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B COMPLEX - GENERAL FEATURES:-

1. Present in all plant and animal cells.

2. Generally act as components of coenzymes in metabolism of carbohydrates, lipids and


proteins, especially in energy-yielding reactions.

 Dietary requirement is closely linked to metabolic rate.

 Absorbed by passive diffusion (except B12) in small intestine and any excess is
excreted in urine i.e. there is little or no tissue storage (except B12, some folic acid).

3. Must be continually supplied in diet (or by ruminal synthesis).

VITAMIN B1 – THIAMINE:-

 Funk (1912) isolated the anti-berberi substance from rice polishing.

 Jansen and Donath (1927) isolated thiamine in its pure form.

 Williams (1936) elucidated the chemical structure of Thiamin:

 A substituted pyrimidine and a thiazole coupled by a methylene bridge.

 It is very water-soluble.

 Readily decomposes in neutral solution.

 Has the characteristic "meaty" odor and flavor.

 The active form is thiamin pyrophosphate (TPP)

 Thiamin is rapidly converted to thiamin pyrophosphate (TPP) in small intestine, brain


and liver.

 TPP is formed from thiamin by the action of thiamine diphosphotransferase (see the
next slide).

 Monophosphate (Thiamin -monophosphate (TMP) and -triphosphate (TTP) forms are also
present.

 Absorption is increased in times of deficiency, but reduced by thyroid hormone, diabetes,


alcohol consumption.

 Thiamine is carried by portal blood to the liver.

 Free thiamine is present in plasma, but the coenzyme (TPP) is the primary cellular component.
Sources:

 Unrefined and enriched cereals, yeast, wheat germ, pork, organ meats, and legumes.

RDA: Infants: 0.3-mg; adults: 1.5 mg; pregnant & lactating women: Increased by 0.4mg & 0.5
mg respectively.

Chemical structure:-

EXISTS IN TWO FORMS:- 2,5-dimethyl-6-amino pyrimidine , 4-methyl-5-β-


hydroxyethylthiazole

Function :

1. Thiamin pyrophosphate (TPP) has a role in carbohydrates metabolism :

a) TPP is an important coenzyme in energy metabolism. It acts as a coenzyme in the


production of ribose, the sugar needed by all cells for the formation of ribonucleic acid (RNA),
which helps produce protein and deoxyribonucleic acid (DNA), the basic substance of genes.

b) It is involved in reactions of oxidative decarboxylation of alpha-keto acids to


aldehydes. This reaction is particularly important in conversion of pyruvate to acetate just
prior to Kreb’s cycle, and in the conversion of alpha ketoglutarate to succinyl coenzyme A
within the Kreb’s cycle.

c) Thiamine is also a cofactor for transketolase. This enzyme is involved in the


conversion of sugars containing 3,4,5,6 or 7 carbons.

2. Thiamin is also been shown to play a role in pathways involved with proteins and fat
metabolism.

3. Thiamin has a specific role in neurophysiology that is independent of its coenzyme function.

Mechanism of action of thiamin. Thiamin pyrophosphate (TPP), the active form of thiamin,
acts as coenzyme for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase reactions
in the TCA cycle and for transketolase in the pentose phosphate pathway.

DEFICIENCY:-

WET BERI BERI:-

 Oedema in legs and face

 Anorexia and dyspepsia

 Calf muscles get tense ,slightly swollen and tender on pressure.


Apex beat is displaced outwards

 Urine volume is diminished but there is no albuminuria

DRY BERI BERI:-

 Polyneuropathy

 Pyruvic and lactic acid is increased.

 Transketolase activity of red cells is decreased

 Muscle becomes wasted and weak.

INFANTILE BERI-BERI:-

• Occurs in breast fed infants 2-5th month.

• In acute form- cardiac failure,dyspnoea, tachycardia and infant may die within 24-48 hrs.

• In chronic form- GI disturbances,constipation and vommitting.

PATHOGENESIS-
Deficiency

Incomplete metabolism of glucose

Accumulation of pyruvic acid & lactic acid in tissue & body fluid

Dilation of peripheral blood vessels

Fluid may leak out through capillaries, producing edema

High cardiac output, heart dilation.

 Causes:

1. It can happen if raw fish containing microbial thiaminases are ingested.


2. Tea may contain antithiamine factors.

3. Chronic alcoholism often leads to thiamine deficiency.

In alcoholics there is:

Reduced intake

Impaired absorption

Impaired use

Reduced storage

Alcohol is high in calorie but low in vitamin B1.

All this can lead to Wernike-Korsakoff syndrome.

4. All diuretics including, Furosemide has been shown to cause thiamine (B-1) deficiency. This
can lead to "wet beriberi" which causes sodium retention, dilation of blood vessels and heart
failure.

ALCOHOL & WERNICKE-KORSAKOFF SYNDROME:-

Ataxia (inability to coordinate muscular movements due to nervous disorders) and confusion

Memory loss

Opthalmoplegia

– can’t follow light source

Nystagmus

-involuntary jerking of the eye

Alcohol dilated cardiomyopathy

DIAGNOSTIC LABORATORY FINDINGS :

 The concentration of pyruvate in the blood is increased, so that the ratio of lactic acid to
pyruvic acid becomes abnormal.
 The measurement of transketolase activity in erythrocytes is a useful test in the diagnosis of
thiamin deficiency.
Treatment

Beri beri-

Thiamine 50 mg IM for 3 days, followed by 10 mg daily orally.

