NAD407 PRINCIPLES OF NUTRITION

THE FAT-SOLUBLE VITAMINS:

A, D, E AND K
DR. SITI SABARIAH BUHARI
Senior Lecturer
Center for Nutrition and Dietetics Study
Faculty of Health Sciences
UiTM Puncak Alam
 THE FAT-SOLUBLE VITAMINS: A, D, E AND K
WHAT U NEED TO KNOW
• SOURCES
• FUNCTIONS
• RECOMMENDATION (RNI 2017) – ADULT
• DEFICIENCY
• TOXICITY
Fat soluble vitamins: An overview
▪ Fat soluble vitamins include Vitamin A, D, E and K.
▪ Fat-soluble vitamins differ from water-soluble vitamins in
term of:
i. Require bile for digestion and absorption.
ii. Travel through lymphatic system.
iii. Many require transport proteins in bloodstream.
iv. Excesses are stored in liver and adipose tissue.
v. Risk of toxicity is greater.
Fat soluble vitamins: An overview
▪ Deficiencies of vitamin A and D are common in the developing
world. WHY?
▪ Lifestyle changes
▪ We work at indoor jobs, exercise at indoor gyms, and protect
ourselves from the sun by using sunscreens when we go out, all
of which limit our ability to get adequate vitamin D from
sunshine.
▪ Even the low-carbohydrate diet craze has had an impact on
the amounts of fat-soluble vitamins consumed from whole
foods because eliminating grains, fruits, and many vegetables
can reduce intake of vitamin E and vitamin A precursors, as
well as vitamin K.
 Vitamin A: An overview
▪ Vitamin A is the first fat soluble vitamin to be found.
▪ Preformed vitamin A (retinoids/ retinyl ester) is found
primarily in animal foods, and the provitamin A forms
(carotenoids) are found in plants.
▪ Three different preformed vitamin A (collectively known as
retinoids) are active in the body:
i. Retinol
ii. Retinal
iii. Retinoic acid.
 Vitamin A: An overview
▪ Preformed vitamin A - Animal foods such as liver, fish, egg
yolks, and dairy products provide, primarily as retinol, or
retinol attached to a fatty acids.
▪ Retinal and retinoic acid can be formed in the body from
retinol.
▪ Provitamin A - Plants contain compounds called carotenoids.
Carotenoids are yellow, orange, and red pigments that give
these colors to fruits and vegetables.
▪ Beta-carotene is the most potent precursor, is plentiful in dark
orange fruits and vegetables such as mangos and apricots.
 Vitamin A: An overview
▪ Other carotenoids that provide some provitamin A activity
include:
i. Alpha-carotene, found in carrots, leafy green
vegetables, and winter squash.
ii. Beta-cryptoxanthin found in mangos, papayas, winter
squash, and sweet red peppers.
iii. Lutein, lycopene, and zeaxanthin are carotenoids with
no vitamin A activity.
▪ All forms of vitamin A in the diet are fairly stable when heated
but may be destroyed by exposure to light and oxygen.
 Vitamin A: An overview

