Vitamins are a group of noncalorigenic organic compound required in tiny amounts for normal metabolism of an organism.“Vitamins” means “vital for life”A compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism & must be obtained from the diet.Vitamins are micronutrients necessary for everyday healthy functioning of the body.

History

The value of eating a certain food to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding liver to a patient would help cure night blindness, an illness now known to be caused by a vitamin A deficiency.In 1749, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy,-a deadly disease with improper collagen formation, causing poor wound healing, bleeding of the gums, severe pain, and death.

Year of discovery Vitamin Source

1909 Vitamin A (Retinol) Cod liver oil

1912 Vitamin B1 (Thiamine) Rice bran

1912 Vitamin C (Ascorbic acid) Lemons

1918 Vitamin D (Calciferol) Cod liver oil

1920 Vitamin B2 (Riboflavin) Eggs

1922 Vitamin E (Tocopherol) Wheat germ oil, Cosmetic and Liver

1926 Vitamin B12 (Cyanocobalamin) Liver

1929 Vitamin K (Phylloquinone)

1931 Vitamin B5 (Pantothenic acid) Liver

1931 Vitamin B7 (Biotin) Liver

1934 Vitamin B6 (Pyridoxine) Rice bran

1936 Vitamin B3 (Niacin) Liver

1941 Vitamin B9 (Folic acid) Liver

• The reason the set of vitamins seems to skip directly from E to K is that the vitamins corresponding to "letters" F-J were either reclassified over time, discarded as false leads, or renamed because of their relationship to "vitamin B", which became a "complex" of vitamins.

• The German scientists who isolated and described vitamin K as because the vitamin is intimately involved in the Koagulation of blood following wounding.

• At the time, most (but not all) of the letters from F-J were already designated, so the use of the letter K was considered quite reasonable.

Previous name Chemical name Reason for name change

Vitamin B4 Adenine DNA metabolite

Vitamin B8 Adenylic acid DNA metabolite

Vitamin F Essential fatty acidsNeeded in large quantities (doesnot fit the definition of a vitamin).

Vitamin G Riboflavin Reclassified as Vitamin B2

Vitamin H Biotin Reclassified as Vitamin B7

Vitamin J Catechol, Flavin Protein metabolite

Vitamin L1 Anthranilic acid Protein metabolite

Vitamin L2 Adenylthiomethylpentose RNA metabolite

Vitamin M Folic acid Reclassified as Vitamin B9

Vitamin O Carnitine Protein metabolite

Vitamin P Flavonoids No longer classified as a vitamin

Vitamin PP Niacin Reclassified as Vitamin B3

Vitamin U S-Methylmethionine Protein metabolite

Where are vitamins found?

• Naturally in foods

• Added to foods

• Pill form in dietary supplements

• Mostly, vitamins are obtained with food, but a few are obtained by other means.

• For example, "gut flora"—produce vitamin K & biotin, • Vitamin D is synthesized in the skin with the help of the

natural ultraviolet wavelength of sunlight. • Humans can produce some vitamins from precursors

they consume. As vitamin A, produced from β-carotene, and niacin, from the amino acid tryptophan.

Because foods provide more than just

vitamins, they are the best way to meet

your needs.

Many are also rich in disease-fighting phytochemicals,

antioxidants, and fiber.

Body Storage

• Human bodily stores for different vitamins vary widely; vitamins A, D & B12 are stored in significant amounts, mainly in the liver.

• Adult human's diet may be deficient in vitamins A and B12 for many months before developing a deficiency condition.

• Vitamin B3 is not stored in the body in significant amounts, so stores may only last a couple of weeks.

Functions of Vitamins• Essential for the normal growth & development of a multicellular

organism. • Vitamins have diverse biochemical functions, as hormones (e.g. vitamin

D), antioxidants (e.g. vitamin E) & mediators of cell signaling & regulators of cell & tissue growth and differentiation (e.g. vitamin A).

• The largest number of vitamins (e.g. B complex) fn. as precursors for enzyme cofactor bio-molecules (coenzymes), that help act as catalysts & substrates in metabolism.

• As part of a catalyst, vitamins are bound to enzymes & are called prosthetic groups. For example, biotin is part of enzymes involved in making fatty acids.

