Download vitamin B 1

Vitamins B group

Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 or Vitamin P or Vitamin PP (Niacin)
Vitamin B5 (Pantothenic acid)
Vitamin B6 (Pyridoxine and Pyridoxamine)
Vitamin B7 or Vitamin H (Biotin)
Vitamin B9 or Vitamin M and Vitamin B-c (Folic acid)

Vitamin B12 (Cyanocobalamin)
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Vitamin B1 (Thiamine)
Composed of a substituted pyridine and thiazole ring.
Thiamine (vitamin B1) was the first of the water-soluble Bvitamin family to be discovered.
Natural Sources
Thiamine are found in many nuts, seeds, brown rice,
seafood, and whole-grain products (Grains are stripped
of the B vitamin content during processing).
Sunflower seeds are a particularly good source.
Legumes, milk, and beef liver.
Stability



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Thiamine is destroyed by prolonged heat.
Food should be cooked in small amounts of water so that
thiamine and other water-soluble vitamins don't leach out.
Baking soda should not be added to vegetables as it breaks
Vitamin B1.
Avoid sulfite preservatives as it breaks Vitamin B1.
Drinking tea with a meal will also drastically decrease the
amount of thiamine that is absorbed by the body.
Vitamin B1 is stable in acid, unstable in aqueous solutions
of PH more than 5.
It is readily oxidized by exposure to the atmospheric
oxygen or by oxidizing agents to thiochrome. (blue
fluorescence), used for the quantitative fluoremetric assay
Role of Thiamine

It is an Co-factor for carbohydrates metabolism
(Kreb’s Cycle). This role enable conversion of blood
sugar (glucose) into biological energy. This is
important for:






Provide energy to the brain.
Improve transmission of nerve impulses through the nerves
by providing them with energy.
Proper function of the heart muscles.
Healthy mucus membrane.
Maintenance of smooth and skeletal muscles.
Formation of RBC’s.

In mammalian cells:


Thiamine HCl is converted to Thiamine Pyrophosphate Cofactor using ATP.
Thiamine pyrophosphate (TPP) is a coenzyme for:
pyruvate dehydrogenase.
 α-ketoglutarate dehydrogenase.
These enzymes function in the metabolism of carbohydrates.
 Transketolase. Transketolase functions in:
 The pentose phosphate pathway to synthesize
NADPH.
 The pentose sugars deoxyribose and ribose involved in
nucleic acids biosynthesis.

Required Daily Amount

The daily requirements are based on the
number of calories in diet.
It is about 0.5 mg/1000 calories.
Average 1.5 mg/ day for 3000 calories.

Daily requirement increase with high
carbohydrate intake and for hard worker or
athletes.
Structure Activity Relationship (SAR)
Essential features for activity:
Methylene bridge.
Amino group in the pyrimidine ring.
Hydroxy ethyl group at the thiazole ring.
Methyl group of pyrimidine ring, when replaced by:
a- Ethyl or propyl groups gives an active compound.
b- Butyl group gives inactive compound.
N
Me
S
NH2
CH2CH2OH
N
N
Me
Vitamin antagonists


Oxythiamine is a competitive inhibitor.
Neopyrithiamine prevent phosphorelation of
hydroxy ethyl group that is essential for activity of
the vitamin.
Pyridine Ring
N
Me
S
OH
CH2CH2OH
N
N
NH2
N
CH2CH2OH
N
Me
Oxythiamine