Conversion of Vitamin A Compounds

Notice that the conversion from retinol to retinal is reversible,
whereas the pathway from retinal to retinoic acid is not.
 Vitamin A: An overview
▪ Major functions of vitamin A:
i. Promoting vision.
ii. Participating in protein synthesis and cell differentiation, thereby
maintaining the health of epithelial tissues and skin.
iii. Supporting reproduction and growth.
▪ Specific functions of vitamin A:
i. Retinol supports reproduction and is the major transport and
storage form of the vitamin.
ii. Retinal is active in vision and is also an intermediate in the
conversion of retinol to retinoic acid.
iii. Retinoic acid acts like a hormone, regulating cell differentiation,
growth, and embryonic development.
 Vitamin A: Retinal and vision
▪ Vitamin A plays two indispensable roles in the eye:
i. it helps maintain a crystal-clear outer window, the cornea,
and
ii. it participates in the conversion of light energy into nerve
impulses at the retina.
▪ In the eye, the retinal form of the vitamin combines with the
protein opsin to form the visual pigment rhodopsin.
▪ Rhodopsin helps transform the energy from light into a nerve
impulse that is sent to the brain. This nerve impulse allows us to
see.
 Vitamin A in Regulating Gene expression: Cell
differentiation
▪ Cell differentiation is the process whereby cells change in
structure and function to become specialized.
▪ In order to affect gene expression, the retinoic acid form of
vitamin A enters the nucleus of specific target cells, where it binds
to protein receptors; this retinoic acid protein receptor complex
then binds to a regulatory region of DNA.
▪ This binding changes the amount of messenger RNA (mRNA) that
is made by the gene → changes the amount of the protein that is
produced.
 Vitamin A: Maintenance of epithelial tissue
▪ The epithelial tissue on the outside of the body is the skin and
vitamin A helps to protect against skin damage from sunlight.
Others includes the skin and the linings of the eyes, intestines,
lungs, vagina, and bladder.
▪ Within the body, vitamin A helps to maintain their integrity of the
mucous membranes of the GI tract.
 Vitamin A: Reproduction and growth
▪ In reproduction, vitamin A is important for the formation of the
heart and circulatory system, the nervous system, respiratory
system, and skeleton.
▪ Lack of vitamin A during embryonic development results in
abnormalities and death.
▪ Poor overall growth is an early sign of vitamin A deficiency in
children. Vitamin A affects the activity of cells that form and
break down bone, and a deficiency early in life can cause
abnormal jawbone growth, resulting in crooked teeth and
poor dental health.
 Vitamin A: Immune system
▪ In the immune system, vitamin A is needed for the
differentiation that produces the different types of immune
cells.
▪ Vitamin A deficiency also reduces the function of specific
immune cells and hinders the normal regeneration of mucosal
barriers damaged by infection.
 Beta-carotene: An antioxidant
▪ Beta-carotene can be converted to vitamin A in the intestinal
mucosa and liver.
▪ Unconverted carotenoids also circulate in the blood and reach
tissues where they may function as antioxidants, a role
independent of any conversion to vitamin A.
▪ Beta-carotene and other carotenoids are fat-soluble
antioxidants that may play a role in protecting cell
membranes from damage by free radicals.
▪ In fact, a diet rich in fruits and vegetables containing beta-
carotene and other carotenoids helps to defend against some
cancers.
Vitamin A: Recommendation (RNI 2017)
 Vitamin A: Deficiency
▪ Possible causes:
i. Insufficient intakes of vitamin A, fat, protein, or the
mineral zinc.
ii. Diet very low in fat can cause a deficiency by reducing
vitamin A absorption.
iii. Protein deficiency can cause vitamin A deficiency
because the retinol-binding protein needed to transport
vitamin A from the liver cannot be made in sufficient
quantities.
iv. When zinc is deficient, the proteins needed for vitamin A
transport and metabolism are lacking.
 Vitamin A: Deficiency
1. Infectious diseases.
• Measles is one of the devastating infectious diseases.
• The severity of the illness often correlates with the degree of
vitamin A deficiency; deaths are usually due to related infections
such as pneumonia and severe diarrhea.
• Treatment by providing large amount of vitamin A.
2. Night blindness.
• In night blindness, the retina does not receive enough retinal to
regenerate the visual pigments bleached by light. The person loses
the ability to recover promptly from the temporary blinding that
follows a fl ash of bright light at night or to see after the lights go
out.
 Vitamin A: Deficiency
3. Blindness (Xerophtlalmia).
• Blindness due to vitamin A deficiency, known as xerophthalmia,
develops in stages.
• At first, the cornea becomes dry and hard because of inadequate
mucus production - a condition known as xerosis.
• Then, corneal xerosis can quickly progress to keratomalacia, the
softening of the cornea that leads to irreversible blindness.
• Night blindness is caused by a lack of vitamin A at the back of
the eye, the retina; total blindness is caused by a lack at the front
of the eye, the cornea.
 Vitamin A: Deficiency
4. Keratinization.
• On the body’s outer surface, the epithelial cells change shape
and begin to secrete the protein keratin – the hard, inflexible
protein of hair and nails.
• The skin becomes dry, rough, and scaly as lumps of keratin
accumulate (keratinization).
• Without vitamin A, the goblet cells in the GI tract diminish in
number and activity, limiting the secretion of mucus. With less
mucus, normal digestion and absorption of nutrients falter, and
this, in turn, worsens malnutrition by limiting the absorption of
whatever nutrients the diet may deliver.
 Vitamin A: Deficiency

As xerophthalmia progresses, the

drying of the cornea results in
ulceration, infection, and ultimately
blindness.

