Micronutrients in Human Nutrition (HND-203)

3(3-0)
Fat Soluble Vitamins; Function & Deficiency Diseases

Dr. Komal Javed

Assistant Professor
SFAS, UMT
 Vitamin A

 Vitamin A was the first fat-soluble vitamin to be recognized

 Three active forms of vitamin A
1. Retinol
2. Retinal
3. Retinoic acid
 Collectively known as retinoids, these compounds are commonly found in foods derived from
animals
 Foods derived from plants provide carotenoids, some of which can be converted to vitamin A
 The most studied of the carotenoids with vitamin A activity is beta-carotene, which can be split
to form retinol in the intestine and liver
 Cont…

 The cells can convert retinol and retinal to the other active forms of vitamin A as needed
 The conversion of retinol to retinal is reversible, but the further conversion of retinal to retinoic acid
is irreversible

 This irreversibility is significant because each form of vitamin A performs a specific function that the
others cannot
Cont…

 After absorption via the lymph system, vitamin A eventually arrives

at the liver, where it is stored
 There, a special transport protein, retinol-binding protein (RBP),
picks up vitamin A from the liver and carries it in the blood
 Cells that use vitamin A have special protein receptors for it, and its
action within each cell may differ depending on the receptor
 For example, retinoic acid can stimulate cell growth in the skin and
inhibit cell growth in tumors
Cont…
Cont…

 In plasma, retinol binds with RBP in a higher-affinity form

 Some of the retinol is oxidized to retinoic acid in the epididymis, which is required for sperm
maturation
 Most of the plasma retinol is transported to the interior of target cells across and across the cell
membrane by a specific receptor
 The retinol is picked up from the membrane by an intracellular structural homolog, called
cellular retinol-binding protein (CRBP), in a lower-affinity form
 Once inside the cells, the low affinity form may be readily used by the cell
 In different subcellular locations, the retinol binding orientation is reversed
 When the body is in need of vitamin A, the retinol dissociates from the CRBP, which is
converted into retinoic acid and bound by CRABP
 CRABP then transports retinoic acid to the nucleus across the nuclear receptor, thereby
activating gene transcription
Roles in the Body

 Vitamin A is a versatile vitamin, known to

regulate the expression of several hundred
genes
 Its major roles include:
 Promoting vision
 Participating in protein synthesis and
cell differentiation, thereby
maintaining the health of epithelial
tissues and skin
 Supporting reproduction and
regulating growth
 As mentioned, each form of vitamin A
performs specific tasks
 Cont…

 Retinol
 Supports reproduction and is the major transport and storage form of the vitamin
 Retinal
 Active in vision and is also an intermediate in the conversion of retinol to retinoic
acid
 Retinoic acid
 Acts like a hormone, regulating cell differentiation, growth, and embryonic
development
 Animals raised on retinoic acid as their sole source of vitamin A can grow
normally, but they become blind because retinoic acid cannot be converted to
retinal
Vitamin role in vision
 Vitamin A plays two indispensable roles in the eye;
 It helps maintain a crystal-clear cornea
 It participates in the conversion of light energy into nerve impulses at
the retina
 Some of the photosensitive cells of the retina contain pigment molecules called
rhodopsin;
Rhodopsin = Opsin (protein)+ retinal molecule
 When light passes through the cornea of the eye and strikes the retina,
rhodopsin responds by changing shape and becoming bleached
 As it does, the retinal shifts from a cis to a trans form, just as fatty acids do
during hydrogenation
 The bleached trans-retinal cannot remain bonded to opsin
Cont…
 When retinal is released, opsin changes shape, thereby disturbing the
membrane of the cell and generating an electrical impulse that travels
along the cell’s length
 At the other end of the cell, the impulse is transmitted to a nerve cell,
which conveys the message to the brain
 Much of the retinal is then converted back to its cis form and combined
with the opsin protein to regenerate the pigment rhodopsin
 Some retinal, however, may be oxidized to retinoic acid, a biochemical
dead end for the visual process
 Visual activity leads to repeated small losses of retinal
 Vitamin A in Protein Synthesis and Cell Differentiation

 Only one-thousandth of the body’s vitamin A is in the retina. Much more is in the
cells lining the body’s surfaces

 It participates in protein synthesis and cell differentiation, a process by which

each type of cell develops to perform a specific function

 All body surfaces, both inside and out, are covered by epithelial cells

 The epithelial tissue on the outside of the body is, of course, the skin—and
vitamin A helps to protect against skin damage from sunlight
 Cont…

 The epithelial tissues that line the inside of the body are the s membranes: the
linings of the mouth, stomach, intestines, lungs, bladder, urethra, uterus,
vagina, eyelids and sinus passageways (Within the body, the mucous
membranes of the GI tract alone line an area larger than a quarter of a football
field) vitamin A helps to maintain their integrity
 Vitamin A promotes differentiation of epithelial cells and goblet cells, one celled
glands that synthesize and secrete mucus
 Mucus coats and protects the epithelial cells from invasive microorganisms and
other potentially damaging substances, such as gastric juices
Vitamin A in Reproduction and Growth
 Vitamin A also supports reproduction and regulates growth
 In men, retinol participates in sperm development
 In women, vitamin A supports normal fetal development during pregnancy
 Children lacking vitamin A fail to grow; given vitamin A supplements, these children gain
weight and grow taller
 The growth of bones is a complex phenomenon of remodeling
 To convert a small bone into a large bone, the bone-remodeling cells must “undo” some parts
of the bone as they go, and vitamin A participates in the dismantling
 The cells that break down bone contain sacs of degradative enzymes

