Investigation
of lipid soluble vitamins functional role in metabolism and cell functions
realization
Lipid-soluble
vitamins
Although
fat-soluble vitamins have been studied intensively and widely used in human nutrition,
we know less about their specific biological function than about the
water-soluble vitamins.
Vitamin
A.
Vitamin A
occurs in two common forms, vitamin A1, or retinol, the form most common in
mammalian tissues and marine fishes, and vitamin, A2, common in freshwater fishes.
Both are isoprenoid compounds containing a six-membered carbocyclic ring and an
eleven-carbon side chain.
http://www.youtube.com/watch?v=dcw1m31zuTE
Vitamin A
Vitamin A
consists of three biologically active molecules, retinol, retinal (retinaldehyde) and retinoic acid.
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All-trans-retinal |
11-cis-retinal |
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Retinol |
Retinoic Acid |
Carotenoids are provitamins of vitamin A. Carotenoids
widely distributed in plants, particularly a-, b-,
and g-carotene.
The carotenes have no vitamin A activity but are converted into vitamin A by
enzymatic reactions in the intestinal mucosa and the liver. b-Carotene, a symmetrical molecule, is cleaved in its
center to yield two molecules of retinol. Retinol occurs in the tissues of
mammals and is transported in the blood.
In vitamin A
deficiency young persons fail to grow, the bones and nervous system fail to
develop properly, the skin becomes dry and thickened, the kidneys and various
glands degenerate, and both males and females become sterile.
Although
all tissues appear to be disturbed by vitamin A deficiency, the eyes are most
conspicuously affected. In infants and young children the condition known as xerophthalmia ("dry eyes") is an early symptom of
deficiency and is a common cause of blindness in some tropical areas where
nutrition is generally poor. In adults an early sign of vitamin A deficiency is
nightblindness, a deficiency in dark adaptation,
which is often used as a diagnostic test.
Detailed
information is available on the role of vitamin A in the visual cycle in
vertebrates. The human retina contains two types of light-sensitive photoreceptor
cells. Rod-cells are adapted to sensing low light intensities, but not colors;
they are the cells involved in night vision, whose function is impaired by
vitamin A deficiency. Cone cells, which sense colors, are adapted for high
light intensities.
Retinal
rod cells contain many membrane vesicles that serve as light receptors. About
one-half of the protein in the membrane of these vesicles consists of the
light-absorbing protein rhodopsin (visual purple). Rhodopsin consists of a protein, opsin,
and tightly bound 11-cis-retinal, the aldehyde of
vitamin A. When rhodopsin is exposed to light, the
bound 11-cis-retinal undergoes transformation into all-trans-retinal, which
causes a substantial change in the configuration of the retinal molecule. This
reaction is nonenzymatic. The isomerization
of retinal is followed by a series of other molecular changes, ending in the
dissociation of the rhodopsin to yield free opsin and all-trans-retinal, which functions as a trigger
setting off the nerve impulse.
11-cis-retinal
all-trans-retinal
In order for rhodopsin to be regenerated from opsin
and all-trans-retinal, the latter must undergo isomerization
back to 11-cis-retinal. This appears to occur in a sequence of enzymatic
reactions catalyzed by two enzymes:
retinal-reductase
all-trans-retinal +
NADH + H+ → all-trans-retinol + NAD+
retinol-isomerase
all-trans-retinol → 11-cis-retinol
retinal-reductase
11-cis-retinol
+ NAD+ → 11-cis-retinal + NADH + H+
The
11-cis-retinal so formed now recombines with opsin to
yield rhodopsin, thus completing the visual cycle.
Since
vitamin A deficiency affects all tissues of mammals, not the retina alone, the
role of retinal in the visual cycle does not represent the entire action of
vitamin A. It appears possible that vitamin A may play a
general role in:
- the transport
of Ca2+ across certain membranes; such a more general role might explain the
effects of vitamin A deficiency and excess on bony and connective tisues;
processes
of growth and cell differentiation;
processes
of glycoproteins formation whoch
are the components of the biological mucosa .
The vitamin A
requirement of man - 1,5-2 milligram per day.
Vitamin A is
met in large part by green and yellow vegetables, such as lettuce, spinach,
sweet potatoes, and carrots, which are rich in carotenes. Fish-liver oils are
particularly rich in vitamin A. However, excessive intake of vitamin A is toxic
and leads to easily fractured, fragile bones in children, as well as abnormal
development of the fetus.
Vitamin
D
Most
important are vitamin D2, or ergocalciferol, and
vitamin D3, or cholecalciferol, the form normally
found in mammals. These compounds may be regarded as steroids.
It
is now known that 7-dehydrocholesterol in the skin is the natural precursor of cholecalciferol in man; the conversion requires irradiation
of the skin by sunlight. On a normal unsupplemented
diet this is the major route by which people usually acquire vitamin D.
Vitamin D is a steroid hormone that
functions to regulate specific gene expression following interaction with its
intracellular receptor. The biologically active form of the hormone is 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also termed calcitriol). Calcitriol functions
primarily to regulate calcium and phosphorous homeostasis.
http://www.youtube.com/watch?v=JwPVibQ6_3Y&feature=related
http://www.youtube.com/watch?v=onSPZ0aBUKM&feature=related
http://www.youtube.com/watch?v=xwNhd2pQL0k&feature=related
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Ergosterol |
Vitamin D2 |
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7-Dehydrocholesterol |
Vitamin D3 |
Cholecalciferol
is converted into its derivative - 25-hydroxycholecalciferol. This product is
more active biologically than cholecalciferol and it
has been found to be the main circulating form of vitamin D in animals, formed
in the liver. But 25-hydroxycholecalciferol was found to be metabolized further
to 1,25-dihydroxycholecalciferol in kidneys. This
compound is still more active; its administration produces rapid stimulation of
Ca2+ absorption by the intestine.
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25-hydroxyvitamin D3 |
1,25-dihydroxyvitamin D3 |
So the kidney
is the site of formation of 1,25-dihydroxycholecalciferol,
which now appears to be the biologically active form of vitamin D, capable of
acting directly on its major targets, the small intestine and the bones.