Wernicke-Korsakoff syndrome-

Thiamine 50 mg IV followed by 50 mg IM daily for a week.

BERIN (VIT B1 inj 100mg/ml) ; tab 100 mg

VITAMIN B2:-

RIBOFLAVIN

Sources: Milk, poultry, fish, enriched grains

RDA: Infants:0.4 mg ; adults:1.7mg; pregnant & lactating women: increase by 0.3mg & 0.5mg
respectively

• Yellow, crystalline compound with yellow-green fluorescence in aqueous solution.

• Only sparingly soluble in water.

• Stable in acid or neutral, but not alkaline solutions.

• Sensitive to light and heat stable.

• Riboflavin is phosphorylated in the intestine to generate FMN (riboflavin 5’-phosphate) by


the action of Flavokinase.

Riboflavin + ATP Flavokinase FMN + ppi

• FMN then reacts with ATP, yielding FAD:

FMN + ATP FAD synthetase FAD + ppi

ppi = inorganic pyrophosphate.

Biologically active forms: FMN & FAD

FUNCTIONS:

Essential in electron transport system, regulatory functions of some hormones connected with
carbohydrate metabolism, role as respiratory coenzyme.
Free riboflavin present in retina is converted by light to a compound involved in stimulation of the
optic nerve.

DEFICIENCY :

Particularly children who don’t drink milk.

Seborrhoeic dermatitis, particularly involving the face (around the nose) and the scrotum or vulva.

Corneal vascularization and inflammation with cloudiness of cornea, watering, burning of eyes,
photophobia and cataract.

ORAL MANIFESTATIONS-

Angular cheilosis, atrophy of filliform papillae, enlarged fungiform papillae, shiny red lips, magenta
tongue/ glossitis, sore tongue.

DIAGNOSTIC LABORATORY FINDINGS :

Excretion in the urine of less than 27 mg of riboflavin per gram of creatinine indicates a deficiency.

The concentration of riboflavin in red blood cells of less than 14 mg / 100 ml is considered to indicate
a potential deficiency.

Treatment –

Riboflavin 5 mg 3 times daily usually given as the vitamin B complex

VITAMIN B3- NIACIN

Sources : meats, poultry, fish, peanuts, and legumes,Milk and eggs are sources of tryptophan
(precursor of niacin)

RDA: Infants: 6mg of NE; Adults:10mg NE;

Pregnant & lactating women: increase by 2mg & 5mg NE respectively.(1NE=1mg niacin / 60 mg
tryptophan)

DISCOVERY:-

• Pellagra was described more than 200 years ago by Casal, a court physician to King Philip V of
Spain, soon after the introduction of corn (maize) into Europe.

• An Italian physician, Frappoli, named the disease pelle agra (rough skin in Italian).

• In 1915 Dr. Joseph Goldberger of the U.S. Public Health Service became convinced that a faulty
diet rather than a bacterial infection was the cause of pellagra. Goldberger and cowworkers
treated the disease pellagra in human beings and in 1928 they showed that boiled yeast
extract can cure pellagra.Hence, Goldberger named niacin as the Pellagra –Preventive factor.

• In 1938 Elvehjem and his group demonstrated that with nicotinic acid they could cure black
tongue in dogs, a condition similar to one seen in humans with pellagra.

• Shortly thereafter, niacin was shown to be effective in the prevention and treatment of
pellagra.

 Beta pyridine carboxylic acid

 Two forms: Nicotinic acid and Nicotinamide. Nicotinamide is the amide derivative of nicotinic
acid.

 In most animal species (including humans) niacin can be synthesized from the essential amino
acid, tryptophan.

 Both forms contain a pyridine ring.

CHEMISTRY AND PROPERTIES :

 Niacin is a slightly water-soluble, light-and heat-stable, weak organic acid. Although


chemically related to nicotine, it possesses very different physiological properties. Niacin
is one of the most stable vitamins, but because it is water soluble, it may be lost in
cooking in water.

METABOLISM :

 Niacin is absorbed in the upper part of the small intestine. It is stored only sparingly in the
kidney, heart, brain, and liver and is excreted in the urine.
 Niacin is synthesized from tryptophan with the aid of other B vitamins, namely,
pyridoxine, riboflavin, and thiamin.

FUNCTION :

 Niacin functions as part of two major coenzymes in energy metabolism, nicotinamide adenine
dinucleotide (NAD) and NAD phosphate (NADP). These coenzymes are hydrogen carriers. And
they are essential in many energy transfer pathways e:g Kreb’s cycle, intracellular respiration,
and fatty acid synthesis. Both of these coenzymes work with TPP and FAD in the net yield of
energy from carbohydrates, fats and proteins.
 Therefore, niacin is vital in the normal function of the central nervous system, in maintaining
the integrity of the skin and mucous membranes, and especially in supplying the needed
coenzyme for the energy cycles.
DEFICIENCY SYMPTOMS:-

1. Pellagra in farm animals and humans (fiery inflammation of tongue, mouth and upper esophagus).

2. Poor growth, enteritis and dermatitis.

3. Occurs in people who subsist mainly on corn which is low in both niacin and tryptophan

4. The signs of pellagra include dermatitis, diarrhea, dementia (the three Ds) and loss of tongue
papillae.

Pellagra is characterized by dermatitis, diarrhea, dementia, glossitis, gingivitis, and generalized


stomatitis.

