Vitamin C, B1, B2 & B3

Water soluble vitamins

It is water-soluble vitamin.

Most animals are able to synthesize all Vit. 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.

VITAMIN C

Natural Source of Vitamin C

Plum Red pepper Guava Kiwifruit

Broccoli Papaya Strawberry Orange

Lemon Grapefruit Mango

L- Ascorbic Acid (Reduced Form)

L-Dehydroascorbic Acid (Oxidized Form)

Vitamin C

RDA: Adults: 60 mg/dayChildren: 30 mg/day

Physiologically active forms for vitamin C

Chemistry and Stability of Vitamin CChemistry and Stability of Vitamin CIt is a It is a weak acid weak acid and its salts called and its salts called ascorbateascorbate..

Unstable in Unstable in alkaline pH, high temperature, and in alkaline pH, high temperature, and in the presence of oxygen or metalsthe presence of oxygen or metals..

The The D-enantiomer of ascorbic acidD-enantiomer of ascorbic acid shows no shows no biological activity.biological activity.

Ascorbic acid is Ascorbic acid is strong reducing agentstrong reducing agent, serves as , serves as an an anti-oxidantanti-oxidant and co-factor in and co-factor in

hydroxylation hydroxylation reactions.reactions.

Ascorbic acid is Ascorbic acid is reversibly oxidized to L- reversibly oxidized to L- dehydroascorbic acid dehydroascorbic acid and both and both L-ascorbic L-ascorbic and and

L-dehydroascorbic acids are L-dehydroascorbic acids are physiologically active forms for vitamin C.physiologically active forms for vitamin C.

Functions of Vitamin CFunctions of Vitamin CAntioxidant function:Antioxidant function: It helps protect against oxidation It helps protect against oxidation by free radicals. by free radicals.

Helps in Helps in detoxification and excretion of drugs :detoxification and excretion of drugs :It maintains the enzyme systems in liver that detoxify It maintains the enzyme systems in liver that detoxify and excrete drugs and toxic pollutants.and excrete drugs and toxic pollutants.

Synthesis of collagenSynthesis of collagen:: The major component of The major component of connective connective tissue in skin, joints, muscles, bones tissue in skin, joints, muscles, bones ligaments, ligaments, tendons, and cartilages.tendons, and cartilages.

Involved in Involved in carnitinecarnitine synthesis synthesis (along with (along with niacin niacin andand vitamin B6vitamin B6) which is an amino acid required in ) which is an amino acid required in breakdown of fats for energy.breakdown of fats for energy.

It is a cofactor in the synthesis of neurotransmittersIt is a cofactor in the synthesis of neurotransmitters as as epinephrine , norepinephrine and serotonin.epinephrine , norepinephrine and serotonin.

Important for healthy immune function:Important for healthy immune function: It is essential It is essential for for (1) (1) optimum activity of WBCs optimum activity of WBCs and (2) and (2) production production of chemical mediatorsof chemical mediators which direct the immune which direct the immune response. Vitamin C seems to (3) response. Vitamin C seems to (3) increase T-increase T-lymphocyte activity, phagocyte function, leukocyte lymphocyte activity, phagocyte function, leukocyte mobility, and possibly antibody and interferon mobility, and possibly antibody and interferon production.production.

Involved in cholesterol breakdownInvolved in cholesterol breakdown and excretion and excretion (cholesterol (cholesterol level increase if vitamin C status is level increase if vitamin C status is impaired).impaired).

Protection of folate and vitamin E from oxidation.Protection of folate and vitamin E from oxidation.

Involved in control of histamine levels:Involved in control of histamine levels: When vitamin When vitamin C status is poor C status is poor High levels of histamine High levels of histamine aggravate allergies, asthma, stomach ulcers, and aggravate allergies, asthma, stomach ulcers, and certain psychiatric disorders.certain psychiatric disorders.

Symptoms of Vitamin C DeficiencyScurvy: 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”.

