Download Vitamin C, B1, B2 & B3

Water soluble vitamins
Vitamin C, B1, B2 & B3
VITAMIN C
It is water-soluble vitamin.
Most animals are able to synthesize all vitamin C
they need from dietary sugars; but humans are
unable.
Also, animals are able to increase synthesis of
vitamin C during stress but humans’ strictly
depend on dietary sources, increases risk of
deficiency during stress time.
Natural Source of Vitamin C
Plum
Broccoli
Lemon
Red pepper
Papaya
Grapefruit
Guava
Kiwifruit
Strawberry
Orange
Mango
Vitamin C
L- Ascorbic Acid
(Reduced Form)
L-Dehydroascorbic Acid
(Oxidised Form)
Physiologically active forms for vitamin C
RDA: Adults: 60 mg/day
Children: 30 mg/day
Chemistry and Stability of Vitamin C
It is a weak acid and its salts called ascorbate.
Unstable in alkaline pH, high temperature, and in
the presence of oxygen or metals.
The D-enantiomer of ascorbic acid shows no
biological activity.
Ascorbic acid is strong reducing agent, serves as an
anti-oxidant and co-factor in hydroxylation
reactions.
Ascorbic acid is reversibly oxidized to Ldehydroascorbic acid and both L-ascorbic and
L-dehydroascorbic acids are physiologically
active forms for vitamin C.
Functions of Vitamin C
Antioxidant function: It helps protect against oxidation by
free radicals.
Helps in detoxification and excretion of drugs :
It maintains the enzyme systems in liver that detoxify
and excrete drugs and toxic pollutants.
Synthesis of collagen: The major component of connective
tissue in skin, joints, muscles, bones ligaments,
tendons, and cartilages.
Involved in carnitine synthesis (along with niacin and
vitamin B6) which is an amino acid required in
breakdown of fats for energy.
It is a cofactor in the synthesis of neurotransmitters as
epinephrine , norepinephrine and serotonin.
Important for healthy immune function: It is essential for
optimum activity of WBCs and production of
chemical mediators which direct the immune response.
Vitamin C seems to increase T-lymphocyte activity,
phagocyte function, leukocyte mobility, and possibly
antibody and interferon production.
Involved in cholesterol breakdown and excretion
(cholesterol level increase if vitamin C status is
impaired).
Protection of folate and vitamin E from oxidation.
Involved in control of histamine levels: When vitamin C
status is poor
High levels of histamine
aggravate allergies, asthma, stomach ulcers, and
certain psychiatric disorders.
Symptoms of Vitamin C Deficiency
Scurvy: Impaired connective tissue synthesis and fragility of
blood vessels causes abnormal bleeding: easy bruising,
subcutaneous hemorrhagic spots, inflamed and
bleeding gums, joint stiffness and pain (due to
bleeding into joints).
Impaired wound healing.
Build-up of keratin in hair follicles producing rough
“sandpaper skin”.
Weakness, exhaustion, fatigue (due to impaired carnitine
synthesis).
Impaired immunity with increased risk of infection.
Diminished antioxidant defenses: increase risk of cancer,
heart disease, stroke, cataract.
Scurvy was common between Sailors, Pirates and others who were
on ships for months without eating fresh fruits and vegetables.
People at High Risk of Vitamin C Deficiency
1. Increased physical stress (e.g. infection, fever,
burns, surgery, trauma to soft tissues or bones,
and chronic illnesses such as hyperthyroidism,
diabetes, rheumatoid arthritis, alcoholism, and
kidney failure).
2. Chronic use of drugs such as aspirin and oral
contraceptives impair vitamin C status.
3. Older people, particularly those with chronic
illness, and aging.
4. Periods of rapid growth–childhood, adolescence,
pregnancy, and lactation.
5. Regular cigarette smoking sharply increases
breakdown and excretion of vitamin C.
Uses of Vitamin C in Prevention and Therapy
Enhance ability to fight infection: Vitamin C stimulates the
activity and ability of WBCs to destroy bacteria and
viruses.
Treatment of cold and flu: At doses of 1-2 g, it slightly
increases body temp.
functions of WBCs and
blood histamine
immune response and
nasal
and bronchial congestion
duration
and
symptoms of Cold and Flu.
 Helps reduce risk of cancer: particularly cancers of
GIT, bladder, breast, pancreas, and uterus
(antioxidant + enhancer for immune defenses
against cancer and + helps detoxify
carcinogenic
food additives e.g. nitrates, pesticides, and
other chemicals and heavy metals).
