Download Avitaminosis - oral signs and treatment.

Vitamins and avitaminosis
Artur Cieślewicz, PhD
Department of Clinical Pharmacology
[email protected]
What are vitamins?
• Vitamins – organic substances necessary for life
• Essential for normal functioning of body
• Cannot be synthesized internally (save for few
exceptions)
• Necessary for growth, vitality, general well-being
Because at one time no one knew the chemical
structure of vitamins and therefore could not give
them a proper scientific name, most are designated
by a letter of the alphabet.
• Found in minute quantities in all natural
food
• Vitamins must be obtained from these
foods or from dietary supplements
• It is imposible to sustain life without
all the essential vitamins
1
• Vitamins cannot replace food, cannot be assimilated
without ingesting food
• They have no callories or energy value of their own
• They are not substitutes for protein or any other
nutrients (mineral, fats, carbohydrates, water)
• Vitamins themselves are not components of body
structures
• One cannot take vitamins, stop eating and expect to
be healthy
• Vitamins regulate metabolism through enzyme
systems (coenzymes, cofactors)
• A single deficiency can endanger the whole body
“Everyone who has in the past eaten processed
sugar, white flour, or canned food has some
deficiency disease, the extent of the disease
depending on the percentage of such deficient food
in the diet”
Dr Tarnel T. Quigley,
The National Malnutrition
Vitamins occur in all organic material
A well-balanced diet should provide all needed
vitamins in sufficent amount
Such diet is very difficult to arrange:
• most of the foods we eat have been processed and
depleted in nutrients
• most restaurants tend to reheat food or keep it warm
under heat lamps which destroys such vitamins as A,
B1 or C.
Vitamins can be divided in two
groups
Water-soluble:
Vitamin C, all B
vitamins
Fat-soluble:
Vitamin A, D, E, K
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Water soluble vitamins
• Circulate freely in the blood, watery fluids
between cells and in the fluids inside cells
• Most of them can move through the
bloodstream without needing carriers (only
B12 needs a binding protein)
• Excesses of water-soluble vitamins are
eliminated by kidneys (except folate and B12
which are regulated by liver and released
through the bile)
Water soluble vitamins
• Inactive until they
are transformed into
their coenzyme
form.
• All of the watersoluble vitamins can
act as important
parts of the
coenzymes that
make enzymatic
reactions possible
Water soluble vitamins
• Water-soluble vitamins are vulnerable to losses
during cooking as they can easily leach out into
cooking water
• Many of these vitamins are sensitive to heat as well
• Water-soluble vitamins are not toxic when consumed
in food. Supplements of water-soluble vitamins are
also not toxic in normal amounts
• Exceptions: B3 (only while taken in the form of niacin,
which can cause skin flushing) and C (can cause
intestinal irritation if taken in large amounts and in the
acidic form)
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Vitamin C (ascorbic acid)
• The most widely used vitamin supplement in the
world
• Lack of vitamin C for long periods of time can result
in scurvy
• By 1617, John Woodall, a surgeon for the British East
India Company, published a cure for scurvy – lemon
juice
• James Lind wrote Treatise on the Scurvy in 1753:
gave some sailors two oranges and one lemon each
day, while other sailors received cider, vinegar, or
other possible scurvy cures. This may have been the
first scientific nutrition experiment in the history of
science. He proved that fresh citrus fruit prevented
and cured scurvy.
Vitamin C (ascorbic acid)
•
•
•
•
•
Until the early twentieth century, the factor in these foods that
prevented scurvy was an unknown antiscorbutic (prevents
scurvy) factor
In 1912, Casimir Funk introduced his theory that scurvy is due to
the absence of an “anti-scurvy vitamine.” This factor was named
vitamin C in the 1920s
Albert Szent-Györgyi isolated a substance he called hexuronic
acid (renamed later to ascorbic acid) because it is a six-carbon
compound – awarded in 1937 with Nobel Prize in medicine
By 1932, vitamin C was isolated and identified, complete with
photographs of the vitamin C crystals
The ascorbic acid molecule was first successfully synthesized in
1933
MAIN FUNCTION
SYNTHESIS OF
COLLAGEN!