** With the help of vitamin A, these enzymes destroy selected sites in the bone, removing the
parts that are not needed
Beta-Carotene as an Antioxidant in the body

 Beta-carotene serves primarily as a vitamin A precursor

 Not all dietary beta-carotene is converted to active vitamin A,
however;
 Some beta-carotene may act as an antioxidant, capable of protecting
the body against disease
Vitamin A Recommendations

 As body can derive vitamin A from various retinoids and carotenoids, its content in
foods and its recommendations are expressed as retinol activity equivalents (RAE)
 Most food and supplement labels with vitamin A use (IU)
 The efficiency of β-carotene absorption is lower (14%) than previously believed
(33%)
 Dietary reference intakes (DRIs) have been determined for vitamin A and are
expressed in micrograms per day (mcg/day)
 The AI for infants is based on the amount of retinol in human milk
 The DRIs for adults are based on levels that provide adequate blood levels and liver
stores and are adjusted for differences in average body size
 Increased amounts of the vitamin during pregnancy and lactation allow for fetal
storage and the vitamin A in breast milk
 No DRIs have been established for the carotenoids
Cont…
 ♦♦ 1 µg RAE
 = 1 µg retinol
 = 2 µg beta-carotene (supplement)
 =12 µg beta-carotene (dietary)
 =24 µg other vitamin A precursor carotenoids
 ♦♦ 1 IU retinol = 0.3 µg retinol or 0.3 µg RAE

 1 µg RAE= 1 µg retinol=12 µg beta-carotene

Vitamin A Recommendations

900 µg/ day 700 µg/ day

 Sources

 Animal
Vitamin A present in the liver or in the fat of milk and eggs. Very high
concentrations of vitamin A are found in cod and halibut liver oils.
 Plant
Provitamin A carotenoids are found in dark green, leafy and yellow-orange
vegetables and fruit; deeper colors are associated with higher carotenoid levels.
Carrots, greens, spinach, orange juice, sweet potatoes, and cantaloupe are rich
sources of provitamin A.
Vitamin A Deficiency

 Vitamin A status depends mostly on:

 The adequacy of vitamin A stores
 Vitamin A status also depends on a person’s protein status because retinol-
binding protein serves as the vitamin’s transport carrier inside the body
 If a person were to stop eating vitamin A–containing foods, deficiency
symptoms would not begin to appear until after stores were depleted—1 to 2
years for a healthy adult but much sooner for a growing child
 Cont…

 An estimated 250 million children worldwide have some degree of vitamin A deficiency and thus are
vulnerable to infectious diseases and blindness
 Major nutrition problem in developing countries
 About 1 to 2 percent of them become blind every year, half of them dying within a year of losing their
sight
 Infectious Diseases
 Vitamin A supports immune function and inhibits replication of the measles virus
 In developing countries around the world, measles is a devastating infectious disease, killing 450
children each day
 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
 Providing large doses of vitamin A reduces the risk of dying from these infections by half
Night Blindness
 Vitamin A supplements also protect against blindness and the complications
of other life-threatening infections, including malaria, lung diseases, and
HIV (human immunodeficiency virus, the virus that causes AIDS)
 Night blindness is one of
 The first detectable signs of vitamin A deficiency and permits early
diagnosis
 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 flash of bright light at night or to see after dark
 In many parts of the world, after the sun goes down, vitamin A–deficient
people become night-blind
 Cont…
 Blindness (Xerophthalmia) Beyond night blindness is total blindness—
failure to see at all
 Blindness due to vitamin A deficiency, known as xerophthalmia, develops
in stages
I. At first, the cornea becomes dry and hard because of inadequate mucous
production—a condition known as xerosis.
II. Then xerosis quickly progresses to keratomalacia, the softening of the
cornea that leads to irreversible blindness
 Night blindness vs Total 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 of vitamin A at the front of the eye,
the cornea
Cont…
 Keratinization
 Vitamin A deficiency affects other surfaces
 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 reduces, and this,
in turn, worsens malnutrition by limiting the absorption of other nutrients from
diet
 Similar changes in the cells of other epithelial tissues weaken defenses, making
infections of the respiratory tract, the GI tract, the urinary tract, and inner ear
 Vitamin A Toxicity

 As a deficiency of vitamin A affects all body systems, so does a toxicity

 Symptoms of toxicity begin to develop when all the binding proteins are loaded, and
vitamin A is free to damage cells

 Toxicity is a real possibility when concentrated amounts of preformed vitamin A in

foods derived from animals, fortified foods, or supplements is consumed

 An Upper Level (UL) has been set for preformed vitamin A (3000 µg/day)
 Vitamin A Toxicity

 Beta-carotene, which is found in a wide variety of fruits and vegetables, is not

converted efficiently enough in the body to cause vitamin A toxicity; instead, it is
stored in the fat just under the skin
 Although overconsumption of beta-carotene from foods may turn the skin yellow,
this is not harmful
 In contrast, overconsumption of beta-carotene from supplements may be quite
harmful
 In excess, this antioxidant may act as a prooxidant (induce oxidative stress)
Cont…
 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
 Birth Defects
 Excessive vitamin A during pregnancy leads to abnormal cell death in the
spinal cord, which increases the risk of birth defects
 In such cases, vitamin A is considered a teratogen (substances cause abnormal
fetal development and birth defects)