesis

– Activated in liver and kidneys

VITAMIN-D


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VITAMIN-D DEFICIENCY• Young animals

– Rickets• Failure of bones to grow properly• Results in “bowed” legs or knock-knees, outward bowed

chest and knobs on ribs• Older animals

– Osteomalacia: Adult form of rickets• Softening of bones, bending of spine, and bowing of legs

– Osteoporosis (porous bones):• Vitamin D plays a major role along with calcium• Loss of vitamin D activity with advancing age• Associated with fractures very serious for geriatrics

Poultry• Decreased egg production & hatchability• Thin-shelled eggs


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VITAMIN-D TOXICITY• Calcification of soft tissue

– Lungs, heart, blood vessels – Hardening of arteries (calcification)

• Hypocalcaemia – Normal is ~ 10 mg/dl– Excess blood calcium leads to stone formation in kidneys

• Lack of appetite• Excessive thirst and urination

• Chicks: 4 X 106 IU/kg diet (3 to 5x required levels)• Pigs: 0.25 X 106 IU/d for 30 days• Infants: 3 X 103 (10x required levels)


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Uses of vitamin D• Vitamin D is more than just a vitamin: it is also a hormone. Research in the last few

years suggests that Vitamin D – traditionally considered a “bone vitamin.• Vitamin D is sufficient enough in the treatment of hopoparathyroidism and in

vitamin D deficiency diseases like reckets, osteomalacia.• It has a role in preventing infections like.• heart diseases and• diabetes mellitus.• The sunshine vitamin vitamin D is used in the treatment of breast and colon

cancers. • Treatment of psoriasis (chronic skin disease where scaly patches can be seen on

elbows, knees, scalp, etc.,• and autoimmune diseases such as multiple sclerosis,insulin dependent diabetes

mellitus are decreased by vitamin D intake.• and rheumatoid arthritis.• In parallel with this explosion of research, there is a change in the

recommendations for optimum intake of this vitamin-hormone.• vitamin D is a central player in calcium and bone metabolism.


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VITAMIN-E


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* Infact vitamin E is the antisterility factor which is necessary for fertility of the male and the birth process of the female and therefore it is also called tocopherols

* Tokos(Greek) means = for child birth…. phero = to bear ol = alcohol.

* It is very essential for the birth process in female and fertility in males and at the same time the compound reacts like an alcohol

VITAMIN-E

*This are mainly 8 compounds, 4-tocopherols 4-tocotrienols


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Vitamin EAlpha-tocopherol most active form in body.

Synthetic form in supplements only ½ as active.

Position of methyl groups on aromatic ring

Tocopherol structure Tocotrienol structure

5,7,8 trimethyltocol) alpha-Tocopherol (α) alpha-Tocotrienol

5,8 diemthyltocol) beta-Tocopherol (β) beta-Tocotrienol

7,8 dimethyltocol) Gamma tocopherol (γ)

Gamma-Tocotirenol

8 mono methyl tocol Delta-tocopherol (δ) Delta-tocotrienol

sources• Dietary sources and

supplements• The following foods are rich in

vitamin E.

. Seeds and seed oils, like sunflower and safflower.

• nuts and nut oils, like almonds

• green leafy vegetables, like spinach, turnip.

• tomatos • mangoes • asparagus • papayas • pumpkin • sweet potato • blue crab


http://www.fruitsinfo.com/fruit-facts/wp-content/uploads/2010/07/Vitamin-E-fruits.jpg


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Vitamin E - Functions

• Stabilize reactions or situations that typically produce free radicals– Nucleic acid and protein

metabolism– Mitochondrial metabolism– Supplementation may

increase antibody production

– When supplemented prior to slaughter, helps maintain meat quality (shelf life, color)


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Vitamin E - Deficiency• Rare – typically associated with fat malabsorption or

excessive intake of polyunsaturated fatty acids (PUFAs)– Erythrocyte hemolysis and hemolytic anemia

• Red blood cell breaks open and spill the contents, perhaps due to PUFA oxidation

• Observed among newborns of several species• Vitamin E treatment resolves hemolytic anemia

– Prolonged deficiency causes neuromuscular dysfunction; affects the spinal cord and the retina

• Degeneration of nerve cells (poultry)


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Vitamin E - Deficiency

• Reproductive failure– Embryonic degeneration– Ovarian failure– Testes degeneration– Fetal resorption

• Derangement of cell permeability– Liver, brain, kidney, or blood capillaries– Brain necrosis (crazy chick disease)

• Muscular lesions– White muscle disease (calves, lamb)– Mulberry disease (pigs)– Stiff lamb disease (skeletal muscle degeneration)

• Failure to growth, unthriftiness


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Side effects/adverse effects.

