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VITAMINS

The vitamins comprise a diverse group of organic compounds required by animals


in small amounts to ensure normal growth and maintenance of health. It is often stated
that vitamins cannot be produced in the body and must, therefore, be supplied in the diet.
Vitamins are essential micronutrients because the animal cannot synthesize such
compounds in amounts adequate for its daily needs. Plants have the ability to synthesize
most of the vitamins and serve as primary sources of these dietary essentials. An
insufficiently of a vitamin in the animal’s diet, or its poor absorption from the digestive
tract, frequently induces a disease with characteristics symptoms. Vitamins may be
classified according to their solubility into two groups: the fat soluble water (A, D, E and
K) and the water soluble vitamin (B group and C). This simple classification reflects to
some extent the function of the vitamins, as the solubility affects their natural distribution
in tissues and their physiological role therein. The ever-increasing use of vitamins in
pharmaceutical preparations makes their determination a matter of foremost importance.
Biological, microbiological and physicochemical methods are used for the determination
of vitamins.

Food Guide Pyramid

Biological role of the B-group vitamins

Several of the B-groups vitamins serve as precursors for enzyme cofactors that
function in the catabolism of foodstuffs to produce energy for the organisms. The dietary
macronutrients such as carbohydrates, lipids and protein are degraded in a three-stage
process to liberate energy. The first step is digestion, during which the macronutrients are
hydrolysed into their component substituents: carbohydrates to glucose and other
monosaccharides, lipids to glycerol and fatty acids, and proteins to amino acids. In the
second stage the monosaccharides, glycerol and fatty acids, and some of the amino acids
are further degraded intracellularly to the key metabolite acetyl coenzyme A (acetyl-
CoA) by processes that generate small amounts of energy-rich adenosine tri-phosphate
(ATP). In the third stage acetyl-CoA is oxidized in the tricarboxylic acid cycle, during
which ATP is produced in large amounts by oxidative phosphortlation. Many enzymatic
reactions involved in the catabolism of foodstuffs depend upon the presence of specific
vitamins, and hence deficiencies of these vitamins lead to metabolic disorders, sometimes
with fatal consequences.

WATER SOLUBLE VITAMIN


Vitamins are essential nutrients found in foods. The requirements are small but
they perform specific and vital functions essential for maintaining health. The two types
of vitamins are classified by the materials in which they will dissolve. Fat-soluble
vitamins -- vitamins A, D, E and K -- dissolve in fat before they are absorbed in the blood
stream to carry out their functions. Excesses of these vitamins are stored in the liver.
Because they are stored, they are not needed every day in the diet. By contrast, water-
soluble vitamins dissolve in water and are not stored; they are eliminated in urine. We
need a continuous supply of them in our diets. The water-soluble vitamins are the B-
complex group and vitamin C.
Water-soluble vitamins are easily destroyed or washed out during food storage or
preparation. Proper storage and preparation of food can minimize vitamin loss. To reduce
vitamin loss, refrigerate fresh produce, keep milk and grains away from strong light, and
use the cooking water from vegetables to prepare soups.

Members of Vitamin B-group:


- thiamin ( vitamin B1)
- riboflavin ( vitamin B2)
- niacin ( vitamin B3)
- pantothenic acid (vitamin B5)
- vitamin B6
- cobolamin (vitamin B12)
- biotin
- folate

Thiamin ( Vitamin B1)

History

Eijkman between 1890 and 1897, discovered feeding chickens on polished rice
induced a polyneuritis resembling beri-beri which could be prevented by addition of rice
polishing (bran) to the avian diet. A few years later Grijns extracted a water soluble heat
labile ‘polyneuritis protective factor’ from rice polishings and correctly concluded that
beri-beri is the result of a dietary lack of an essential nutrient. By 1926, Jansen and
Donath had succeeded in isolating the factor in crystalline form from rice bran extracts.
Ten years later R.R. Williams elucidated the structure of thiamin and accomplished its
synthesis.

Structure

The thiamin molecule comprises substituted pyrimidine and thiazole moieties linked
by a methylene bridge and systematically named as 3-(2’-methyl-4’-amino-5’-
pyrimidylene)-4-methyl-5-(â-hydroxyethyl)-thiazole. In living tissues thiamin, in the
form of the diphosphate ester, thiamin pyrophosphate (TPP) functions as the prosthetic
group of several enzymes in which it as tight but non-covalent binding affinity for the
apoenzyme (enzyme protein). Small amounts of the monophosphate (TMP) ad
triphosphate (TTP) esters of thiamin occur in animal tissues. For food supplementation
purposes thiamin is chiefly used in the form of its chloride hydrochloride(thiamin
hydrochloride) double salt.

Thiamin

Thiamin pyrophosphate

Physical and chemical properties


Thiamin hydrochloride is a colourless crystalline substance with a yeast-like odour
and a salty nut-like taste. It is readily soluble in water (100 g/100 mL), less soluble in
glycerol (5 g/100 mL), sparingly soluble in 95% ethanol (1 g/100 mL) and absolute
ethanol (0.3 g/100 mL) and insoluble in fat solvents such as diethyl ether, chloroform,
benzene and hexane. Since the thiamin molecule contains quaternary nitrogen, it is a
strong base and will be completely ionized over the entire range of pH normally
encountered in foods. The hydrochloride salt is hygroscopic and usually exists as the
hemihydrate containing the equivalent of about 4% water. The melting point is about 270
ºC with decomposition. Another commercial form of the vitamin, thiamin mononitrate, is
practically nonhygroscopic and is especially recommended for the enrichment of flour
mixes.

Biochemical and physiological functions

Thiamin, in the form of TPP, participates in carbohydrate metabolism by


functioning as a cofactor in a number of reactions involving the tricarboxylic acid cycle
and the pentose phosphate pathway. Pyvurate undergoes a TPP dependent oxidative
decarboxylation to form the important energy rich thioester acetyl-CoA, and á-
ketoglutarate undergoes similar decarboxylation to form the anologuous succinyl-CoA.
TPP participates in transketolase reactions in the pentose phosphate pathway, the
principal functions of which is to provide a source of ribose for nucleotide and nucleic
acid synthesis, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) for
the synthesis of fatty acid. Furthermore, TPP is required for the oxidative decarboxylation
of the branched chain keto acids formed after deamination of the amino acids leucine,
isoleucine and valine. There is also evidence that thiamin is involved directly in nerve
transmission. Thiamine helps the body cells convert carbohydrates into energy. It is also
essential for the functioning of the heart, muscles, and nervous system.
Deficiency signs

The classic pathological condition resulting from a gross deficiency of thiamin in


humans I beri-beri which is prevalent in Far Eastern populations where unfortified
polished rice is the staple diet. Beriberi is a vitamin deficiency disease, caused by
inadequate bodily stores of thiamine (Vitamin B1). It can damage the heart and nervous
system. There are two major manifestations of thiamine deficiency: cardiovascular
disease (wet beriberi) and nervous system disease ("dry beriberi" and Wernicke-
Korsakoff syndrome). Wernicke-Korsakoff syndrome is a brain disorder involving loss of
specific brain functions caused by a thiamine. Dry beriberi is somewhat of a misnomer
because both types are most often caused by excessive alcohol consumption. Symptoms
of dry beriberi include pain, tingling, or loss of sensation in hands and feet (peripheral
neuropathy), muscle wasting with loss of function or paralysis of the lower extremities,
and potentially brain damage and death. Wet beriberi is characterized by swelling
(edema), increased heart rate (tachycardia), lung congestion, and enlarged heart related to
congestive heart failure. Beriberi has become very rare in the United States because most
foods are now vitamin-enriched, which means that a normal diet contains adequate
amounts of thiamine.
As a result, beriberi now occurs primarily in patients who abuse alcohol, because
drinking heavily can lead to malnutrition and poor absorption and storage of thiamine.
This is the cause of "wet brain" or Wernicke-Korsakoff syndrome, which is alcohol-
related brain damage affecting language and thinking. Beriberi can also occur in breast-
fed infants when the mother has an inadequate intake of thiamine. It can also affect
infants fed unusual formulas with inadequate thiamine supplements. Others at risk for
beriberi include patients undergoing dialysis, patients receiving high doses of diuretics,
and people in developing countries with limited diets who consume milled rice.
Neurologic symptoms are caused by degeneration of the nerve fibers and their insulation.
Heart failure is the most common cause of death in people with beriberi.the neurological
and cardiovascular disorders that arise from a deficiency of thiamin are attributable to the
dependence of the brain and heart upon thiamin for their energy supply. The involvement
of thiamin in carbohydrate metabolism explains why the thiamin requirement varies with
the proportion of carbohydrate in the diet and is increased under conditions that elevate
the metabolic rate. Both dietary lipid and protein exert a thiamin sparing action.