Large doses platelet aggregation
reduce risk of
blood clots. In addition, vitamin C the strength of
blood vessel walls. By these mechanisms, vitamin C
can protect from coronary heart disease,
thrombotic stroke, and peripheral vascular disease.
Protection from heavy metals: It absorption and
detoxification and excretion of heavy metals.
Improves healing of wounds and fractures in burns,
trauma, and surgery.
Iron deficiency (by iron absorption from meals).
Preventing and curing Scurvy.
Recommended Therapeutic Doses
For scurvy, 100-250 mg once or twice daily.
For treating the common cold, 1-3 g daily.
During acute stress, 1 g (3 times daily)
For preventing sunburn, 2 g of vitamin C and 1000 IU
vitamin E has been used.
Toxicity and Side Effects of Vitamin C
Vitamin C is generally regarded as safe in usual
doses (up to 1000 mg). Dental erosion may occur
from chronically chewing vitamin C tablets.
High doses of vitamin C more than 2000 mg/day may
induce kidney stones, severe diarrhea, nausea, and
gastritis. Large doses may precipitate hemolysis in
patients with glucose 6-phosphate 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.
Vitamin C- Drug Interaction
Vitamin C chromium and aluminium absorption. Patients
with renal failure who take (Al) compounds should
avoid vitamin C in doses above the RDA.
Vitamin C can destroy dietary vitamin B12 (so, it must be
taken at least 2 hours after meals).
 Acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and
increase plasma salicylate levels .
High doses of vitamin C can the response to warfarin,
possibly by causing diarrhea and reducing Warfarin
absorption
 Aspirin increases elimination of vitamin C. It reduces
tissue and leukocyte uptake of vitamin C, leaving
more in the plasma to be excreted into the urine.
Estrogens can
breakdown.
vitamin C absorption or
its
Vitamin B Group
1. Vitamin B1 (Thiamine)
5. Vitamin B6 (Pyridoxine)
2. Vitamin B2 (Riboflavin)
6. Vitamin B7 or Vitamin H
(Biotin)
3. Vitamin B3 (Niacin)
7. Vitamin B9 or Vitamin M
or (Folic acid)
4. Vitamin B5 (Pantothenic
acid)
8. Vitamin B12
(Cyanocobalamin)
Water Soluble Vitamins
Vitamin B Group
Vitamin B1 (Thiamine)
Vitamin B1 (Thiamine)
The 1st water-soluble B-vitamin family to be discovered.
Since body reserve of thiamine is small (~30mg), a steady
dietary supply of it is important to avoid deficiency.
Because of its central role in energy production, most of
thiamine is located in the muscles.
Once thiamine absorbed, it is rapidly transformed into the
active form, thiamin pyrophosphate (TPP) which acts
as a coenzyme.
Methyl
Bridge
Pyrimidine
Ring
Thiazole Ring
Thiamin or Aneurine
(Coenzyme form)
Daily Required amount and Sources
RDA (Recommended Dietary Allowance )is based on
the number of calories in diet:
Vitamin B1 requirement
Energy requirement
1.5 mg/day
Adult male: 3000 k cal.
1.1 mg/day
Female:
2100 k cal
1mg/day
Children : 1700-2000 k cal
Daily requirement increases with high carbohydrate
intake and for hard worker or athletes.
Stability of Thiamine
Stable in crystalline form but not so in solution.
Destroyed by prolonged heat, baking soda (with heating),
sulfite preservatives.
Unstable in aqueous solutions with pH > 5.0. At pH 8.0 or
above, thiamine turns yellow and is destroyed by a
complex series of irreversible reactions.
In strong alkaline solution with the presence of oxidizing
agents, e.g. potassium ferricyanide, thiamine is
converted to thiochrome, which is blue fluorescent
compound and is used for fluoremetric determination
of vitamin B1 in foods, pharmaceutical
preparations, and biological fluids.
Thiochrome
Functions of Vitamin B1
1. It act as co-enzyme (TPP) in carbohydrate metabolism
(for glycolysis and Kreb’s cycle enzymes: pyruvate
dehydrogenase and α-ketoglutarate dehydrogenase), which
enable conversion of glucose into biological energy
through oxidative decarboxylation reactions. This role is
important:
 To provide energy to the brain.
 To improve transmission of nerve impulses by
providing nerves with energy.
To increase the efficiency of the heart muscles.
For the formation of RBC’s.
2. It act as co-enzyme for transketolase which functions in:
The pentose phosphate pathway to synthesize
NADPH.
The pentose sugars: deoxyribose and ribose are
involved in nucleic acids biosynthesis.
Thiamine Antagonists
 Oxythiamine is a competitive inhibitor (Amino group
in pyrimidine ring is replaced by hydroxyl group).