• Taking vitamin E supplements for up to 4 months at doses of 530 mg or 800 IU (35 times the current RDA) had no negative side-effect on general health,

• body weight,• levels of body proteins,• lipid levels, • liver or kidney function• thyroid hormones• amount or kinds of blood cells• and bleeding time over doses may cause Nausea,vomitng,diarrhoea.• vitamin E products in excess of 1200 IU daily may interfere with absorption and metabolism of

vitamins A and K. But one can get benefits with much lower levels of vitamin. • individuals who are vitamin K(people who are on blood thinners) deficient should not take

alpha-tocopherol supplements without close medical supervision because of the increased risk

of hemorrhage.

Physiological role/importance of vitamin E• Vitamin E plays an important role as an antioxident and protect the body cells from the damage

caused by free radicals.• These free radicals are highly reactive and distructive compounds formed as a result of oxidative

deterioration(metabolism) of polyunsaturated fats.

• Factors contributing for free radical genaration in the body include smoking and exposure to Uv- radiations.

• Tocopherols (Vitamin E) are equipped to perform a unique function. They can interrupt free radical chain reactions by capturing the free radical; this imparts to them their antioxidant properties.

• The free hydroxyl group on the aromatic ring is responsible for the antioxidant properties. The hydrogen from this group is donated to the free radical, resulting in a relatively stable free radical form of the vitamin.



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VITAMIN K


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*Vitamin K is a fat-soluble vitamin that plays *Vitamin K is known as the clotting vitamin . * They are 2-methyl-1,4-naphthoquinone

*Vitamin K exists in both natural and *The natural forms of vitamin K include

*while synthetic froms are vitamin

an important role in blood clotting

derivativeforms.

K1(phylloquinone and

K2 (menaquinone from the purified fish meal,

K4(menadiol sodium phosphateK3(menadione

*Vitamin K1 is also called phylloquinones, is *The second basic type, called menaquinones, is made by bacteria in the large intestine

made by plants.

is made by bacteria in the large intestine .

VITAMIN K

synthetic

*Vitamin K (K from "Koagulations-Vitamin”.(clotting of blood)in German

http://en.wikipedia.org/wiki/Methyl

http://en.wikipedia.org/wiki/1,4-naphthoquinone

http://en.wikipedia.org/wiki/German_language


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Fat-soluble vitamin:K1 (Phylloquinone) K2 (Menaquinone)

Synthesized by:• Vegetable and plants.

Synthesized by:• Bacterial flora of the gut• Minor source


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• Bacterial synthesis in GI tract

• Leafy green vegetables

• Cruciferous vegetables

• Liver• Milk

Vitamin K Sources


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• Vitamin K1 produced by plants and algae– Broccoli, kale, chard; plant oils like canola

and soybean• Hydrogenated soybean oil has ineffective K

• Vitamin K2 produced by bacteria in gut– Food Sources: fermented soybean

(Natto); dairy products, egg yolk

Vitamin K Sources

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What are current public health recommendations for vitamin K?

Adequate Intake (AI) for Vitamin K

Life Stage Age Males (mcg/day)

Females (mcg/day)

Infants 0-6 months 2.0 2.0 Infants 7-12 months 2.5 2.5 Children 1-3 years 30 30 Children 4-8 years 55 55 Children 9-13 years 60 60 Adolescents 14-18 years 75 75

Adults 19 years and older 120 90

Pregnancy 18 years and younger - 75

Pregnancy 19 years and older - 90

Breast-feeding

18 years and younger - 75

Breast-feeding

19 years and older - 90

Recommended Daily Intake


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• Chief functions in the body– Synthesis of blood-clotting proteins

and bone proteins that regulate blood calcium

Vitamin K


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• Synthesis of bone proteins that regulate blood calcium; prevent bone loss

• Integration of calcium into bones• Prevent calcium deposition in blood

vessels (vascular calcification)• Maintain blood vessel elasticity

Vitamin K: Other Functions


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Metabolic Functions of Vitamin K1

Vitamin K1 Promotes Blood ClottingInvolved in synthesizing 4 blood-clotting factors!


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TOXIC & DEFICIENCY OF VITMIN K

• No known adverse Toxicity• If on anticoagulant medications should keep vitamin K

intake consistent! Changes in intake can increase or decrease drug effectiveness.

• Deficiency• Heart Disease and Vitamin K deficiency go hand in hand!• Deficiency severe enough to affect blood clotting is

extremely rare.

TOXIC EFFECT


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Fat soluble Vitamins - By Dr. P. Ravisankar.

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Transcript of Fat soluble Vitamins - By Dr. P. Ravisankar.