Early symptoms of pellagra are similar to those produced in other B complex deficiency states:
weakness, persistent fatigability, irritability, headache, and depression. Soreness and
inflammation of the tongue (glossitis) and mouth (stomatitis) aggravated by highly seasoned
foods is also a frequent complaint. The tongue is sore, swollen, scarlet in color, and smooth.
Glossitis and stomatitis may be the earliest clinical signs of niacin deficiency. The gingiva may
be involved in aniacinosis with or without tongue changes. The most common finding is
necrotizing ulcerative gingivitis, usually in areas of local irritation.
Oral manifestations of vitamin B-complex and niacin deficiency in experimental animals
include black tongue and gingival inflammation with destruction of the gingiva, periodontal
ligament, and alveolar bone. Necrosis of the gingiva and other oral tissues, as well as
leukopenia, are terminal features of niacin deficiency in experimental animals.
The dermatitis tends to be most severe in areas of exposure to chronic irritation, sun, or heat.
The most likely to be affected are the face, neck backs of the hands, wrists, elbows, knees, and
perineal folds. The lesions are usually symmetrical. The margins of the lesions are usually
sharply demarcated from normal skin, one of the more important features that differentiate it
from other types of dermatitis. At first there is redness and thickening of the skin, followed
eventually by a variegated dermatitis with brown, scaly areas alternating with areas of areas
of depigmented, shiny, shrunken skin.
Diarrhea is due to inflammation of the mucosal lining of the esophagus, stomach, and colon.
Depression, confusion, hallucinations, and delirium can result from degeneration of nerve and
brain cells.
The clinical diagnosis of pellagra rests largely on the identification of the skin and oral changes
(cheilosis, and angular stomatitis) plus complaints of gastrointestinal upsets.

Characteristic skin rash : casal’s necklace


ORAL MANIFESTATIONS-

Angular cheilosis; mucositis; stomatitis; ulcerative gingivitis; denuded tongue; glossitis; glossodynia;
tip of tongue is red & swollen; dorsum is dry & smooth,salivation profuse

DIAGNOSTIC LABORATORY FINDINGS :

Urinary excretion of niacin metabolite falls to low levels. Excretion of 0.5mg of N’-methylniacinamide
per gram of creatinine suggests a niacin deficiency.

Treatment

· Nicotinamide (approximately 100 mg 6th hrly orally) with a maintenance dose of 50 mg daily. mostly
vitamin B complex is given, as other deficiencies are often present.

· increase in the protein content of the diet.

Niacin – excess state : It causes facial flushing, decreased blood lipids and can cause liver damage.
Chronic overdosing can require a liver transplant.

VITAMIN B4:- Choline

Sources: whole grains, whole breads, and numerous herbs and herbal extracts such as cloves, ginger.

FUNCTIONS:

 “Lipotrophic”
 Crucial component of the neurotransmitter acetylcholine (muscle movement and brain
function).
 Regulates liver function & necessary for normal fat metabolism.

Deficiency:

Alzheimer’s, Parkinson’s, Cardiovascular disease

Dosages

300 – 3500 mg, Alzheimer’s - 5000 mg.

Toxicity

Choline has no known toxicity, except at exceedingly high doses (5000 mg to 10, 000+mg) a strong
“fishy” smell is noticed (tri methyl aminuria).
VITAMIN B5:- Pantothenic Acid

Sources:

Meats, poultry, fish, eggs, whole-grain cereals, and legumes

RDA: Adults- 5 to 10mg

HISTORY :

The discovery of pantothenic acid stemmed from investigation of yeast growth factor and a liver
filtrate factor.

It was named pantothenic acid by R.J. Williams in 1938 because of its distribution in many foods.

CHEMISTRY AND PROPERTIES :

 Free pantothenic acid is a yellow oily liquid that has never been crystallized. It is easily
destroyed by heat. The calcium salt (calcium pantothenate) crystallizes readily, and this is the
form in which it is generally available. It is soluble in water and is more stable to heat than
pantothenic acid.

FUNCTION :

Pantothenic acid is a critical component of coenzyme A (CoA). In this manner, it is involved in


acyltransfer reactions of fat, carbohydrates and protein metabolism.

This vitamin is also active in the synthesis of cholesterol, steroid hormones, porphyrins (a
component of Hb) and phospholipids.

Another function of CoA is the transfer of succinyl and malonyl groups, it also carries the acyl
units for fatty acid synthesis and amino acid activation. It initiates the Krebs cycle and releases
ATP.

CLINICAL DIAGNOSIS OF DEFICIENCY :

In humans, a deficiency is rare and can be induced experimentally. The symptoms are fatigue, sleep
disturbances, headaches, malaise, nausea, and abdominal stress. Burning, prickling sensation
(paresthesia) of the hands and feet, cramping of the leg muscles, and impaired coordination are
additional findings.