Dietary Sources and Requirements

All plant and animal tissues contain thiamin and it is therefore present in all
natural unprocessed foods. Rich sources of thiamin include yeast and yeast extract, wheat
bran, oatmeal, whole-grain cereals, pulses, nuts, lean pork, heart, kidney and liver. Beef,
lamb, chicken, eggs, vegetables, and fruits contain intermediate amounts, while milk
contains a relatively low amount. In cereal grains the thiamin is very unevenly
distributed, being relatively low in the starchy endosperm and high in the germ. The
milling of cereals removes most of the thiamin, so white flour, breakfast cereals and, in
certain countries, polished rice are enriched by addition of the vitamin. Other frequently
enriched foodstuffs are breads, macaroni, spaghetti and milk modifiers (chocolate, malt,
etc). The major form of thiamin in meat products is TPP, which exists as a protein
complex. The dietary requirement for thiamin is proportional to the caloric intake of the
diet and ranges from 1.0-1.5 mg/day for normal adults. If the carbohydrate content of the
diet is excessive then an in thiamin intake will be required.

Toxicity

Thiamin is of extremely low toxicity when administered orally to humans, excess


amounts being excreted in the urine. Large parenteral doses administed over a long
period of time have been reported to produce clinical manifestations and, in some cases,
even death.

Metabolism

Thiamin is adsorbed in the small intestine by an active transport process and is


rapidly deposited in the muscle, liver and other organs, where it is phosphorylated to the
biologically active form, TPP. Approximately 80% of the total thiamin deposited exists
as TPP, with 10% as TTP and the remainder as unesterified thiamin and TMP. Of the
three phosphate esters, TPP possesses full thiamin activity, TMP is completely inactive,
and any activity previously attributed to TTP results from partial conversion to TPP by in
vivo enzymatic hydrolysis of the terminal ester bond.

Bioavailability

Thiamin appears to be well utilized, whether supplied by diets containing wheat


or animal protein. Certain shellfish and freshwater fish contain thiaminases whose action
can cause symptoms of beri-beri in those Southeast Asian populations that consume
fermented raw fish. The tannis and other polyphenol compounds present in tea and coffee
have marked anti-thiamin activity.
Riboflavin (Vitamin B2)

History

The existence of a heat-stable growth factor in yeast extracts was first discovered
by Emmelt and Luros in 1920. in 1932, Warburg and Christian isolated from yeast a
yellow enzyme which contained a non-protein component subsequently shown to be a
phosphate ester of an alloxazine derivative. The structure of riboflavin was determined by
Kuhn’s group in 1933 and the vitamin was first synthesized by Karrer’s group in 1935.

Structure

The structures of the riboflavin compounds that occur in nature are depicted in
figure above. The parent riboflavin molecule comprises a substituted isoalloxazine
moiety with a ribitol side chain and s systematically named as 7,8-dimetyl-10-(1’-D-
ribityl)-isoalloxazine. The principal forms of riboflavin found in nature are riboflavin-5’-
phosphate (= flavin mononucleotide, FMN) and riboflavin-5’-adenosyldiphosphate (=
flavin adenine dinucleotide,FAD). FMN is actually not a nucleotide, as the compound
attached to the flavin moiety is the sugar alcohol ribitol and not the aldose sugar ribose,
and the isoalloxazine ring is not a purine r a pyrimidine. FAD is composed of a
nucleotide (adenosine monophosphate, AMP) and the so-called flavin pseudonucleotide.
In biological tissues, FAD and, to a lesser extent, FMN occur almost entirely as
prosthetic groups for a variety of flavin enzymes (flavoproteins) concerned with
oxidoreductive processes. In most flavoproteins the flavins are bound tightly but non-
covalently to the apoenzymes. These also occur both as prosthetic groups in the group of
respiratory enzymes known as flavoproteins and alsp free, when they are referred to as
coenzymes.

Riboflavin
Flavin mononucleotide (FMN)

Flavin adenine dinucleotide (FAD)

Physical and Chemical properties

Riboflavin crystallizes in the form of yellow to orange-yellow needles with a


melting point of about 280 Cº. the compound is odourless and has an unpleasant bitter
taste. In neutral aqueous solution riboflavin exhibits a strong yellow-green fluorescence
which reaches a maximum at pH 6.7-6.8. riboflavin is only sparingly soluble in water
(10-13 mg/100 mL at 25-27.5 ºC; 19 mg/100 mL at 40 ºC; 230 mg/100 mL at 100 ºC)
and even less soluble in absolute ethanol (4.5 mg/100 mL at 27 ºC). The vitamin is
readily soluble, but unstable, in dilute alkali. There is n solubility in acetone, dietyl ether,
chloroform or benzene. A saturated aqueous solution of riboflavin has a pH of 5.5-7.2 ;
pKa values are 1.9 and 10.2 (20 ºC). The solubilty of riboflavin in water is increased in
the presence of aromatic compounds such as nicotinamide, and practical use of this
property is made in pharmaceutical preparations. The sodium salt of FMN is very soluble
in water, and FAD is freely soluble in water.

Dietary sources and requirement

Living cells require FMN and FAD as the prosthetic groups of a variety of
enzymes, and hence the flavins are found at least in small amounts in all natural
unprocessed food. Yeast extract is exceptionally rich in riboflavin, and liver and kidney
are also rich sources. Wheat bran, eggs, meat, milk and cheese are imported sources in
diets containing these foods. Cereal grains contain relatively low concentration of
riboflavin, but are imported sources in those parts of the world where cereals constitute
the staple diet. The milling of cereals results in considerable loss of riboflavin, so white
flour is enriched by addition of the vitamin. The enrichment of bread and breakfast
cereals contributes significantly to the dietary supply of riboflavin. Polished rice is not
usually enriched, since the yellow colour of the vitamin would present problems.
However, most of the riboflavin content of the whole brown rice is retained if the rice is
steamed prior to milling. In most foods the riboflavin is present in the form of protein-
bound flavins, predominantly as FAD. Egg white and egg yolk contain specialized
riboflavin binding proteins that are required for storage of free riboflavin in the egg for
use by the developing embryo. The daily requirement for riboflavin is 1.2-1.7 mg/day for
normal adults.

Biochemical and physiological functions

The flavin enzymes play a vital role in carbohydrate and lipid catabolism by catalysing:

(1) the reoxidationof reduced nicotinamide adenine dinucleotide (NADH)


(2) the oxidation of the tricarboxylic acid cycle intermediary, succinate, to
fumarate
(3) the oxidation of saturated fatty acid acyl-CoA to á,â-unsaturated fatty acyl-
CoA in the â-oxidation of fatty acid.

In all of these reactions the reduced flavin (FADH2 or FMNH2) is reoxidized by


the cytochrome electron-transport chin with the eventual transfer of the hydrogen to
molecular oxygen to form water. The flavin enzymes are also involved in the
biosynthesis of long-chain saturated fatty acids and in the catabolism of biogenic amines
and purine bases arising from the degradation of nucleic acids. In addition, they are
necessary for the conversion of vitamin B6 and folic acid to their coenzyme forms and in
the conversion of tryptophan to NAD+.

Deficiency signs

Unlike the case with gross thiamin deficiency, no pathologically severe signs
attributed to riboflavin deficiency have been observed in humans. Signs of riboflavin
deficiency have been induced experimentally in volunteers whose diets were lacking only
in riboflavin or who were fed riboflavin antagonists. Deficiency signs in man usually
include lesions of the lips (cheilosis) and angles of the mouth (angular stomtitis), a
fissured and magenta-coloured tongue (glossitis), seborrhoeic follicular keratosis of the
nose and forehead, and dermatitis of the anogenital region. Ophthalmic symptoms are a
superficial vascularization of the cornea accompanied by intense photophobia.

Toxicity

The low solubility of riboflavin and the limited capacity of intestinal absorption
mechanisms probably account for the lack of toxicity following oral doses of up to 20 mg
daily.

Metabolism

The FAD and FMN present in the ingested food are released from their mainly
noncovalent association with proteins by gastric acidification and are enzymatically
dephosphorylated in the upper gut. The free riboflavin is absorbed in the small intestine
by an active transport process and is phosphorylated in the mucosal cells to FMN. FMN
then enters the portal system, where it becomes loosely associated with plasma albumin,
and is trasported to the liver. Conversion of FMN to FAD and binding to specific
flavoproteins occurs in most tissues, but particularly in the small intestine, liver, heart and
kidney. The liver is the major storage site of the vitamin and contains about one-third of
the total body flavins, 70-90% of which is in the form of FAD. Other storage sites are the
spleen, kidney and cardiac muscle. These depots maintain significant amounts of the
vitamin even in severe deficiency states.

Bioavailability

Riboflavin is obtained directly from foods naturally rich in the derivatized


vitamin, such as bovine milk and eggs, and from foodstuffs to which riboflavin has been
added during manufacture, the flavoprotein content of food containing noncovalently
bound flavins provides an indirect source of riboflavin.