When vitamin A is deficient immature cells can’t differentiate

normally, and instead of mucus secreting cells, they become
cells that produce keratin.
 Vitamin A: Toxicity
▪ Preformed vitamin A can be toxic.
▪ Toxicity can be acute or chronic.
▪ Symptoms of acute toxicity:
▪ Nausea, vomiting, headache, dizziness, blurred vision, and
a lack of muscle coordination.
▪ Scenario 1: Arctic explorers who consumed polar bear
liver, which contains about 100,000 µg of vitamin A in just
3 ounces.
▪ Scenario 2: Supplements of preformed vitamin A also
have the potential to deliver a toxic dose.
 Vitamin A: Toxicity
▪ Symptoms of chronic toxicity:
▪ The symptoms of chronic toxicity include weight loss, muscle
and joint pain, liver damage, bone abnormalities, visual
defects, dry scaling lips, and skin rashes.
▪ Scenario: Chronic toxicity occurs when preformed vitamin
A doses as low as 10 times the RDA are consumed for a
period of months to years.
 Vitamin A: Toxicity
1. Bone defects:
• Excessive intake of vitamin A over the years may weaken the bones and
contribute to fractures and osteoporosis.
• Vitamin A suppresses bone building activity, stimulates bone-dismantling
activity, and interferes with vitamin D’s ability to maintain normal blood
calcium.
2. Birth defects:
• Excessive vitamin A during pregnancy leads to abnormal cell death in
the spinal cord, which increases the risk of birth defects.
• High intakes (10,000 IU of supplemental vitamin A daily) before the
seventh week of pregnancy appear to be the most damaging.
 Most supplements provide some or all their vitamin A as
carotenoids.
Carotenoid: Toxicity

Large daily intakes of carotenoids usually from carrot juice or

Beta-carotene supplements, however, lead to a condition known
as hypercarotenemia → Carotenoids stored in the adipose
tissue give the skin a yellow-orange color.

It is not known to be dangerous, and when intake decreases, the

skin returns to its normal color.

But overconsumption of beta-carotene from supplements may be

quite harmful.
Carotenoid: Toxicity
 Carotenoid: Toxicity
▪ In excess, this antioxidant may act as a prooxidant →
promoting cell division and destroying vitamin A.
▪ Two clinical research trials found an increased incidence of
lung cancer in cigarette smokers who took Beta-carotene
supplements.
▪ Smokers are advised to avoid Beta-carotene supplements
and to rely on food sources to obtain carotenoids in their diet.
▪ The small amounts found in standard strength multivitamin
supplements are not likely to be harmful for any group.
 Vitamin D is known as the “sunshine
vitamin” because it can be produced or
synthesized in the skin by exposure to
ultraviolet light.

Therefore, vitamin D is not an essential

Vitamin D: nutrient; given enough time in the sun,
people need no vitamin D from foods.
An overview
The active form of vitamin D is actually
a hormone because it is produced in one
organ, the skin, and affects other organs,
primarily the intestine, bone, and kidney.
 Vitamin D: An overview

Vitamin D Synthesis and Activation

The precursor of vitamin D is made in the liver from cholesterol. The
activation of vitamin D is closely regulated
by parathyroid hormone. The final product, active vitamin D, is also
known as 1,25-dihydroxycholecalciferol (or calcitriol).
 Vitamin D: Sources
▪ Vitamin D comes in many forms, but the two most important in the diet
are a plant version called vitamin D2 or ergocalciferol and an
animal version called vitamin D3 or cholecalciferol.
▪ Sources:
▪ The major source of vitamin D for most humans is exposure to
sunlight.
▪ From foods include liver; fatty fish such as salmon, mackerel, and
sardines; cod liver oil; and egg yolks.
▪ Fortified milk and fortified breakfast cereals (may contain vitamin
D3 or another active form of the vitamin called vitamin D2) are
important sources of vitamin D.
 Vitamin D and bone health
▪ The principal function of vitamin D is to maintain levels of
calcium and phosphorus in the blood that favor bone
mineralization.
▪ When blood calcium levels drop too low the parathyroid gland
releases parathyroid hormone (PTH).
▪ PTH release stimulates enzymes in the kidney to convert 25-
hydroxy vitamin D3 to the active form of the vitamin.
▪ Active vitamin D functions by binding to vitamin D receptor
proteins at target tissues and affecting gene expression →
helps to increase blood calcium levels.
 Vitamin D and bone health
▪ Vitamin D raises blood concentrations of bone minerals in three ways:
1. When the diet is sufficient, vitamin D enhances their absorption
from the GI tract.
2. When the diet is insufficient, vitamin D provides the needed
minerals from other sources: reabsorption by the kidneys and
mobilization from the bones into the blood.
3. The vitamin may work alone, as it does in the GI tract, or in
combination with parathyroid hormone, as it does in the bones
and kidneys.
▪ In addition, vitamin D also helps bones grow denser and stronger
as they absorb and deposit these minerals.
Vitamin D and bone health