Burning feet syndrome- in prisnors of war and is associated with reduced capacity for
acetylation
DIAGNOSTIC LABORATORY FINDINGS :

Urinary excretion of less than 1 mg / day is considered abnormally low in adults.

THERAPY :

No definite therapeutic regimen for dealing with pantothenic acid deficiency has been presented.

Multivitamin B complex preparations usually contain pantothenic acid.

VITAMIN B6:- PYRIDOXINE

SOURCES :

Poultry, fish, liver, kidney, potatoes, bananas, spinach, and unrefined whole grains (oats and wheat)

RDA: Adults: 2mg

Pregnant & lactating women: increase by 2.5mg

Vitamin B6 is not a single vitamin but rather a group of metabolically and functionally interrelated
pyridines : namely, pyridoxine, pyridoxamine (the amine of pyridoxine), and pyridoxal. Each of these
substances is widely distributed in foods and is present in both free and bound forms.

HISTORY :

 This vitamin factor was discovered in 1934. The researcher also showed that this vitamin could
cure scaly dermatitis in rats, which is the reason it is called the ‘Antiacrodynia (antiscaling)
factor’.
 Pyridoxal and pyridoxamine occur mainly in animal products, whereas pyridoxine is found
mostly in plant products. Pyridoxine has often been used as the collective term for all three,
but in the current nomenclature the term vitamin B6 is used as the generic descriptor for all
three.

CHEMISTRY :

 Pyridoxine is a water-soluble, white crystalline compound that is stable to heat and strong
acids.

 Vitamin B6 can interfere with the action of levodopa, which is used to treat Parkinson’s
disease. Estrogens (such as those used in contraceptive pills) and corticosteroids have an
effect on Vitamin B6 metabolism.
FUNCTION :

 The principal vitamin activity resides in the enzymatically active coenzyme form, pyridoxal-5
phosphate.

1. Role in protein metabolism :

i) Transamination, deamination, desulfuration and decarboxylation reaction

ii) needed for porphyrin formation

iii) conversion of tryptophan to niacin.

2. Role in carbohydrate metabolism – Pyridoxine acts with enzyme phophorylase in the beakdown of
glucose to glucose-1-phosphate.

3. Role in fat metabolism:

i) Conversion of linoleic acid to arachidonic acid

ii) formation of sphinogolipids in myelin sheath.

4. It is also involved in CNS metabolism of such substance as serotonin, dopamine and others.

CLINICAL DIAGNOSIS OF DEFICIENCY :

A frank deficiency of Vitamin B6 in humans is rare because of its widespread distribution in natural
foodstuffs. An experimental deficiency produced cheilosis, glossitis and stomatitis, and an itching and
burning dermatitis with redness in the nasolabial folds. Subjective symptoms accompanying these
signs were loss of appetite, nausea, drowsiness, and peripheral neuropathy.

DIAGNOSTIC LABORATORY FINDINGS :

 Vitamin B6 deficiency produces increased urinary excretion of xanthurenic acid after


administration of a test dose of typtophan. Normal subjects excrete less than 30 to 50 mg of
xanthurenic acid in a 24 hour period.

THERAPY :

 When primary deficiency of this vitamin is suspected in an adult, a daily dosage of 10 mg is


given. In iron-resistant hypochromic anemia, doses up to 100 mg / day have been given.
Certain drugs, such as isoniazid, produce a need for a supplement of vitamin B6.
 Adult: Upto 150 mg daily(also given IV , SC , IM )

COMBINATIONS:

• PYRICONTIN-F ( pyridoxine HCL100mg;folic acid 5mg)


• SPERA 69 (pyridoxine HCL (SR) 100mg; folic acid 5mg)

• NEUROBION FORTE TAB (thiamin mono nitrate 10mg, riboflavin 10mg, pyridoxine HCL 3mg,
cyanocobalamin 15mcg, nicotinamide 45mg ,Ca pantothenate 50mg).

TOXICITY :

 Vitamin B6 is the most toxic water-soluble vitamin because it can be stored in the muscle and
liver.
 Long-term megadosing may cause permanent neurologic damage that include numbness in
extremities and uncoordinated muscle movement.
 Toxicity has been described when used in excess by the alcoholic to overcome a vitamin B6
deficiency.

VITAMIN B7- BIOTIN

SOURCES : liver, egg yolk, soya flour, cereals, and yeast.

Synthesized in intestine by micro-organisms

RDA: Adults:100 to 300 mcg

DISCOVERY:-

• Boas (1927) observed that when raw egg white was given as the main source of protein in the
diets of rats, they developed symptoms of dermatitis, retarted growth,loss of hair and loss of
muscular control. All these symptoms were prevented by egg yolk. The factor was called “anti-
egg white injury factor”.

• In 1931, Gyogy named this factor ‘vitamin H”.

• In 1942, Melville et al isolated vitamin H from milk and named it as vitamin “Biotin”

CHEMISTRY :

• When biotin was discovered, it was considered part of the “bios”


needed for yeast growth. Raw egg white contains avidin, which strongly binds biotin.
However, when egg white is cooked, avidin loses its ability to bind biotin.