Niacin ( Vitamin B3)

History

The human disease of pellagra was first described in Spain by Casal in 1735 after
the introduction of maize into Europe from the Americas. In the 1920s, Goldberger
(USA) reported that pellagra and black tongue in dogs responded to treatment with
animal protein and also to boiled protein-free extracts of yeast. In 1937, Elvehjem found
that the active component in liver extracts used to successfully treat canine black tongue
was nicotinamide, and reports that nicotinic acid cured pellagra soon followed. Because
nicotinic acid has been known chemically since 1897, it has never been assigned a letter,
but it is included among the vitamins of the B group. Nicotinic acid and nicotinamide had
been isolated from the coenzymes now known as NADP and NAD by 1934-1935. Hence,
knowledge of their biochemical roles in electron-transfer reactions preceded the
discovery of their nutritional significance. By 1946, the metabolism of dietary tryptophan
to an active form of the vitamin had been demonstated.

Structure and Property

Niacin is the generic descriptor for two vitamers, nicotinic acid and nicotinamide,
which are systematically named as pyridine-3-carboxylic acid and pyridine-3-
carboxamide, respectively. Vitamin B3, or niacin, is a member of the B-vitamin family. It
is water-soluble, which means it is not stored in body and needs to be frequently
replenished. There are two forms of vitamin B3, niacin (also known as nicotinic acid) and
niacinamide (also known as nicotinamide). Both forms work the same way as an
important nutrient in body, but are used to treat different conditions. Body needs vitamin
B3 to turn carbohydrates into energy. Without B3, body systems would grind to a halt.
B3 is also involved in the breakdown of fat and cholesterol, which is why niacin
(nicotinic acid) has been found to be a good cholesterol-lowering agent.
Body uses vitamin B3 to make various compounds, such as sex hormones and
adrenal hormones. It can also help the body get rid of toxic and harmful chemicals, and it
helps with blood sugar control. Most people get enough of this vitamin just from the
foods they eat. Health care provider may prescribe a vitamin B3 supplement for high
cholesterol or other conditions. It is important that health care provider closely monitors
while body are taking high doses of vitamin B3 because it can cause serious side effects,
such as liver damage, at these dosages. In living tissues nicotinamide is the reactive
moiety of the coenzymes NAD and NADP. The coenzymes are composed of a nucleotide
(AMP) and a pseudonucleotide containing the nicotinamide moiety. The oxidized forms
of the coenzymes carry a positive charge (NAD+ and NADP), reduced forms carrying
two electrons and one proton (and associated with an additional proton) are represented
as NADH and NADPH. Although the coenzymes are only loosely associated with the
apoenzyme during catalysis, most cellular NAD and NADP is stored in the cytoplasm
bound to protein.

Nicotinamide adenine dinucleotide (NAD+)


Nicotinamide adenine dinucleotide phosphate (NADP+)

Physical and Chemical Properties

Nicotinic acid crystallizes into colourless needles (m.p. 235 ºC) which are odourless
and have a tart taste, the crystals of nicotinamide (m.p 129 ºC) are similar but have a
bitter taste. Nicotinic acid is sparingly soluble in water (1.67 g/100 mL at 25 ºC) and
ethanol (0.73 g/100 mL) and insoluble in acetone and dietyl ether. It is, however, freely
soluble in boiling water. The pH of a saturated aqueous solution is 3 and the pKa is 4.8
(25 ºC). the sodium salt of nicotinic acid is readily soluble in water (71 g/100 mL) and
yields a solution of about pH 7. Nicotinamide is readily soluble in water (100 g/100 mL)
and ethanol (67 g/100 mL). There is solubility in acetone and very slight solubility in
dietyl ether and chloroform. An aqueous solution of nicotinamide yields a pH of 6 and
the pKa is 3.3 (20 ºC). Both nicotinic acid and nicotinamide have the properties of bases
and form quaternary ammonium salts when in acid solution. Nicotinic acid, being
amphoteric, forms carboxylic acid salts when in a basic solution, but nicotinamide
possesses no acidic properties.

Dietary sources and requirement

Our bodies actually manufacture vitamin B3 from protein, so if eating enough


protein, we will also be getting enough vitamin B3. The best sources of vitamin B3 are
found in protein-rich foods such as lean meats, chicken, fish, eggs, cooked dried beans
and peas, liver, nonfat or low fat milk and cheese, soybeans, and nuts. Other good sources
include brewer's yeast, wheat germ, enriched breads and cereals, whole grains (except
corn), mushrooms, and green vegetables. Vitamin B3 can be lost in cooking water, so we
should steam, bake, or stir-fry vegetables when possible. If our health care provider
advises to take extra vitamin B3, can purchase niacin or niacinamide supplements in a
variety of forms, including tablets in strengths of 25 mg, 50 mg, 100 mg, 250 mg, and
500 mg. Although timed-release tablets and capsules are available, and have advantages,
there are studies showing that timed-release niacin may cause liver damage. Niacin is
also available as inositol hexaniacinate, a preparation developed in Europe. Inositol
hexaniacinate is a sustained-release delivery method that is not thought to lead to liver
disorders. The daily requirement for niacin is 13-19 mg per day for a normal adult.
Requirements for niacin may be higher for those who have cancer, those who are being
treated with isoniazid (for tuberculosis), women taking oral contraceptives, and people
with protein deficiencies.

Biochemical and physiological functions

The nicotinamide nucleotide coenzymes, NAD and NADP, function as proton and
electron carriers in a wide variety of oxidation-reduction reactions. Examples are
reactions concerned with the release of energy from carbohydrates, fatty acids and amino
acids, and with the synthesis of amino acid, fatty acids and pentoses for nucleotide and
nucleic acid production. Carbohydrate catabolism involves the conversion of glucose to
pyruvate by anaerobic glycolysis and ander aerobic conditions, the oxidative
decarboxylation of pyruvate to acetyl-CoA, which is further metabolized in the
tricarboxylic acid cycle. A number of NAD+ linked substrate dehydrogenations occur
during this process and the NADH is itself dehydrogenated by the flavin enzymes. Under
anaerobic conditions the NADH generated during glycolysis is oxidized by transferring
its hydrogen to pyruvate to form lactate. The reducing equivalents (NADPH) for fatty
acid biosynthesis are produced by the pentose phosphate pathway. NADH required for
gluconeogenesis is generated via the oxidation of fatty acids and deaminaiton of amino
acids.

Deficiency signs

A deficiency in niacin results in pellagra, which is a nutritional disease endemic


among poor communities who subsist chiefly on maize. The prognosis is complicated by
signs of protein energy malnutrition and by an imbalance of amino intake, particularly,
low levels of tryptophan and high levels of leucine. The disease is diagnosed in the early
stages by a sunburn like dermatitis affecting skin areas exposed to light. The dermatitis
may progress to a scaled and cracked condition, and in chronic cases the skin becomes
rough and thickened with a brown pigmentation. Gastrointestinal disturbances (abnormal
pain, diarrhea and loss of appetite) may also appear, accompanied by oral lesions similar
to those described for riboflavin. Early neurological symptoms include tremor,
irritability, anxiety and depression, with delirium and dementia sometimes occuring
insevere and chronic cases.

Toxicity

Nicotinic acid administered orally at doses as low as 100 mg/day causes


peripheral vasodilation with the appearance of skin flushing. In high doses, nicotinic acid
competes with uric acid for excretion, leading to an increase in the incidence of acute
gouty arthritis. Of greatest concern is possible liver damage, and in one report severe
jaundice occurred at doses of 750 mg/day for only 3 months. Nicotinamide does not
cause vasodilatation, but is otherwise two to three times as toxic as th acid.

Metabolism

Ingested nicotinamide nucleotides are hydrolysed in the small intestine, and the
liberated nicotinamide, along with nicotonic acid and tryptophan, is absorbed and
transported to the liver. In the liver, tryptophan and the niacin vitamins are converted via
a common intermediary (nicotonic acid ribonucleotide) into NAD, some of which is
utilized by the liver itself. Vitamin B6 is a required coenzyme for at least four steps in the
tryptophan-niacin pathway. The surplus NAD is hydrolysed in the liver to free
nicotinamide, which is then released into the general circulation accompanied by the
nicotinic acid that was not metabolized. On reaching the tissues, the niacin vitamers are
used for the intracellular synthesis of NAD and NADP. There is a continuous turnover of
these nucleotides in the body and very little storage. Excess niacin is converted in the
liver to methyl derivatives, which are excreted in the urine.

Bioavailability

The in vivo conversion of tryptophan to NAD is inadequate to meet the total


coenzyme requirement in humans, and niacin must be included in the diet. The utilization
of tryptophan as a precursor of NAD depends upon the dietary supply of other essential
amino acids. If the supply falls, less typtophan is utilized in protein synthesis and more
becomes available for conversion to NAD. A high dietary intake of leucine interferes
with tryptophan metabolism and increases and requirement for niacin.