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Vitamin C (ascorbic acid)
Deficiency of vitamin C is apparent in many body
systems. Blood vessels are dependent on vitamin C
to maintain their collagen. Bleeding gums and small
hemorrhages under the skin can be signs of
developing vitamin C deficiency. With severe
deficiency, the muscles deteriorate, including the
heart muscle. Wounds fail to heal and teeth become
loosened because collagen cannot be formed.
Infections are common. Death from scurvy can be
from internal hemorrhaging. Scurvy is easily
reversed with fresh fruit and vegetables.
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B Vitamins
• The B vitamins were identified and isolated early in the
twentieth century when refined grains were first found to
cause deficiency diseases.
• Work so closely together that it is hard to tell which
individual B vitamin is missing when a deficiency occurs.
• The B vitamins need to be taken together in food or in
supplements.
B Vitamins
• Other nutrients also interact with the B vitamins: a
mineral, iron and an essential amino acid, tryptophan,
are both needed to synthesize niacin,vitamin B3.
• The best way to avoid a deficiency of B vitamins is to
eat a varied diet of fresh fruit, an abundance of
vegetables, whole grains, legumes, nuts and seeds,
and other food as desired.
• Some of these B vitamins can also be made by
friendly bacteria in a healthy colon and absorbed into
circulation.
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B1 (Thiamin)
• First discovered in Japan in the early
1900s, when the lack of thiamin in white
rice caused beriberi
• First synthesized in 1936
• Found in rice bran and rice germ, both
of which are removed when white rice
is made from brown rice
B1 (Thiamin)
Functions:
- Promotes growth
- Aids digestion, especially of carbohydrates
- Improves mental attitude
- Keeps nervous system, muscles and heart
functioning normally
- Helps fight air- or seasickness
- Relieves dental postoperative pain
- Aids in treatment of herpes zoster
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B1 (Thiamin)
Deficiency:
- Common among alcoholics, who often have
inadequate food intakes
- Alcohol impairs the absorption of thiamin, while
increasing excretion of thiamin
- Tannins in tea and coffee can oxidize thiamin,
reducing the availability of thiamin in the diet
- Extreme thiamin deficiency can lead to an enlarged
heart, weight loss, muscular weakness, poor shortterm memory, and cardiac failure
- If thiamin is absent or too low in the diet for prolonged
periods, this can result in beriberi (can cause damage
to the nervous system, heart, and muscles)
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B2 (Riboflavin)
• Discovered as a growth factor in the early
nineteenth century
• Has a greenish-yellow color, which led to one
of its early names, vitamin G.
• In 1935, riboflavin was first synthesized in the
lab, and by 1938, its structure was
determined
• When taken in excess of needs, riboflavin is
responsible for the bright yellow color of urine
B2 (Riboflavin)
Functions:
- Aids in growth and reproduction
- Promotes healthy skin, nails, hair
- Helps eliminate sore mouth, lips and
tongue
- Benefits vision, alleviates eye fatigue
- Functions with other substances to
metabolize carbohydrates, fats and proteins
- Works as a part of FAD and FMN coenzyme:
reduction and oxidation cycle of glutathione,
activation of pyridoxine, TCA
B2 (Riboflavin)
Deficency:
Ariboflavinosis: inflammation of the
membranes of the eyes, the mouth, the skin,
and the gastrointestinal tract. Also can cause
sensitivity to light. Cracks on the side of the
mouth are another possible sign of riboflavin
deficiency.