 Neopyrithiamine (It prevents the phosphorilation of
hydroxy ethyl group that is essential for activity
of the vitamin B1).
 Thiaminase (found in raw fish destroys vitamin B1).
Causes of Thiamine Deficiency
Malnutrition.
A diet high in thiaminase-rich foods (raw freshwater
fish, raw shellfish, ferns)
Foods having anti-thiamine factors (tea, coffee etc.).
Chronic consumption of alcohol
Diagnostic Testing for Vitamin B1 deficiency
A diagnosis test for B1 deficiency can be determined by
measuring transketolase levels of erythrocyte.
Diseases of Vitamin B1 deficiency
Beriberi is the deficiency disease caused by lack of thiamine
resulted from malnutrition, alcoholism or other causes.
There are two major types of beriberi:
A. Dry beriberi: affect the nervous system
B. Wet beriberi: affects the cardiovascular system
and ends by Wernicke-Korsakoff
syndrome which affect the nervous
system.
Dry Beri-beri
Wet Beri-beri
Symptoms:
Symptoms :
Difficulty in walking
Painful tender muscles
Loss of sensation in hands
and feet
Loss of muscle function or
paralysis of the lower legs
Mental confusion/speech
difficulties
Vomiting and anorexia.
Dyspnea
orthopnea
Increased heart rate, enlarged
heart, heart failure.
Swelling of the lower legs.
Wernicke–Korsakoff syndrome:
-Ophthalmoplegia (paralysis
of one or more extraocular
muscles which are responsible
for eye movements)
-Confusion
- Coma
- Death if untreated.
Diseases of Vitamin B1 deficiency (BERI-BERI)
People at high risk of Vitamin B1 Deficiency
Heavy alcohol consumers (Alcohol reduces absorption of
thiamin and interferes with its conversion to TPP).
Much consumption of coffee and black tea depletes
thiamin stores in the body and hinder its absorption.
Patients having liver cirrhosis, malabsorption syndromes,
diabetes, kidney disease, or hypermetabolim.
The elderly peoples with poor nutritional status and
difficulties with absorption.
Folate deficiency impairs absorption of thiamin.
 Infants who are breastfed by thiamin deficient-mothers
can rapidly develop life-threatening signs of
thiamin deficiency.
Use of Thiamine in prevention and Therapy
1. Nerve disorders: Supplemental thiamin may be
effective in inflammatory nerve disorders (such as
trigeminal neuralgia) and in diabetic neuropathy.
2. Central nervous system disorders: e.g. Alzheimer’s
disease, anxiety, and depression associated with
anxiety.
3. Heart failure: Particularly in the elderly chronic heart
failure that responds poorly to conventional
medical therapy.
4. Anemia: Thiamin deficiency produces an anemia
resembling that of folate or vitamin B12 deficiency
(with macrocytosis) that responds to thiamin.
5. Disease caused by heavy alcohol consumption.
Vitamin B1- Drug Interactions
Oral contraceptives, antibiotics, sulfa drugs, and certain
types of diuretics may lower thiamine levels in the
body.
Vitamin B1 may intensify the effects of neuromuscular
blockers that are used during some surgical
procedures.
B vitamins are best absorbed as a complex, and magnesium
also promotes the absorption of thiamine.
Toxicity
Thiamin is virtually nontoxic.
 Doses > 200mg may cause drowsiness in some people.
 Rare, but severe, allergic reactions may be happened with
injectable thiamin.
Vitamin B2 (Riboflavin)
Vitamin B2 (Riboflavin)
Riboflavin is defined chemically as 7,8-Dimethyl10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]
benzo [g] pteridine-2,4-dione and is a
yellow to orange-yellow powder and soluble
in water.
It is the precursor of phosphorylated coenzymes:
FMN, FAD, and flavin coenzymes linked
covalently to specific tissue proteins, at the 8α methyl position of the isoalloxazine ring.
Riboflavin is stored mainly in liver, kidney and heart
as it is or as FAD (70- 90%) or FMN.
Ribose moiety
Isoalloxazine moiety
Riboflavin phosphate
Riboflavin = Vitamin B2
Flavin adenine dinucleotide (FAD)
Required Daily Amount and Sources
RDA is an average of 1.5 mg/ day
Mushrooms
Mature Soya beans
Yoghurt
Spinach
Milk – Egg
Calf liver
Stability of Riboflavin
Riboflavin and its coenzymes are sensitive to alkali and
acid but in the presence of light or UV light.
Riboflavin is photodegraded to yield lumiflavin (7,8,10trimethylisoalloxazine) under alkaline conditions and
to lumichrome (7,8-dimethylalloxazine) under acidic
conditions, and these products are biologically
inactive .
