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Essential nutrients

that your body needs
in small amounts to
grow, reproduce, &
maintain good health.

What are
vitamins?
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 acids Needed in large quantities (does
not 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.
Vitamin Rich Diet
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-08
Vitamin C.
• Vitamin A
• Vitamin D
• Vitamin E
Need fat to be properly
• Vitamin K absorbed.
Are stored in the body.
Can accumulate to point
of toxicity.
 B Vitamins
 Thiamine (B1)
 Riboflavin (B2)
 Niacin (B3)
 Vitamin B6 (pyridoxine) Need water to be properly absorbed.
 Vitamin B12 (cobalamine)
 Folate (B9) Enter bloodstream directly.
 Pantothenic acid (B5)
Are not stored for extended periods.
 Biotin (B7)
 Vitamin C (Ascorbic acid) Excess amounts are excreted.
Thiamin

Biotin Riboflavin

Coenzymes that
help numerous
energy-producing
reactions
Pantothenic Niacin
Acid

Vitamin B6
Anti-infective vitamins
Destroyed 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.
Retinol (one vitamer of Vitamin A)
• "vitamin A," which
includes the compounds
retinal, retinol, and many
carotenoids.
• Liver
• Fish liver oil
• Dark green leafy
• Egg
vegetables,
• Yolk,
• Carrots,
• Milk, Butter,
• Some yellow & red
Cheese etc.
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
Bound to an amino acid
Bile acid made from cholesterol (hydrophobic) from protein (hydrophilic)
Small intestine
Stomach
Short-chain
fatty acids Medium-chain
fatty acids
Glycerol

Chylomicrons

Capillary network Lacteal
(lymph)

Blood vessels

Via lymph to blood
Via blood to liver

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

Micelle
Protein

Triglyceride

Long-
Chylomicron chain
fatty
acids

• 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.

Fig. 5-17b, p. 152
Intestinal Villus and Microvilli

Stem
cells

Secretory
cells
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,
Group
by 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 250 500
Adolescents,
• 10–18 years 330–400 600
Adults Females,
• 19–65 years 270 500
• 65+ years 300 600
Adults Males,
• 19–65 years 300 600
• 65+ years 300 600
Pregnant women 370 800
Lactating women 450 850
Measurement
Older Method
• To express the vitamin A • 1 IU retinol = 0.3 mg
activity of carotenoids in retinol
diets on a common basis, a
Joint FAO/WHO Expert Group • 1 IU b-carotene = 0.6 mg
in 1967 introduced the b-carotene
concept of the retinol
• 1 IU retinol = 3 IU b-
equivalent (RE) among food
sources of vitamin A: carotene.
– 1mg retinol = 1 RE
– 1mg b-carotene = 0.167 mg
RE
– 1mg other provitamin A
carotenoids = 0.084 mg RE.
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
Strong evidence to show link
between vitamin A deficiency and
mortality

…. in areas where Vitamin A Deficiency is
prevalent, improving vitamin A status
can
reduce mortality in children 6-59 months
by 23-34%

Source: various citations
• 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 Vitamin D3 – Cholecalciferol

• Exogenous Sources • Exogenous Sources
– Foods of plant – Foods of animal
origin origin
– Dietary – Dietary
supplements supplements
– Fortified food stuffs – Fortified food stuffs
– Milk – Milk
Cod liver oil, fortified
margarine, milk and Infant
milk formulas
yogurt, salmon & sardines
Egg, Liver

Dietary Sources
•About 2.5mcg for older children &
Other Sources
adults
•10mcg for children up to 5 yrs. & for
pregnant & lactating mothers
Skin exposure to
sunlight
25-hydroxy vitamin D (D3)