Panthothenic acid ( vitamin B5)


Structure and Property

Vitamin B5 (Pantothenic Acid), another of the B complex vitamins, is a yellow


viscous oil found usually as the calcium or sodium salt that is, calcium pantothenate. It is
present in all living cells and is very important to metabolism where it functions as part of
the molecule called coenzyme A or CoA. Pantothenic acid is found in yeasts, molds,
bacteria, and plant and animal cells, as well as in human blood plasma and lymph fluid.
B5 is stable to moist heat and oxidation or reduction (adding or subtracting an electron),
though it is easily destroyed by acids (such as vinegar) or alkalis (such as baking soda)
and by dry heat. Over half of the pantothenic acid in wheat is lost during milling, and
about one-third is degraded in meat during cooking. In many whole foods, vitamin B5 is
readily available.

Dietary sources and Requirements:

The name pantothenic acid comes from the Greek word pantos, meaning
"everywhere," referring to its wide availability in foods. Therefore, it is easily accessible
in the diet, and deficiency is uncommon, except in those with a highly processed diet,
since much of the available vitamin B5 activity is lost during refinement of foods. Good
sources of pantothenic acid include the organ meats, brewer’s yeast, egg yolks, fish,
chicken, whole grain cereals, cheese, peanuts, dried beans, and a variety of vegetables,
such as sweet potatoes, green peas, cauliflower, and avocados. Vitamin B5 is also made
by the bacterial flora of human intestines, another source for this important metabolic
assistant or coenzyme. The RDA for pantothenic acid is about 5 mg. for children and 10
mg. for adults. Many other sources feel the minimum needs are more likely to be about
25–50 mg., and 50–100 mg. is probably a good "insurance" range. Therapeutic ranges are
more like 250–500 mg. daily and even higher, taken, of course, along with the other B
complex vitamins. Individual needs vary according to food intake, degree of stress, and
whether one is pregnant or lactating. Those people who eat a diet of processed foods,
have a stressful lifestyle, or have allergies require higher amounts of pantothenic acid.
For all of the problems discussed here, 250–500 mg. taken twice daily is a safe and
beneficial amount.

Biochemical and physiological Functions

Pantothenic acid as coenzyme A is closely involved in adrenal cortex function and


has come to be known as the "antistress" vitamin. It supports the adrenal glands to
increase production of cortisone and other adrenal hormones to help counteract stress and
enhance metabolism. Through this mechanism, pantothenic acid is also thought to help
prevent aging and wrinkles. It is generally important to healthy skin and nerves. Through
its adrenal support, vitamin B5 may reduce potentially toxic effects of antibiotics and
radiation. As the coenzyme, pantothenic acid is important in cellular metabolism of
carbohydrates and fats to release energy. As coenzyme A, it supports the synthesis of
acetylcholine, a very important neurotransmitter agent that works throughout the body in
a variety of neuromuscular reactions. Coenzyme A is vital in the synthesis of fatty acids,
cholesterol, steroids, sphingosines, and phospholipids. It also helps synthesize porphyrin,
which is connected to hemoglobin.

Uses

Pantothenic acid, found in a wide range of sources, is used in a wide variety of


conditions. Again, it is known as the "antistress" vitamin and is used to relieve fatigue
and stress and the many problems induced by stress, through its support of the adrenal
glands. Allergies, headaches, arthritis, psoriasis, insomnia, asthma, and infections have
all been treated with some effectiveness using vitamin B5, possibly through its adrenal
support and adequate production of adrenocorticosteroids. Vitamin B5 has also been used
after surgery when there is paralysis of the gastrointestinal (GI) tract to stimulate GI
peristalsis. It has been helpful in many cases for people who grind their teeth at night, a
problem called bruxism. Other conditions treated by this vitamin are nerve disorders such
as neuritis, epilepsy, and multiple sclerosis and various levels of mental illness and
alcoholism. Of course, the effectiveness may vary in all these situations according to
amount supplemented, length of time used, and individual responsiveness. Sound
research to support the use of pantothenic acid in many of these treatments or for its
energy-enhancing or antiaging effects is lacking, although some research has shown
positive results from the use of calcium pantothenate in reducing arthritis symptoms of
joint pain and stiffness.

Deficiency and toxicity

As with other B vitamins, there are no specific toxic effects from high doses of
pantothenic acid. Over 1,000 mg. daily has been taken for over six months with no side
effects; when 1,500 mg. or more is taken daily for several weeks, some people experience
a superficial sensitivity in their teeth. However, it is possible that if B5 is taken without
other B vitamins, it may create metabolic imbalance. Fatigue is probably the earliest and
most common symptom of pantothenic acid deficiency, though it is an unlikely vitamin
deficiency because of the availability of B5 in many foods, plus the fact that it is also
produced by our intestinal bacteria. A diet high in refined and processed foods or a
reduction or destruction of intestinal flora, most commonly by antibiotic use, can lead to
a vitamin B5 deficiency. Teenagers are more likely to experience a deficiency, because
their diets often include high amounts of "fast foods" sugars, and refined flours (all low in
B vitamins). And the problem may be compounded because the acne often associated
with this type of diet is commonly treated with tetracycline antibiotics, which reduce the
intestinal bacteria and thereby the production of pantothenic acid in the colon.
Studies of pantothenic acid deficiency in rats showed increased graying of the fur,
decreased growth, and, in the extreme, hemorrhage and destruction of the adrenal glands.
In humans, the decreased adrenal function caused by B5 deficiency can lead to a variety
of metabolic problems. Fatigue is most likely; there may also be physical and mental
depression, a decrease in hydrochloric acid production and other digestive symptoms,
some loss of nerve function, and problems in blood sugar metabolism, with symptoms of
hypoglycemia (low blood sugar) being the most common. Pantothenic acid affects the
function of cells in all systems, and a deficiency may reduce immunity, both cellular and
antibody responses. Other symptoms of B5 deficiency include vomiting, abdominal
cramps, skin problems, tachycardia, insomnia, tingling of the hands and feet, muscle
cramps, recurrent upper respiratory infections, and worsening of allergy symptoms.

Vitamin B6 ( Pyridoxine, pyridoxal, pyridoxamine)

Structure and Property

Vitamin B6 (Pyridoxine) is a very important B vitamin, especially for women. It


seems to be connected somehow to hormone balance and water shifts in women. Vitamin
B6 is actually three related compounds, all of which are found in food--pyridoxine,
pyridoxal, and pyridoxamine. Pyridoxal is the predominant biologically active form;
however, in vitamin supplements, pyridoxine is the form used because it is the least
expensive to produce commercially. Vitamin B6 is stable in acid, somewhat less stable in
alkali, and is fairly easily destroyed with ultraviolet light, such as sunlight, and during the
processing of food. It is also lost in cooking or with improper food storage. Pyridoxine is
absorbed readily from the small intestine and used throughout the body in a multitude of
functions. Fasting and reducing diets usually deplete the vitamin B6 supply unless it is
supplemented. Usually within eight hours, much of the excess is excreted through the
urine; some B6 is stored in muscle. It is also produced by the intestinal bacteria. The
structure above is I = pyridoxine, II = pyridoxal phosphate III = pyridoxal IV = 4-
pyridoxolactone.
Dietary sources and Requirements

Vitamin B6 in its several forms is widely available in nature, though not many
foods have very high amounts. Since it is lost in cooking and in the refining or processing
of foods, it is not the easiest B vitamin to obtain in sufficient amounts from the diet,
especially if we eat much processed food, as it is not one of the vitamins replaced in
"enriched" flour products such as cereals and pastries. The best sources of vitamin B6 are
meats, particularly organ meats, such as liver, and the whole grains, especially wheat.
Wheat germ is one of the richest sources. Besides meat, good protein sources of B6
include fish, poultry, egg yolk, soybeans and other dried beans, peanuts, and walnuts.
Vegetable and fruit sources include bananas, prunes, potatoes, cauliflower, cabbage, and
avocados. As examples of how easily vitamin B6 is lost in the processing of food, raw
sugar cane has a good amount, while refined sugar has none; whole wheat flour contains
nearly 0.5 mg. of pyridoxine (wheat germ and wheat flakes have much more), while
refined wheat flour has almost none, and even whole wheat bread has lost nearly all of its
vitamin B6.
Requirements: Vitamin B6 intake, though based on many factors, is determined
primarily by protein intake, because it is so important to protein metabolism. The RDA
for adults is a minimum of 2 mg. of B6 per 100 grams of protein consumed. In children,
it ranges from 0.6-1.2 mg. per 100 grams of protein. However, the need for vitamin B6
increases in a variety of situations. During pregnancy and lactation and with birth control
pill or estrogen use, higher levels are required. For those who eat a high-sugar or
processed-food diet or a high-protein diet, requirements for B6 are greater and
deficiencies or depletion are more common. When there is impairment of the digestive
system, cardiac failure, or radiation use, or even just the aging process, needs for vitamin
B6 are increased. Drugs that influence needs for B6 are oral contraceptives, isoniazid (for
tuberculosis), hydralazine (for high blood pressure), amphetamines, reserpine (for high
blood pressure), and some antibiotics. More B6 is utilized with an increased intake of the
amino acid methionine. Adequate magnesium in the body is important to the functions of
vitamin B6. A safe, basic intake for vitamin B6 is probably 10-15 mg. per day, though
much higher daily amounts are easily tolerated. B6 should also be taken along with other
B vitamins to prevent metabolic imbalance. For therapeutic purposes, amounts between
50-100 mg. (this is the quantity pyridoxal-5-phosphate usually comes in) are most
common, and up to 200-500 mg. per day in time-release forms is used for some
conditions, such as premenstrual problems and depression. With the current questions
about neurologic side effects associated with megadoses of vitamin B6, particularly as
pyridoxine hydrochloride, I suggest limiting regular daily intake to 500 mg. daily or
1,000 mg. for a short course of treatment, such as one to two weeks; also, take some
additional magnesium, 200-300 mg, which may help reduce any neurologic concerns.