• Vitamins also act as coenzymes to carry chemical groups between enzymes. As, folic acid carries various forms of carbon group – methyl, formyl & methylene - in the cell-assisting enzyme reactions are vitamins' best-known function.

• Vitamins are essential for the healthy maintenance of the cells, tissues, and organs.

• Helps to efficiently use chemical energy provided by food & to help process the proteins, carbohydrates, & fats required for respiration.

Deficiencies• Vitamins deficiencies of are classified as…• A. Primary deficiencies &• B. Secondary deficiencies. • Primary deficiency occurs when an organism does not get enough of

the vitamin in its food. • Secondary deficiency may be due to an underlying disorder that

prevents or limits the absorption or use of the vitamin, due to a “lifestyle factor”, such as smoking, excessive alcohol consumption, or the use of medications that interfere with the absorption or use of the vitamin.

• People who eat a varied diet are unlikely to develop a severe primary vitamin deficiency.

• In contrast, restrictive diets have the potential to cause prolonged vitamin deficits, which may result in often painful & potentially deadly diseases.

Side Effects and Overdose

Some vitamins have documented side effects that tend to be more severe with a larger dosage. The likelihood of consuming too much of any vitamin from food is remote, but overdosing from vitamin supplementation does occur. Side effects such as nausea, diarrhea, and vomiting.Recovery is often accomplished by reducing the dosage. Concentrations of vitamins an individual can tolerate vary widely, and appear to be related to age and state of health.In the US, overdose exposure to all formulations of vitamins was reported by 62,562 individuals in 2004 (nearly 80% of these exposures were in children <age of 6), leading to 53 "major" life-threatening outcomes & 3 deaths.

• There are 13 vitamins having human importance.• They are classified as either water-soluble or fat

soluble. • Fat-soluble vitamins-Four (4)

These are…A, D, E & K (ADEK) and • Water-soluble vitamins-Nine (9)

These are… B vitamins-08Vitamin C.

• Vitamin A • Vitamin D• Vitamin E• Vitamin K

Need fat to be properly absorbed.Are stored in the body.Can accumulate to point of toxicity.

B Vitamins Thiamine (B1) Riboflavin (B2) Niacin (B3) Vitamin B6 (pyridoxine) Vitamin B12 (cobalamine) Folate (B9) Pantothenic acid (B5) Biotin (B7)

Vitamin C (Ascorbic acid)

Need water to be properly absorbed.

Enter bloodstream directly.

Are not stored for extended periods.

Excess amounts are excreted.

Anti-infective vitaminsDestroyed by heat, light, wet, storage

2 groups of compounds have vitamin A activity:-Animal origin: Retinoids-preformed (Retinol, Retinaldehyde, & Retinoic acid)

-Plant origin: Carotenoids (provitamin A).6mcg of β-carotene is equivalent to 1mcg of

preformed retinol.

• Liver• Fish liver oil• Egg• Yolk, • Milk, Butter, Cheese

etc.

• Dark green leafy vegetables, • Carrots, • Some yellow & red fruits.

Vitamin A Metabolism• Digestion frees vitamin A & carotenoids from food. Retinyl esters are hydrolysed & retinol & freed

carotenoids are incorporated into water-miscible micelles.• Retinol & some carotenoids enter the enterocyte brush border by diffusion from micelle.• Here, some of the carotenoids are converted to retinol by a cleavage enzyme.• Retinol is trapped intracellularly by re-esterification or binding to specific intracellular binding proteins.

Retinyl esters & unconverted carotenoids together with other lipids are incorporated into chylomicrons, & delivered to the blood.

• Tissues extract most lipids & some carotenoids from circulating chylomicrons, but most retinyl esters are stripped , hydrolysed & taken up primarily by hepatocytes. If not immediately needed, retinol is re-esterified & retained in the hepatic fat-storing cells (variously called adipocytes, stellate cells, or Ito cells).

• The hepatocytes take in substantial amounts of carotenoids. Whereas most of the body’s vitamin A reserve remains in the liver, carotenoids are also deposited elsewhere in fatty tissues throughout the body .

• The RBP-retinol complex (holo-RBP) is secreted into the blood & associates with transthyretin. The transthyretin-RBP-retinol complex circulates in the blood, delivering the retinol to tissues;

• Holo-RBP transiently associates with target tissue membranes, and specific intracellular binding proteins then extract the retinol. Some of the transiently sequestered retinol is released into the blood unchanged and is recycled

• A limited reserve of intracellular retinyl esters is formed that subsequently can provide functionally active retinol and its oxidation products (i.e. isomers of retinoic acid) as needed intracellularly.