1,25-dihydroxycholecalciferol promotes absorption of Ca2+ from
the intestine into the blood, through its ability to stimulate the biosynthesis
of specific protein(s) that participate in transport or binding of Ca2+ in the
intestinal mucosa. This role of 1,25-dihydroxycholecalciferol
is integrated with the action of parathyroid hormone. Whenever the Ca2+
concentration of the blood becomes lower than normal, the parathyroid glands
secrete larger amounts of parathyroid hormone. This hormone acts on the kidney,
stimulating it to produce more 1,25-dihydroxycholecalciferol
from its precursor 25-hydroxycholecalciferol.
Rickets, a
disease of growing bone, is developed in the deficiency of vitamin D in
organism.
http://www.youtube.com/watch?v=n7vybcT9_F4
As with
vitamin A, excessive intake of vitamin D causes the bones to become fragile and
to undergo multiple fractures, suggesting that both vitamins play a role in
biological transport and deposition of calcium.
Most natural
foods contain little of vitamin D; vitamin D in the diet comes largely from
fish-liver oils, liver, yoke of eggs, butter. Vitamin D preparations available
commercially are products of the ultraviolet irradiation of ergosterol
from yeast.
About 2,5-10 mkg of vitamin D is required
by an adult daily and 12-25 mkg by children. The
vitamin can be stored in sufficient amounts in the liver for a single dose to
suffice for some weeks.
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a-Tocopherol |
Vitamin
E was first recognized as a factor in vegetable oils that restores fertility in
rats grown on cow's milk alone and otherwise incapable of bearing young. It was
isolated from wheat germ and was given the name tocopherol.
Several different tocopherols having vitamin E
activity have been found in plants; the most active and abundant is a-tocopherol.
The
deficiency of tocopherol produces many other symptoms
besides infertility in male and female, e.g., degeneration of the kidneys, the deposition
of brown pigments in lipid depots, necrosis of the liver, and dystrophy, or
wasting, of skeletal muscles.
Tocopherols have been
found to have antioxidant activity; i.e., they prevent the autoxidation
of highly unsaturated fatty acids when they are exposed to molecular oxygen.
One of the functions of tocopherol may be to protect
highly unsaturated fatty acids in the lipids of biological membranes against
the deleterious effects of molecular oxygen. Normally, autoxidation
products of unsaturated fats do not occur in the tissues, but in tocopherol deficiency they are detectable in the fat
depots, liver, and other organs.
Due
to the hydrophobic side radical tocopherol can be
built into the phospholipid matrix of biological
membranes and stabilize the mobility and microviscosity
of membrane proteins and lipids.
Tocopherol
is the most potent natural antioxidant.
About 10-20
mg of vitamin E is required per day.
The most
abundant sources of vitamin E are oils (sunflower, corn, soybean oils), fresh vegetables,
animal stuffs (meat, butter, egg yoke).
http://www.youtube.com/watch?v=8oRUF_g-J3k&feature=related
Vitamin K
The K
vitamins exist naturally as K1 (phylloquinone) in green
vegetables and
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Vitamin K1 |
Vitamin K2 |
Vitamin |
Vitamin K was first
discovered as a nutritional factor required for normal blood-clotting time. At
least two forms of vitamin K are known; vitamin K2 is believed to be the active
form. Vitamin K deficiency cannot readily be produced in rats and other mammals
because the vitamin is synthesized by intestinal bacteria.
http://www.youtube.com/watch?v=DVGsnlVCoeA
http://www.youtube.com/watch?v=WI24c2LYFug&feature=related
The only
known result of vitamin K deficiency is a failure in the biosynthesis of the
enzyme proconvertin in the liver. This enzyme
catalyzes a step in a complex sequence of reactions involved in the formation
of prothrombin, the precursor of thrombin, a protein
that accelerates the conversion of fibrinogen into fibrin, the insoluble
protein constituting the fibrous portion of blood clots.
The compound dicumarol, an analog of vitamin K, produces symptoms in
animals resembling vitamin K deficiency; it is believed to block the action of
vitamin K. Dicumarol is used in clinical medicine to
prevent clotting in blood vessels. Dicumarol is the antivitamin of vitamin K.
Some evidence
indicates that vitamin K may function as a coenzyme in a specialized route of
electron transport in animal tissues; since vitamin K is a quinone
which can be reduced reversibly to a quinol, it may serve as an electron carrier.
Function
aids in
reducing excessive menstrual flow
aids
the absorption of calcium in bone
essential
for normal liver functioning
essential
for synthesis of four proteins that act in coagulation
important
in maintaining vitality and longevity
necessary
for formation of prothrombin which is required
for effective blood clotting
involved
in electron transport mechanism and oxdative
phosphorylation
Food Source
alfalfa
blackstrap
molasses
broccoli
Brussels
sprouts
cauliflower
cereals
cow's
milk
egg
yolks
fish
liver oils
green
plants, such as lettuce
kelp
leafy
green vegetables, such as cabbage, spinach
meats,
such as pig and beef liver
peas
polyunsaturated
oils
potatoes
string
beans
yogurt
Effective
With
Increased
Intakes Needed
after
prolonged paraffin ingestion
for
those with biliary obstructions
for
those with liver disease
if
taking antibiotics for long duration
if
you have a malabsorption disease
in
newborn babies
in
overdose of anticoagulant drugs, such as Warfarin, Dicoumarol, which neutralize the effect of Vitamin K
Used For
anticoagulant
drug overdose
hemorrhagic
disease in newborn babies
inhibiting
some cancer tumors
overcoming
inability to absorb vitamins
overcoming
effects of antibiotics on intestinal bacteria
protection
against osteoporosis
Destroyed By
acids
alkalis
commercial
processing
light
and ultra-violet irradiation
oxidizing
agents
Symptoms of
Deficiency
excessive
bleeding and hemorrhage
In babies:
bleeding
from the stomach, intestines, umbilical cord site
Deficiency
Caused By
In Babies:
low
levels in human breast milk
poor
transfer across placenta
sterile
intestine with no bacteria
In Adults:
as a
consequence of sprue
Celiac's
Disease
destruction
of intestinal bacteria by antibiotics
lack
of bile salts
liver
conditions, such as viral hepatitis
surgical
removal of intestines
prolonged
ingestion of liquid paraffin
Deficiency
Leads To
inability
of blood to coagulate
Hypovitaminos
of vitamin K in man can be developed in liver diseases when there is the
decrease of bile acids amount in intestine and as result the inhibition of fat
soluble substances absorption is observed.