• D2 or D3 is hydroxylated by hepatic
Levels of Serum 25(OH)D
vitamin D 25-hydroxylase
• Major circulating form of Vitamin D • Deficiency is <10ng/ml (25nmol/L)
• Measurement of vitamin D status • Insufficiency is between 10 & 30ng/ml
• “Inactive” hormone (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.
Endogenous Production
– Prolonged sun exposure does not result in
excess production and toxic levels
• 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.
Activation of vitamin D3
(cholecalciferol)
• 1) Site: In the liver Cholecalciferol reaching either by chylomicron
remnants or by DBP, is hydroxylated into 25-OH D3.
• The efficiency of the liver enzyme 25-hydroxylase to convert
cholecalciferol into 25-OH D3 is related to the vitamin D status. (This
enzyme is more efficient during periods of vitamin D deprivation)
• 2) Most of the 25-OH D3 made in the liver is secreted into the blood
and transported by DBP.
• Blood is the largest single pool of 25-OH D3 & the circulating
concentration of 25-OH D3 is used as a measure of vitamin D status
(should be maintained > 30ng/ml)
• 25-OH D3 levels vary depending on both dietary intake of vitamin D
& exposure to sunlight
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 α -hydroxylase or
“1-hydroxylase”
• Active 1,25 (OH)2D3 or Calcitriol fns. like a steroid
hormone & has many target tissues.
• The activity of 1-hydroxylase is stimulated by low
plasma Ca, parathyroid hormone (PTH) & low levels of
active 1,25 (OH)2D3
• High concentrations of 1,25 (OH)2D3 & plasma P inhibit
1-hydroxylase activity
Assessment of Vit D Status
25(OH) Vitamin D 1,25 (OH)2 Vitamin D
• ½ life 4 to 6 hours
• ½ life 2 to 3 weeks • 15 to 60 pg/mL or 36 to
• 10 to 50 ng/mL or 25 to 144 pmo/L
125 nmol/L • 0.4% free
• 0.03% free • NOT USEFUL
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 • Brain
vitamin D responsive
• Heart
elements
• Cells • Skin
– Activated B & T • Gonads & Prostate*
– Lymphocytes
• Pancreas
– Mononuclear cells
– Beta-islet cell • Parathyroid Gland
– Keratinocytes • Bone
• Breast* • GI Tract
• Skeletal muscle
• Kidney
• Small intestine & Colorectal*
• 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 ++
& PO 4
---
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
Calcitriol
• Vitamin D ↑es absorption of Ca++ from
both gut & bone
• PTH ↑es re-absorption of calcium from
bone
• Both Vitamin “D” & PTH reduces urinary
excretion of Ca++.
• Intestine: Elevated calcium & phosphate
absorption by increased 1,25[OH]2D production
[calcitriol]
• Kidneys: Decreased calcium excretion,
increased phosphate excretion
• Bone: Elevated Ca++ & P resorption by
increasing doses, at low doses [bone formation]
• Net effect on serum level: Elevation of
calcium and decreased phosphate.
Dosage & Frequency Indications
• Prophylactic uses: Dose
400IU/day
• Vitamin D deficiency states as rickets:
• Nutritional vitamin D 1. Vitamin D resistant rickets: High dose of
deficiency: 3000-4000 calcidiol [1-α -[OH]D3] is effective.
IU/day 2. Vitamin D dependent rickets
3. Senile or postmenopausal osteoporosis
• Once/2-6mo for obstructive 4. Fanconi syndrome: To raise PO4--- levels
jaundice & steatorrhea. 5. Osteomalacia
6. Intestinal malabsorption & CLD
7. Abnormal Ca++ & PO4---
• Vitamin D deficiency states as rickets:
• Prophylactic uses: Dose 1. Vitamin D resistant rickets: x-linked
400iu/day hereditary disease [vit. D metabolism-
normal, but homeostasis of Ca++ & PO4--- are
• For nutritional vitamin D disarranged]
• High dose of calcidiol [1-alfa[OH]D3] is
deficiency: 3000-4000 effective calcitriol [1,25[OH]2D3]
2. Vitamin D dependent rickets: due to defect in
iu/day renal hydrolation mechanism {calciferol
[25[OH]D3] to calcitriol [1,25[OH]2D3}
• Once/2-6 months for • Calciferol: Ergocalciferol [vitamin D2]&
obstructive jaundice & cholecalciferol [vitamin D3]