Emulsification

Hydrolysis

Micellization

Uptake

Micelles are emulsified fat droplets formed by bile surrounding monoglycerides & long chain fatty acids ( 20 carbons) to absorb them–Water miscible-soluble in water–diffuse into intestinal cells

Bile acid made from cholesterol (hydrophobic)Bound to an amino acid

from protein (hydrophilic)

Small intestineStomach

Medium-chain fatty acids

Glycerol

Chylomicrons

Capillary network Lacteal (lymph)

Blood vessels

Via blood to liver

Glycerol & small lipids such as short- & medium-chain fatty acids can move directly into the bloodstream.

Via lymph to blood

Short-chain fatty acids

Fig. 5-17b, p. 152

Monoglyceride

Protein

Micelle

Triglyceride

Long-chain fatty acids

Chylomicron

•Large lipids such as monoglycerides & long-chain fatty acids combine with bile, forming micelles that are sufficiently water soluble to penetrate the watery solution that bathes the absorptive cells.

•There the lipid contents of the micelles diffuse into the cells.

Intestinal Villus and Microvilli

Secretory cells

Stem cells

Emulsification

Micellar Formation

Hydrolysis

Absorption

Re-esterification

Lipoprotein formation/transport

Emulsification

Micellar Formation

Hydrolysis

Absorption

Re-esterification

Lipoprotein formation/transport

• Largest and least dense• Carry triglyceride from intestine to body via lymph

system• Cells strip them of TAG as they move through the

lymph, become smaller & after 14hrs most of TAG depleted

• Remaining remnants (PL, protein) which are collected by liver cells in blood & re-used or recycled.

In the retina, retinaldehyde functions as the prosthetic group of the light sensitive opsin proteins, forming RHODOPSIN (in rods) & IODOPSIN (in cones).

Estimated mean requirement and safe level of intake for vitamin A, by group

Group Mean requirement Recommended safe intake

(mg RE/day) (mg RE/day)Infants and children• 0–6 months 180 375• 7–12 months 190 400• 1–3 years 200 400• 4–6 years 200 450• 7–9 years 250 500Adolescents,• 10–18 years 330–400 600Adults Females,• 19–65 years 270 500• 65+ years 300 600Adults Males,• 19–65 years 300 600• 65+ years 300 600Pregnant women 370 800Lactating women 450 850

Measurement

• To express the vitamin A activity of carotenoids in diets on a common basis, a Joint FAO/WHO Expert Group in 1967 introduced the concept of the retinol equivalent (RE) among food sources of vitamin A:– 1mg retinol = 1 RE– 1mg b-carotene = 0.167 mg RE– 1mg other provitamin A

carotenoids = 0.084 mg RE.

Older Method• 1 IU retinol = 0.3 mg retinol• 1 IU b-carotene = 0.6 mg b-

carotene• 1 IU retinol = 3 IU b-carotene.

Functions of Vitamin A

Vitamin A (retinol) is an essential for..• Normal functioning of the visual system; forms retinal

photochemical rhodopsin• Growth and development; • Maintenance of epithelial cellular integrity, • Immune function, and • Reproduction. • Anticarcinogenic• Anti-infective functions etc.

Pharmacological Preparation

• Oral capsule-Soft gelatin• Topical-Retinol cream• Isotretinoin-Acne preparation• Tretinoin-Acne preparation• Psoriasis

1.Replacement therapy in Vitamin A deficiency states as night blindness, impared dark adaptation, lichen planus, dry skin & other hyperkeratosis:

– Age<1 yr. with eye changes: 2 cap first day; 2 cap 2nd day & 2 caps after 2 wks.– Age>1 yr. with eye changes: 4 caps 1st day; 4 caps 2nd day & 4 caps after 14 dys.– No eye change: Single dose.

2. Pharmacotherapy:– Acne: Retin A cream, Tretinoin, Isotretinoin.– Psoriasis.– Premenstrual disturbances.– GI disorders associated with disturbances in lipid absorption.– Prophylactically to suspected individual.