Vitamin K is
produced by many microorganisms in the intestine. also
Plants (cabbage, tomato, lettuce)are natural sources of vitamin K.
Adult person
requires 200-300 mkg of vitamin K per day.
Thiamin
(Vitamin B1)
Thiamin (also spelled
thiamine) is a water-soluble B vitamin, previously known as vitamin B1 or aneurine. Isolated and characterized in the 1930s, thiamin was
one of the first organic compounds to be recognized as a vitamin. Thiamin
occurs in the human body as free thiamin and as various phosphorylated
forms: thiamin monophosphate (TMP), thiamin triphosphate (TTP), and thiamin pyrophosphate (TPP), which
is also known as thiamin diphosphate.
Function
Coenzyme
function
Thiamin pyrophosphate (TPP)
is a required coenzyme
for a small number of very important enzymes. The synthesis of TPP from free thiamin
requires magnesium, adenosine triphosphate (ATP), and
the enzyme, thiamin pyrophosphokinase.
Pyruvate dehydrogenase, α-ketoglutarate
dehydrogenase, and branched chain ketoacid
(BCKA) dehydrogenase each
comprise a different enzyme complex found within cellular organelles called
mitochondria. They
catalyze the decarboxylation of pyruvate, α-ketoglutarate, and
branched-chain amino acids to form acetyl-coenzyme A, succinyl-coenzyme
A, and derivatives of branched chain amino acids, respectively; all products
play critical roles in the production of energy from food. In addition to the
thiamin coenzyme (TPP), each dehydrogenase complex
requires a niacin-containing coenzyme (NAD), a riboflavin-containing coenzyme
(FAD), and lipoic acid.
Transketolase
catalyzes critical reactions in another metabolic pathway known as the pentose
phosphate pathway. One of the most important intermediates of this pathway is
ribose-5-phosphate, a phosphorylated 5-carbon sugar
required for the synthesis of the high-energy ribonucleotides, ATP and guanosine triphosphate (GTP). It
is also required for the synthesis of the nucleic acids, DNA and RNA, and the niacin-containing
coenzyme NADPH, which is essential for a number of biosynthetic reactions.
Because transketolase decreases early in thiamin
deficiency, measurement of its activity in red blood cells has been used to
assess thiamin nutritional status.
Deficiency
Beriberi, the disease
resulting from severe thiamin deficiency, was described in Chinese literature
as early. Thiamin deficiency affects the cardiovascular, nervous, muscular, and gastrointestinal
systems. Beriberi has been termed dry, wet, or cerebral, depending on the
systems affected by severe thiamin deficiency.
Dry beriberi
The main feature of dry
(paralytic or nervous) beriberi is peripheral neuropathy. Early in the course
of the neuropathy, "burning feet syndrome" may occur. Other symptoms
include abnormal (exaggerated) reflexes as well as diminished sensation and
weakness in the legs and arms. Muscle pain and tenderness and difficulty rising
from a squatting position have also been observed. Severely thiamin
deficient individuals may experience seizures.
http://www.youtube.com/watch?v=PD_CoEngu4M&feature=related
Wet beriberi
In addition to
neurologic symptoms, wet (cardiac) beriberi is characterized by cardiovascular
manifestations of thiamin deficiency, which include rapid heart rate,
enlargement of the heart, severe swelling (edema), difficulty breathing, and ultimately congestive
heart failure.
Cerebral beriberi
Cerebral beriberi may
lead to Wernicke's encephalopathy and Korsakoff's psychosis, especially in people who abuse
alcohol. The diagnosis of Wernicke's encephalopathy
is based on a "triad" of signs, which include abnormal eye movements,
stance and gait abnormalities, and abnormalities in mental function that may
include a confused apathetic state or a profound memory disorder termed Korsakoff's amnesia or Korsakoff's
psychosis. Thiamin deficiency affecting the central nervous system is referred
to as Wernicke's disease when the amnesic state is
not present and Wernicke-Korsakoff syndrome (WKS)
when the amnesic symptoms are present along with the eye movement and gait
disorders. Most WKS sufferers are alcoholics, although it has been observed in
other disorders of gross malnutrition, including stomach cancer and AIDS.
Administration of intravenous thiamin to WKS patients generally results in
prompt improvement of the eye symptoms, but improvements in motor coordination
and memory may be less, depending on how long the symptoms have been present.
Recent evidence of increased immune cell activation and increased free radical
production in the areas of the brain that are selectively damaged suggests that oxidative stress plays an important role in
the neurologic pathology of thiamin deficiency.
Causes of
thiamin deficiency
Thiamin deficiency may result from
inadequate thiamin intake, increased requirement for thiamin, excessive loss of
thiamin from the body, consumption of anti-thiamin factors in food, or a
combination of these factors.
Inadequate
intake
Inadequate consumption of thiamin is the
main cause of thiamin deficiency in underdeveloped countries. Thiamin deficiency
is common in low-income populations whose diets are high in carbohydrate and low in thiamin (e.g.,
milled or polished rice). Breast-fed infants whose mothers are thiamin
deficient are vulnerable to developing infantile beriberi. Alcoholism, which is
associated with low intake of thiamin among other nutrients, is the primary
cause of thiamin deficiency in industrialized countries.
Increased
requirement
Conditions resulting in an increased requirement
for thiamin include strenuous physical exertion, fever, pregnancy,
breast-feeding, and adolescent growth. Such conditions place individuals with
marginal thiamin intake at risk for developing symptomatic thiamin deficiency.
Recently, malaria patients in
Excessive
loss
Excessive loss of thiamin may precipitate thiamin
deficiency. By increasing urinary flow, diuretics may prevent reabsorption of thiamin by the kidneys and increase its
excretion in the urine, although this remains quite controversial. Individuals
with kidney failure requiring
hemodialysis lose thiamin at an
increased rate and are at risk for thiamin deficiency. Alcoholics who maintain
a high fluid intake and urine flow rate may also experience increased loss of
thiamin, exacerbating the effects of low thiamin intake.
Anti-thiamin
factors (ATF)
The presence of anti-thiamin factors (ATF) in
foods also contributes to the risk of thiamin deficiency. Certain plants
contain ATF, which react with thiamin to form an oxidized, inactive product.