1 Enzymes in the liver add a hydroxyl

group (OH) to carbon number 25
(calcidiol).

2 Enzymes in the kidney add a

hydroxyl group (OH) to carbon
number 1, forming active vitamin D
(calcitriol).
Vitamin D and bone health
3 Low levels of active vitamin
D stimulate calcium
absorption from the
intestine. Higher levels act
with parathyroid hormone
(PTH) at the bone to increase
bone breakdown and at the
kidney to increase calcium
retention.

4 Blood calcium and

phosphorus are maintained
at levels that support bone
mineralization.
 Vitamin D and other roles
▪ Vitamin D is needed to maintain normal functioning of the
parathyroid gland and is an important immune system regulator.
▪ In many cases, vitamin D enhances or suppresses the activity of genes
that regulate cell growth.
▪ Vitamin D also plays a role in preventing cells from being
transformed into cancerous cells → Studies now support the
hypothesis that vitamin D deficiency increases the risk of developing
and dying from colon, breast, ovarian, and prostate cancers.
Vitamin D: Recommendation (RNI 2017)
Vitamin D: UL
 Vitamin D: Deficiency and toxicity
Deficiency Toxicity
▪ Dietary calcium cannot be ▪ Not caused by natural foods
absorbed. and / or sun exposure.

▪ Adult: Osteomalacia. ▪ Oversupplementation and

▪ Children: Rickets. overfortification pose risk.

▪ Certain population are ▪ UL for adults: 50 µg/day

particularly at high risk → low
exposure to sunlight and low
food with vitamin D.
 Vitamin D: Deficiency
▪ Rickets:
▪ First recognized in the 1600s, was common during the
Industrial Revolution when large numbers of poorly nourished
children lived under a layer of smog in the newly
industrialized cities.
▪ In children who are deficient in vitamin D, bones are weak
because they do not contain enough calcium and phosphorus.
▪ Characterized by bone deformities such as narrow rib cages,
known as pigeon breasts, and bowed legs.
▪ The legs bow because the bones are too weak to support the
weight of the body.
 Vitamin D: Deficiency
▪ Rickets:
▪ To prevent
rickets, the
American
Academy of
Pediatrics
recommends a
minimum daily
intake of 400 IU
vitamin D for all
infants, children,
and adolescents.
 Vitamin D: Deficiency
▪ Osteomalacia:
▪ Because bone growth is complete in adults, osteomalacia
does not cause bone deformities, but bones are weakened
because not enough calcium is available to form the mineral
deposits needed to maintain healthy bone.
▪ Insufficient bone mineralization leads to fractures of the
weight-bearing bones such as those in the hips and spine.
▪ Osteomalacia also causes bone pain and muscle aches and
weakness. The bones become increasingly soft, flexible,
brittle, and deformed.
VITAMIN E
 Vitamin E: An overview
▪ It was first identified as a fat-soluble component of grains that
was necessary for fertility in laboratory rats.
▪ The chemical name for vitamin E, tocopherol, is from the Greek
tos, meaning childbirth, and phero, meaning to bring forth.
▪ When chemists isolated four different tocopherol compounds,
they designated them by the fi rst four letters of the Greek
alphabet: alpha, beta, gamma, and delta.
▪ The tocopherols consist of a complex ring structure and a long
saturated side chain.
 Vitamin E: An overview
▪ The positions of methyl groups (CH3) on the side chain and their
chemical rotations distinguish one tocopherol from another.
▪ Alpha-tocopherol is the only one with vitamin E activity in the
human body.
▪ The other tocopherols are not readily converted to alpha-
tocopherol in the body, nor do they perform the same roles.
▪ Although vitamin E has been promoted to slow aging, cure
infertility, reduce scarring, and protect against air pollution,
research has not shown it to be useful for these purposes.
 Vitamin E: Sources