Therefore, phototherapy of neonatal jaundice and of
certain skin disorders may promote systemic
riboflavin deficiency.
Functions of Vitamin B2
1. Energy production:
The active forms of riboflavin are the
phosphorylated coenzymes FMN and FAD which
play central roles in about 150 oxidation-reductions
reactions and are involved in:
Metabolism of carbohydrates, fat, and protein.
Production of adenosine triphosphate (ATP) through
cellular respiration in mitochondria.
Activation of vitamin B12, folate, vitamin B6 and the
conversion of tryptophan to niacin.
2. Antioxidant action:
Riboflavin is a cofactor of glutathione reductase. This
enzyme helps in recycle of oxidized glutathione, which
plays a key role in maintaining proper function and
preventing oxidative stress in human cells including
erythrocytes.
Causes of Riboflavin Deficiency
Malnutrition.
Health conditions which affect intestinal absorption.
Increase of vitamin excretion from the body.
Diagnostic testing for vitamin B2 Deficiency
A positive diagnostic test of serum riboflavin is by
measuring glutathione reductase levels of
erythrocytes.
Symptoms of vitamin B2 deficiency (Ariboflavinosis)
Red, scaly, painful, and itchy patches on sensitive
skin (around nose, ears, mouth, labia majora (female), and
the scrotum (male).
Painful fissures and cracks form at the angles of the
mouth (angular stomatitis) and on the lips (cheilosis),
usually associated with bacterial and fungal infection. The
tongue and throat become purplish and painful.
Mouth ulcers
Red, scaly, painful
skin
angular stomatitis
Cheilosis
Mouth ulcers
Redness, burning, excessive tearing of eye.
Anemia with decreased production of red blood cells.
Deficiency of riboflavin typically produces symptoms
of vitamin B6 and niacin deficiency.
Redness, burning,
tearing of eyes
Anemia
Symptoms of niacin
deficiency
People at high risk of vitamin B2 deficiency
Children, and adolescent, athletes, as well as during pregnancy
and lactation (cases with a high-energy output) need
additional vitamin B2.
People under high stress
Diabetics may have low level of riboflavin as a result of
increased urinary excretion.
The elderly people (nutritional inadequacy and problems with
absorption)
Patients administering thyroid hormones, oral contraceptives,
phenothiazines, barbiturates, probenacid, and Tricyclic
antidepressant.
Use of Vitamin B2 in Prevention and Therapy
Detoxification: Riboflavin helps liver to detoxify pesticides,
chemicals, and other environmental toxins.
Increasing the antioxidant capacity throughout the body and
especially for lens of the eye.
Ample intake of riboflavin help decrease the
incidence of cataracts.
As a cofactor of glutathione reductase, riboflavin
with vitamin C increase body's level of glutathione
(antioxidant).
Ample riboflavin intake maintains healthy skin and mucous
membranes.
It may be beneficial in stomatitis, cheilosis, and skin
eruptions and rashes.
Vitamin B2 – Drug interaction
Probenecid (anti-gout) and propantheline bromide
(antipeptic ulcers) both delays and impairs its
absorption.
Phenothiazines (antipsychotic drugs) increase the
excretion of riboflavin, thus lowering serum levels.
Oral contraceptives may also decrease its serum levels.
Riboflavin interferes with the absorption and
effectiveness of anti-malarial (ex. chloroquine),
tetracycline antibiotics and sulfa-containing drugs.
Assay of Vitamin B2
Lumiflavin method:
Riboflavin solution or biological
sample is irradiated in alkaline
medium to yielded a chloroformsoluble lumiflavin, measured by
fluoremetry.
VITAMIN B3
(NIACIN & NIACINAMIDE)
Vitamin B3 (Niacin & Niacinamide)
Two main forms of Vitamin B3 are found in foods:
nicotinic acid (niacin) and nicotinamide
(niacinamide).
Niacin can be partially satisfied by intake of
tryptophan, which is converted by the liver
into niacin.
60 mg of tryptophan can be converted into
about 1mg of niacin.
 Dietary requirements for niacin are described in
terms of niacin equivalents (NEs):
1NE = 60mg of tryptophan = 1mg of niacin
RDA: 13- 20 mg/day
Sources of Vitamin B3
Nicotinic acid or Niacin
Meat
Rice bran
Nicotinamide or Niacinamide
Fish
Sheep liver
Prawns
Cow’s milk
Groundnuts
Chilgozas
Turnip
Beet greens
Yeast
Bran
Pharmacokinetics of Vitamin B3
Absorption:
At low concentration by active transportation.
