INVESTIGATION OF WATER SOLUBLE (COENZYME) VITAMINS FUNCTIONAL ROLE IN METABOLISM AND CELL FUNCTIONS REALIZATION

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.

 

 

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

 

 

 

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.

 

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.

Vitamin E

 

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 K2 (menaquinone) produced by intestinal bacteria and K3 is synthetic menadione. When administered, vitamin K3 is alkylated to one of the vitamin K2 forms of menaquinone.

 

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 Thailand were found to be severely thiamin deficient more frequently than non-infected individuals. Malarial infection leads to a large increase in the metabolic demand for glucose. Because thiamin is required for enzymes involved in glucose metabolism, the stresses induced by malarial infection could exacerbate thiamin deficiency in predisposed individuals. HIV-infected individuals, whether or not they had developed AIDS, were also found to be at increased risk for thiamin deficiency. The lack of association between thiamin intake and evidence of deficiency in these HIV-infected individuals suggests that they had an increased requirement for thiamin. Further, chronic alcohol abuse impairs intestinal absorption and utilization of thiamin; thus, alcoholics have increased requirements for thiamin.

 

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 Nigeria, an acute neurologic syndrome (seasonal ataxia) has been associated with thiamin deficiency precipitated by a thiaminase in African silkworms, a traditional high-protein food for some Nigerians.

 

Sources

 Food sources

 

A varied diet should provide most individuals with adequate thiamin to prevent deficiency. In the U.S. the average dietary thiamin intake for young adult men is about 2 mg/day and 1.2 mg/day for young adult women. A survey of people over the age of 60 found an average dietary thiamin intake of 1.4 mg/day for men and 1.1 mg/day for women. However, institutionalization and poverty both increase the likelihood of inadequate thiamin intake in the elderly.Whole grain cereals, legumes (e.g., beans and lentils), nuts, lean pork, and yeast are rich sources of thiamin. Because most of the thiamin is lost during the production of white flour and polished (milled) rice, white rice and foods made from white flour (e.g., bread and pasta) are fortified with thiamin in many Western countries. A number of thiamin-rich foods are listed in the table below along with their thiamin content in milligrams (mg). For more information on the nutrient content of foods, search the  USDA food composition database.

 

 

 

 

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 U.S. and other developed countries. Research has focused on the role of nutritional  antioxidants because of evidence that light-induced oxidative damage of  lens proteins may lead to the development of age-related cataracts. A  case-control study found significantly decreased risk of age-related cataract (33% to 51%) in men and women in the highest  quintile of dietary riboflavin intake (median of 1.6 to 2.2 mg/day) compared to those in the lowest quintile (median of 0.08 mg/day in both men and women) (17). Another case-control study reported that individuals in the highest quintile of riboflavin nutritional status, as measured by red blood cell glutathione reductase activity, had approximately one half the occurrence of age-related cataract as those in the lowest quintile of riboflavin status, though the results were not statistically significant (18). A cross-sectional study of 2,900 Australian men and women, 49 years of age and older, found that those in the highest quintile of riboflavin intake were 50% less likely to have cataracts than those in the lowest quintile. A  prospective study of more than 50,000 women did not observe a difference between rates of cataract extraction between women in the highest quintile of riboflavin intake (median of 1.5 mg/day) and women in the lowest quintile (median of 1.2 mg/day). However, the range between the highest and lowest quintiles was small, and median intake levels for both quintiles were above the current RDA for riboflavin. A recent study in 408 women found that higher dietary intakes of riboflavin were inversely associated with five-year change in lens opacification. Although these observational studies provide support for the role of riboflavin in the prevention of cataracts, placebo-controlled intervention trials are needed to confirm the relationship.

 

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 U.S., wheat flour and bread have been enriched with riboflavin (as well as thiamin, niacin, and iron) since 1943. Data from large dietary surveys indicate that the average intake of riboflavin for men is about 2 mg/day and for women is about 1.5 mg/day; both intakes are well above the RDA. Intake levels were similar for a population of elderly men and women (1). Riboflavin is easily destroyed by exposure to light. For instance, up to 50% of the riboflavin in milk contained in a clear glass bottle can be destroyed after two hours of exposure to bright sunlight. Some foods with substantial amounts of riboflavin are listed in the table below along with their riboflavin content in milligrams (mg). For more information on the nutrient content of foods, search the  USDA food composition database.

 

 

 

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)

Niacin

 

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 2 grams per day can decrease cholesterol and triglyceride levels, and along with diet and exercise can slow or reverse the progression of heart disease. 

 

 

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 United States, the average dietary intake of niacin is about 30 mg/day for young adult men and 20 mg/day for young adult women. In a sample of adults over the age of 60, men and women were found to have an average dietary intake of 21 mg/day and 17 mg/day, respectively. Some foods with substantial amounts of niacin are listed in the table below along with their niacin content in milligrams (mg). Food composition tables generally list niacin content without including niacin equivalents (NE) from tryptophan, or any adjustment for niacin bioavailability. For more information on the nutrient content of specific foods, search the  USDA food composition database; data included in the table below are from this database.

 

 

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 9 grams per day used to treat high cholesterol for months or years (8). Immediate-release (crystalline) nicotinic acid appears to be less toxic to the liver than extended release forms. Immediate-release nicotinic acid is often used at higher doses than timed-release forms, and severe liver toxicity has occurred in individuals who substituted timed-release niacin for immediate-release niacin at equivalent doses (33). Skin rashes and dry skin have been noted with nicotinic acid supplementation. Transient episodes of low blood pressure (hypotension) and headache have also been reported. Large doses of nicotinic acid have been observed to impair glucose tolerance, likely due to decreased insulin sensitivity. Impaired glucose-tolerance in susceptible (pre-diabetic) individuals could result in elevated blood glucose levels and clinical diabetes. Elevated blood levels of uric acid, occasionally resulting in attacks of gout in susceptible individuals, have also been observed with high-dose nicotinic acid therapy (34). Nicotinic acid at doses of 1.5 to 5 grams/day has resulted in a few case reports of blurred vision and other eye problems, which have generally been reversible upon discontinuation. People with abnormal liver function or a history of liver disease, diabetes, active peptic ulcer disease, gout, cardiac arrhythmias, inflammatory bowel disease, migraine headaches, and alcoholism may be more susceptible to the adverse effects of excess nicotinic acid intake than the general population (8).

 

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.

 

 

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.