N
Me
Me
Neopyrithiamine
Thiaminase in raw fish destroy vitamin B1
Causes of Deficiency
A lack of thiamine can be caused by:
Malnutrition.
A diet high in thiaminase-rich foods (raw freshwater fish, raw
shellfish, ferns)
Foods high in anti-thiamine factors (tea, coffee, nuts).
Chronic consumption of alcohol.
Diagnostic Testing for B1 Deficiency
A diagnosis test for B1 deficiency can be determined by measuring
transketolase levels of erythrocyte
Deficiency
Beriberi: The syndrome typically causes poor appetite,
abdominal pain, heart enlargement, constipation,
weakness, swelling of limbs, muscle spasms, insomnia,
and memory loss (all reversed on treatment).
Wernicke-Korsakoff syndrome: Resulted from untreated
Beriberi and characterized by confusion, disorientation,
inability to speak, numbness or tingling of extremities,
edema, nausea, vomiting, visual difficulties, and may
progress to psychosis, coma, and death. Even in advanced
states, this condition can be reversible if B1 is given.
Risk Factors for Deficiency
The leading risk factor for thiamine deficiency is alcoholism.
Alcohol acts directly to destroy thiamine and increases it’s
excretion.
Liver cirrhosis, malabsorption syndromes, diabetes, kidney
disease, or hypermetabolic conditions also have increased
susceptibility to B1 deficiency.
The elderly peoples with poor nutritional status and difficulties
with absorption.
Others with nutritionally inadequate diets, or an increased need as
a result of stress, illness, or surgery may benefit from additional
vitamin B1 intake.
Use of tobacco products, or carbonate and citrate food additives
can impair thiamine absorption.
Side Effects
In very unusual, large doses of thiamine may cause rashes,
itching, or swelling. These reactions are more common with
intravenous injections than oral supplements.
Interactions
Oral contraceptives, antibiotics, sulfa drugs, and certain types
of diuretics may lower thiamine levels in the body.
Taking this vitamin may also intensify the effects of
neuromuscular blocking agents that are used during some
surgical procedures.
B vitamins are best absorbed as a complex, and magnesium
also promotes the absorption of thiamine
Vitamin B2
Riboflavin, lactoflavin, Vitamin G
CH 2OH
Ribose moiety
(HO-C-H)3
CH 2
Me
N
N
O
Isoalloxazine moiety
Me
NH
N
O
Vit B2 = Riboflavin
It chemically has a three rings structure (isoalloxazine) linked
to ribityl moiety.
Riboflavin is a yellow to orange- yellow powder, soluble in
water (1:3000 to 1:20000) due to internal crystalline structure,
urea or niacinamide are used to solubilize riboflavin when high
concentrated solution needed.
Natural Sources
 Milk, cheese, egg white and liver.
 leafy green vegetables, almonds and mature soybeans
 Yeast.
Other sources:
 Added as food colouring
 Fortify some foods as baby foods, breakfast cereals,
sauces, processed cheese, fruit drinks and vitaminenriched milk).
Required Daily Amount

1.3- 1.6 mg/day.
Stability
Vitamin B2 is unstable to light in both acidic
and basic medium.
 Under acidic condition light produce
lumichrome.
 In alkaline PH light produce
lumiflavin.
Both are inactive biologically.
CH 2OH
(HO-C-H)3
CH 2
N
Me
N
O
NH
Me
N
O
Light (OH)
medium
Vit B2 = Riboflavin
CH 3
Me
Me
N
N
O
NH
N
Me
Me
Light in (H)
medium
N
O
NH
N
O
O
Lumiflavine
H
N
Lumichrome
Role of Vitamin B2

Riboflavin is converted to the active forms:
Riboflavin-Mononucleotide more correct RiboflavinMonophosphate (FMN).
 Riboflavin-Adenine Dinucleotide more correct
Riboflavin-Adenine Diphosphate (FAD).

The Active forms work as co-enzymes for about 150
oxidation-reduction reactions involved in:
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Carbohydrate, Proteins and fat metabolism
Activation of vitamin B12 and folate.
Protection of erythrocytes and other cells from oxidative stress.
Absorption
Riboflavin is absorbed in the proximal
intestine.
Riboflavin is stored mainly in the liver, kidney
and heart in the form of FAD (70- 90%) or
FMN or Riboflavin.
Causes of Riboflavin Deficiency
 Not getting enough of the vitamin from the diet.
 A result of conditions that affect absorption in the
intestine.
 The body not being able to use the vitamin.
 An increase in the excretion of the vitamin from the
body.
Ariboflavinosis
Symptoms of riboflavin deficiency:
 Cracked and red lips.
 Inflammation of the lining of mouth and tongue.
 Mouth ulcers, angular cheilitis.
 Dry and scaling skin and iron-deficiency anemia.
 The eyes become bloodshot, itchy and sensitive to
bright light.
Angular cheilitis: is an inflammatory lesion at the
corner of the mouth. Usually associated with a fungal
(Candidal) or bacterial (Staphylococcal) infection The
condition manifests as deep cracks or splits. In severe
cases, the splits can bleed when the mouth is opened.
Diagnostic Testing of B2 Deficiency
A positive diagnostic test of serum riboflavin by
measuring glutathione reductase levels of
erythrocytes.
Risk Factors for Deficiency

People under high stress, including those experiencing
surgery, chronic illnesses, liver disease, or poor
nutritional status.

Diabetics have a tendency to be low on riboflavin as a
result of increased urinary excretion.

Athletes, and anyone else with a high-energy output
will need additional vitamin B2.

The elderly due to nutritional inadequacy as well as
problems with absorption.
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Smokers and alcoholics are at higher risk for
deficiency as tobacco and alcohol suppress
absorption.