41

Relative Contraindications

• Hypervitaminosis• Early pregnancy

• Routine consumption of large amounts of vitamin A over a period of time can result in toxic symptoms, including liver damage, bone abnormalities and joint pain, alopecia, headaches, vomiting, and skin desquamation.

• Hypervitaminosis A appears to be due to abnormal transport and distribution of vitamin A and retinoids caused by overloading of the plasma transport mechanisms.

• Overdose may causes xerosis of lips, rough skin, dry hair.• Teratogenicity: Craniofacial malformations, phycomotor

retardation, congenital heart defect & CNS malformation

Hypervitaminosis A

• Defined as vitamin A toxicity resulting from excessive intake of vitamin A

• SS: – Nausea & headache– Increased intracranial pressure– Skin desquamation

Vitamin A Deficiency

An estimated 127 million preschool aged children are vitamin A deficient and thus are at increased risk of death, mainly from diarrhea, measles and malaria

Deficiency Disorders

• Occular: Night blindness, Xeropthalmia• Extraoccular: Follicular hyperkeratosis• Susceptibility to infection• Growth failure• Calculi (Vesicle, Renal)• PEM

• Vitamin D (D3)is a Pro-hormone.

• It is a member of steroid derivatives.• Precursor: 7-dehydrocholesterol.• Active form: 1,25-dihydroxyvitamin

D (D3)/1,25-(OH)2D or calcitriol.

Forms of Vitamin D

Vitamin D2 –Ergocalciferol

• Exogenous Sources– Foods of plant origin– Dietary supplements– Fortified food stuffs– Milk

Vitamin D3 – Cholecalciferol

• Exogenous Sources– Foods of animal origin– Dietary supplements– Fortified food stuffs– Milk

Dietary SourcesOther Sources

Cod liver oil, fortified margarine, milk and Infant milk formulas

yogurt, salmon & sardines

Egg, Liver

Skin exposure to sunlight

•About 2.5mcg for older children & adults

•10mcg for children up to 5 yrs. & for pregnant & lactating mothers

25-hydroxy vitamin D (D3)

• D2 or D3 is hydroxylated by hepatic vitamin D 25-hydroxylase

• Major circulating form of Vitamin D• Measurement of vitamin D status• “Inactive” hormone

Levels of Serum 25(OH)D

• Deficiency is <10ng/ml (25nmol/L)• Insufficiency is between 10 & 30ng/ml

(25-75nmol/L)• Circulating 1,25(OH)D levels fall

<40nmol/L,.• 25-OH D3 levels vary depending on both

dietary intake of vitamin D & exposure to sunlight

• For bone health & other conditions, optimal is up to 90nmol/L & it should be 100nmol/L for those >70 yrs.

• 7-dehydrocholesterol is synthesized in the sebaceous glands of the skin, secreted onto the surface

• During exposure to the sunlight, ultraviolet B photons (290-315 nm) are absorbed by epidermis & convert 7-dehydrocholesterol to “previtamin D3”

• The previtamin D3 is then thermally isomerized within 2-3 days into vitamin D3 (cholecalciferol)- (25 hydroxyvitamin D/ (25(OH)D))

• Cholecalciferol (vitamin D3) diffuses from the skin & is transported in the blood with vitamin D-binding protein (DBP) & delivered to liver.

1) Cholecalciferol (D3) reaching the liver either by chylomicron remnants or by DPB, is hydroxylated into 25-OH D3 (Calcidiol).

2) Most of the 25-OH D3 is secreted into the blood & transported to the kidney by DBP.

3) In the kidney it is hydroxylated to 1,25 (OH)2D3 the “active vitamin D” by 25-OH, D3-1 -hydroxylase or “1-hydroxylase”

• Active 1,25 (OH)2D3 or Calcitriol fns. like a steroid hormone & has many target tissues.

Metabolism of Vitamin D• Vitamin D3 is metabolized first in the liver to 25-hydroxyvitamin D

(calcidiol) & subsequently in the kidneys to 1,25-(OH)2D (calcitriol) to produce a biologically active hormone.

• The 1,25-(OH)2D, is present in the blood complexed to vitamin D-binding protein.