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 DeficiencyPeople at High Risk of Vitamin C Deficiency

1.1. Increased physical stress Increased physical stress (e.g. infection, (e.g. infection, fever, burns, surgery, trauma to soft tissues or fever, burns, surgery, trauma to soft tissues or bones, and chronic illnesses such as bones, and chronic illnesses such as hyperthyroidism, diabetes, rheumatoid arthritis, hyperthyroidism, diabetes, rheumatoid arthritis, alcoholism, and kidney failure).alcoholism, and kidney failure).

22. . Chronic use of drugsChronic use of drugs such as aspirin and oral such as aspirin and oral contraceptives impair vitamin C status.contraceptives impair vitamin C status.

33. . Older people, particularly Older people, particularly those with chronic those with chronic illness, and aging.illness, and aging.

44. . Periods of rapid growth–Periods of rapid growth–childhood, childhood, adolescence, pregnancy, and lactation.adolescence, pregnancy, and lactation.

55. . Regular cigarette smoking Regular cigarette smoking sharply increases sharply increases breakdown and excretion of vitamin C.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 re-absorption 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 ↓ vitamin C absorption or ↑ its breakdown.

Water Soluble VitaminsWater Soluble Vitamins

Vitamin B Group

Vitamin B1 (Thiamine)

1 .Vitamin B1 (Thiamine) 5 .Vitamin B6 (Pyridoxine)

2 .Vitamin B2 (Riboflavin) 6 .Vitamin B7 or Vitamin H (Biotin)

3 .Vitamin B3 or (Niacin) 7 .Vitamin B9 or Vitamin M or (Folic acid)

4 .Vitamin B5 (Pantothenic acid)

8 .Vitamin B12 (Cyanocobalamin)

Vitamin B GroupVitamin B Group

Vitamin B1 (Thiamine)Vitamin B1 (Thiamine)The 1The 1stst water-soluble B-vitamin family to be discovered. water-soluble B-vitamin family to be discovered.

Since body reserve of thiamine is small (~30 mg), a Since body reserve of thiamine is small (~30 mg), a steady dietary supply of it is important to avoid deficiency.steady dietary supply of it is important to avoid deficiency.

Because of its central role in energy production, most of Because of its central role in energy production, most of thiamine is located in the muscles.thiamine is located in the muscles.

Once thiamine absorbed, it is rapidly transformed into the Once thiamine absorbed, it is rapidly transformed into the active form, active form, thiamin pyrophosphate (TPP) thiamin pyrophosphate (TPP) which acts as a which acts as a coenzyme.coenzyme.

PyrimidinePyrimidine RingRing

MethylMethyl BridgeBridge Thiazole RingThiazole Ring

Thiamine or AneurineThiamine or Aneurine(Coenzyme form)(Coenzyme form)

Daily Required amount and SourcesDaily Required amount and Sources

RDA (Recommended Dietary Allowance) is based RDA (Recommended Dietary Allowance) is based on the number of calories in diet: on the number of calories in diet:

Energy requirement Energy requirement Adult male: 3000 k cal.Adult male: 3000 k cal.Female: 2100 k calFemale: 2100 k calChildren : 1700-2000 k calChildren : 1700-2000 k cal

Daily requirement increases with high Daily requirement increases with high carbohydrate intake and for hard worker or athletes.carbohydrate intake and for hard worker or athletes.

Vitamin B1 Vitamin B1 requirementrequirement1.5 mg/day 1.5 mg/day 1.1 mg/day 1.1 mg/day

1mg/day 1mg/day

Stability of ThiamineStability of ThiamineStable in crystalline form but not so in solution.Stable in crystalline form but not so in solution.

Destroyed by prolonged heat, baking soda (with Destroyed by prolonged heat, baking soda (with heating), sulfite preservatives.heating), sulfite preservatives.