steatorrhea
• Cholestyramine & liquid paraffin: ↓
absorption
• Phenytoin & phenobarbitone: ↓
response of target tissue to calcitriol
{1,25[OH]2D3} in rickets & osteomalcia
• Birth – age 50 yrs. -200 IU/d
• 51 – 70 yrs.-400 IU/d
• Aged >70 yrs. -600 IU/d
• Supplemental intake of 400IU/d ↑es 25(OH)D levels
by 2.8-4.8ng/mL
• Additional intake of approximately 1700IU/d are
required to raise levels from 20-32ng/mL
• Tolerable Upper Limit: 2000IU/d-established.
• “An intake for all adults of >/= 1000IU/d is
needed to bring vitamin D concentration
in no less than 50% of the population up
to 75nmol/L.” (30ng/mL)
Calcitonin
• Peptide hormone secreted by thyroid
gland
• Reduces bone resorption, serum Ca &
PO4
• Bone formation initially, is not
impaired, but ultimate, it is reduced,
[osteoporosis]
• Calciferol [1,25[OH]2D3] is best studied of
the active vitamin D metabolites &
specific receptor for this molecule have
been identified.
Right – bowed legs
Rickets Left – knocked knees
•Defined as an interruption
in the development and
mineralization of the
growth plate of bone
resulting in growth
retardation and skeletal
deformities.
•Other Causes: Nutritional,
renal phosphate wasting…
• Adult equivalent of rickets & accompanies
that disorder in children
• Defined as inadequate or delayed
mineralization of bone with deposition of
uncalcified bone matrix
• Complication of chronic renal failure
Compensatory hyperparathyroidism

Mobilizes skeletal calcium

Reduction in bone mineral density

Precipitates or exacerbates osteoporosis

• Also a mineralization defect of the collagen
matrix increases fracture risk and bone pain
Decreased 25(OH) Vit D Increased 25(OH) Vit D
• Inadequate exposure to Vitamin D intoxication
sunlight – Vitamin D or 25(OH) Vit D
• Inadequate dietary intake – Hypercalcemia
– Toxicity usually associated
• Vitamin D malabsorption with 25(OH) Vit D
• Severe hepatocellular disease concentration >150 ng/mL
• Increased catabolism
• Increased loss- Nephrotic
syndrome
Decreased 1,25 (OH)2 Vit D Increased 1,25 (OH)2 Vit D

• Renal failure • Primary
• Hypoparathyroidism hyperparathyroidism
• Hyperphosphatemia • Pregnancy
• Hypercalcemia of • Lymphoma
malignancy • Granulomatous diseases
25(OH) Vit D Deficiency
• Validity of reference • 38% of nursing home
range is 30 ng/mL residents
• Major health problem for • >50% of African Americans
adults >50 y of age. in US
• >40% of hospitalized
patients in Boston- 32% of
students & doctors 18-29 y
of age at winter’s end
• 1,25-Dihydroxy Vitamin D interacts with a
specific nuclear receptor-Vitamin D
receptor (VDR)
• VDR complexes with another receptor
forming a heterodimeric complex
• Complex seeks out specific DNA sequences
known as Vitamin D-responsive elements
• Enhancement or inhibition of transcription
of Vitamin D-Responsive Genes
Treatment of Psoriasis

• Exploits potent anti-proliferative activity
of 1,25-dihydroxyvitamin D.
• Keratinocytes growth is markedly
inhibited & induced to differentiate
• Topical activated vitamin D analog
developed
Regulation of Cell Growth