• Free calcitriol crosses the plasma membrane & interacts with a specific nuclear VDR & this complex binds to a specific vitamin D-responsive element & with associated transcription factors (e.g. retinoid X receptor), enhances transcription of mRNAs which code for Ca++-transporting proteins, bone matrix proteins, or cell cycle-regulating proteins to stimulates intestinal absorption of Ca++ & PO4

--- & mobilizes Ca++ & PO4--- by

stimulating bone resorption to restore blood levels of Ca++ & PO4--- to

normal.

http://www.nature.com/nrc/journal/v3/n8/fig_tab/nrc1144_F2.html

Nuclear Vitamin D Receptor

• 200 human genes contain vitamin D responsive elements

• Cells– Activated B & T– Lymphocytes– Mononuclear cells– Beta-islet cell– Keratinocytes

• Breast*• Skeletal muscle• Small intestine & Colorectal*

• Brain• Heart• Skin• Gonads & Prostate*• Pancreas• Parathyroid Gland• Bone• GI Tract• Kidney

• Vitamin D is required to maintain normal blood Ca++ levels & PO4---, for

the normal bone mineralization, muscle contraction, nerve conduction, and general cellular functions.

• This active form regulates the transcription of a number of vitamin D-dependent genes which code for Ca++-transporting proteins & bone matrix proteins.

• It also modulates the transcription of cell cycle proteins, which ↓ cell proliferation & ↑ cell differentiation of a number of specialized cells of the body (e.g. osteoclastic precursors, enterocytes, keratinocytes) in bone resorption, intestinal Ca++ transport & skin.

• Vitamin D also possesses immunomodulatory properties that may alter responses to infections of psoriasis & other skin disorders.

• Intestine: ↑ed Ca++ & PO4--- absorption by 1,25[OH]2D

• Kidneys: Ca++ & PO4--- excretion may be ↓ed by 25[OH]D

& 1,25[OH]2D

• Bone: ↑ed Ca++ & PO4--- resorption by 1,25[OH]2D. Bone

formation: by 24,25[OH]2D.

• Net effect on serum levels: ↑ed both Ca++ & PO4--- level.

• Rickets in children• Osteomalacia (Bone softening) in adults• Osteoporosis

Dosage & Frequency• Prophylactic uses: Dose 400IU/day• Nutritional vitamin D deficiency:

3000-4000 IU/day• Once/2-6mo for obstructive

jaundice & steatorrhea.

Indications

• Vitamin D deficiency states as rickets:1. Vitamin D resistant rickets: High dose

of calcidiol [1--[OH]D3] is effective.

2. Vitamin D dependent rickets3. Senile or postmenopausal osteoporosis4. Fanconi syndrome: To raise PO4

--- levels

5. Osteomalacia6. Intestinal malabsorption & CLD7. Abnormal Ca++ & PO4

---

Some vitamin ‘D’ is stored in adipose tissue & rest are

cleared by liver.

• Hypercalciuria,• Hypercalcaemia (idiopathic

infantile hypercalcaemia),• Renal damage,• Polyurea,• Metastatic calcification.

• Renal dysfunction• Hypercalcaemia• Metastatic calcification

Recommended Nutrient Intakes (RNIs) for Vitamin D

Group RNI (mg/day)aInfants and children• 0–6 months 5• 7–12 months 5• 1–3 years 5• 4–6 years 5• 7–9 years 5Adolescents• 10–18 years 5Adults• 19–50 years 5• 51–65 years 10• 65+ years 15Pregnant women 5Lactating women 5

a Units: for vitamin D, 1 IU = 25ng, 40 IU = 1mg, 200 IU = 5mg,400IU = 10mg, 600 IU = 15mg, 800 IU = 20mg.

• “Vitamin E” refers to a family of 8 naturally-occurring homologues, synthesized by plants from homogentisic acid.

• 4 tocoferols (, β,…) & 4 tocotrienols• Precursor: All are derivatives of 6-chromanol• Active form: -tocoferol• It is the major lipid-soluble antioxidant in the cell

antioxidant defense system (in cell membranes & plasma proteins) & is exclusively obtained from diet.

• Location: Primarily within the phospholipid bilayer of cell membranes.

• Vegetable Oils,

• Whole Grains,

• Nuts And Seeds,

• Asparagus,

• Peaches,

• Spinach,

• Avocado

• Carrots (Least) etc.

• Protects cell membranes: Principally it protect PUFAs & other components of cell membranes & LDL from free radicals oxidation.

• It is particularly effective in preventing lipid peroxidation-a series of chemical reactions involving the oxidative deterioration of PUFAs.