FUNCTION :

1. The most important role of biotin is in carboxylation reactions, particularly in fatty acid
synthesis. Biotin functions in the enzyme pyruvate carboylase, during the conversion of pyruvate
to oxalacetate in Krebs cycle.

2. Biotin is involved in deamination reaction with aspartic acid, serined threonine.


3. Biotin functions as a coenzyme involving the addition of carbon dioxide in the formation of
purines, which are important constituents of DNA and RNA.

CLINICAL DIAGNOSIS OF DEFICIENCY :

 Because it is found in most foods and is also synthesized by intestinal bacteria, deficiency
states are recognized only when diets have included large amounts of raw egg white.
 Human biotin deficiency has been encountered in infants treated with sulfadrugs and in adults
whose diet consisted mainly of raw egg whites. Biotin deficiency has been reported in patients
maintained for long periods of time on intravenous feeding.
 Deficiency causes inflammation of the skin and the tongue (dermatitis and glossitis), loss of
hair (alopecia) and skin disease (dermatosis), loss of appetite and sleep, nausea, muscular
pains, increased skin sensitivity (hyperesthesia), and burning and prickling sensations
(paresthesia).
 Consumption of an occasional raw egg, as in eggnog, will not precipitate deficiency symptoms.
It is only when large amounts (20 or more eggs per day) are consumed that a problem occurs.

VITAMIN B8:- INOSITOL

SOURCES: Brown rice, cereals, citrus fruits, desiccated liver and fresh liver, green leafy vegetables,
lecithin ,whole grain bread.

FUNCTIONS:

 Nerve Transmission: Important especially to patients suffering from diabetes.


 Protect Against Colon Cancer
 Relieves Stress Symptoms in obsessive compulsive disorder and panic attacks, as effective as
fluvoxamine (antidepressant )and did not have side effects similar to fluvoxamine.
 Lowers risk of Polycystic Ovary Syndrome (PCOS)

VITAMIN B9- Folate, folacin, and folic acid

Sources: Cereals fortified with folate, green leafy vegetables, legumes, sunflower seeds, fruits such as
oranges and strawberries.

RDA: Infants: 30 mcg; adults: 400 mcg; Pregnancy & lactation : doubled

The term folacin is the generic descriptor for folic acid, pteroylmonoglutamin acid, and related
compounds exhibiting the biological activity of folic acid.

DISCOVERY AND HISTORY :

 During the 1930s and 1940s the classic studies of Dr. Lucy Wills, described an antianemic
factor for the treatment of tropical macrocytic anemia in pregnant women.
 This factor was present in green leaves. The word ‘folic’ is derived from the Latin word
‘folium’, meaning leaf. Therefore, the preparation was called folic acid. Folic acid (folate or
folacin) was finally synthesized in 1946 by a team of industrial chemists.

CHEMISTRY :

 Folic acid is yellow crystalline substance sparingly soluble in water, that is destroyed when
heated in neutral or alkaline media. The conjugated forms of the vitamin, known as a “folate”,
is converted to folic acid in the tissues. In addition from 50-95% of folate is destroyed in
cooking, canning and other processing.

ABSORPTION :

 Only about 10% of the various forms of folate in most foods are absorbed, with the exception
of those in liver, yeast and egg yolk. Folic acid is absorbed by active transport, and methylated
prior to passage into portal blood. Folate from food is absorbed by the gastrointestinal tract
and is stored primarily in the liver and RBC. It supports the growth of such microorganisms in
the body as Lactobacillus casei and Streptococcus faecalis.

FUNCTION :

1. Tetrahydrofolate (THF), an active form of this enzyme, is a cofactor for enzymes involved in the
synthesis of purines and pyrimidines, which form DNA and RNA.

2. THF is of particular importance in the formation of both RBC and WBC.

3. Folic acid coenzymes are also responsible for the formation of body protein from glycine and serine.

4. THF acts as a cofactor in methylation of homocysteine to methionine.this reaction is linked to


vitamin B12 metabolism.

FOLIC ACID DEFICIENCY :

Folic acid deficiency is probably the most common vitamin deficiency in humans because body’s
stores of folate are relatively low which can last for upto 4 months only.It often occurs:

 as a complication of gastro-intestinal disease

 following therapy with certain drugs e.g., methotrexate, Oral contraceptives, antiepileptic
drugs

 in chronic alcoholics

 malnourished elderly persons

 in pregnant women because of increased demand


 secondary to vit. B12 deficiency.

 Folic acid deficiency may cause Megaloblastic anemia. Clinically, the patient has tissue anemia
characterized by weakness, fainting attacks, severe paleness of skin, and congestive heart
failure. There are no central nervous system abnormalities, which is a key factor in
distinguishing between folic acid deficiency and vitamin B12 deficiency. It should be stressed
that a folacin supplement will cure the anemia caused by vitamin B12 deficiency but will not
alleviate the neurological symptoms that accompany this anemia.
 (Hermos et al 1972) In folate deficiency, there are impaired production of DNA and
unsynchronism between protein synthesis and cell division which prevent cell maturation
from reaching completion. A consequence is that the epithelial barrier function is affected.
 (Newberne 1977) Folate deficiency has also been related to decrease in host
immunocompetence.