• Vitamin D concentrations >30ng/mL are
necessary for maximal extra-renal,
intracellular production of 1,25(OH)2
Vitamin D
• Inverse association established
– Prostate cancer
– Colorectal cancer-50% reduction in risk with
serum 25(OH) vitamin D concentrations of
>/= 32 ng/mL,
Essential Hypertension &
Cardiac Outcomes
• Essential hypertension – inverse
correlation between 1,25(OH)2 vit D levels
and plasma renin activity
• Coronary angiography patients with
vitamin D levels <10ng/mL (vs 30ng/mL)
– 3X more likely to die of heart failure
– 5X more likely to die of sudden cardiac death
• Antihypertrophic system in cardiac muscle
Skeletal Muscle
• Activation of VDR in myocytes leads to
protein synthesis and muscle cell growth
• Higher vitamin D levels associated with
improved muscular function and strength.
• Decreased levels associated with muscle
weakness and pain among adults with
osteomalacia.
Autoimmunity

• T cell-medicated
• Hypothesis that vitamin D regulates the
differentiation & activity of CD4+ T cells
• Inhibits T helper cell development & cytokine
production
• Expansion of regulatory T cells
• ↓es in autoimmune response & severity of
symptoms
“Adequate” vitamin D concentration might
mitigate or prevent the onset of:
– DM type 1
– Multiple sclerosis
– Rheumatoid arthritis
– Crohn’s disease
• Hypercalciuria,
• Hypercalcaemia (idiopathic
infantile hypercalcaemia),
• Renal damage,
• Polyurea, • Renal dysfunction
• Metastatic calcification.
• Hypercalcaemia
• Metastatic
calcification

Some vitamin ‘D’ is
stored in adipose
tissue & rest are
cleared by liver.
Calcium homeostasis
• low blood
• calcium
• calcium
• parathyroid
• gland
• PTH
• bone
• intestine
• calcitriol
Recommended Nutrient
Intakes (RNIs) for Vitamin D
Group RNI (mg/day)a
Infants and children
• 0–6 months 5
• 7–12 months 5
• 1–3 years 5
• 4–6 years 5
• 7–9 years 5
Adolescents
• 10–18 years 5
Adults
• 19–50 years 5
• 51–65 years 10
• 65+ years 15
Pregnant women 5
Lactating women 5
a Units: for vitamin D, 1 IU = 25ng, 40 IU = 1mg, 200 IU = 5mg,
400IU = 10mg, 600 IU = 15mg, 800 IU = 20mg.
Summary Slide
• Vitamin D is a fat soluble hormone produced by the
body and further transformed into active metabolites
• Require VDR for biologic effect
• Increase absorption of Ca+ and PO4- in small intestine,
resorption of Ca+ in kidney
 Works in your body like a hormone

• Toxicity effects of elevated vit. D: hypercalcemia
• High levels of vitamin D are associated with lower
incidence of some types of cancers
 Deficiency: insufficient calcium levels
 Causes Rickets

 Osteomalacia

 Osteoporosis

 Ergocalciferol (D2)  Cholecalciferol (D3)
• “Vitamin E” refers to a family of 8 naturally-occurring
homologues, synthesized by plants from homogentisic
acid.
• 4 tocoferols (α , β,…) & 4 tocotrienols
• Precursor: All are derivatives of 6-chromanol
• Active form: α -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.
• The term “vitamin E” refers to a family of 8 naturally-
occurring homologues that are synthesized by plants
from homogentisic acid.
• Vitamin E is the major lipid-soluble antioxidant (in cell
membranes & plasma proteins) in the cell antioxidant
defense system & is exclusively obtained from diet.
• Precursor: All are derivatives of 6-chromanol
• Vitamin E is located primarily within the phospholipid
bilayer of cell membranes.
• Vegetable Oils, • Peaches,
• Whole Grains, • Spinach,
• Nuts And Seeds, • Avocado
• Asparagus, • 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.
FUNCTIONS
• The main function of vitamin E is anti
oxidant. It intercepts free radicals &
prevents destruction of cell membrane.
• It protects the fat in LDL from oxidation.
• It inhibits platelets aggregation.
• It enhances vasodilatation.
• It inhibits the activity of protein kinase C.
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 α -tocopherol then enters the peripheral cells within
the intact lipoprotein through the LDL receptor pathway, or
taken up by HDL binding sites.
Approximate biological activity of naturally
Occurring
tocopherols and tocotrienols compared
with d-a-tocopherol
Common name Biological activity compared with
d-a-tocopherol (%)