Birth control pills may possibly reduce riboflavin
levels, as can phenothiazine tranquilizers, tricyclic
antidepressants, and probenecid.

Recent advances in human genetics indicate that
certain genotypes are at greater risk for riboflavin
deficiency than others.
Uses

High doses of riboflavin(400 mg/day) have been
shown to reduce the frequency and severity of
migraine headaches by half in susceptible people.

Riboflavin help decrease the incidence of cataracts.

Improve memory.

Riboflavin and vitamin C both help boost the body's
level of glutathione which is an antioxidant.

Healthy development of the fetus.
Interactions
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Probenecid (anti-gout) and propantheline bromide
(anti-peptic ulcers) both delays and impairs
absorption.
Phenothiazines (antipsychotic drugs) increase the
excretion of riboflavin, thus lowering serum levels.
Oral contraceptives may also decrease serum levels.
Tricyclic antidepressants may lower the levels of
riboflavin in the body.
Absorption of riboflavin is improved when taken
together with other B vitamins and vitamin C.
Riboflavin interferes with the absorption and
effectiveness of anti-malarial (ex. chloroquine),
tetracycline antibiotics and sulfa-containing drugs.
Assay

Direct fluoremetry.

Lumiflavin method in which riboflavin is
irradiated in alkaline medium to yielded a
chloroform-soluble lumiflavin, measured
fluoremetry. It is preferred in biological
samples.
Vitamin B3
(Niacin, Nicotinic acid, Nicotinamide,
Vitamin P, Vitamin PP)
CONH2
COOH
N
Nicotinic acid
N
Nicotinamide
Natural Sources

Tuna is one of the best sources of niacin.

Most processed grain products are fortified
with niacin.

Cottage cheese, milk are highest in
Tryptophan and about half of the Tryptophan
consumed is used to make niacin.
Required Daily Amount

About 7 mg/ 1000 calories.

13- 20 mg/day.
Role of Vitamin B3

It is act as co-enzyme in oxidation-reduction
reactions:

Catabolic reactions:
 NAD+/NADH

Anabolic reactions:
 NADP+/NADPH
Pharmacokinetics

Absorption:
At low concentration by active transportation.
 At high concentration by passive diffusion.
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Transportation:
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Both Nicotinic acid (NA) AND Nicotinamide (NAm)
bind to plasma proteins for transportation.
Biosynthesis:

The liver can synthesize Niacin from the essential
amino acid Tryptophan, but the synthesis is extremely
slow and requires vitamin B6 (60 mg of Tryptophan=
1mg of niacin). Bacteria in the gut may also perform
the conversion but are inefficient.
Required Daily Amount

13- 20 mg/day
Deficiency

Pellagra: A serious deficiency of niacin. The
main results of pellagra can easily be
remembered as "the four D's": diarrhea,
dermatitis, dementia, and death. It is very
rare now, except in alcoholics, strict
vegetarians, and people in areas of the world
with very poor nutrition.

Milder deficiencies of niacin can cause
dermatitis around the mouth and rashes,
fatigue,
irritability,
poor
appetite,
indigestion, diarrhea, headache.
Risk Factors for Deficiency
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Vegans, and others who do not eat animal protein,
should consider taking a balanced B vitamin
supplement.
Others people under high stress, chronic illnesses, liver
disease may need extra niacin and other B vitamins.
People over 55 years old are more likely to have a poor
dietary intake.
Certain metabolic diseases also increase the requirement
for niacin.
Those who abuse nicotine, alcohol or other drugs are
very frequently deficient in B vitamins, but use of niacin
with alcohol can cause seriously low blood pressure.
General Uses
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Niacin in very large doses (2-3 g/day) is used
to decrease blood cholesterol levels and
reduce the risk of heart attack.
In certain conditions (gout, diabetes, peptic
ulcer, liver or kidney disease, and high
blood pressure).
Niacinamide used on a long-term basis to
prevent the onset of juvenile diabetes
(children).
Treatment of Pellagra.
Side Effects
In large amounts Niacin commonly causes
flushing and headache. This can be avoided by
taking it in the form of inositol hexaniacinate.
Interactions

Niacin with high blood pressure medication may cause
hypotension.

Isoniazid inhibits the body's ability to make Niacin
from tryptophan. Extra niacin may be required.

Supplements may also be needed by women taking oral
contraceptives.

Cholestyramine and cholestipol (medications to lower
cholesterol) should be taken at a different time than
Niacin or they will reduce its absorption.