FOLIC ACID & PREGNANCY :-

 To prevent neural tube defects, like spina bifida in children-All women of child bearing age
should take:
 400 micrograms of folic acid
 4 mg if history of seizure disorders

ORAL CHANGES :

Folic acid-deficient animals demonstrate necrosis of the gingiva, periodontal ligament, and
alveolar bone without inflammation. The absence of inflammation is the result of deficiency-
induced granulocytopenia.

 In humans with folic acid deficiency states, generalized stomatitis occurs, which may be
accompanied by ulcerated glossitis and cheilitis. Glossitis is the principal oral symptom is a
burning sensation in the tongue. The tongue is red, sore, and swollen. Angular cheilosis and
gingivitis are also present. Folic acid deficient animals have shown to be vulnerable to
ulcerations and infections of lips, tongue, gingiva, periodontium and oropharynx. This
succeptibility to infection may be related to impairment in host defence factors. They show
decrease in cell-mediated immune responses and in impairment in the permeability barriers
of oral mucosa.

 (Vogel et al 1980) found that folic acid supplementation may increase resistance to the
development of periodontal inflammation in humans. Pregnancy and use of oral
contraceptives have been associated with decreased folate serum levels. This has been
attributed to the decreased folate serum levels. This has been attributed to the increased
level of female sex hormones affecting the absorption and utilization of folic acid. In a clinical
study of pregnant women, a reduction in gingival inflammation occurred with the use of
topical folate mouth rinses; no change was found with systemic folic acid. Vogel
et al 1980 postulated that decreased resistance of gingiva to inflammatory changes associated
with pregnancy and the use of oral contraceptives may be related, in part, to suboptimal
levels of folic acid in the gingiva.

 Phenytoin interferes with the absorption of cellular utilization of folic acid. Vogel 1977
hypothesized that phenytoin-induced aberration of folate metabolism could render the
gingiva more succeptible to irritation from local etiologic factors, thereby enhancing
susceptibility to gingival overgrowth.

DIAGNOSTIC LABORATORY FINDINGS :

 The normal serum folate level ranges from 6 to 10 nanograms per milliliter. Folate deficiency
is possible if the serum level is below 6 ng / ml. Normal values for red cell folacin are 160 to
650 ng / ml. Therefore a level of less than 160 ng / ml in red cells is indicative of a deficiency.

TREATMENT-

 Folate deficient megaloblastic anemia: adult- 5mg daily for 4 mnths.

 Prophylaxis of megaloblastic anemia in pregnancy : adult – 0.2 to 0.5 mg daily

 Prophylaxis of Neural tube defect in pregnancy : adult – 4 to 5 mg daily starting before


pregnancy & continued through 1st trimester.

 As supplement for women of child bearing potential – 0.4 mg daily.

 Available brands: TAB B9 5mg; TAB FH12 5mg; TAB FOLDIVIT 5mg

COMBINATIONS:

 FOLERA – MD (folic acid 5mg; methyl cobalamin 750mcg;DHA 200mg capsules)

 VITCOFOL DPS FDC (folic acid 200 mcg , vit B12 5 mcg, nicotinamide 20mg/ 5ml) – glossitis,
stomatitis, aphthous ulcers, megaloblastic anemia.

 VITCOFOL INJ (folic acid 15 mg; vit B12 500mcg;nicotinamide 200 mg;vial)- 1ml IM daily.

VITAMIN B12: Cobalamin

Sources: Liver, whole milk, eggs, oysters ,fresh shrimp, pork & chicken.

RDA: Infants- 0.5 mcg ; Adults:3 mcg; pregnant & lactating women : increase by 30%.First 6 weeks of
pregnancy: 600 g/day required 1 month before conception
DISCOVERY:-

• Pernicious anemia was first described by Thomas Addison of London in 1849.

• In 1929 W.B. Castle demonstrated that ingesting a combination of beef muscle and gastric
juice was effective in the treatment of pernicious anemia.

• In 1948 Shorb reported that the liver extracts used to overcome anemia also had growth-
promoting properties for a Lactobacillus species. Rickes and associates isolated the red
crystalline cyanocobalamin (vitamin B12).

ABSORPTION AND TRANSPORT-

• Two steps are required for the body to absorb vitamin B12 from food. First, hydrochloric acid
in the stomach separates vitamin B12 from the protein to which vitamin B12 is attached in
food. After this, vitamin B12 combines with a protein made by the stomach called intrinsic
factor and is absorbed by the body.

• Vitamin B12 is liberated from protein complexes in food by gastric enzymes and then binds to a
vitamin B12-binding protein ('R' binder) related to plasma transcobalamin I (TCI), derived from
saliva. Vitamin B12 bound to 'R' binder is released by pancreatic enzymes and becomes bound
to intrinsic factor.

• Intrinstic factor carries it to specific receptors on the surface of the mucosa of the ileum.
Vitamin B12 enters the ileal cells and intrinsic factor remains in the lumen. Vitamin B12 is
transported from the enterocytes to the bone marrow and other tissues by the glycoprotein
transcobalamin II (TCII).