• d-a-tocopherol 100
• d-b-tocopherol 50
• d-g-tocopherol 10
• d-d-tocopherol 3
• d-a-tocotrienol 30
• d-b-tocotrienol 5
• d-g-tocotrienol Unknown
• d-d-tocotrienol Unknown
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.
Toxicity
• Vitamin E has very low toxicity, 100–200mg of
the synthetic a-tocopherol are consumed widely
as supplements .
• Evidence of pro-oxidant damage has been
associated with the feeding of supplements at
very high doses (e.g. >1000mg/day).
• Nevertheless, the recent report from The
Netherlands of ↑ed severity of RTIs in persons
>60 yrs. receiving 200mg vitamin E/day for
15mo, is an indication of a pro-oxidant effect.
TOXICITY

Excess vitamin 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 deficiency
•Severe vitamin E deficiency causes:
Neurological symptoms (impaired
coordination) & muscle weakness.
Increased risk of cardiovascular diseases
Hemolytic anemia in children
May be seen in patients with severe fat
malabsorption, cystic fibrosis, CLD & in
premature infants.
Genetic disease affacting the transfer
protein of α -tocoferol.
THERAPEUTIC 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 vitamins
 3 compounds have the biological vitamin K
activity:
-Phylloquinone-K1 (Plant)
-Menaquinone-K2 (Bacterias)
-Menadione.
• Animal liver
• Fish liver oil • Spinach, lettuce, parsley
• Vegetable oil (Raw)
• Almonds & peanuts • Synthesized by bacterial
flora (K2) in colon & supply
• Leafy vegetables
40-50% of human
• Avocado & broccoli requirements.
• Daily requirements: 80mcg
in adults.
Vitamin K

Dietary
Sources

Function: Essential for blood clotting and bone
metabolism
FUNCTIONS
•Vitamin K is needed for production of
vitamin K-dependent coagulation factors in
the liver.
•Other functions include:
Assist in bone mineralization. The
mineral binding capacity of osteocalcin
requires vit K.
Gas6 is vit K-dependent protein
identified in 1993. It is important for
neuronal function.
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
• Vitamin K is an essential fat-soluble
micronutrient, which is needed for a unique
post-translational chemical modification in a
small group of proteins with calcium-binding
properties, collectively known as vitamin K-
dependent proteins or Gla proteins.
• Thus far, the only unequivocal role of vitamin K
in health is in the maintenance of normal
coagulation.
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 25
Adolescents
Females, 10–18 years 35–55
Males, 10–18 years 35–55
Adults
Females
• 19–65 years 55
• 65+ years 55
Males
• 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.
Vitamin K deficiency
 Is uncommon in adults. Only those with severe
liver disease & those on oral anticoagulants are at
risk.
 Exclusively breast fed & premature babies are at
risk coz human milk is low in vitamin E & their gut is
not yet colonized with bacteria.
 Hemorrhagic disease of the newborn is a serious
threat to life & routine vit k prophylaxis is
recommended by the AAP.
Fat-soluble
vitamin A Retinol, retinal,normal vision, integrity of ocular disturbances
retinoic acid,epithelial cells (mucous leading to blindness,
β-carotene (plant ) membranes and skin), growth retardation, dry
reproduction, embryonic skin, diarrhea,
development, growth, immune vulnerability to infection
response
vitamin D Calciferol, calatriolmaintenance of blood calcium and defective bone growth in
(1,25-dihydroxy phosphorus levels, proper children, soft bones in
vitamin D1 ormineralization of bones adults
vitamin D
hormone),
cholecalciferol (D3;
plant),
ergocalciferol (D2;
animal )
vitamin E Alpha-tocopherol, antioxidant; interruption of free peripheral neuropathy,
tocopherol, radical chain reactions; protection breakdown of red blood
tocotrienol of polyunsaturated fatty acids, cells
cell membranes
vitamin K Phylloquinone, synthesis of proteins involved in impaired clotting of the
Menaquinone, blood coagulation and bone blood and internal