Transdermal Nicotine used with Niacin is likely to
cause flushing and dizziness.

Carbamazepine (an antiseizure medication) is more
likely to cause toxicity in combination with niacin.

Nicotinic acid reacts with hemoglobin and myoglobin
in meat to form a brightly coloured complex, and thus
has been used as a food additive, typically to improve
the colour of ground meat.

Concomitant use of Niacin with Statin class drugs to
lower cholesterol can cause myopathy.
Vitamin B5
(Pantothenic acid)


It is a peptide substance composed of Pantoic acid and bAlanine.
It can be present as the Calcium salt or the Alcohol
“Pantothenol”.
Pantoic acid CH3 OH
HO
CH2 C
CH
b-Alanine
O
C
NH
CH2 CH2 COOH
CH3
Pantothenic Acid
CH3 OH
HO
CH2 C
CH
O
C
NH
CH3
Pantothenol
CH2 CH2 CH2OH
Natural Sources

Animal Sources:
Liver, kidney and Heart.
 Milk and Milk Products (Cheese, Yogurt and Butter).

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Plant Sources:
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Cereals
Honey and Molasses.
Yeasts.
Role of Vitamin B5

It is a part of Co-enzyme A that assists the
following reactions:

Formation of Sterols
Dehydrocholesterol).
(Cholesterol
and

Formation of Fatty acids.

Formation of Keto acids such as Pyruvic acid.
7-
Required Daily Amount



4 Years and over 10 mg
Less than 4 years 5 mg
Infants 3 mg
Deficiency


Rare to occur.
When occur it leads to Paresthesias (is a sensation
of tingling, pricking, or numbness of a person's skin).
Uses:



Treat and prevent deficiency state.
Supplements in cases of inadequate diet.
It is Described for:
Diabetic neuropathy.
 Arthritis.
 In hair dyes.

Uses of Dexpantothenol

Topically for:
Burning
 Itching
 Irritation


To Relive gas retention.
Vitamin B6
Pyridoxine
CH2OH
CHO
HO
H3C
CH2OH
HO
N
H3C
Pyridoxol
H3C
CH2OH
N
Pyridoxine
N
Pyridoxal
CH2NH2
HO
CH2OH
COOH
HO
H3C
CH2OH
N
Pyridoxic Acid
Natural Sources

Vitamin B6 is found in: Cereals, Beans,
Meat, Liver, Fish, Yeast, Nuts and some
fruits as Banana and Potatoes.

It is also produced by bacterial flora in the
colon.
Role of Vitamin B6

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
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Vitamin B6 is needed for more than 100 enzymes
involved in protein metabolism.
It is also essential for red blood cell metabolism and
hemoglobin formation.
The nervous and immune systems need vitamin B6 to
function efficiently.
It is also needed for the conversion of Tryptophan (an
amino acid) to Niacin (Vitamin B3).
Vitamin B6 also helps maintain blood glucose within a
normal range. When caloric intake is low vitamin B6
help to convert stored carbohydrate or other nutrients
to glucose to maintain normal blood sugar levels.
Required Daily Amount

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





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
Babies under six months 0.3 mg
Babies Six months to one year old 0.6 mg.
Children 1- 3 years old 1.0 mg
4- 6 years old 1.1 mg
7- 10 years old 1.4 mg
Males aged 11-14 years 1.7 mg
15 years and older 2.0 mg
Females 11-14 years 1.4 mg
Female 15- 18 years 1.5 mg
Women age 19 years and older 1.6 mg
Pregnancy 2.2 mg
Lactation (2.1 mg).
Adults 1.4- 2.2 mg
Causes of Deficiency

Individuals with a poor quality diet or an
inadequate B6 intake.

Alcoholics because alcohol also promotes the
destruction and loss of vitamin B6 from the
body.

Older people.

Asthmatic children treated with theophylline
because it decreases body stores of vitamin B6.
Deficiency
Signs of vitamin B6 deficiency include:

Skin: Dermatitis (skin inflammation), Stomatitis
(inflammation of the mucous lining of any of the
structures in the mouth), Glossitis (is inflammation
or infection of the tongue ).

Neurological
abnormalities:
Depression,
confusion, and convulsions.