Consuming large amounts of tea and coffee (including decaffeinated), as well as
chewing tea leaves and betel nuts, have been associated with thiamin depletion
in humans due to the presence of ATF. Thiaminases are
enzymes that break down thiamin in food. Individuals who habitually eat certain
raw freshwater fish, raw shellfish, and ferns are at higher risk of thiamin
deficiency because these foods contain thiaminase
that normally is inactivated by heat in cooking. In
Sources
Food
sources
A varied diet should provide most
individuals with adequate thiamin to prevent deficiency. In the
|
Food |
Serving |
Thiamin (mg) |
|
Lentils (cooked) |
1/2 cup |
0.17 |
|
Peas (cooked) |
1/2 cup |
0.21 |
|
Long grain brown rice (cooked) |
1 cup |
0.19 |
|
Long grain white rice, enriched
(cooked) |
1 cup |
0.26 |
|
Long grain white rice, unenriched (cooked) |
1 cup |
0.04 |
|
Whole wheat bread |
1 slice |
0.10 |
|
White bread, enriched |
1 slice |
0.11 |
|
Fortified breakfast cereal |
1 cup |
0.5-2.0 |
|
Wheat germ breakfast cereal |
1 cup |
4.47 |
|
Pork, lean (cooked) |
3 ounces* |
0.72 |
|
Brazil nuts |
|
0.18 |
|
Pecans |
|
0.19 |
|
Spinach (cooked) |
1/2 cup |
0.09 |
|
Orange |
1 fruit |
0.10 |
|
Cantaloupe |
1/2 fruit |
0.11 |
|
Milk |
1 cup |
0.10 |
|
Egg (cooked) |
1 large |
0.03 |
http://www.youtube.com/watch?v=Q5BCmsixuqM
Riboflavin (Vitamin B2)
Riboflavin is a water-soluble
B vitamin, also known as vitamin B2. In the body, riboflavin is primarily found
as an integral component of the coenzymes, flavin
adenine dinucleotide (FAD) and flavin
mononucleotide (FMN). Coenzymes derived from riboflavin are termed flavocoenzymes, and enzymes that use a flavocoenzyme
are called flavoproteins.
Function
Oxidation-reduction
(redox) reactions
Living organisms derive most of their energy from
oxidation-reduction (redox) reactions, which are
processes that involve the transfer of electrons. Flavocoenzymes
participate in redox reactions in numerous metabolic
pathways. Flavocoenzymes are critical for the metabolism of
carbohydrates, fats, and proteins. FAD is part of the electron transport (respiratory)
chain, which is central to energy production. In conjunction with cytochrome
P-450, flavocoenzymes also participate in the
metabolism of drugs and toxins.
Antioxidant
functions
Glutathione reductase is a FAD-dependent enzyme that participates in the redox
cycle of glutathione. The glutathione redox cycle
plays a major role in protecting organisms from reactive oxygen species, such as hydroperoxides. Glutathione reductase
requires FAD to regenerate two molecules of reduced glutathione from oxidized
glutathione. Riboflavin deficiency has been associated with increased oxidative
stress. Measurement of glutathione reductase activity
in red blood cells is commonly used to assess riboflavin nutritional status.
Glutathione peroxidase,
a selenium-containing enzyme, requires two molecules of reduced glutathione to
break down hydroperoxides (see diagram).
Xanthine oxidase, another
FAD-dependent enzyme,
catalyzes the oxidation of hypoxanthine and xanthine
to uric acid. Uric acid is one of the most effective water-soluble antioxidants in the blood. Riboflavin
deficiency can result in decreased xanthine oxidase activity, reducing blood uric acid levels.
Nutrient Interactions
B-complex vitamins
Because flavoproteins
are involved in the metabolism of several other vitamins (vitamin B6, niacin,
and folic acid), severe riboflavin deficiency may affect many enzyme systems. Conversion of most naturally available vitamin B6 to its
coenzyme form, pyridoxal 5'-phosphate (PLP), requires
the FMN-dependent enzyme, pyridoxine 5'-phosphate oxidase
(PPO). At least two studies in the elderly have documented significant
interactions between indicators of vitamin B6 and riboflavin nutritional
status. The synthesis
of the niacin-containing coenzymes, NAD and NADP, from the amino acid, tryptophan, requires the
FAD-dependent enzyme, kynurenine mono-oxygenase. Severe riboflavin deficiency can decrease the
conversion of tryptophan to NAD and NADP, increasing the risk of niacin
deficiency. Methylene tetrahydrofolate
reductase (MTHFR) is a FAD-dependent enzyme that
plays an important role in maintaining the specific folate
coenzyme required to form
methionine from homocysteine
(see diagram). Along with other B
vitamins, increased riboflavin intake has been associated with decreased plasma
homocysteine levels. Recently, increased plasma
riboflavin levels were associated with decreased plasma homocysteine
levels, mainly in individuals
homozygous for the C677T
polymorphism of the MTHFR gene and in individuals with low folate intake. Such results illustrate that chronic disease
risk may be influenced by complex interactions between genetic and dietary
factors.
Iron
Riboflavin deficiency alters iron metabolism.
Although the mechanism is not clear, research in animals suggests that
riboflavin deficiency may impair iron absorption, increase intestinal loss of
iron, and/or impair iron utilization for the synthesis of hemoglobin. In
humans, improving riboflavin nutritional status has been found to increase
circulating hemoglobin levels. Correction of riboflavin deficiency in
individuals who are both riboflavin and iron deficient improves the response of
iron-deficiency anemia to iron therapy.
Deficiency
Ariboflavinosis is the medical name for clinical riboflavin
deficiency. Riboflavin deficiency is rarely found in isolation; it occurs
frequently in combination with deficiencies of other water-soluble vitamins.
Symptoms of riboflavin deficiency include sore throat, redness and swelling of
the lining of the mouth and throat, cracks or sores on the outsides of the lips
(cheliosis) and at the corners of the mouth (angular stomatitis), inflammation and redness of the tongue (magenta
tongue), and a moist, scaly skin inflammation (seborrheic
dermatitis). Other symptoms may involve the formation of blood vessels in the
clear covering of the eye (vascularization of the
cornea) and decreased red blood cell count in which the existing red blood
cells contain normal levels of hemoglobin and are of normal size (normochromic normocytic anemia).