Unstable in aqueous solutions with pH > 5.0. At pH 8.0 Unstable in aqueous solutions with pH > 5.0. At pH 8.0 or above, thiamine turns yellow and is destroyed by a or above, thiamine turns yellow and is destroyed by a complex series of irreversible reactions.complex series of irreversible reactions.

In strong alkaline solution with the presence of In strong alkaline solution with the presence of oxidizing agents, e.g. oxidizing agents, e.g. potassium ferricyanide, thiamine is potassium ferricyanide, thiamine is converted to thiochromeconverted to thiochrome, which is blue fluorescent , which is blue fluorescent compound and is used for fluoremetric determination of compound and is used for fluoremetric determination of vitamin B1 in foods, pharmaceutical preparations, and vitamin B1 in foods, pharmaceutical preparations, and biological fluids.biological fluids.

ThiochromeThiochrome

Functions of Vitamin B1Functions of Vitamin B11.1. It act as co-enzyme (TPP)It act as co-enzyme (TPP) in carbohydrate metabolism in carbohydrate metabolism

(for glycolysis and Kreb’s cycle enzymes: pyruvate (for glycolysis and Kreb’s cycle enzymes: pyruvate dehydrogenase and dehydrogenase and α-α-ketoglutarate dehydrogenase), ketoglutarate dehydrogenase), which enable which enable conversion of glucose into biological energy conversion of glucose into biological energy through oxidative decarboxylation reactionsthrough oxidative decarboxylation reactions. This role is . This role is important:important:

To provide energy to the To provide energy to the brainbrain.. To improve transmission of nerve impulses by To improve transmission of nerve impulses by providing providing nervesnerves with energy. with energy. To increase the efficiency of the To increase the efficiency of the heartheart muscles. muscles. For the formation of For the formation of RBC’sRBC’s..

22. It act as co-enzyme for transketolase which functions . It act as co-enzyme for transketolase which functions in:in:

The pentose phosphate pathway to synthesize The pentose phosphate pathway to synthesize NADPHNADPH..The pentose sugars: deoxyribose and ribose are The pentose sugars: deoxyribose and ribose are involved in involved in nucleic acids biosynthesisnucleic acids biosynthesis..

Thiamine Antagonists Oxythiamine is a competitive inhibitor (Amino group

in pyrimidine ring is replaced by hydroxyl group).

Neopyrithiamine (It prevents the phosphorylation 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-beriSymptoms:Difficulty in walkingPainful tender musclesLoss of sensation in hands and feetLoss of muscle function or paralysis of the lower legsMental confusion/speech difficultiesVomiting and anorexia.

Symptoms :Dyspnea OrthopneaIncreased 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 DeficiencyPeople at high risk of Vitamin B1 Deficiency

Heavy alcohol consumers Heavy alcohol consumers (Alcohol reduces absorption (Alcohol reduces absorption of thiamin and interferes with its conversion to TPP).of thiamin and interferes with its conversion to TPP).

Much consumption of coffee and black tea Much consumption of coffee and black tea depletes depletes thiamin stores in the body and hinder its absorption.thiamin stores in the body and hinder its absorption.

Patients having Patients having liver cirrhosis, malabsorption liver cirrhosis, malabsorption syndromes, syndromes, diabetes, kidney disease, or hypermetabolim.diabetes, kidney disease, or hypermetabolim.

The elderly peoples The elderly peoples with poor nutritional status and with poor nutritional status and difficulties with absorption.difficulties with absorption.

Folate deficiency Folate deficiency impairsimpairs absorption of thiamin.absorption of thiamin. Infants who are breastfed by thiamin deficient-Infants who are breastfed by thiamin deficient-mothers mothers can rapidly develop life-threatening signs of can rapidly develop life-threatening signs of thiamin deficiency.thiamin deficiency.