Vitamin B6 deficiency also can cause anemia.
Uses
Treatment and Prevention of deficiency.
 For people are high risk of deficiency.
 Can also described in:

 Acne
 Kidney
stones
 Premenstrual syndromes
 Improve some CNS conditions.
Side Effects

Too much vitamin B6 can result in nerve
damage to the arms and legs. This
neuropathy is usually related to high
intake of vitamin B6 and is reversible
when supplementation is stopped.
Interaction

Some Drugs increase the excretion of
Vitamin B6 by the body as:
 Chloramphenicol.
 Oral
Contraceptives.
 Cycloserine.
 Isoniazide.
 L-Dopa
Vitamin B7
(Vitamin H, Biotin, Growth Factor, Co-enzyme R)

It is 2-Imidazolidinone tetrahydrothiophene-4-valeric
acid.
H
H
N
S
H
O
H
N
H
(CH2)4-COOH
Natural Sources







Liver.
Meat.
Kidney
Yeast
Egg yolk
Mushrooms
Milk and milk products.
Role of Vitamin B7




It is a co-enzyme for several carboxylation
reactions.
Important for carbon dioxide fixation.
Important for Carbohydrates and Fats metabolism.
Co-factor for Pyruvate carboxylase.
Required Daily Amount

100- 200 mg/day.
Deficiency
Only induced in experimental animals not observed in
human:
 Skin lesions
 Retarded growth
 Hair loss
Biotin Antagonists

Structural analogs:
Biotin sulfonate
 Desthiobiotin
 Imidazolidone acids.


Avidin in Raw egg combines and inactivate
Biotin.
Uses




Treat and prevent deficiency conditions.
Supplement in cases of inadequate diet.
In vitamin B-Complex to improve glucose
metabolism.
In skin disease as Acne and Dermatitis.
Vitamin B9
(Vitamin M, Vitamin B-c, Folic acid )

Conjugate of Pteridine, p-Aminobenzoic acid and
Glutamic acid.
Pteridine
N
H2N
N
p-Aminobenzoic acid
N
N
OH
CH2 NH
O
C
Glutamic acid
COOH
NH CH
CH2
CH2
COOH
Natural Sources





Liver.
Yeast
Fruits
Leafy Vegetables
Milk and milk products.
Role of Vitamin B9
Folic acid
Folic Acid
reductase
Dihydrofolate Dihydrofolic acid
(DHF)
reductase
Tetrahydrofolate
(THF)
THF act as Co-enzyme for:
 Leucopoiesis (Production of Leukocytes).
 Erythropoiesis (Production of Erythrocytes).
 Nucleoprotein synthesis.
Required Daily Amount

0.1- 0.8 mg/day.
Deficiency
Very rare due to:
 Malabsorption (due to alcoholism).
 Impaired Hepatic functions (due to alcoholism).
Leads to:
 Glossitis (is inflammation or infection of the tongue ).
 Megaloblastic anemia
 Leucopenia
Biotin Antagonists

Structural analogs:

Sulfonamides.
Uses



Treat and prevent deficiency conditions.
Supplement in cases of inadequate diet.
Treatment of chronic intestinal and liver
diseases.
B vitamins Deficiency
Vitamin B1 (Thiamine) deficiency causes Beriberi.
Symptoms of this disease of the nervous system include weight loss,
emotional disturbances, Wernicke's encephalopathy (impaired
sensory perception), weakness and pain in the limbs, periods of
irregular heartbeat, and edema (swelling of bodily tissues). Heart
failure and death may occur in advanced cases. Chronic thiamine
deficiency can also cause Korsakoff's syndrome, an irreversible
psychosis characterized by amnesia and confabulation.
Vitamin B2 (Riboflavin) deficiency causes Ariboflavinosis.
Symptoms may include cheilosis (cracks in the lips), high sensitivity
to sunlight, angular cheilitis, glossitis (inflammation of the tongue),
seborrheic dermatitis or pseudo-syphilis (particularly affecting the
scrotum or labia majora and the mouth), pharyngitis, hyperemia,
and edema of the pharyngeal and oral mucosa.
Vitamin B3 (Niacin) deficiency, along with a
deficiency of tryptophan causes Pellagra.
Symptoms include aggression, dermatitis,
insomnia, weakness, mental confusion, and
diarrhea. In advanced cases, pellagra may lead
to dementia and death.
Vitamin B5 (Pantothenic acid) deficiency can
result in acne and Paresthesia, although it is
uncommon.
Vitamin B6 (Pyridoxine) deficiency may lead to
anemia, depression, dermatitis, high blood
pressure (hypertension) and elevated levels of
homocysteine.
Vitamin B7 (Biotin) deficiency does not typically
cause symptoms in adults but may lead to
impaired growth and neurological disorders in
infants.
Vitamin B9 (Folic acid) deficiency results in
elevated levels of homocysteine. Deficiency in
pregnant women can lead to birth defects.
Vitamin B12 (Cyanocobalamin) deficiency causes
pernicious anemia, memory loss and other
cognitive decline. It is most likely to occur among
elderly people as absorption through the gut
declines with age. In extreme (fortunately rare)
cases paralysis can result.
Vitamin B12
(Cyanocobalamin, Antipernicious anemia factor)
Structure
B12 is the most chemically complex of all the vitamins. The
structure of B12 is based on a Corrin ring, similar to the
Porphyrin ring found in Heme, Chlorophyll, and
Cytochrome. The central metal ion is Co (cobalt). Four of
the six coordinations od Co are provided by the Corrin ring
nitrogens, and a fifth by a dimethylbenzimidazole group.
The sixth coordination can be:
 Cyano group (-CN) Cyanocobolamin
 Hydroxyl group (-OH) Hydroxycobalamin
 Methyl group (-CH3) Methylcobalamin (MeB12)
 5'-deoxyadenosyl group Adenosylcobalamin (AdoB12).
Natural Sources