Severe riboflavin deficiency may result in decreased conversion of vitamin B6
to its coenzyme
form (PLP) and decreased conversion of tryptophan to niacin (see Nutrient
Interactions).
Preeclampsia is defined as the presence of
elevated blood pressure, protein in the urine, and edema (significant swelling) during
pregnancy. About 5% of women with preeclampsia may progress to eclampsia, a significant cause of maternal death. Eclampsia is characterized by seizures, in addition to high
blood pressure and increased risk of hemorrhage (severe bleeding). A study in
154 pregnant women at increased risk of preeclampsia found that those who were
riboflavin deficient were 4.7 times more likely to develop preeclampsia than
those who had adequate riboflavin nutritional status. The cause of
preeclampsia-eclampsia is not known. Decreased
intracellular levels of flavocoenzymes could cause mitochondrial dysfunction,
increase oxidative stress, and interfere
with nitric oxide release and thus blood vessel dilation—all of these changes
have been associated with preeclampsia. However, a small randomized, placebo-controlled,
double-blind trial in 450 pregnant women at high risk for preeclampsia found
that supplementation with 15 mg of riboflavin daily did not prevent the
condition.
Risk
factors for riboflavin deficiency
Alcoholics are at increased risk for riboflavin
deficiency due to decreased intake, decreased absorption, and impaired
utilization of riboflavin. Additionally, anorexic individuals rarely consume
adequate riboflavin, and lactose intolerant individuals may not consume milk or
other dairy products which are good sources of riboflavin. The conversion of
riboflavin into FAD and FMN is impaired in hypothyroidism and adrenal insufficiency. Further, people who
are very active physically (athletes, laborers) may have a slightly increased
riboflavin requirement. However, riboflavin supplementation has not generally
been found to increase exercise tolerance or performance.
Disease
Prevention
Cataracts
Age-related cataracts are the leading cause of
visual disability in the
Disease
Treatment
Migraine
headaches
Some evidence indicates that impaired mitochondrial oxygen metabolism in the
brain may play a role in the pathology of
migraine headaches. Because riboflavin is the precursor of the two flavocoenzymes (FAD and FMN) required by the flavoproteins of the mitochondrial electron transport chain, supplemental
riboflavin has been investigated as a treatment for migraine. A randomized
placebo-controlled trial examined the effect of 400 mg of riboflavin/day for
three months on migraine prevention in 54 men and women with a history of
recurrent migraine headaches. Riboflavin was significantly better than placebo
in reducing attack frequency and the number of headache days, though the
beneficial effect was most pronounced during the third month of treatment. A
more recent study by the same investigators found that treatment with either a
medication called a beta-blocker or high-dose riboflavin resulted in clinical
improvement, but each therapy appeared to act on a distinct pathological mechanism:
beta-blockers on abnormal cortical information processing and riboflavin on
decreased brain mitochondrial energy reserve. A small study in 23 patients
reported a reduction in median migraine attack frequency after supplementation
with 400 mg of riboflavin daily for three months. Additionally, a 3-month
randomized, double-blind, placebo-controlled study that administered a
combination of riboflavin (400 mg/day), magnesium, and feverfew to migraine
sufferers reported no therapeutic benefit beyond that associated with taking a
placebo containing 25 mg/day of riboflavin). Compared to baseline measurements
in this trial, both the placebo and treatment groups experienced some benefits
with respect to the mean number of migraines, migraine days, or migraine index.
Although these findings are preliminary, data from most studies to date suggest
that riboflavin supplementation might be a useful adjunct to pharmacologic
therapy in migraine prevention.
Sources
Food
sources
Most plant and animal derived foods contain
at least small quantities of riboflavin. In the
|
Food |
Serving |
Riboflavin (mg) |
|
Fortified cereal |
1 cup |
0.59 to 2.27 |
|
Milk (nonfat) |
1 cup ( |
0.34 |
|
Cheddar cheese |
|
0.11 |
|
Egg (cooked) |
1 large |
0.27 |
|
Almonds |
|
0.23 |
|
Salmon (cooked) |
3 ounces* |
0.12 |
|
Halibut (broiled) |
|
0.08 |
|
Chicken, light meat (roasted) |
|
0.08 |
|
Chicken, dark meat (roasted) |
|
0.16 |
|
Beef (cooked) |
|
0.16 |
|
Broccoli (boiled) |
1/2 cup chopped |
0.10 |
|
Asparagus (boiled) |
6 spears |
0.13 |
|
Spinach (boiled) |
1/2 cup |
0.21 |
|
Bread, whole wheat |
1 slice |
0.06 |
|
Bread, white (enriched) |
1 slice |
0.08 |
http://www.youtube.com/watch?v=qpvNaGIJMzw
Supplements
The most common forms of riboflavin available in
supplements are riboflavin and riboflavin 5'-monophosphate. Riboflavin is most
commonly found in multivitamin and vitamin B-complex preparations (26).
Safety
Toxicity
No toxic or adverse effects of high
riboflavin intake in humans are known. Studies in cell culture indicate that
excess riboflavin may increase the risk of DNA strand breaks in the presence of
chromium (VI), a known carcinogen (27).
This may be of concern to workers exposed to chrome, but no data in humans are
available. High-dose riboflavin therapy has been found to intensify urine color
to a bright yellow (flavinuria), but this is a
harmless side effect. The Food and Nutrition Board did not establish a
tolerable upper level of intake (UL) when the RDA was revised in 1998 (1).
Drug
interactions
Several early reports indicated that women taking
high-dose oral contraceptives (OC) had diminished riboflavin nutritional
status. However, when investigators controlled for dietary riboflavin intake,
no differences between OC users and non-users were found (1). Phenothiazine derivatives like the anti-psychotic
medication chlorpromazine and tricyclic
antidepressants inhibit the incorporation of riboflavin into FAD and FMN, as do
the anti-malarial medication, quinacrine, and the
cancer chemotherapy agent, adriamycin
(4). Long-term use of the anti-convulsant, phenobarbitol may increase destruction of riboflavin, by
liver enzymes, increasing the risk of deficiency (3).