Use of Thiamine in prevention and Therapy

1.1. Nerve disorders:Nerve disorders: Supplemental thiamin may be Supplemental thiamin may be effective in inflammatory nerve disorders (such as effective in inflammatory nerve disorders (such as trigeminal neuralgia) and in diabetic neuropathy.trigeminal neuralgia) and in diabetic neuropathy.

2. 2. Central nervous system disorders:Central nervous system disorders: e.g. Alzheimer’s e.g. Alzheimer’s disease, anxiety, and depression associated disease, anxiety, and depression associated

with with anxiety.anxiety.

3. 3. Heart failure:Heart failure: Particularly in the elderly chronic heart Particularly in the elderly chronic heart failure that responds poorly to conventional failure that responds poorly to conventional

medical therapy.medical therapy.

4. 4. Anemia:Anemia: Thiamine deficiency produces an anemia Thiamine deficiency produces an anemia resembling that of folate or vitamin B12 deficiency resembling that of folate or vitamin B12 deficiency (with macrocytosis) that responds to thiamine.(with macrocytosis) that responds to thiamine.

5. Disease caused by heavy alcohol consumption5. 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.

ToxicityThiamin 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)Vitamin B2 (Riboflavin)

RiboflavinRiboflavin is defined chemically as 7,8-Dimethyl- is defined chemically as 7,8-Dimethyl-10-[(2S,3S,4R)-2,3,4,5-10-[(2S,3S,4R)-2,3,4,5-

tetrahydroxypentyl] tetrahydroxypentyl] benzo [g] benzo [g] pteridine-2,4-dione and is a pteridine-2,4-dione and is a yellow to yellow to orange-yellow orange-yellow powder and powder and soluble soluble in in water.water.

It is the precursor of phosphorylated It is the precursor of phosphorylated coenzymes: coenzymes: FMN, FAD, and flavin coenzymes FMN, FAD, and flavin coenzymes linked linked covalently to specific tissue proteins, at the 8-α covalently to specific tissue proteins, at the 8-α methyl position of the isoalloxazine ring.methyl position of the isoalloxazine ring.

Riboflavin is stored mainly in Riboflavin is stored mainly in liver, kidney and liver, kidney and heartheart as it is or as as it is or as FADFAD (70- 90%) or (70- 90%) or FMN.FMN.

Flavin adenine dinucleotide (FAD)Flavin adenine dinucleotide (FAD)

Rib

ose

mo

iety

Rib

ose

mo

iety

Isoalloxazine moietyIsoalloxazine moiety

Riboflavin = Vitamin B2Riboflavin = Vitamin B2

Flavin mononucleotide (FMN)Flavin mononucleotide (FMN)

Required Daily Amount and SourcesRequired Daily Amount and Sources

RDA is an average of 1.5 mg/ dayRDA is an average of 1.5 mg/ day

MushroomsMushrooms YoghurtYoghurt Milk – EggMilk – Egg

Mature Soya beansMature Soya beans SpinachSpinach Calf liverCalf liver

Stability of Riboflavin

Riboflavin and its coenzymes are Riboflavin and its coenzymes are sensitive to alkali sensitive to alkali and acid but in the presence of light or UV lightand acid but in the presence of light or UV light. .

Riboflavin is photodegraded to yield Riboflavin is photodegraded to yield lumiflavinlumiflavin (7,8,10-trimethylisoalloxazine) (7,8,10-trimethylisoalloxazine) under alkaline under alkaline conditions conditions and and to to lumichromelumichrome (7,8- (7,8-dimethylalloxazinedimethylalloxazine) under acidic conditions) under acidic conditions, and these , and these products are biologically inactive .products are biologically inactive .

Therefore, phototherapy of neonatal jaundice and of Therefore, phototherapy of neonatal jaundice and of certain skin disorders may promote systemic riboflavin certain skin disorders may promote systemic riboflavin deficiency.deficiency.