Other symptoms: sore throat with redness
and swelling of the mouth and throat mucosa,
glossitis (magenta tongue with atrophy)
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B3 (Niacin)
• Can be found in two different forms: niacin
(nicotinic acid) and niacinamide
(nicotinamide); nicotinic acid can be easily
converted into nicotinamide in the body
• Niacin is used in two coenzyme forms: NAD
and NADP, which are required by hundreds
of enzymes
• Niacin can be made in the body from
tryptophan
B3 (Niacin)
Functions:
Helps reduce cholesterol and triglicerides
Aids in metabolizing fats and promoting a healthy digestive
system
Gives healthier looking skin
Helps prevent and ease severity of migraine headaches
Increases circulation and reduces high blood pressure
Eases some attacks of diarrhea
Reduces the unpleasant symptoms of vertigo in Meniere’s
disease
Increases energy through proper utilization of food
Helps eliminate canker sores and bad breath
B3 (Niacin)
Deficency:
The deficiency disease is called pellagra.
Pellagra is characterized by the four Ds: diarrhea, dermatitis,
dementia, and death. Pellagra killed thousands of people in the
South in the early twentieth century who were eating a diet
consisting of mostly corn. Most of the niacin in corn is
unavailable for easy assimilation, and corn is also low in
tryptophan.
In Mexico, pellagra is rare even in people on low-protein corn
diets because the corn is soaked in lime before the tortillas are
cooked. This process releases the niacin for absorption.
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Biotin
• Originally reffered as vitamin H
• Discovered in late 1930s when animals
developed skin problems when fed only with
egg whites
• It took forty years of research to confirm biotin
as a B vitamin because deficiency is so rare.
• Can be synthesized only by bacteria, algae,
yeasts, molds, and a few plant species.
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Biotin
• Coenzyme in four important
carboxylases:
– Acetyl-CoA carboxylase helps make fatty
acids
– Pyruvate carboxylase helps make blood
sugar from fats and protein
– Methylcrotonyl-CoA carboxylase helps
metabolize the amino acid leucine
– Propionyl-CoA carboxylase helps burn fats
Biotin
Functions:
- Aids in keeping hair from turning gray
- Helps in preventing treatment of
baldness
- Eases muscle pains
- Alleviates eczema and dermatitis
Biotin
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•
•
•
•
Deficency has been noted in prolonged intravenous feeding
where biotin was omitted
Also from long-term consumption of raw egg whites (Biotin can
bind to avadin, a protein found in egg whites. Cooking
inactivates this bond, so cooked egg whites do not bind biotin.)
Deficiency can result from a genetic lack of biotinidase, an
enzyme that releases biotin from small proteins. Rare hereditary
disorder.
Deficiency symptoms: eczema of face and body, extreme
exhaustion, impairment of fat metabolism, anorexia, alopecia,
depression
Usually deficiency of biotin is very rare because it is
synthesized by bacteria living in healthy large intestines
(the wall of large intestine has a specialized process for the
uptake of biotin)
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B5 (pantothenic acid)
• Has been found in every living cell
(plant and animal tissues and
microorganisms)
• Identified in 1933 by Roger William as a
growth factor for yeast
• Forms a large part of the coenzyme A
molecule.
B5 (pantothenic acid)
Functions
- Vital for proper functioning of adrenal glands
- Essential for convertion of fat and sugar to energy
- Necessary for synthesis of antibodies, utilization of
PABA and choline
- Aids in wound healing
- Fights infections (synthesis of antibodies)
- Treats postoperative shock
- Prevents fatigue
- Reduces adverse and toxic effects of many
antibiotics
- Lowers cholesterol and triglicerides
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B5 (pantothenic acid)
Pantothenic acid deficiency is very rare and
seen only in cases of severe malnutrition.
Pantothenic acid is found in many common
foods and average diets are thought to have
an adequate amount of it. Pantothenic acid is
also made by the normal bacteria that live in
the colon.
Deficiency symptoms: hypoglycemia,
duodenal ulcers, blood and skin disorders.