Biochemical and physiological Functions

Pyridoxine and its coenzyme form, pyridoxal-5-phosphate, have a wide variety of


metabolic functions in the body, especially in amino acid metabolism and in the central
nervous system, where it supports production of gamma-aminobutyric acid (GABA).
Many reactions, including the conversion of tryptophan to niacin and arachidonic acid to
prostaglandin E2 require vitamin B6. The pyridoxal group is important in the utilization
of all food sources for energy and in facilitating the release of glycogen (stored energy)
from the liver and muscles. It helps as well in antibody and red blood cell production
(hemoglobin synthesis) and in the synthesis and functioning of both DNA and RNA. By
helping maintain the balance of sodium and potassium in the body, vitamin B6 aids fluid
balance regulation and the electrical functioning of the nerves, heart, and musculoskeletal
system; B6 is needed to help maintain a normal intracellular magnesium level, which is
also important for these functions. The neurotransmitters norepinephrine and
acetylcholine and the allergy regulator histamine are all very important body chemicals
that depend on pyridoxal-5-phosphate in their metabolism. Also, the brain needs it to
convert tryptophan to serotonin, another important antidepressant neurotransmitter.
Pyridoxine is especially important in regard to protein metabolism. Many amino
acid reactions depend on vitamin B6 to help in the transport of amino acids across the
intestinal mucosa into the blood and from the blood into cells. By itself and with other
enzymes, pyridoxal-5-phosphate helps build amino acids, break them down, and change
one to another and is especially related to the production and metabolism of choline,
methionine, serine, cysteine, tryptophan, and niacin. The body has a high requirement for
vitamin B6 during pregnancy. It is important for maintaining hormonal and fluid balance
of the mother and for the developing nervous system of the baby. Pyridoxine may
somehow be related to the development and health of the myelin covering of the nerves,
which allows them to conduct impulses properly.

Uses

With its many functions, there is also a wide range of clinical uses of vitamin B6,
clearly being most helpful when symptoms and diseases are related to a
pyridoxine/pyridoxal-5-phosphate depletion or deficiency. Recently there has been
widespread use of higher doses of B6, usually from 50-200 mg. per day (though some
studies use 500 mg. per day of pyridoxine in time-release form) for premenstrual
symptoms, especially water retention, which can lead to breast soreness and emotional
tension. Pyridoxine has been very helpful in this role, probably because of its diuretic
effect through its influence on sodium-potassium balance and its mysterious influence on
the hormonal system. Vitamin B6 also helps with the acne that often develops
premenstrually, as well as with dysmenorrhea, or menstrual pain; magnesium is usually
used as well in all of these menstrual-related problems. In pregnancy, B6 has been helpful
in many women for controlling the nausea and vomiting of morning sickness, which
some authorities feel is highly related to vitamin B6 deficiency. It seems that whenever
there are increased levels of estrogen in the body, more B6 is required. This occurs not
only in pregnancy but also for women who take birth control pills and those
postmenopausal women on estrogen treatment as well. It is likely that some of the
emotional symptoms experienced by many women on the pill, such as fatigue, mood
swings, depression, and loss of sex drive, may be related to a deficiency of B6 and
thereby helped by supplementation.
Vitamin B6 is used for people with stress conditions, fatigue, headaches, nervous
disorders, anemia, and low blood sugar or diabetes, and in men for prostatitis, low sex
drive, or hair loss. Pyridoxal-5-phosphate (P5P) is occasionally used in formulas or as an
individual supplement for certain conditions. As the active coenzyme of pyridoxine, P5P
can go more directly into the metabolic cycles and does not have to be converted; thus, it
may be more helpful than pyridoxine alone in such problems as fatigue, allergies, viral
disease, chemical sensitivities, mental illness, and cancer. Pyridoxine supplementation is
also used for a variety of skin problems--dandruff, eczema, dermatitis, and psoriasis. In
regard to the nervous system, vitamin B6 has been supportive in cases of epilepsy,
Parkinson's disease, multiple sclerosis, and neuritis. Vitamin B6 therapy, from 100-300
mg. daily for 8-12 weeks, appears to reduce carpal tunnel syndrome and increase the
ability to use the hands in most patients.
Pyridoxine is a natural diuretic and is often helpful not only for the previously
mentioned premenstrual problems but also in overweight and fluid-retaining people and
as an adjunct to blood pressure control. Vitamin B6 (along with magnesium) has received
some note in regard to preventing the formation of kidney stones or the recurrence of
stones in those who have had them. In his book Nutrition and Vitamin Therapy (Grove
Press, 1980), Michael Lesser, M.D., states that in a study reported in 1974 by the Journal
of Urology, 10 mg. of vitamin B6 and 300 mg. of magnesium oxide prevented recurrence
in about 80 percent of patients with a long history of kidney and urinary tract stone
formation. Dr. Lesser also noted that the B6-magnesium combination helps in some
hyperactive kids and those with fits or problems of autism. He states that pyridoxine in
fairly large doses will stimulate dream activity as well as reduce the potential toxicity of
barbiturate drugs, carbon monoxide and some other chemical exposures, and irradiation.
Vitamin B6 works best when taken with magnesium, zinc, riboflavin, and brewer's yeast
or the other B vitamins. Pyridoxine, probably more than the other B vitamins except folic
acid, is supportive of healthy immune function. B6 deficiency can produce immune
weakness, and B6 treatment may be helpful against infections and cancer. Recent studies
have shown that pyridoxine can inhibit the growth of some cancer cells, specifically mice
and human melanoma cells. Further research with B6 will likely find an even wider range
of uses.

Deficiency and toxicity

There is basically no toxicity with pyridoxine at reasonable daily dosages, though


there has been some recent concern about this. Regular oral intake of 200 mg. and
intravenous doses of 200 mg. have shown no side effects. Usually, the toxic doses are
much higher, between 2Ð5 grams. Some recent reports in the medical literature show that
regular usage of over 2,000 mg. per day, which some women especially have been taking,
are correlated with episodes of peripheral neuritis. Although the experience of weakness
or tingling of arms or legs has been transient and mostly correctable by decreasing the B6
dosage, this does warrant some concern about excessive use of B6, especially long-term
use. Since part of the neuropathy problem comes from the liver's inability to convert all
of the pyridoxine to active P5P, this concern can be lessened by supplementing some of
the B6 as pyridoxal-5-phosphate (as I have done in many of my programs), especially
when the dose of vitamin B6 exceeds 200 mg. per day. In addition, using increased
amounts of magnesium with the higher levels of vitamin B6 will reduce the occurrence of
the peripheral neuritis.
Deficiency, as usual, is a bigger concern with vitamin B6, as it is with all the B
vitamins. So many functions are performed by pyridoxine that its deficiency affects the
whole body. Most of these deficiency symptoms are fairly vague. Muscle weakness,
nervousness, irritability, and depression are not uncommon. Many of the symptoms are
similar to those of both niacin and riboflavin deficiencies; depression is common in all of
them. Metabolically, pyridoxine deficiency has a dramatic effect on amino acid
metabolism, with a decreased synthesis of niacin from tryptophan, a decrease in
neurotransmitter chemicals, and a decrease in hemoglobin production. Fatigue, nervous
system symptoms, and anemia are all influenced by deficiency. Further nerve-related
problems include paraesthesia, incoordination, confusion, insomnia, hyperactivity, and,
more severely, neuritis, electroencephalogram (EEG) changes, and convulsions. Other
problems include dermatitis or cracks and sores at the corners of the mouth and eyes and
visual disturbances.
There is special concern about deficiency during pregnancy, when vitamin B6
needs are higher, as it may cause water retention and the nausea and vomiting of morning
sickness and has been correlated with a higher incidence of common problems of later
pregnancy, such as toxemia (preeclampsia, high blood pressure, edema, and hyper-
reflexes) and eclampsia (those same symptoms plus seizures). B6 deficiency in later
pregnancy can be associated with birthing difficulties. There is also an increased
likelihood of diabetic and blood sugar problems in pregnancy when vitamin B6 is
deficient. Overall, vitamin B6 deficiency can cause a variety of nervous symptoms, skin
problems, and amino acid/protein metabolic abnormalities. These can lead to the more
common expressions--headache, dizziness, inability to concentrate, irritability and
epileptic-type activity, labile depression, and weakness. Water retention is common.
Nausea, vomiting, and dry skin, especially extensive dandruff and a cracked sore mouth
and tongue are also more likely with vitamin B6 deficiency.