Bacteria such as Streptomycin and Bacillus
present in the intestinal flora produce the vitamin
required for man and animals.
The vitamin is stored in the liver with estimated
t1/2 400 days.
B12 can be obtained from animal products only
such as:
Liver and Meat
 Fish and Eggs
 Milk and Dairy products

Pharmacokinetics

Vitamin B12 in food is bound to the protein.

Hydrochloric acid in the stomach releases
free vitamin B12.

Once released vitamin B12 combines with a
substance called intrinsic factor (IF). This
complex can then be absorbed by the
intestinal tract.
Role of Vitamin B12




Essential for the maturation of Erythrocytes.
Protects against Pernicious anemia.
Essential for cell growth and reproduction.
Essential for the formation of myelin and
nucleoproteins.
Required Daily Amount
Males and
Females (μg/day)
Pregnancy
(μg/day)
Lactation
(μg/day)
1-3
0.9
N/A
N/A
4-8
1.2
N/A
N/A
9-13
1.8
N/A
N/A
14-18
2.4
2.6
2.8
19 and older
2.4
2.6
2.8
Age (y)
Causes of deficiency





Inability to absorb vitamin B12 from food.
Vegetarians who do not consume any
animals products.
Stomach or intestinal disorder that limits
the absorption of vitamin B12.
Inadequate production of intrinsic factor
(pernicious anemia).
Competition for available B12 by parasites.
Symptoms of vitamin B12 deficiency

Pernicious Anemia: It is a type of Megaloblastic
anemia characterized by decreased number of
enlarged red blood cells.

Neurological changes such as numbness and tingling
in the hands and feet.

Demyelination and irreversible nerve cell death.

Difficulty in maintaining balance,
confusion, dementia, poor memory.
depression,

In infants cause movement disorders and delayed
development
Uses





Treat and prevent deficiency conditions in
combination with the intrinsic factor.
Supplement in cases of inadequate diet or
patient receiving antagonists.
Radioactive B12 to diagnose Pernicious anemia.
In combination with Folic acid to treat
Megaloblastic anemia.
Large doses (5- 10 g IV) of Hydroxycobalamin
used in cyanide poisoning where it combine
with cyanide ion to form harmless B12.
Interaction

Some Drugs interfere with it absorption such as:

Alcohol, Aminosalicylic acid, Colchicine, Neomycin,
Cholestyramine (Questran®), anticonvulsants (Phenytoin),
the metformin (Glucophage®).

Vitamin C supplements can destroy dietary vitamin
B12 and should be taken 2 hrs after meals.

H2 blockers include cimetidine, Proton pump
inhibitors (PPIs) (omeprazole) reduce secretion of
gastric acid and pepsin as a result reduce absorption
of protein-bound (dietary) vitamin B12.
Vitamin C
(Ascorbic acid, Anti- Scurvy)



Vitamin C is a water-soluble vitamin.
Almost all animals and plants synthesize
their own vitamin C.
Vitamin C was first isolated in 1928 and in
1932 it was proved to be the agent which
prevents scurvy.
Chemistry




Vitamin C is a weak acid, called Ascorbic
acid or its salts “Ascorbate”.
It is the L-enantiomer of Ascorbic acid.
The D-enantiomer shows no biological
activity.
Commercial vitamin C is often a mix of
Ascorbic acid, Sodium ascorbate and/or
other Ascorbates.
OH
O
HO
O
H
HO
OH
Sources