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B6 (pyridoxine)
• Discovered in the 1930s
• A group of closely related substances
(pyridoxine, pyridoxal, pyridoxamine), all of
which can be converted to the most active
coenzyme form, Pyridoxal Phosphate (PLP)
• Extensively stored in muscle tissue
because PLP is a coenzyme to the enzyme
glycogen phosphorylase, catalizing the
release of glucose from glycogen
• Depleted by alcohol drinking
B6 (pyridoxine)
Functions:
- Takes part in the synthesis of many neurotransmitters
(serotonine, dopamine, GABA, norepinephrine)
- Serves as a coenzyme in the synthesis of nucleic acids
- Must be present for the production of antibodies and red blood
cells
- Required for the proper absorption of B12
- In combination with folic acid can help break down
homocysteine, significantly lowering the risk of heart disease
- Strenghthens the immune system
- Takes part in the convertion of tryptophan to niacin
- Helps reduce dry mouth and urination problems caused by
tricyclic antidepressants
B6 (pyridoxine)
Deficiency:
- causes depression and confusion (brain
wave abnormalities and convulsions in
extreme deficiency)
- Anemia, seborrheic dermatitis, glossitis
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Folate
• Isolated from spinach in 1945
• Known also as Bc or vitamin M
• Primary coenzyme form:
TetraHydroFolate (THF) – needed to
transfer one-carbon units
• Synthetic folic acid from supplements
has a higher bioavailability than the
naturally occurring folates
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Folate
Functions:
- Essential for the formation of red blood cells
- Important for the production of nucleic acids
- Essential for the division of body cells
- Needed for utilization of sugar and amino acids
- Lowers homocysteine levels, reducing the risk of heart disease
- Protects against birth defects (neural tube defects)
- Improves lactation
- Protects against intestinal parasites and food poisoning
- Promotes healthier looking skin
- Act as an analgesic for pain
- Act as a preventive for canker sores
- Helps ward off anemia
Folate
Deficiency:
- Lack of folate in the diet can cause neural tube
defects in an embryo of a pregnant woman
- Deficiency signs include anemia and deterioration of
the gastrointestinal tract
- The anemia results from abnormal blood cell division
resulting in fewer and larger red blood cells
(megaloblastic anemia)
- Other symptoms are: weakness, sore tongue, head
aches, heart palpitations, irritability and behavioral
disorders
Folate
Deficiency:
- Folate deficiency can be caused by inadequate
absorption, inadequate consumption, or unusually
high metabolic needs for this vitamin
- Drugs that can interfere with folate include aspirin,
anticancer drugs, antacids, and oral contraceptives
- Older people tend to have higher homocysteine
levels and are encouraged to meet or exceed the
RDA for folate
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B12 (cobalamine)
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•
•
•
•
•
•
Discovered in 1930s simultaneously by two research teams
The only vitamin that conatins mineral elements (cobalt)
Chemical structure revealed in 1956
The most complex vitamin
Coenzyme forms: methylcobalamine and deoxyadenosyl
cobalamine
Commonly known as „red vitamine” (as it is a red crystalline
compound)
Not well assimilated through stomach (needs to be combined
with calcium during absorption)
Can be stored in the body (it’s up to 3 years to deplete this
supply)
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B12 (cobalamine)
Functions:
- required for the synthesis of hemoglobin
- needed for DNA synthesis in the rapidly dividing cells
of the bone marrow
- Helps break down homocysteine, lowering the risk of
heart disease
- Promotes growth and increases apetite in children
- Maintains healthy nervous system
- Relieves irritability, improves concentration, memory
and balance
- Helps protect against smoking-induced cancer
B12 (cobalamine)
Deficiency:
- Usually not from lack of intake, but rather from lack of absorption
- Lack of vitamin B12 or folate can lead to the production of large,
immature, hemoglobin-poor red blood cells (pernicious
anemia, most common in those over 60 years of age)
- Folate cannot be properly utilized if vitamin B12 is low or absent
- If folate or vitamin B12 is absent, symptoms of folate anemia can