• Inhibit platelet aggregation• Enhances vasodilatation.

Free Radicals and Diseases

• Small intestine: Tocopherol esters are hydrolysed & incorporated into micelle which aggregates, solubilizes & then transports them to the brush border membrane of the enterocyte, probably by passive diffusion.

• Enterocyte: Tocopherol is incorporated into chylomicrons & secreted into the intercellular space & lymphatic system & transported in the blood by the plasma lipoproteins & erythrocytes to liver, & incorporated into hepatocytes as chylomicron remnants.

• During the catabolism of chylomicrons by cellular lipoprotein lipase tocopherol can be transferred to HDLs & then can transfer to other circulating lipoproteins, such as LDLs & VLDLs.

• Most -tocopherol then enters the peripheral cells within the intact lipoprotein through the LDL receptor pathway, or taken up by HDL binding sites.

Excretion

• Primarily oxidized to a-tocopheryl quinone that can be conjugated to yield the glucuronate after prior reduction to the hydroquinone.

• This glucuronide is excreted in the bile as such or further degraded in the kidneys to a-tocopheronic acid glucuronide and hence excreted in the bile.

• Some vitamin E may also be excreted via cutaneous sebaceous glands.

TOXICITYTOXICITY

Excess vitamin Evitamin E may cause:

Impaired blood clotting leading to increased risk of bleeding in some persons.

It is recommended that vitamin E supplements to be stopped one month before elective surgery.

Vitamin E deficiencyVitamin E deficiency

•Severe vitamin E deficiency causes:Severe vitamin E deficiency causes:

Neurological symptoms (impaired coordination) & muscle weakness.

Increased risk of cardiovascular diseases

Hemolytic anemia in children

THERAPEUTIC USESTHERAPEUTIC USES

Prevention of cardiovascular diseases

Diabetes Mellitus

Cancer prevention

Boost immunity

Dementia

• Vitamin K is the family name for a series of fat-soluble compounds

Synonym: Antihaemorrhagic vitamins3 compounds have the biological vitamin K activity:

-Phylloquinone-K1 (Plant)-Menaquinone-K2 (Bacterias)-Menadione.

• Animal liver• Fish liver oil• Vegetable oil• Almonds & peanuts• Leafy vegetables• Avocado & broccoli

• Spinach, lettuce, parsley (Raw)• Synthesized by bacterial flora

(K2) in colon & supply 40-50% of human requirements.

• Daily requirements: 80mcg in adults.

Functions

• Production of vitamin K dependant clotting factors in liver.

Assists in bone mineralization by the synthesis of bone Ca++ binding proteins.

• Neuronal function maintenance.

• Prophylaxis & treatment of bleeding due to deficiency of clotting factors

• Prophylactically with prolonged salisylate therapy as.• Co-therapy with prolonged antimicrobial therapy.• Obstructive jaundice or malabsorption syndrome,

regional ileitis, steatorrhoea etc.• CLD-Cirrhosis, viral hepatitis• Premature infants & haemorrhagic disease of the

newborn• Antidote of oral anticoagulant

Metabolism• Absorption: 80% of dietary vitamin K, mainly phylloquinone (K1), is

absorbed chemically unchanged from the proximal intestine with micelles.• Within the intestinal mucosa it is incorporated into chylomicrons, & enters

the blood• In circulation, phylloquinone is rapidly cleared by lipoprotein lipase at the

surface of capillary endothelial cells.• >1/2 of the circulating phylloquinone remain associated with triglyceride

rich lipoproteins, with the remainder being equally distributed between LDLs and HDLs.

• Storage: Liver stores normally comprise about 90% menaquinones & 10% phylloquinone

• Excretion: Vitamin K is extensively metabolized in the liver & excreted in the urine & bile.

Group RNIa (mg/day)

Infants and children• 0–6 months 5• 7–12 months 10• 1–3 years 15• 4–6 years 20• 7–9 years 25AdolescentsFemales, 10–18 years 35–55Males, 10–18 years 35–55AdultsFemales• 19–65 years 55• 65+ years 55Males• 19–65 years 65• 65+ years 65• Pregnant women 55• Lactating women 55

Deficiency Disorders

• Uncommon in adults. Only those with severe liver disease or those on oral anticoagulants are at risk.

• Bleeding tendency due to hypoprothombinaemia & other clotting factors.