Vitamin C is obtained through the diet by
the vast majority of the world's population.
The richest natural sources are fruits and
vegetables.
Plant source
Amount
Plant source
Amount
Plant source
Amount
Plant
source
Amount
plum
3150
Apricot
10
Papaya
60
Lettuce
4
Camu Camu
2800
Plum
10
Strawberry
60
Cucumber
3
Wolfberry
2500
Watermelon
10
Orange
50
Eggplant
2
Rose hip
2000
Banana
9
Lemon
40
Fig
2
Acerola
1600
Carrot
9
cantaloupe
40
Bilberry
1
Red pepper
190
Avocado
8
Cauliflower
40
Horned
melon
0.5
Parsley
130
Crabapple
8
Grapefruit
30
Medlar
0.3
Guava
100
Peach
7
Papaya
60
Lettuce
4
Kiwifruit
90
Apple
6
Strawberry
60
Cucumber
3
Broccoli
90
Blackberry
6
Orange
50
Eggplant
2
Loganberry
80
Beetroot
5
Lemon
40
Fig
2
Redcurrant
80
Pear
4
cantaloupe
40
Spinach
30
Mandarin
30
Lime
20
Tomato
10
Mango
20
Chemical Synthesis
H
HO
H
H
CHO
CH2OH
OH
H
OH
H
H
Reduction HO
Acetobacter
H
OH
OH
Oxidation
H
OH
OH
CH2OH
CH2OH
CH2OH
H
HO
H
H
OH
C=O
CH2OH
Sorbitol
Glucose
OH
Sorbose
OH
H
O
HO
O
H
HOH2C
HO
H
HO
OH
Ketal formation
Acetone
protection of
O-dihydroxy
Lactonization
CH2OH
OH
O
H HO
CH2OH
CH2OH
H
OH
H
OH
HO
H
OH
HO
Enolization
H
H
OH
C-OH
C=O
COOH
COOH
H
H
Oxidation
Hydrolysis
O
O
CH2
O
O
O
H
CH2OH
Stability




Ascorbic acid is reversibly oxidized to LDehydroascorbic acid on exposure to copper,
heat and / or mild alkaline.
Both ascorbic and dehydroascorbic acids are
physiologically active forms of vitamin C.
Further oxidation of L- Dehydroascrbic acid
to 2,3-Diketo- gluconic acid and oxalate is
irreversible.
Ascorbic acid is strong reducing agent, serves
as an anti-oxidant and co-factor in
hydroxylation reactions.
Required Daily Amount


Adults: 60 mg/day
Children: 30 mg/day
Role of Vitamin C

It is a cofactor in the synthesis
norepinephrine from dopamine.
of

Vitamin C is also involved in a variety of
metabolic processes including oxidationreduction reactions and cellular respiration,
carbohydrate metabolism, synthesis of lipids
and proteins.

vitamin C are attributed primarily to
antioxidant and free radical scavenging effects
that maintain proper immune system.

T-lymphocyte activity, phagocyte function,
leukocyte mobility, and possibly antibody and
interferon production seem to be increased by
vitamin C.

Involved in the synthesis of Collagen the
major component of ligaments, tendons,
cartilages and skin.

Involved in tyrosine metabolism.
Vitamin C deficiency

Fatigue, personality changes, decline in psychomotor
performance and motivation.
Vitamin C deficiency over 3-5 months results in
Symptomatic Scurvy:
 In Adults: Scurvy leads to the formation of liver
spots on the skin, spongy gums, and bleeding from all
mucous membranes. The spots are most abundant on
the thighs and legs, and a person with the ailment
looks pale, feels depressed, and is partially
immobilized. In advanced scurvy there are open,
suppurating wounds and loss of teeth. Severe scurvy
may progress to neuritis, jaundice, fever, dyspnea,
and death.


In infants, symptoms: anorexia, irritability,
growth
retardation,
thigh
tenderness,
pseudoparalysis, bleeding around the lower ends of
the leg bones (femur and tibia) causing pain. If left
untreated, scurvy can proceed to collagen
deficiency, seizures, shock or sudden death.

It was common between Sailors, Pirates and others
who were on ships that were out to sea longer than
perishable fruits and vegetables could be stored.
Diagnosis of Scurvy

Fasting blood ascorbic acid levels:





levels below 0.10 mg/dL are considered deficient.
levels of 0.10-0.19 mg/dL are considered low.
levels of 0.2 mg/dL or greater are acceptable
levels greater than 0.6 mg/dL likely rule out scurvy.
White blood cell ascorbic acid concentration is
considered a more accurate measurement of vitamin
C nutritional status:




with a level of zero suggesting scurvy.
0-7 mg/dL suggesting deficiency.
8-15 mg/dL considered low.
15 mg/dL or greater is adequate vitamin C status.
Uses

Oral Vitamin C:
Preventing and treating scurvy.
 Preventing deficiency in people with gastrointestinal
diseases and those on chronic total parenteral nutrition
or chronic hemodialysis.
 Increasing iron absorption from the gastrointestinal
tract.
 Increasing the healing rate of wounds, burns, fractures,
ulcers, and pressure sores.
 Preventing and treating the common cold and other
viral infections, bronchitis, human immunodeficiency
virus (HIV) disease.