Functions of Vitamin B2Functions of Vitamin B21. 1. Energy production:Energy production:

The The active forms active forms of riboflavin are the of riboflavin are the phosphorylated coenzymes phosphorylated coenzymes FMN and FAD FMN and FAD which which play play central roles in about 150 oxidation-central roles in about 150 oxidation- reductions reductions reactions and are involved in:reactions and are involved in:

Metabolism of carbohydrates, fat, and protein.Metabolism of carbohydrates, fat, and protein. Production of adenosine triphosphate (ATP) Production of adenosine triphosphate (ATP) through cellular respiration in mitochondria.through cellular respiration in mitochondria.Activation of vitamin B12, folate, vitamin B6 Activation of vitamin B12, folate, vitamin B6 and and the the conversion of conversion of tryptophan to niacintryptophan to niacin..

2. Antioxidant action:2. Antioxidant action:Riboflavin is a Riboflavin is a cofactor of glutathione reductasecofactor of glutathione reductase. This . This

enzyme helps in recycle of oxidized glutathione, which enzyme helps in recycle of oxidized glutathione, which plays a key role in maintaining proper function and plays a key role in maintaining proper function and preventing oxidative stress in human cells including preventing oxidative stress in human cells including erythrocytes.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)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

angular stomatitisRed, scaly, painful skin

Cheilosis Mouth ulcers

Redness, burning, excessive tearing of eye. Redness, burning, excessive tearing of eye.

AnemiaAnemia with decreased production of red blood with decreased production of red blood cells.cells.

Deficiency of riboflavin typically produces Deficiency of riboflavin typically produces symptoms symptoms of vitamin B6 and niacin deficiency.of vitamin B6 and niacin deficiency.

Redness, burning,Redness, burning, tearing of eyes tearing of eyes

AnemiaAnemia Symptoms of niacin Symptoms of niacin deficiencydeficiency

People at high risk of vitamin B2 deficiencyPeople at high risk of vitamin B2 deficiency

Children, and adolescent, athletes, as well as during Children, and adolescent, athletes, as well as during pregnancy pregnancy and lactation (cases with a high-energy and lactation (cases with a high-energy output) need additional vitamin B2.output) need additional vitamin B2.

People under high stressPeople under high stress

Diabetics may have low level of riboflavin as a result of Diabetics may have low level of riboflavin as a result of increased urinary excretion.increased urinary excretion.

T he elderly people (nutritional inadequacy and problems T he elderly people (nutritional inadequacy and problems with absorption)with absorption)

Patients administering thyroid hormones, oral Patients administering thyroid hormones, oral contraceptives, phenothiazines, barbiturates, probenacid, contraceptives, phenothiazines, barbiturates, probenacid, and Tricyclic antidepressant.and Tricyclic antidepressant.

Use of Vitamin B2 in Prevention and TherapyUse of Vitamin B2 in Prevention and Therapy

Detoxification:Detoxification: Riboflavin helps liver to detoxify Riboflavin helps liver to detoxify pesticides, pesticides, chemicals, and other environmental toxins.chemicals, and other environmental toxins.

Increasing the Increasing the antioxidantantioxidant capacity throughout the body capacity throughout the body and especially for and especially for lens of the eye.lens of the eye.

Ample intake of riboflavin help Ample intake of riboflavin help decrease the decrease the incidence of cataracts.incidence of cataracts.

As a cofactor of glutathione reductase, riboflavin As a cofactor of glutathione reductase, riboflavin with vitamin C increase body's level of glutathione with vitamin C increase body's level of glutathione (antioxidant).(antioxidant).

Ample riboflavin intake maintains Ample riboflavin intake maintains healthy skin and healthy skin and mucous membranesmucous membranes..

It may be beneficial in It may be beneficial in stomatitis, cheilosis, and skin stomatitis, cheilosis, and skin eruptions and rashes.eruptions and rashes.

Vitamin B2 – Drug interactionVitamin B2 – Drug interaction

ProbenecidProbenecid (anti-gout) and (anti-gout) and propantheline bromide propantheline bromide (antipeptic ulcers) both (antipeptic ulcers) both delays and impairs its delays and impairs its absorptionabsorption..