Cobalamin (Vitamin B12)

Structure and Property

Vitamin B12 (Cobalamin) is named the "red vitamin," as it is a red crystalline


compound. B12 is unique in that it is the only vitamin that contains an essential mineral--
namely, cobalt. Cobalt is thereby needed to make B12 and so is essential for health. B12
is unique also in that it is required in much tinier amounts than the other B vitamins. Only
3-4 mcg. (micrograms, or thousandths of a milligram) are needed at minimum; however,
higher levels, up to 1 mg., are often used therapeutically. Vitamin B12 is a very complex
molecule. Besides cobalt, it also contains carbon, oxygen, phosphorus, and nitrogen.
Cobalamin is stable to heat, though sensitive in heated acid or alkali solution, slightly
sensitive to light, and destroyed by oxidizing and reducing agents and by some heavy
metals.
Vitamin B12 was isolated in 1926 as the factor that treated a feared disease,
pernicious anemia--termed "pernicious" because it could be fatal, most often from
neurologic degeneration. But the substance cobalamin, when given orally (actually liver
was used as the cure; it contains high amounts of B12), did not cure all of the people with
the disease, and some people still developed pernicious anemia. It was later found that a
mucoprotein enzyme produced by the stomach (by the parietal cells that also make
hydrochloric acid) was also needed for vitamin B12 to be absorbed into the body from
the intestines. This enzyme has been termed the "intrinsic factor," while vitamin B12 is
the "extrinsic factor." Aging, stress, and problems with the stomach or stomach surgery
weaken the body's ability to produce the "intrinsic factor"; also, some people appear to
have a genetic predisposition that makes them more prone to pernicious anemia.
Hydrochloric acid helps the absorption of B12; if acid production is weak, the absorption
is lessened. Calcium and thyroid hormone assist as well. Pregnancy, absorb this
important vitamin. Aging more likely lessens some of the many factors needed for ideal
absorption of B12, so deficiency symptoms are more common in older people.
Cobalamin is absorbed primarily from the last part of the small intestine, the
ileum. In the blood, it is bound to a protein globulin to be carried to the various tissues.
The body actually stores vitamin B12, so any deficiencies may take several years to
develop. The highest concentrations of B12 are found in the liver, heart, kidney,
pancreas, brain, testes, blood, and bone marrow--all active metabolic tissues. The "red
vitamin" is very important to the blood. Cobalamin is made in nature by microbial
synthesis--produced by bacteria in the intestinal tracts of animals and stored in their
tissues. Some B12 is made during fermentation of foods as well. Cobalamin is the
naturally occurring vitamin B12. Cyanocobalamin, as B12 is often known, is actually the
commercial variety of B12 and contains a cyanide molecule attached to the cobalt. B12 is
not synthesized but, like penicillin, must be grown in bacteria or molds and then
processed. Other forms of B12 include hydroxycobalamin (technically, vitamin B12a),
aquacobalamin (vitamin B12b), and nitrocobalamin (vitamin B12c).

Dietary sources and Requirements

Vitamin B12 is found in significant amounts only in the animal protein foods.
B12 is also manufactured by bacteria in the human intestines, but it is not known how
much we can naturally absorb and utilize from that source. In general, digestion and
absorption must be good for adequate B12 to be obtained. Many laxatives and overuse of
antacids can reduce absorption and deplete stores of B12. Our primary food sources of
vitamin B12 include meat, most fish, especially the oily ones (trout, herring, and
mackerel), crabs and oysters, eggs (the yolk), and milk products, especially yogurt. Organ
meats such as liver, heart, and kidney are particularly high. The vegan--that is, the strict
vegetarian who consumes no animal-source foods--is not getting the necessary vitamin
B12 from diet (although tempeh, a fermented soybean product, and some sprouts may
contain some vitamin B12); thus, vegans will often need an additional supplement (which
absorbs well) or periodic injections.
Vitamin B12 is essential but required only in minute amounts; 3-4 mcg. is needed
in most adults to prevent deficiency, and at least that amount is required by pregnant or
lactating women, as well as infants and growing children. From 10-20 mcg. daily is a
good insurance level, although certain people may need increased amounts with higher
protein intake. Vitamin B12 is often taken in higher doses, 500-1000 mcgs. per day, to
relieve fatigue. Injections of B12 in these amounts are used to treat a variety of low-
energy and mental symptoms previously described as well as during some weight loss
programs. When there is fatigue or anemia, it is a good idea to get the blood level of B12
checked by a doctor. It may lead to a very simple and successful treatment.

Biochemical and physiological Functions

Although vitamin B12, cobalamin, apparently does not have as many functions as
some of the other B vitamins, it has some very important ones. It is essential for the
metabolism of the nerve tissue and necessary for the health of the entire nervous system.
It stimulates growth and increases appetite in children. Cobalamin, along with iron, folic
acid, copper, protein, and vitamins C and B6, is needed for the formation of normal red
blood cells. Vitamin B12 is the "energy" vitamin, as it often increases the energy level,
whether obtained from eating the B12 foods or from supplemental use. There may be
several reasons for this. Cobalamin stimulates the utilization of proteins, fats, and
carbohydrates. It also helps iron function better in humans and is important for the
synthesis of DNA and RNA, as well as for production of choline, another B vitamin, and
methionine, an amino acid.

Uses

Vitamin B12 is generally known as the longevity vitamin, possibly because it


helps the energy level and activity of the nervous system of the elderly. B12 injections
(the main therapeutic use of this vitamin) have been a common practice of many doctors
for the treatment of fatigue, and, in my experience, it works very often. However, it
would only be a "cure" when the tiredness is a result of B12 deficiency. There are many
reasons for fatigue. As we age, our digestion and absorption are not usually as finely
tuned as when we were young, particularly when we eat and live the way most of us late
twentieth-century beings do. And vitamin B12, even though it is needed in such small
doses, is one of the most difficult vitamins to acquire through diet and to metabolize. The
"red vitamin" is the main "antifatigue" vitamin; often given along with folic acid, it helps
energy and prevents most anemia, provided there is good iron absorption and
hydrochloric acid production. Medically speaking, it is wise to check patients with
fatigue for anemia and to measure vitamin B12 and folic acid levels before embarking on
a treatment regimen.
B12, given intramuscularly, usually in doses of 500-1,000 mcg. (0.5-1.0 mg.), is
used once, twice, or three times weekly for a period of time to both give energy and, in
adults, help with appetite suppression in weight loss programs. These amounts also
replenish the vitamin B12 stores. It has a mild diuretic effect as well and may be used
premenstrually to diminish water retention symptoms. In the treatment of pernicious
anemia and the earlier symptoms of vitamin B12 deficiency, injections of cobalamin or
its variants are usually necessary because most everyone with deficiency has poor
absorption. It is difficult to become B12 deficient from diet alone, unless we are on a
strict vegan diet for years. In any anemia, really, it is wise to supplement B12, because it
helps the red blood cells develop to a point where protein, folic acid, iron, and vitamin C
can then complete their maturation so that we can better carry oxygen and energy to all of
our cells.
Vitamin B12 will stimulate growth in many malnourished children. In older
people, it has helped with energy levels as well as psychological symptoms, including
senile psychosis. B12 has also been used to help treat osteoarthritis and osteoporosis and
for neuralgias, such as Bell's palsy, trigeminal neuralgia, or diabetic neuropathy. It has
likewise been used in the treatment of hepatitis, shingles, asthma, other allergies, allergic
dermatitis, urticaria, eczema, and bursitis. Cobalamin has been used for many other
symptoms besides fatigue, including nervousness and irritability, insomnia, memory
problems, depression, and poor balance. Vitamin B12 is something to keep in mind when
we are not "feeling our oats."