• Folate necessary for DNA synthesis is not met by low levels of vitamin B 12 .

CHEMISTRY :

Vitamin B12 is called cyanocobalamin.

Cooking has little effect on its activity.

Vitamin B12 is not a single substance but consists of cyanocobalamin, hydroxycobalamin and
nitrocobalamin.

FUNCTIONS :

1. Vitamin B12 works in conjunction with THF in the synthesis of nucleoproteins for DNA and RNA
synthesis and for the formation of Hb.

2. Vitamin B12 functions in the synthesis of myelin sheath and the transfer of folate into cells.
3. The replication of gastrointestinal cells, bone cells and nerve cells depend on vitamin B12
involvement in DNA synthesis.

4. Vitamin B12 also functions in protein, fat and carbohydrate metabolism.

DEFICIENCY :

Causes-

Low dietary intake, Nitrous oxide (inactivates B12),

Impaired absorption-stomach(Pernicious anemia,Gastro intestinal surgery , digestive disorders, celiac


disease or Crohn's disease)

Neural tube defects in fetus, such as spina bifida and anencephaly.

Auto immune disorder with genetic predisposition associated with human leukocyte antigen (HLA-
A2,A3,B7 & A blood group.

Triad : Generalized weakness, a sore & painful tongue, numbness & tingling of extremities. (CNS
symptoms may appear in absence of anemia & irreversible).

Pernicious anemia or hunter addison anemia or addison biermer disease

ORAL MANIFESTATIONS:

HUNTERS GLOSSITIS OR MOELLERS GLOSSITIS : Glossitis, glossodynia & glossopyrosis along with
smooth , bald tongue (beefy red colored), aphthous ulcers.

Excess can mask vitamin B12 deficiency and inactivates phenytoin , an anticonvulsant drug used by
epileptics.

Anti pernicious anemia factor (cyano cobalamin) in treatment of trigeminal neuralgia ( massive doses
of 1000 mcg daily).

Treatment

MECOBALAMIN

PARENTERAL

Megaloblastic anemia: adult- 500 mcg daily IM/IV 3 times/ wk. maintenance dose : after about 2 mnth
of therapy, reduce dose to single admin of 500 mcg every 1-3 mnth.

• COBALVIT (mecobalamin 500 mcg; folic acid 1.5 mg tab)


• COBALVIT INJ (methyl cobalamin 1000mcg,thiamine 100 mg, pyridoxine 100 mg, D-panthenol
50 mg, niacinamide 10 mg /2ml ).

• METHOVIT INJ( vit C 150 mg, niacinamide 12mg,mecobalamin 200 mg,folic acid 0.7 mg;amp

• NUROKIND PLUS (methyl cobalamin 1.5mg,folic acid 1.5 mg,vit.B1 10mg,vit.B6 3mg,alpha lipoic
acid 100mg ; cap) –

Diabetic neuropathy & cardio vascular diseases.

IM Ampoules contains 100mg Thiamine (B1), 100mg Pyridoxine (B6) and 1mg Cyanocobalamine (B12)
Coated Tablets contains 100mg Thiamine (B1), 200mg Pyridoxine (B6) and 0, 2mg Cyanocobalamine
(B12)

VITAMIN B13- OROTIC ACID

SOURCES: Root vegetables such as: carrots, beets, potatoes, onions, and garlic.

• It is not really recognized as a vitamin, since it is manufactured by the body by intestinal flora.

• It is primarily used for metabolization of folic acid and vitamin B12.

• It assists the absorption of essential nutrients especially calcium and magnesium and helps
the production of genetic material.

• It may be beneficial after a heart attack and has been used in conditions such as multiple
sclerosis and chronic hepatitis.

• It is also reported to prevent liver-related complications and premature aging

VITAMIN B15:-PANGAMIC ACID

• Good sources : whole grain cereals, brown rice,, pumpkin and sesame seeds, organ meats and
eggs.

USES:

• Angina, Asthma, Hypertension, Emphysema, Alcoholism, Cancer, Cirrhosis of the liver,


Hepatitis, Arteriosclerosis, Lowering cholesterol levels, Headaches, Emotional and mental
stress & Shown to decrease severity of pain and morning stiffness in rheumatoid arthritis
sufferers.

DOSAGE: 3 tablets daily

DEFICIENCY AND TOXICITY:

• There are no known toxic effects & side effects from even high amounts ; 50–100 mg (&
greater) 3 times/d .
VITAMIN C :- ASCORBIC ACID

SOURCES

• Fruits: Citrus fruits and juices(orange and grape), Mango,Papaya, Pineapple, Strawberries,
raspberries, blueberries, Watermelon.

• Vegetables: Cauliflower ,Green and red peppers, Spinach, cabbage, Sweet potatoes,
Tomatoes.

RDA: Infants-35mg , Adults-60mg ,Pregnant & lactating women- increase by 20mg & 40mg
respectively.

DISCOVERY :-

 In 1953, a Scottish surgeon, James Lind first described scurvy.


 In 1932, C.G. King isolated vitamin C from lemons and identified it as the ‘antiscorbutic’
(scurvy-preventing) vitamin.
 Because this vitamin was the third to be discovered, it was called vitamin C. It is also
called ascorbic acid (a shortened form of antiscorbutic) because it is an acid with
antiscorbutic properties.