Niacin (Vitamin B5)
|
|
|
|
Nicotinamide |
Nicotinic Acid |
Niacin exists in two forms,
nicotinic acid and nicotinamide. Both forms are
readily absorbed from the stomach and the small intestine. Niacin is stored in
small amounts in the liver and transported to tissues, where it is converted to
coenzyme forms. Any excess is excreted in urine. Niacin is one of the most
stable of the B vitamins. It is resistant to heat and light, and to both acid
and alkali environments. The human body is capable of converting the amino acid
tryptophan to niacin when needed. However, when both tryptophan and niacin are
deficient, tryptophan is used for protein synthesis.
Structure of NAD+
There are two coenzyme forms of niacin: nicotinamide adenine dinucleotide
(NAD+) and nicotinamide adenine dinucleotide
phophate (NADP+). They both help break down and
utilize proteins, fats, and carbohydrates for energy. Niacin is essential for
growth and is involved in hormone synthesis.
Pellagra results from a combined deficiency of
niacin and tryptophan. Long-term deficiency leads to central nervous system
dysfunction manifested as confusion, apathy, disorientation, and eventually
coma and death. Pellagra is rarely seen in industrialized countries, where it
may be observed in people with rare disorder of tryptophan metabolism (Hartnup's disease), alcoholics, and those with diseases
that affect food intake.
http://www.youtube.com/watch?v=UrDeVyiXzyg&feature=related
The liver
can synthesize niacin from the essential aminoacid tryptophan, but the synthesis
is extremely slow; 60 mg of tryptophan are required to make one milligram of
niacin. Dietary niacin deficiency tends to occur only in areas where people eat
corn, the only grain low in niacin, as a staple food, and that don't use lime
during maize (corn) meal/flour production. Alkali lime releases the tryptophan
from the corn so that it can be absorbed in the gut, and converted to niacin.
Niacin plays an important
role in the production of several sex and stress-related hormones, particularly
those made by the adrenal gland. Niacin, when taken in large doses, increases
the level of high density lipoprotein (HDL) or "good" cholesterol in
blood, and is sometimes prescribed for patients with low HDL, and at high risk
of heart attack. Niacin (but not niacinamide) is also
used in the treatment of hyperlipidemia because it
reduces very low density lipoprotein (VLDL), a precursor of low density
lipoprotein (LDL) or "bad" cholesterol, secretion from the liver, and
inhibits cholesterol synthesis.
The main problem with the
clinical use of niacin for dyslipidemia is the
occurrence of skin flushing, even with moderate doses.
Recommended intake is expressed as milligrams of
niacin equivalents (NE) to account for niacin synthesized from tryptophan. High
doses taken orally as nicotinic acid at 1.5 to
The nicotinamide form
of niacin in multivitamin and B-complex tablets do not work for this purpose.
Supplementation should be under a physician's guidance.
Food
sources
Good sources of niacin include yeast, meat,
poultry, red fishes (e.g., tuna, salmon), cereals (especially fortified cereals),
legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide
some niacin. In plants, especially mature cereal grains like corn and wheat,
niacin may be bound to sugar molecules in the form of glycosides, which
significantly decrease niacin bioavailability.
In the
|
Food |
Serving |
Niacin (mg) |
|
Chicken (light
meat) |
3 ounces*
(cooked without skin) |
7.3 |
|
Turkey (light
meat) |
|
5.8 |
|
Beef (lean) |
|
3.1 |
|
Salmon
(chinook) |
|
8.5 |
|
Tuna (light, packed in water) |
|
11.3 |
|
Bread (whole
wheat) |
1 slice |
1.3 |
|
Cereal
(unfortified) |
1 cup |
5-7 |
|
Cereal
(fortified) |
1 cup |
20-27 |
|
Pasta
(enriched) |
1 cup (cooked) |
2.3 |
|
Peanuts |
|
3.8 |
|
Lentils |
1 cup (cooked) |
2.1 |
|
Lima beans |
1 cup (cooked) |
1.8 |
|
Coffee (brewed) |
1 cup |
0.5 |
Common side effects of nicotinic acid include
flushing, itching, and gastrointestinal disturbances such as nausea and
vomiting. Hepatotoxicity (liver cell damage),
including elevated liver enzymes and jaundice, has been observed at intakes as
low as 750 mg of nicotinic acid/day for less than three months (34, 35).
Hepatitis has been observed with timed-release nicotinic acid at dosages as
little as 500 mg/day for two months, although almost all reports of severe
hepatitis have been associated with the timed-release form of nicotinic acid at
doses of 3 to
Nicotinamide
Nicotinamide is
generally better tolerated than nicotinic acid. It does not generally cause
flushing. However, nausea, vomiting, and signs of liver toxicity (elevated
liver enzymes, jaundice) have been observed at doses of 3 grams/day (33). Nicotinamide has resulted in decreased insulin sensitivity
at doses of 2 grams/day in adults at high risk for insulin-dependent diabetes
http://www.youtube.com/watch?v=MLFZ8CsrJqU&feature=related
Pantothenic Acid (Vitamin B3)
Pantothenic Acid
Pantothenic acid, also called vitamin B3, is a water-soluble
vitamin required to sustain life. Pantothenic acid is
needed to form coenzyme-A (CoA), and is critical in
the metabolism and synthesis of carbohydrates, proteins, and fats. Its name is
derived from the Greek pantothen meaning "from
everywhere" and small quantities of pantothenic
acid are found in nearly every food, with high amounts in whole grain cereals,
legumes, eggs, meat, and royal jelly.
Pantothenic acid is stable in moist heat. It is destroyed by
vinegar (acid), baking soda (alkali), and dry heat. Significant losses occur
during the processing and refining of foods. Pantothenic
acid is released from coenzyme A in food in the small intestine. After
absorption, it is transported to tissues, where coenzyme A is resynthesized. Coenzyme A is essential for the formation of
energy as adenosine triphosphate (ATP) from
carbohydrate, protein, alcohol, and fat.
Coenzyme A
is also important in the synthesis of fatty acids, cholesterol, steroids, and
the neurotransmitter acetylcholine, which is essential for transmission of
nerve impulses to muscles.
Dietary deficiency occurs in
conjunction with other B-vitamin deficiencies. Pantothenic
acid is used in the synthesis of coenzyme A (abbreviated as CoA).
Coenzyme A may act as an acyl group carrier to form
acetyl-CoA and other related compounds; this is a way
to transport carbon atoms within the cell. The transfer of carbon atoms by
coenzyme A is important in cellular respiration, as well as the biosynthesis of
many important compounds such as fatty acids, cholesterol, and acetylcholine.