Deficiency and toxicity

There have been no known toxic effects from megadoses of vitamin B12.
Thousands of times more than the RDA have been injected both intravenously and
intramuscularly without any ill consequences. On the contrary, there is often some
benefit. Vitamin B12 deficiency usually results from a combination of factors. Restricted
diets, as seen in vegetarians or poor nations, can be very limited in B12. Since the
absorption into the body is so finely tuned, depletion and deficiency occur even more
commonly from poor digestion and assimilation, or from deficient production of intrinsic
factor. That is why it is so important to be aware of B12 and use some sort of
supplementation once a deficiency has been diagnosed. Vitamin B12 blood levels, along
with folic acid levels, are the most common vitamin tests performed by doctors. As we
age, it is more likely that we may become B12 deficient. Also, alcoholics and people with
malabsorption or dementia may have low B12 levels. Since the body stores vitamin B12,
it may take several years to become deficient with dietary restriction or a decrease in
intrinsic factor.
The strict vegetarian has more concern than the average meat- and dairy-eating
person. B12 is not found in the vegetable kingdom other than in foods fermented by
certain bacteria; thus most fermented foods have some vitamin B12. However, in
vegetarians, there is usually a high folic acid intake, and since folic acid and B12 work
similarly in the body, a B12 deficiency may be masked for a period of time, and then
more pronounced symptoms may occur. If B12 is deficient in an animal eater, then we
pretty much know there is a problem in absorption of the vitamin. Most problems of B12
deficiency affect the blood, energy level, state of mind, and nervous system. Often, subtle
symptoms may start with the nervous system. Vitamin B12 nourishes the myelin sheathes
over the nerves, which help maintain the normal electrical conductivity through the
nerves. Soreness or weakness of the arms or legs, decreased sensory perceptions,
difficulty in walking or speaking, neuritis, a diminished reflex response, or limb jerking
may result from B12 deficiency. Psychological symptoms may include mood changes
with mental slowness may be one of the first symptoms.
With B12 deficiency, the body forms large, immature red blood cells, resulting in
a "megaloblastic" anemia. Pernicious anemia refers to the deficiency in blood cells as
well as the myriad of psychological and nerve symptoms. The anemia usually generates
more fatigue and weakness. Menstrual problems, even amenorrhea (lack of menstrual
flow), may also occur in B12-deficient women. The problems related to the nervous
system caused by vitamin B12 deficiency can lead to permanent damage, not correctable
by B12 supplementation. This irreversible nerve damage may occur when the B12
deficiency effect on the red blood cells is masked by adequate levels of folic acid, as I
mentioned. More severe pernicious anemia can cause a red, sensitive tongue, referred to
as "strawberry tongue," which may even ulcerate, and nerve or brain and spinal cord
degeneration, which can cause weakness, numbness, tingling, shooting pains, and sensory
hallucinations. Paranoid symptoms may even occur. In the early part of this century,
pernicious anemia was often a fatal disease.

Vitamin C ( Ascorcic acid )

History

The concept of an antiscorbutic vitamin was postulated by Funk in 1912 after


Holz and Frohlich in 1907 induced scurvy in guinea pigs. By 1924, Zilva had obtained
concentrates of the antiscorbutic factor from lemons and showed that the factor possessed
strong reducing properties. Isolation of an antiscorbutic ‘hexuronic acid’ in crystalline
form was achieved from cabbage and adrenal glands by Szent-Gyorgyi in 1928 and from
lemon juice by Waugh and King in 1932. The synthesis of an identical substance by
Reichstein in 1933 confirmed that the hexuronic acid was the vitamin ascorbic acid.

Structure and property

The term vitamin C is used as the generic descriptor for all compounds exhibiting
qualitatively the biological activity of ascorbic acid. The principal natural compound with
vitamin C activity is L-ascorbic acid, which is systematically named l-threo-2-hexenono-
1-4-lactone. Vitamin C or Ascorbic acid, is the enolic form of 3-oxo-L
gulofuranolactone. It can be prepared by synthesis from glucose, or extracted from plant
sources such as rose hips, blackcurrants or citrus fruits. It is easily oxidised in air. It is
essential for the formation of collagen and intercellular material, bone and teeth and for
the healing of wounds. It helps maintain elasticity of the skin, aids the absorption of iron
and improves resistance to infection. It is used in the treatment of scurvy. May prevent
the occurrence and development of cancer. Vitamin C (Ascorbic Acid) has many
important functions in the body. It is a powerful antioxidant, protecting against oxidative
damage to DNA, membrane lipids and proteins. It is involved in the synthesis of
numerous substances such as collagen, certain hormones and transmitters of the nervous
system, lipids and proteins. It is necessary for proper immune function, a fact that has led
many to use vitamin C to prevent or treat colds, although this has not been supported by
current studies. It may, however, shorten or reduce the severity of a cold.

Ascorbic acid (vitamin C )

Physical and chemical properties

L-ascorbic acid is an almost odourless white or very pale yellow crystalline


powder with a pleasant sharp taste and a melting point of about 190 ºC with
decomposition. It is readily soluble in water (33 g/100 mL at 25 ºC) less soluble in 95%
ethanol (3.3 g/100 mL), absolute ethanol (2 g/100 mL), acetic acid (0.2 g/100 mL) and
acetonitrile (0.05 g/100 mL) and insoluble in fat solvents. The solubility in vegetable oils
at room temperature is very low but increases sharply with increasing temperature. the
carbonyl enediol group of ascorbic acid confers strong reducing properties to the
molecule, as indicated by its ability to reduce Fehling’s or Tollen’s solution at room
temperature.
Dietary sources and requirements

Fresh fruits (especially citrus fruits and blackcurrants) and green vegetables
constitute rich sources of vitamin C. Potatoes contain moderate amounts but, because of
their high consumption, represent the most important source of the vitamin in the diet.
Liver, kidney and heart are good sources, but muscle meats and cereal grains do not
contain the vitamin. Human milk provides enough ascorbic acid to prevent scurvy in
breast-fed infants, but preparations of cow’s milk are a poor source owing to oxidative
losses incurred during processing. Besides this, also good sources of Vitamin C are
Broccoli, Brussels sprouts, cauliflower, cabbage, mangetout, green leafy vegetables, red
peppers, chilies, watercress, parsley, blackcurrants, strawberries, kiwi fruit, guavas, citrus
fruit.
Daily requirements is 30 mg/day in children and 40-80 mg/day in adults. An
increase of 100 mg/day is required in pregnancy and severe stress (or trauma) due to a
rapid depletion of adrenal stored vitamin C. However, the decrease in adrenal vitamin C
levels could be due to a rapid either to redistribution of the vitamin to areas that need it or
an overall increased utilization.
Biochemical and physiological functions

Ascorbic acid acts as an important redox compound in destroying toxic free


radicals in cell metabolism. A deficiency of the vitamins causes impaired formation of
collagen in the basement membrane of capillaries. The synthesis of collagen involves the
enzymatic hydroxylation of proline to hydroxyproline. The latter amino acid, which is not
supplied in the diet, is a principal constituent of the collagen fibres. The hydroxylation of
lysine is necessary for the subsequent formation of cross-links in the fibres. Research into
collagen metabolism suggests that ascorbate is concerned generally with protein
biosynthesis and specificially with collagen biosynthesis.
Deficiency signs

A deficiency of vitamin C results in scurvy, the symptoms of which are


heamorrhages in the gums, skin, bones and joints, and the failure of wound healing.
Scurvy is a condition characterized by general weakness, anemia , gum disease
(gingivitis), and skin hemorrhages resulting from a lack of ascorbic acid (Vitamin C) in
the diet. Scurvy is now most frequently seen in older, malnourished adults.

Toxicity

Toxicity does not normally occur, since vitamin C is water soluble and is
regularly excreted by the body. Recent studies have shown, however, that excessive
doses of vitamin C (many times more than the recommended amount) can lead to
toxicity. The most common manifestations of vitamin C toxicity are kidney stones , and
in very rare circumstances, anemia (caused by interference with vitamin B12 absorption).
Diarrhea is also a possible but uncommon symptom associated with massively increased
intake of vitamin C. ascorbic acid is generally regarded as being nontoxic. With
excessive dietary intakes almost all the digested amount is excreted in the urine. In
healthy individuals, daily dosages of up to at least 1 g may be taken over a period of
weeks without the manifestations of toxic symptoms.

Metabolism

Many animals can synthesize ascorbic acid by the glucuronic acid pathway, but
humans and other primates, in common with guinea pigs and fruit-eating bats, lack the
enzyme which catalyses the final step, and thus rely upon their diet to provide the
vitamin. Ascorbic acid is absorbed in the small intestine by an active transport
mechanism and assimilated by the tissues. The metabolism follows the pathways of
oxidation whereby two electrons are removed in succession to yield firstly the ascorbate
free radical and then dehydroascorbate. A minor pathway is the sulphation of ascorbate to
ascorbate-2-sulphate, which is unlikely to possess antiscorbutic properties.

Biotin ( B7)

Structure and property

The biotin molecule is a fusion of an imidazolidone ring with a


tetrahydrothiophene ring bearing a pentanoic (valeric) acid side chain and systematically
named 2’-keto-3,4-imidazolido-2-tetrahydrothiophene-n-valeric acid. The molecule
contains three asymmetric carbon atoms, and hence eight stereoisomers are possible.
Also called vitamin H. the majority is covalently bound to the protein structure
(apoenzyme) of biotin dependent enzymes via a peptide bond between the carboxyl group
of biotin and the å-amino group of a lysine residue. Proteolysis of the enzyme liberates a
natural water-soluble fragment called biocytin, which is biologically active.

Physical and chemical properties

Synthetic d-biotin crystallizes as fine colourless needles which melt at 232 ºC


with decomposition. Biotin in its free acid form is only very sparingly soluble in water at
25 ºC (20 mg/100 mL) and in 95% ethanol (80 mg/100 mL) but is more soluble in hot
water. It is soluble in dilute alkali, sparingly soluble in dilute acid, and practically
insoluble in fat solvents, including chloroform, dietyl ether and petroleum ether biotin
salts are significantly more water soluble than the acid form of biotin.