PhenothiazinesPhenothiazines (antipsychotic drugs) (antipsychotic drugs) increase the increase the excretion of riboflavinexcretion of riboflavin, thus lowering serum levels., thus lowering serum levels.

Oral contraceptives Oral contraceptives may also may also decrease its serum decrease its serum levelslevels..

Riboflavin interferes Riboflavin interferes with the with the absorption and absorption and effectiveness effectiveness of anti-malarial (ex. chloroquine), of anti-malarial (ex. chloroquine), tetracycline tetracycline antibiotics and sulfa-containing drugs.antibiotics and sulfa-containing drugs.

Assay of Vitamin B2Assay of Vitamin B2

Lumiflavin methodLumiflavin method: :

Riboflavin solution or biological Riboflavin solution or biological sample sample is irradiated in alkaline is irradiated in alkaline medium to yielded a chloroform-medium to yielded a chloroform- soluble soluble lumiflavin, measured by lumiflavin, measured by fluoremetry.fluoremetry.

VITAMIN B3 (NIACIN & NIACINAMIDE)

Vitamin B3 (Niacin & Niacinamide) Two main forms of Vitamin B3 are found in Two main forms of Vitamin B3 are found in foods: foods: nicotinic acid nicotinic acid (niacin) and (niacin) and nicotinamidenicotinamide

(niacinamide).(niacinamide).

Niacin can be partially satisfied by intake of Niacin can be partially satisfied by intake of tryptophantryptophan, which is converted by the , which is converted by the liver liver into niacin.into niacin.

60 mg of tryptophan 60 mg of tryptophan can be converted into can be converted into about about 1mg of niacin.1mg of niacin.

Dietary requirements for niacin are described in Dietary requirements for niacin are described in terms of terms of niacin equivalents (NEs):niacin equivalents (NEs):

1NE = 60mg of tryptophan = 1mg of niacin1NE = 60mg of tryptophan = 1mg of niacin

RDA: 13- 20 mg/day

Sources of Vitamin B3Nicotinic acid or Niacin Nicotinamide or Niacinamide

Meat Fish Sheep liver Prawns Cow’s milk

Rice bran Groundnuts Chilgozas Turnip Beet greens

Yeast Bran

Pharmacokinetics of Vitamin B3Absorption:

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

1.1. It acts as a co-enzyme in oxidation reduction It acts as a co-enzyme in oxidation reduction reactions:reactions:

Catabolic Rxn: in form of NADCatabolic Rxn: in form of NAD++/NADH/NADH Anabolic Rxn: in form of Anabolic Rxn: in form of NADPNADP++/NADPH/NADPH

Therefore, it is required for functions of >200 enzymes Therefore, it is required for functions of >200 enzymes dealing with the biosynthesis of several compounds dealing with the biosynthesis of several compounds e.g. e.g. fatty acids, steroids fatty acids, steroids andand catabolism of fuel catabolism of fuel molecules for energy.molecules for energy.

2. DNA replication and repair: 2. DNA replication and repair: It is vital for synthesis of DNA-bound nuclear proteins It is vital for synthesis of DNA-bound nuclear proteins

((histoneshistones) which are important in the repair of ) which are important in the repair of damaged DNA strands caused by oxidation, damaged DNA strands caused by oxidation, radiation, or other environmental stress.radiation, or other environmental stress.

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).

3. Antioxidant functions: It plays an important role in antioxidant systems, particularly in the liver.

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 rashesFatigueIrritability Poor appetiteIndigestionWeight lossHeadache

Glossitis Dermatitis around mouth

Headache Fatigue Poor appetite Indigestion

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 disordersDeath.

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).

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 drugs severe hypotension.

Extra niacin may be required in case of people taking Isoniazid (Inhibits biotransformation of tryptophan to niacin) and 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