be present (slowed DNA synthesis, which shows up first as
defective red blood cells)
- Deficiency of vitamin B12 first shows as a paralysis that begins in
the extremities and moves inward
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Fat-soluble vitamins
• Vitamins A, D, E, and K
• Are found in the liver and the fatty
tissues of the body where they are
stored and used
• Require bile in order to be absorbed
into the lymph system from the
intestines
Vitamin A
• 300 B.C.: the Hippocratic School of Medicine
recommended liver (rich in vitamin A) for children
with night blindness or infections
• Vitamin A was the first vitamin discovered
• In 1907, the fat-soluble vitamin A was found
necessary for growth
• In 1930 it was learned that there were two related
forms: beta-carotene and a fat-soluble Vitamin A
• Vitamin A was first synthesized in 1947
• Most of the vitamin A in the body is stored in the
liver in the form of retinyl palmitate
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Vitamin A
Functions:
- Antioxidant activity (beta-carotene)
- Counteracts night blindness, weak eyesights; aids
in the treatment of many eye disorders
- Builds resistance to respiratory infections
- Keeps the outer layers of tissues and organs healthy
- Helps in the removal of age spots
- Promotes growth, strong bones, healthy skin,
hair, teeth and gums
- Helps treat acne, superficial wrinkles, impetigo, boils,
carbuncules and open ulcers when applied externally
- Aids in the treatment of emphysema and
hyperthyroidism
Vitamin A
- Severe vitamin A deficiency is one of the
leading causes of blindness in children:
- 11-cis-retinal is required for the production of
rhodopsin in rods
- retinoic acid is required for the maintenance and
integrity of the corneal epithelium
- Over half of a million children lose their
sight each year from severe vitamin A
deficiency.
- The blindness results from a lack of
vitamin A in the cornea of the eye
(xerophthalmia).
- In the first stage of xeropthalmia, the
cornea becomes hard and dry, (xerosis).
- Xerosis can progress to a softening of the
cornea that can lead to irreversible
blindness.
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Vitamin A
• Other effects
– vitamin A deficiency results in multiple abnormalities in
innate and adaptive immunity
– all epithelial tissues are sensitive to a lack and excess of
vitamin A; deficiency in skin appears as dryness
– teratogenicity: excess or deficiency causes birth defects or
the death of the embryo; therefore, in 2005 the FDA
approved new regulations including the registry of all
patients to whom retinoids were prescribed
– Acute Promyelocytic Leukemia: beneficial effect of
introducing all-trans-retinoic acid to the therapy; however, in
some cases retinoic acid syndrome was developed (fever,
respiratory distress, changes in hemostasis, and acute renal
failure)
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Vitamin D (calciferol)
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•
•
•
•
•
First named in 1922 by researchers who learned of a fat-soluble
substance that played an important role in bone growth
In 1931 vitamin D2 was synthesized, and the structure of vitamin
D was established by 1936
More accuratly: vitamin D is a prohormone – must be
metabolized to a biologically active form that functions as a
steroid hormone
Main function: regulating calcium and phosphorus to make
bones strong
Is necessary in the diet only for people who get too little
sun to make their own vitamin D
very hard to find in a natural diet as it occurs in only a few
foods (it is present in unfortified foods in only very small and
variable quantities)
Vitamin D (calciferol)
Functions:
- Properly utilizes calcium and phosphorus
necessary for strong bones and teeth
- Taken with vitamins A and C can aid in
preventing colds
- Helps in treatment of conjunctivitis
- Aids in assimilating vitamin A
- Aids the functioning of the immune system
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Vitamin D (calciferol)
- Deficiency: rickets, severe tooth
decay, osteomalacia, senile
osteoporosis
- A deficiency of vitamin D makes it
difficult to keep enough calcium in
the bloodstream → releasing
calcium from bones
- Severe deficiency of vitamin D in
childhood: the bones fail to
mineralize properly → the arms