Topically Vitamin C is used for:

Improving skin conditions, protecting against
free radicals and pollutants.

Improving photo-aged skin.

It is also applied topically for ulcerative
mucositis associated with radiation therapy.
Parenterally Vitamin C is used for:
 Preventing and treating vitamin C deficiency.
 Correcting tyrosinemia in premature infants on
high-protein diets.
Other Effects of Vitamin C




Decrease the risk of atherosclerosis and
peripheral arterial disease.
decrease the risk of developing mouth cancer
and other cancers.
Taking high doses of vitamin C orally might
decrease the duration of cold symptoms by
doses of at least 2 g/day.
Taking vitamin C orally seems to decrease
gastritis associated with acid suppressive
therapy in patients with Helicobacter pylori
infection.

Topical vitamin C can decrease the degree
and duration of erythema.

Vitamin C orally along with antihypertensive
medications appears to decrease systolic
blood pressure, but not diastolic pressure.

Consuming vitamin C from dietary sources
seems to lower blood concentrations of lead
in cases of toxicity.

Reduce risk of Age-related mascular
degeneration (AMD).
Side Effects

Vitamin C is generally regarded as safe in amounts
obtained from foods side effects are rarely reported
including nausea, vomiting, heartburn, abdominal
cramps, and headache. Dental erosion may occur from
chronically chewing vitamin C tablets.

High doses/toxicity: High doses of vitamin C greater
than 2000 mg/day. These include kidney stones, severe
diarrhea, nausea, and gastritis. Large doses may
precipitate hemolysis in patients with glucose 6phosphate dehydrogenase deficiency.

Vitamin C is metabolized to oxalic acid. Increased
consumption increases the urinary concentration of
oxalic acid and increases the risk of oxalate stone
formation
Effect of Vitamin C on some Drugs

Chromium:
absorption.
Vitamin
C
increases
chromium

Copper: High doses of vitamin C (1500 mg daily) can
decrease serum levels of copper and the copper
transport protein.

Grape: Patients with hypertension who take both
vitamin C (500 mg/day) and grape seed polyphenols
(1000 mg/day) have significantly increased systolic
and diastolic blood pressure.

Vitamin B12: vitamin C can destroy dietary vitamin
B12. Vitamin C supplements must be taken at least 2
hours after meals.

Acetaminophen (Tylenol): High doses of vitamin C (3
g) competitively inhibits sulfate conjugation of
acetaminophen, increasing the half-life.

Aluminum: Vitamin C can increase the amount of
(Al) absorbed. Patients with renal failure who take
(Al) compounds chronically should avoid vitamin C
in doses above the RDA.

Aspirin: Acidification of the urine by vitamin C
could increase reabsorption of salicylates by the
renal tubules, and increase plasma salicylate levels .

Chemotherapy: Vitamin C (antioxidants) during
chemotherapy could reduce the activity of
chemotherapy drugs which generate free radicals.

Estrogens: Increases in plasma estrogen levels
of up to 55% occur under some circumstances
when vitamin C is taken concurrently with
oral contraceptives or hormone replacement
therapy including topical products.

Warfarin (Coumadin): High doses of vitamin
C may reduce the response to warfarin,
possibly by causing diarrhea and reducing
warfarin absorption.
Drugs affect Vitamin C level

Aspirin increases elimination of vitamin C. It
reduces tissue and leukocyte uptake of vitamin C,
leaving more in the plasma to be filtered into the
urine.

Diuretics increases urinary losses of vitamin C, due
to increased water excretion.

Estrogens can reduce vitamin C absorption or
increase its breakdown.

Smokers have lower plasma levels of vitamin C than
nonsmokers due to increased use of vitamin C to
counteract free radicals in cigarette smoke.
Doses

For scurvy, 100-250 mg once or twice daily.

For treating the common cold, 1-3 g daily.

During acute stress, vitamin C 1 g 3 times daily

For chronic hemodialysis in adults, 100-200 mg
per day is recommended.

For preventing sunburn, 2 g of vitamin C and
1000 IU vitamin E has been used.