Food sources :

Amla is the richest natural source.

Other good sources are citrus fruits such as orange, lemon, grapefruit. It is also present in gram,
sprouted green gram.

Fresh meat and milk contain only small quantities.

Chemistry :

 water soluble

 strong reducing properties

Absorption :

 actively transported by a sodium-dependent mechanism.

 passive diffusion

Humans, other primates, and the guinea pig, unlike other animal species, cannot
synthesize ascorbic acid in their tissue. Therefore, they require a daily dietary source of this vitamin.
Storage :

no extensive storage

adrenal cortex, contain relatively large amounts of ascorbic acid. Leukocytes

Functions :

1. Vitamin C has a key role in the formation of collagen & intercellular material, bone & teeth, & in the
course of wound healing.

2. Ascorbic acid functions as a cofactor for hydroxylation reactions such as formation of


hydroxyproline and hydroxylysin which is necessary in the synthesis of collagen.

3. Vitamin C is involved in phagocytosis and acts as a detoxifying agent.

4. Vitamin C is involved in reduction of minerals, eg., ferric iron to ferrous iron and hence vitamin C
enhances iron absorption and plays a number of roles that relate to hematology.

5. The participation of vitamin C in the synthesis of hormones by the adrenal glands may account for
its high concentration in adrenal tissues.

6. Although it had been thought that vitamin C supplementation might exert an antistress action, this
has not shown to take place in humans.

7. Ascorbic acid is used as a food additive antioxidant to prevent enzymatic browning of fruits and
potatoes.

• Hydroxylation reactions have the most common nutritional role for vitamin C.

• It is also essential in the synthesis of nor—epinephrine, serotonin carnitine.

• Besides the action as an antioxidant, it also acts as chemopreventive agent by decreasing


nitrosation and also affect the action microphages and leukocytes.

• Vitamin C readily scavenges reactive oxygen and nitrogen species, such as superoxide and
hydroperoxyl radicals, aqueous peroxyl radicals, singlet oxygen, ozone, peroxynitrate,
nitrogen dioxide, nitroxide radicals, and hypochlorous acid, thereby effectively protecting
other substrates from oxidative damage.

• Vitamin C can also act as a coantioxidant by regenerating α-tocopherol from the α-


tocopheroxyl radical, produced via scavenging of lipid-soluble radicals.

DEFICIENCY OF VITAMIN C :

Severe vitamin C deficiency results in scurvy.


CLINICAL FEATURES :

 hemorrhagic diathesis

 retardation of wound healing.

 Bleeding, swollen, spongy gingiva

 loosened teeth

 hemorrhagic lesions into the muscles of the extremities, the joints, and sometimes the nail
beds

 petechial hemorrhages, often around hair follicles

 increased susceptibility to infections

PATHOPHYSIOLOGY:

 defective formation and maintenance of collagen

 retardation or cessation of osteoid formation

 impaired osteoblastic function

 increased capillary permeability

 susceptibility to traumatic hemorrhages

 hyporeactivity of the contractile elements of the peripheral blood vessels

 sluggishness of blood flow

POSSIBLE ETIOLOGIC RELATIONSHIPS BETWEEN ASCORBIC ACID AND PERIODONTAL DISEASE

Woolfe et al 1980 have suggested that ascorbic acid may play a role in periodontal disease by one or
more of the following mechanisms:

1. Low levels of ascorbic acid influence the metabolism of collagen within the periodontium,
thereby affecting the ability of the tissue to regenerate and repair itself.

2. Ascorbic acid deficiency interferes with bone formation, leading to loss of periodontal bone.

3. Ascorbic acid deficiency increases the permeability of the oral mucosa and of normal human
crevicular epithelium.
4. Increasing levels of ascorbic acid enhance both the chemotactic and migratory action of
leukocytes without influencing their phagocytic activity.
5. An optimal level of ascorbic acid is apparently required to maintain the integrity of the
periodontal microvasculature, as well as the vascular response to bacterial irritation and
wound healing.
6. Depletion of vitamin C may interfere with the ecologic equilibrium of bacteria in plaque and
thus increase its pathogenicity.

TOXICITY :
Ordinarily ascorbic acid is not toxic.

The eyes, adrenal glands and brain have the ability to store high concentration of vit. C for
about 3 months.

The toxicity symptoms include:

 gastrointestinal upset
 diarrhea
 orange-colored urine
 interference with anticoagulants
 iron toxicity
 production of oxalates or kidney stones

Treatment-

Scurvy: Adult - 25-75mg daily(prevention) &


treatment > / = 250 mg daily in divided doses(also given via IM/ IV/ SC ).
Child - 1mnth to 4 yr - 125-250 mg daily
4 to 12 yr - 250- 500 mg
12 to 18 yr - 500 mg – I g

CONCLUSION:-

• Organic compounds that regulate body functions and promote growth.

• Vegans should be conscious of vitamin B12 intake because it is not present in plant foods.

• Some conditions warrant an increase in vitamin C intake, such as exposure to cigarette smoke,
environmental stress, growth, and sickness.

• Using megadoses of multivitamins or supplements is not recommended.