and legs become bowed (rickets)
Vitamin D (calciferol)
- Deficiency: rickets, severe tooth
decay, osteomalacia, senile
osteoporosis
- A deficiency of vitamin D makes it
difficult to keep enough calcium in
the bloodstream → releasing
calcium from bones
- Severe deficiency of vitamin D in
childhood: the bones fail to
mineralize properly → the arms
and legs become bowed (rickets)
- In very severe cases, low levels of
blood calcium affect the nerves
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Vitamin E (tocopherol)
• Discovered at the University of California at Berkeley in
1922, where it was found to be essential to maintain
fertility
• Pure alpha-tocopherol was first isolated from wheat germ
oil in 1936
• The tocopherols are divided into four types: alphatocopherol, beta-tocopherol, gamma-tocopherol, and
delta-tocopherol
• Also in the vitamin E family are the very similar
tocotrienols (alpha-, beta-, gamma-, and delta-tocotrienol)
• All tocopherols and all tocotrienols have the ability to
donate a hydrogen atom to neutralize free radicals
– However, only α-tocopherol provides vitamin E biologic activity in
humans
Tocopherol structures
Vitamin E (tocopherol)
Functions:
- The main role: an antioxidant to neutralize free radicals in cell
membranes, in mitochondrial membranes, and in LDL
- Enhances activity of vitamin A
- Important as vasodilator and anticoagulant
- Protects lungs from air pollution by working with vitamin A
- Helps to prevent various forms of cancer
- Prevents and dissolves blood clots
- Alleviates fatigue
- Accelerates healing of burns
- Lowers risk of ischemic heart disease and stroke
- Decreases risk of Alzheimer’s disease
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Vitamin E (tocopherol)
Deficiency:
- Occurs rarely, virtually never as a result of
dietary deficiency:
- Genetic defect in α-tocopherol transfer protein
- Genetic defect in lipoprotein synthesis
- Fat malabsorption syndromes
- The primary manifestations of human vitamin
E deficiency include spinocerebellar ataxia,
skeletal myopathy, and pigmented
retinopathy
- Earliest observed symptom is hypo- or
a-reflexia
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Vitamin K
• Discovered by a Danish scientist, Henrik Dam, in
the late 1920s: he discovered a factor that was
causing excessive bleeding and was missing
from some diets; called the new coagulation
vitamin Koagulationsvitamin
• Fat-soluble vitamin needed for blood coagulation
• There are 3 forms of vitamin K: K1
(phylloquinone, synthesized by plants), K2
(menaquinone, synthesized by bacteria) and K3
(menadione, synthetic; in USA forbidden by FDA
due to potential toxicity in human use)
Vitamin K
Functions:
- Is necessary for the liver to synthesize
prothrombin
- Needed to enable osteocalcin to bind
minerals to bones
- Helps in preventing internal bleeding and
hemorrhages
- Aids in reducing excessive menstrual flow
- Promotes proper blood clotting
Vitamin K
• Healthy adults rarely have a deficiency of vitamin
K, because it is abundant in food and in addition, the
bacteria in the large intestine synthesize vitamin K2.
Moreover, vitamin K can be used over and over
again in a conservation cycle.
• Vitamin K-responsive hemorrhagic events were
observed in patients receiving antibiotics (e.g., some
2nd and 3rd generation cephalosporins)
• Symptoms of vitamin K deficiency include
nosebleeds, bleeding gums, prolonged bleeding
from cuts, or blood in the urine or stool
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Vitamin K
• Infant vitamin K deficiency can cause intracranial
hemorrhage (bleeding inside the skull) and can be
life-threatening. As many as one in five thousand
infants may develop vitamin K deficiency bleeding
unless supplemental vitamin K is given.
• Newborns may be deficient in vitamin K, because:
– Vitamin K levels in breast milk are low
– Bacteria to make vitamin K in the large intestine may not yet
be ready.
– The vitamin K conservation cycle may not be developed
• Because of these reasons, newborn infants are
routinely given an injection of 1000 mcg of vitamin
K1
Literature
Blake S.(2008) Vitamins and minerals
demystified.
Mindell E. (1999) Earl Mindell’s vitamin
bible for the twenty-first century
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Thanks for your attention
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