Dietary deficiency occurs in conjunction with other B-vitamin deficiencies. In
studies, experimentally induced deficiency in humans has resulted in headache,
fatigue, impaired muscle coordination, abdominal cramps, and vomiting.
In
studies, experimentally induced deficiency in humans has resulted in headache,
fatigue, impaired muscle coordination, abdominal cramps, and vomiting.
Biotin (Vitamin B8)
Biotin is a water soluble vitamin and a member of
Vitamin B complex. Also known as Vitamin
H, Bios II, Co-enzyme R. Its natural form is D-biotin. It was isolated from liver in 1941 by Dr.
Paul Gyorgy.
http://www.youtube.com/watch?v=o9lJoKoF4DE
FUNCTION
• co-enzyme in wide variety of body
metabolic reactions
• needed for production of energy from carbohydrates, fats and
proteins
• needed for interconversions
• essential for maintenance of healthy skin, hair, sweat
glands, nerves, bone marrow and glands producing sex hormones
FOOD SOURCE
• Brewer's
Yeast
• cheese
• eggs
• maize
• fish, fatty, white
• meats, especially pig liver and kidney
• milk
• oats
• wheat bran
• wheat germ
• wholemeal grains
• unpolished brown rice
• vegetables
• yoghurt
EFFECTIVE WITH INCREASED INTAKES NEEDED
• by newborn children being fed on dried milk
• during stress situations
• when on antibiotic therapy
USED FOR
• seborrheic
dermatitis
• Leiner's Disease
• alopecia (hair falling out in
handfuls)
• scalp disease
• skin complaints
• preventing cot death (given to babies)
DESTROYED BY
• leaching
into cooking
• drying
of milk for baby foods
SYMPTOMS OF DEFICIENCY
In babies:
• dry
scaling of the scalp and face
• persistent diarrhea
In adults:
• depression
• diminished
reflexes
• fatigue
• hair loss
• increase in blood cholesterol levels
• loss of appetite
• muscular pains
• nausea
• pale, smooth tongue
• sleepiness
DEFICIENCY LEADS TO
• specific anemia
• deficiency may be induced by excessive intake of raw egg
whites, which contain the protein Avidin which
immobilizes Biotin
SYMPTOMS OF TOXICITY
• toxicity unknown
High quality Vitamin B (Biotin) can be purchased
from Global Herbal Supplies
Biotin is the most stable of B vitamins. It is
commonly found in two forms: the free vitamin and the protein-bound coenzyme
form called biocytin. Biotin is absorbed in the small
intestine, and it requires digestion by enzyme biotinidase,
which is present in the small intestine. Biotin is synthesized by bacteria in
the large intestine, but its absorption is questionable. Biotincontaining
coenzymes participate in key reactions that produce energy from carbohydrate
and synthesize fatty acids and protein.
Avidin is a protein in raw egg white, which can bind to the
biotin in the stomach and decrease its absorption. Therefore, consumption of
raw whites is of concern due to the risk of becoming biotin deficient. Cooking
the egg white, however, destroys avidin. Deficiency
may develop in infants born with a genetic defect that results in reduced
levels of biotinidase. In the past, biotin deficiency
was observed in infants fed biotin-deficient formula, so it is now added to
infant formulas and other baby foods.
Vitamin B6
http://www.youtube.com/watch?v=zwUc5gHoF_U&feature=related
Pyridoxal, pyridoxamine and
pyridoxine are collectively known as vitamin B6. All three compounds are efficiently
converted to the biologically active form of vitamin B6, pyridoxal
phosphate. This conversion is catalyzed by the ATP requiring enzyme, pyridoxal kinase.
http://www.youtube.com/watch?v=Q9yBs6wvMFc
Vitamin B6 is present in three forms: pyridoxal, pyridoxine, and pyridoxamine.
All forms can be converted to the active vitamin-B6 coenzyme in the body. Pyridoxal phosphate (PLP) is the
predominant biologically active form. Vitamin B6 is not stable in heat or in
alkaline conditions, so cooking and food processing reduce its content in food.
Both coenzyme and free forms are absorbed in the small intestine and
transported to the liver, where they are phosphorylated
and released into circulation, bound to albumin for transport to tissues.
Vitamin B6 is stored in the muscle and only excreted in urine when intake is
excessive.
PLP participates in amino acid synthesis and the interconversion of some amino acids. It catalyzes a step in
the synthesis of hemoglobin, which is needed to transport oxygen in blood. PLP
helps maintain blood glucose levels by facilitating the release of glucose from
liver and muscle glycogen. It also plays a role in the synthesis of many
neurotransmitters important for brain function. This has led some physicians to
prescribe megadoses of B6 to patients with
psychological problems such as depression and mood swings, and to some women
for premenstrual syndrome (PMS). It is unclear, however, whether this therapy
is effective. PLP participates in the conversion of the amino acid tryptophan
to niacin and helps avoid niacin deficiency. Pyridoxine affects immune
function, as it is essential for the formation of a type of white blood cell.
Populations at risk of vitamin-B6 deficiency
include alcoholics and elderly persons who consume an inadequate diet.
Individuals taking medication to treat Parkinson's disease or tuberculosis may
take extra vitamin B6 with physician supervision. Carpal tunnel syndrome, a
nerve disorder of the wrist, has also been treated with large daily doses of
B6. However, data on its effectiveness are conflicting.
Folic
Acid, Folate, Folacin
(Vitamin B9)
Folic Acid
Folacin or folate, as it is usually
called, is the form of vitamin B9 naturally present in foods, whereas folic
acid is the synthetic form added to fortified foods and supplements. Both forms
are absorbed in the small intestine and stored in the liver. The folic acid
form, however, is more efficiently absorbed and available to the body. When
consumed in excess of needs, both forms are excreted in urine and easily
destroyed by heat, oxidation, and light.
Folic acid is a water soluble vitamin and is a
member of the Vitamin B complex. Also known as Folacin,
pteroyl-L-glutamic acid (PGA), vitamin Bc or vitamin M. Folic acid and its derivatives (mostly the
tri and heptaglutamyl peptides) are widespread in
nature. It is a specific growth factor for certain micro-organisms. Found in yeast and liver in 1935.
