Vitamin C, B1, B2

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Vitamin C, B1, B2 B3
Water soluble vitamins
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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.

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Natural Source of Vitamin C
Guava
Kiwifruit
Red pepper
Plum
Strawberry
Orange
Broccoli
Papaya
Grapefruit
Mango
Lemon
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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
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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 L-
  dehydroascorbic acid and both L-ascorbic and
  L-dehydroascorbic acids are physiologically
  active forms for vitamin C.

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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.

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• 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.

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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.
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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 growthchildhood,
adolescence, pregnancy, and lactation. 5.
Regular cigarette smoking sharply increases
breakdown and excretion of vitamin C.
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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).

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• 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.

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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.

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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.

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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 re- absorption of salicylates by the
  renal tubules, and increase plasma salicylate
  levels .

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• 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 vitamin C absorption or its
  breakdown.

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Vitamin B Group
5. Vitamin B6 (Pyridoxine) 1. Vitamin B1 (Thiamine)
6. Vitamin B7 or Vitamin H (Biotin) 2. Vitamin B2 (Riboflavin)
7. Vitamin B9 or Vitamin M or (Folic acid) 3. Vitamin B3 (Niacin)
8. Vitamin B12 (Cyanocobalamin) 4. Vitamin B5 (Pantothenic acid)
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Water Soluble Vitamins
Vitamin B Group
Vitamin B1 (Thiamine)
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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
Thiazole Ring
Pyrimidine Ring
Thiamin or Aneurine
(Coenzyme form)
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Daily Required amount and Sources

• RDA (Recommended Dietary Allowance )is based on
  the number of calories in diet
• Energy requirement
• Adult male 3000 k cal.
• Female 2100 k cal
• Children 1700-2000 k cal
• Daily requirement increases with high
  carbohydrate intake and for hard worker or
  athletes.

Vitamin B1 requirement 1.5 mg/day 1.1 mg/day
1mg/day
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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 gt 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
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Functions of Vitamin B1

• It act as co-enzyme (TPP) in carbohydrate
  metabolism (for glycolysis and Krebs cycle
  enzymes pyruvate dehydrogenase and
  a-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 RBCs.
• 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.

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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

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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
• Dry beriberi affect the nervous system
• Wet beriberi affects the cardiovascular system
  and ends by Wernicke-Korsakoff syndrome which
  affect the nervous system.

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Wet Beri-beri Dry Beri-beri
Symptoms Dyspnea orthopnea Increased heart rate, enlarged heart, heart failure. Swelling of the lower legs. WernickeKorsakoff syndrome -Ophthalmoplegia (paralysis of one or more extraocular muscles which are responsible for eye movements) -Confusion - Coma - Death if untreated. 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.
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Diseases of Vitamin B1 deficiency (BERI-BERI)
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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.

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Use of Thiamine in prevention and Therapy

• 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.
  Alzheimers 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.

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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 gt 200mg may cause drowsiness in some
  people.
• Rare, but severe, allergic reactions may be
  happened with injectable thiamin.

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Vitamin B2 (Riboflavin)
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Vitamin B2 (Riboflavin)

• Riboflavin is defined chemically as
  7,8-Dimethyl- 10-(2S,3S,4R)-2,3,4,5-tetrahydrox
  ypentyl 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 8- a 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.
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Isoalloxazine moiety
Riboflavin phosphate
Ribose moiety
Riboflavin Vitamin B2
Flavin adenine dinucleotide (FAD)
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Required Daily Amount and Sources
RDA is an average of 1.5 mg/ day
Mushrooms
Yoghurt
Milk Egg
Calf liver
Mature Soya beans
Spinach
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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
  (7,8,10- trimethylisoalloxazine) under alkaline
  conditions and to lumichrome (7,8-dimethylalloxaz
  ine) under acidic conditions, and these products
  are biologically inactive .
• Therefore, phototherapy of neonatal jaundice and
  of certain skin disorders may promote systemic
  riboflavin deficiency.

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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.

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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.
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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
Mouth ulcers
angular stomatitis
Cheilosis
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• 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.

Anemia
Symptoms of niacin deficiency
Redness, burning, tearing of eyes
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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.

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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.

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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.

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Assay of Vitamin B2
Lumiflavin method Riboflavin solution or
biological sample is irradiated in alkaline
medium to yielded a chloroform- soluble
lumiflavin, measured by fluoremetry.
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VITAMIN B3 (NIACIN NIACINAMIDE)
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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
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Sources of Vitamin B3
Nicotinic acid or Niacin
Nicotinamide or Niacinamide
Prawns
Cows milk
Meat
Fish
Sheep liver
Rice bran
Groundnuts
Chilgozas
Turnip
Beet greens
Bran
Yeast
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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.
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Functions of Vitamin B3

• 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 gt200
  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)

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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).
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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

Dermatitis around mouth
Glossitis
Headache
Fatigue
Poor appetite
Indigestion
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• 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 (Casals 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 tryptophan- deficient food e.g
corn).
Death.
Dermatitis of exposed skin
Mental disorders
Inflamed mouth
Diarrhea
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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.

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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)
• 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.

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• 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.

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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 gt 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.

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Vitamin B3 Drug Interactions

• Niacin with antihypertensive drugs severe
  hypotension.
• 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.

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• 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).

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THANX