Dietary sources and requirements

Biotin is present at very low concentration in all natural foodstuffs. Most of the
biotin content of animal products, nuts, seeds, and yeast is in a protein bound form. A
higher percentage of free water extractable biotin occurs in vegetables, green plants, fruit,
milk and rice bran. Rich sources of biotin include yeast, wheat bran, oatmeal, nuts, liver,
kidney and eggs. Muscle meats, fish, dairy products and cereals contain smaller amounts,
but are important contributors to the dietary intake.
Daily requrements is 150-200 µg/day. Therapeutic use in babies with infantile
seborrhea (cradle cap) and Leiner’s disease.

Biochemical and physiological functions

Biotin functions as the prosthetic group in carboxylase enzymes, which are


capable of taking up bicarbonate ions as the carboxyl donor and transferring them to
specific substrates. The regeneration of glucose (gluconeogenesis) from lactate produced
during exercise takes place in the liver and requires means of bypassing several energy
barriers in the glycolytic pathway. The bypassing of the phosphoenolpyruvate to pyruvate
reaction is achieved by the actions of two enzymes that are unique to glconeogenesis. The
biotin dependent pyruvate carboxylase catalyses the formation of oxaloacetate from
pyruvate, and phosphoenolpyruvate carboxykinase, which is not biotin-dependent,
converts oxaloacetate to phosphoenolpyruvate. Pyruvate carboxylase is allosterically
activated by acetyl-CoA, which will be abundant when energy intake exceeds demand.
The glucose thus produced in the liver is then returned to the muscle for energy storage in
the form of glycogen. The formation of oxaloacetate is also important in lipid
biosynthesis through its role in tansporting acetyl-CoA from within the mitochondrion to
the cytosol. This involves the continous removal of oxaloacetate from the mitochondrion,
abd its replacement by the action of pyruvate carboxylase is necessary to maintain normal
tricarboxylic acid cycle activity. Malonyl-CoA, which is required for fatty acid
biosynthesis, is formed by the biotin dependent carboxylation of acetyl-CoA.

Deficiency signs
The human requirements for biotin are normally met through the combined
dietary supply and endogenous microbial synthesis in the gut. A primary biotin
deficiency state is therefore extremely rare, especially where a well-balanced diet
prevails. Deficiency states have been induced in adult volunteers by feeding low-biotin
diets containing a high proportion of raw egg white. An initial scaly dermatitis was
followed by nonspecific symptoms that included extreme lassitude, anorexia, muscular
pains, hyperaesthesia and localized paraesthesia. All of these signs and symptoms
responded to injctions of 150-300 µg of biotin per day. Seborrhoeic dermatitis of the
scalp and a more generalized dermatitis known as Leiner’s disease have been reported in
breast-fed infants when the mother is malnourished. These symptoms are relieved when
biotin is administered to the mothers.

Toxicity

Biotin toxicity in humans has not been reported. It is presumably low, snce infants
have tolerated injections of 10 mg daily for 6 months with no adverse effects

Metabolism

Most of the biotin in foods is incoporated in the biotin dependent enzymes,


although some free biotin may be present. The peptide bond linking the biotin moiety to
the lysine residue of the enzymes is resistant to hydrolysis by proteolytic enzymes in the
intestinal tract, so the main digestion product is biocytin. Biocytin is readily absorbed,
and then enzymatically hydrolysed to free biotin. In the tissues, biotin is covalently
bound to the apoenzymes of biotin-dependent enzymes to form the active holoenzyme.
Biotin is conserved very efficiently in the body owing to resorption by the kidney and the
protein binding of plasma biotin, which reduces filtration at the glomerulus. On
catabolism of the biotin-dependent enzymes, the biocytin is hydrolysed by a specific
peptidase, permitting reutilization of the vitamin. There is a low, but significant, activity
of biotin absorption in the colon, suggesting that biotin synthesized by, and released
from, intestinal bacteria can be absorbed.

Folic Acid

Structure and property

Folic acid or pteroylglutamic acid (PGA) is also known as vitamin M or vitamin


Bc. Folic acid is the name given to a closely related group of widely distributed
compounds whose vitamin activity is similar to that of the cobalamins. Folic acid works
along with vitamin B12 and vitamin C to help the body digest and utilize proteins and to
synthesize new proteins when they are needed. It is necessary for the production of red
blood cells and for the synthesis of DNA (which controls heredity and is used to guide
the cell in its daily activities). Folic acid also helps with tissue growth and cell function.
In addition, it helps to increase appetite when needed and stimulates the formation of
digestive acids. Synthetic folic acid supplements may be used in the treatment of
disorders associated with folic acid deficiency and may also be part of the recommended
treatment for certain menstrual problem and leg ulcers.
This compound is frequently abbreviated to PteGlu (named after the pteroic acid
and glutamate moieties) but in this text it will be referred to in most cases simply as PGA.
The fundamental unit of PGA comprises a bicyclic pterin moiety linked by a metylene
bridge to p-aminobenzoic acid, which is joined by peptide linkage to a single molecule of
l-glutamic acid. The latter moiety is essential for vitamin activity. PGA is not a natural
physiological form of the vitamin, the pteridine ring of natural folates is reduced to give
either the 7,8-dihydrofolate (DHF) or 5,6,7,8-tetrahydrofolate (THF).

Folic acid

Dietary sources and requirements

Sources:Beans and legumes, Citrus fruits and juices, Wheat bran and other whole
grains, Dark green leafy vegetables, Poultry, pork, shellfish, Liver. Dietary requirements
which is the body requires 50-200 µg folic acid per day such as about 10-25% of daily
dietary intake. Storage in the body is in the form of 5-metyl THF. An increase in the daily
intake of folate in pregnancy is needed due to an increased number of rapidly
proliferating cells present in the blood. Certain drugs such as anticonvulsants and oral
contraceptives can impair the absorption of folate ( anticonvulsants also increase the rate
of folate metabolism).

Deficiency signs

Folic acid deficiency may cause poor growth, graying hair, inflammation of the
tongue (glossitis) , mouth ulcers , peptic ulcer , and diarrhea .It may also lead to certain
types of anemias. A deficiency in folate leads to a lack of adequate DNA replication and
consequent impaired cell division, especially in the haemopoietic tissue of the bone
marrow and the epithelial cells of the gastrointestinal tract. In the bone marrow the
erythroblasts fail to divide properly and become enlarged, and the circulating red blood
cells are macrocytic and fewer in number than normal. This condition, megaloblastic
anaemia, is particularly common in pregnancy, during which there is an increased
metabolic demand for folate. The effect of folate deficiency upon cell renewal of the
intestinal mucosa causes gastrointestinal disturbances and also has adverse consequents
upon overall nutritional status.

Toxicity

Toxicity from excessive folic acid intake does not normally occur, as folic acid is
water soluble and regularly excreted by the body. Folate is generally considered to have a
low acute and chronic toxicity for humans. Gastrointestinal disturbances and neurological
symptoms such as altered sleep patterns, malaise and irritability have been reported in a
study with healthy volunteers receiving daily doses of 15 mg of PGA.

Recommendations

Recommended daily allowances (RDAs) are defined as the levels of intake of


essential nutrients that, on the basis of scientific knowledge, the Food and Nutrition
Board judges to be adequate to meet the known nutrient needs of practically all healthy
persons. The best way to get the daily requirement of essential vitamins is to eat a
balanced diet that contains a variety of foods from the food guide However, pregnant
women often require additional supplementation as prescribed by a health care provider.
Adequate folic acid is important for pregnant women because it has been shown to
prevent some kinds of birth defects, including neural tube defects such as spina bifida.
Many foods are now fortified with folic acid to help prevent these kinds of birth defects.
Women in their childbearing years should make an effort to consume foods that are good
sources of folic acid. Studies published by the Centers for Disease Control and
Prevention (CDC) suggest that women who receive supplements of folic acid before
conception may reduce the risk for neural tube defects by 50%. Women who plan to
become pregnant may want to discuss taking a multivitamin with their health care
provider if they are not already doing so. Specific recommendations for each vitamin
depend on age, gender, and other factors (such as pregnancy).
REFERENCES

[1] G.F.M. Ball (1994). “ Water Soluble Vitamin Assays in Human Nutrition”.
Chapman & Hall, London.

[2] Manzur-Ul-Haque Hashmi (1973). “ Assays of Vitamins in Pharmaceutical


Preparations”. John Wiley & Sons, London.

[3] Jagannath Ganguly (1989).”Biochemistry of Vitamin C”. CRD Press,Inc, Boca


Raton, Florida.

[4] Christopher J. Bates. “Vitamins: Fat and Water Soluble: Analysis”. MRC Human
Nutrition Research, (formerly MRC Dunn Nutritional Laboratory), Cambridge,
UK, Encyclopedia of Analytical Chemistry.

[5] R. Chumnantana1, N. Yokochi, T. Yagi (2005). “Vitamin B6 compounds prevent


the death of yeast cells due to menadione, a reactive oxygen generator”.
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