All forms of this vitamin are readily converted
to the coenzyme form called tetrahydrofolate (THFA),
which plays a key role in transferring single-carbon methyl units during the
synthesis of DNA and RNA, and in interconversions of
amino acids. Folate also plays an important role in
the synthesis of neurotransmitters. Meeting folate
needs can improve mood and mental functions.
Function
involved in the formation of new cells
involved in the metabolism of ribonucleic acids (RNA) and
deoxyribonucleic acids (DNA), essential for protein synthesis, formation of
blood and transmission of genetic code
essential during pregnancy to reduce the risk of neural tube
defects (birth defects affecting the brain and/or spinal cord)essential for the
normal growth and development of the fetus
involved in the biosynthesis of purines,
serines and glycine
involved in some functions associated with Vitamin B12
necessary for building resistance to diseases in the thymus
gland of new born babies and infants
may reduce the risk of cervical dysplasia
necessary for red blood cell production
Food Source
bananas
Brewers's Yeast
citrus fruits, peeled
eggs
fatty fish
fresh nuts
green leafy vegetables
meats, especially pig liver and kidney
milk
oats
pulses, such as lentils
roasted nuts
soy products, such as tofu
unpolished brown rice
wheat germ
wheat bran
wheat grains
Effective With
B-Complex
B12
Biotin
Pantothenic Acid
Vitamin C
Increased Intakes Needed
by alcohol drinkers
by the elderly
during pregnancy and breastfeeding
if taking contraceptive pill
if taking the drugs, Aspirin, Cholestyramine, Isethionate, Isoniazid, Methotrexate, Pentamidime, Phenytoin (may be neutralized), Primidone,
Pyrimethamine, Triamterene,Trimethoprim
Used For
malabsorption in geriatric patients
megaloblastic anemia
mental deterioration
psychosis
schizophrenia
Destroyed By
leached into cooking water
processing and cooking of vegetables, fruits and dairy products
unstable to oxygen at high temperatures but protected by
Vitamin C
Symptoms of Deficiency
breathlessness
fatigue
irritability
sleeplessness
weakness
Deficiency Leads To
Various conditions relating to childbirth:
abortion
birth defects, such as neural tube defect which causes spina bifida
hemorrhage following birth
premature birth
premature separation of the placenta from the uterus
toxemia
As well as:
megaloblastic anemia (red blood cells are large and uneven with a
shortened life span)
mild mental symptoms, such as forgetfulness and confusion
Symptoms
of Toxicity
Folic Acid has a low toxicity but occasionally
the following symptoms occur:
abdominal distension
flatulence (gas/wind)
irritability
loss of appetite
nausea
over-activity
sleep disturbance
symptoms of fever
temperature rise
Long term high doses may cause Vitamin B12 losses
from the body
http://www.youtube.com/watch?v=4-pMZRxyasU&feature=related
http://www.youtube.com/watch?v=TLDodF9kkRo&feature=related
http://www.youtube.com/watch?v=_QFl7BnWhpQ&feature=related
Folate deficiency is one of the most common vitamin
deficiencies. Early symptoms are nonspecific and include tiredness,
irritability, and loss of appetite. Severe folate
deficiency leads to macrocytic anemia, a condition in
which cells in the bone marrow cannot divide normally and red blood cells
remain in a large immature form called macrocytes.
Large immature cells also appear along the length of the gastrointestinal
tract, resulting in abdominal pain and diarrhea.
Pregnancy is a time of rapid
cell multiplication and DNA synthesis, which increases the need for folate. Folate deficiency may
lead to neural tube defects such as spina bifida
(failure of the spine to close properly during the first month of pregnancy)
and anencephaly (closure of the neural tube during fetal development, resulting
in part of the cranium not being formed). Seventy percent of these defects
could be avoided by adequate folate status before
conception, and it is recommended that all women of childbearing age consume at
least 400 micrograms (μg) of folic acid
each day from fortified foods and supplements. Other groups at risk of
deficiency include elderly persons and persons suffering from alcohol abuse or
taking certain prescription drugs.
Vitamin B12
Vitamin B12 is found in its free-vitamin form,
called cyanocobalamin, and in two active coenzyme
forms. Absorption of vitamin B12 requires the presence of intrinsic factor, a protein
synthesized by acid-producing cells of the stomach. The vitamin is absorbed in
the terminal portion of the small intestine called the ileum. Most of body's
supply of vitamin B12 is stored in the liver.
Vitamin B12
Vitamin B12 is defficiently conserved in the body, since most of it is secreted
into bile and reabsorbed. This explains the slow development (about two years)
of deficiency in people with reduced intake or absorption. Vitamin B12 is
stable when heated and slowly loses its activity when exposed to light, oxygen,
and acid or alkaline environments.
Vitamin B12 coenzymes help recycle folate coenzymes involved in the synthesis of DNA and RNA, and
in the normal formation of red blood cells. Vitamin B12 prevents degeneration
of the myelin sheaths that cover nerves and help maintain normal electrical
conductivity through the nerves.
|
|
|
Active center of tetrahydrofolate
(THF). Note that the N5 position is the site of attachment of methyl groups,
the N10 the site for attachment of formyl and formimino groups and that both N5 and N10 bridge the methylene and methenyl groups |
Vitamin-B12 deficiency results in pernicious
anemia, which is caused by a genetic problem in the production of intrinsic
factor. When this occurs, folate function is
impaired, leading to macrocytic anemia due to interference
in normal DNA synthesis. Unlike folate deficiency,
the anemia caused by vitamin-B12 deficiency is accompanied by symptoms of nerve
degeneration, which if left untreated can result in paralysis and death.
http://www.youtube.com/watch?v=IQ0Aet8FVVU&feature=related
http://www.youtube.com/watch?v=DQ7IHIgw1ic&feature=related
Since vitamin B12 is well conserved in the body,
it is difficult to become deficient from dietary factors alone, unless a person
is a strict vegan and consumes a
diet devoid of eggs and dairy for several years. Deficiency
is usually observed when B12 absorption is hampered by disease or surgery to
the stomach or ileum, damage to gastric mucosa by alcoholism, or prolonged use
of anti-ulcer medications that affect secretion of intrinsic factor. Agerelated decrease in stomach-acid production also reduces
absorption of B12 in elderly persons. These groups are advised to consume
fortified foods or take a supplemental form of vitamin B12.