▪ Dietary sources include nuts and peanuts; plant oils, such as soybean,
corn, and sunflower oils; leafy green vegetables; and wheat germ.
▪ Some is consumed in fortified foods and supplements; but the vitamin E
from these sources may not be efficient to meet requirement.
▪ The synthetic form of alpha-tocopherol found in dietary supplements and
fortified foods is composed of 8 different isomers.
▪ Therefore, synthetic alpha-tocopherol provides half of the biological
activity of natural alpha-tocopherol; 10 mg of synthetic alpha-tocopherol
provides the function of 5 mg of natural alpha-tocopherol.
 Vitamin E: An overview
▪ Because vitamin E is sensitive to destruction by oxygen, metals,
light, and heat, some is lost during food processing, cooking, and
storage.
▪ Although it is relatively stable at normal cooking temperatures,
the vitamin E in cooking oils may be destroyed if the oil is
repeatedly heated to the high temperatures used for deep-fat
frying.
▪ Values of the vitamin E in foods reflected all of the tocopherols
and were expressed in “milligrams of tocopherol equivalents.”
▪ These measures overestimated the amount of alpha-tocopherol.
Vitamin E: Recommendation (RNI 2017)
Vitamin E: UL (RNI 2017)
 Vitamin E: Deficiency and Toxicity
Deficiency Toxicity
▪ Rare from poor dietary intake. ▪ Toxicity is rare.
▪ Usually associated with diseases ▪ The UL for vitamin E (1000
of fat malabsorption such as cystic milligrams) is more than 65 times
fibrosis. greater than the recommended
▪ This classic sign of vitamin E intake for adults (15 milligrams).
deficiency, known as erythrocyte ▪ Extremely high doses of vitamin E
hemolysis, is seen in premature may interfere with the blood-
infants. clotting action of vitamin K and
▪ Prolonged vitamin E deficiency enhance the effects of drugs used
also causes neuromuscular to oppose blood clotting, causing
dysfunction involving hemorrhage.
▪ the spinal cord and retina of the
eye.
 Vitamin K: An overview
▪ As with other fat-soluble vitamins, vitamin K is found in several
forms.
▪ Phylloquinone is the form found in plants and the primary
form in the diet.
▪ A group of vitamin K compounds, called menaquinones, are
found in fish oils and meats and are synthesized by
bacteria, including those in the human intestine.
▪ Sources: The best dietary sources are liver and leafy green
vegetables such as spinach, broccoli, brussels sprouts, kale, and
turnip greens.
 As with other fat-soluble vitamins, vitamin K is
found in several forms.

Phylloquinone is the form found in plants and

Vitamin the primary form in the diet.

K: An
overview A group of vitamin K compounds, called
menaquinones, are found in fish oils and
meats and are synthesized by bacteria,
including those in the human intestine.
Sources: The best dietary sources are liver
and leafy green vegetables such as spinach,
broccoli, brussels sprouts, kale, and turnip
greens.
 Vitamin K: Blood clotting
▪ Vitamin K is a coenzyme needed for the production of the
blood-clotting protein prothrombin and other specific blood-
clotting factors.
▪ When activated they lead to the formation of fibrin, the
protein that forms the structure of a blood clot.
▪ To prevent blood loss, these tears must be repaired with blood
clots.
▪ When any of the blood clotting factors is lacking, hemorrhagic
disease results.
Vitamin K: Blood clotting
 Vitamin K: Other functions
▪ Several studies have demonstrated that low-dietary vitamin K
intake is associated with low bone mineral density or increased
fractures.
▪ Vitamin K dependent proteins in blood vessels may be involved
in preventing calcification of blood vessels and loss of
elasticity.
Vitamin K: Recommendation (RNI 2017)
 Vitamin K: Deficiency and Toxicity
Deficiency Toxicity
▪ Abnormal coagulation is the major ▪ No documented side effects up to
symptom. 370 µg/day.
▪ May result from fat malabsorption ▪ No UL set
and long-term use of antibiotics. ▪ High dose can interfere with
▪ Most common in newborns. anticoagulant drugs.
THE END
 Self-check!
1. How Is vitamin A involved in the perception of light?
2. What is Beta-carotene?
3. Why is vitamin D is called ‘sunshine vitamin’?
4. What is the primary function of vitamin D?
5. Name TWO sources of vitamin E in the diet.
6. What is the main function of vitamin K?