At high concentration by passive diffusion.
Transportation:
Both Nicotinic acid and Nicotinamide 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 B1, B2, and
B6 (60 mg of Tryptophan
1mg of niacin).
Bacteria in the gut may also perform the conversion
but are inefficient.
Functions of Vitamin B3
1. It acts as a co-enzyme in oxidation reduction reactions:
Catabolic Rxn: in form of NAD+/NADH
Anabolic Rxn: in form of NADP+/NADPH
Therefore, it is required for functions of >200 enzymes
dealing with the biosynthesis of several compounds
e.g. fatty acids, steroids and catabolism of fuel
molecules for energy.
2. DNA replication and repair:
It is vital for synthesis of DNA-bound nuclear proteins
(histones)
3. Antioxidant functions:
It plays an important role in antioxidant systems,
particularly in the liver.
4. Blood sugar regulation:
It is a component of the glucose tolerance factor
(GTF), which together with insulin, helps to
control blood glucose.
5. Fat and cholesterol metabolism:
It lowers levels of total and LDL cholesterol in the
blood, while increasing levels of HDL
cholesterol (the healthy, protective form of
cholesterol).
Vitamin B3 Deficiency Diseases
1. Milder deficiency of niacin (as well as tryptophan)
can cause:
 Glossitis (inflammation of the tongue
leading to purplish discoloration)
Dermatitis around the mouth and rashes
Fatigue
Irritability
Poor appetite
Indigestion
Weight loss
Headache
Glossitis
Dermatitis around
mouth
Fatigue
Poor appetite
Indigestion
Headache
2. Severe deficiency leads to Pellagra: Characterized by
Inflamed mouth (painful swollen tongue and
fissured lips) and GIT.
Diarrhea
Dermatitis in the exposed skin of hands, face, neck
(Casal’s necklace)
Dementia and mental disorders
Death.
It is very rare now, except in alcoholics, strict vegetarians,
and people with very poor nutrition (or niacin or tryptophandeficient food e.g corn).
Inflamed mouth
Diarrhea
Dermatitis of
exposed skin
Mental disorders
Death.
People at high risk of vitamin B3 deficiency
People with very poor nutrition (or niacin or
tryptophan- deficient food e.g corn).
People with deficiencies in vitamin B6 or
riboflavin (conversion of tryptophan to
niacin is reduced
niacin stores in the
body is reduced).
People with inflammatory bowel disease and
other digestive disorders
malabsorption
of niacin.
Heavy alcohol consumption interferes with
absorption and metabolism of niacin.
People under high stress, chronic illnesses, liver
disease.
Uses in prevention and Therapy
Mental illness e.g. schizophrenia: Niacinamide can
be effective with traditional medical treatment.
Atherosclerosis and heart attack: Niacin in very
large doses (2-3 g/day):
(1) Lower total and LDL cholesterol
and
raising HDL cholesterol.
(2) Dilates blood vessels
lowers
blood pressure.
Arthritis: Niacin helps in treatment of osteoarthritis.
Diabetes: Niacinamide slow down the development
of nephropathy in diabetes and delay need for
insulin therapy in juvenile diabetes.
Protection against environmental toxins:
The antioxidant function of niacin
help protect liver against damage
from pesticides, chemicals, alcohol,
and drugs.
Headache: Niacin help in prevention of
headache.
Treatment of Pellagra.
Toxicity and side effects of vitamin B3
Large doses (500 mg) of niacin (but not niacinamide)
can cause dilation of capillaries
tingling and
flushing of the skin.
Flushing of the skin is usually worse if nicotinic acid
is taken on an empty stomach, therefore it should
be taken just after meals.
Niacin in the form of niacinamide does not produce
these side effects.
At doses of > 2.5 g / day, it can produce hypotension,
dizziness, increased blood sugar and uric acid,
liver dysfunction, and increased risk of peptic
ulcer. These effects are gradually adopted and
decreased and are reversible on withdrawal of
nicotinic acid.
Vitamin B3 – Drug Interactions
Niacin with antihypertensive
hypotension.
drugs
severe
Extra niacin may be required in case of people taking
Isoniazid (Inhibits biotransformation of tryptophan
to niacin ), by women taking oral contraceptives.
Bile
acid sequesterants e.g. Cholestyramine and
cholestipol should be taken at a different time than
niacin (not niacinamide) otherwise they will
reduce its absorption.
Carbamazepine may cause toxicity with niacin.
The combination of niacin and statin is often used
to treat lipid triad (high LDL and TG, low
HDL) may cause myopathy (myopathy is a
muscular disease in which the muscle
fibers do not function, resulting in muscular
weakness).
THANX