Water soluble vitamins Vitamin C B 1 B

Water soluble vitamins Vitamin C, B 1, B 2 & B 3

VITAMIN C v. It is water-soluble vitamin. v. Most animals are able to synthesize all vitamin C they unable. v. 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 ØIt is a weak acid and its salts called ascorbate. ØUnstable in alkaline p. H, high temperature, and in the presence of oxygen or metals. ØThe D-enantiomer of ascorbic acid shows no biological activity. ØAscorbic acid is strong reducing agent, serves as an anti-oxidant and co-factor in hydroxylation reactions. ØAscorbic acid is reversibly oxidized to L- dehydroascorbic acid and both L-ascorbic and L-dehydroascorbic acids are physiologically active forms for vitamin C.

Functions of Vitamin C ØAntioxidant function: It helps protect against oxidation by free radicals. ØHelps in detoxification and excretion of drugs : It maintains the enzyme systems in liver that detoxify and excrete drugs and toxic pollutants. ØSynthesis of collagen: The major component of connective tissue in skin, joints, muscles, bones ligaments, tendons, and cartilages. ØInvolved in carnitine synthesis (along with niacin and vitamin B 6) which is an amino acid required in breakdown of fats for energy. ØIt is a cofactor in the synthesis of neurotransmitters as epinephrine , norepinephrine and serotonin.

ØImportant 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. ØInvolved in cholesterol breakdown and excretion (cholesterol level increase if vitamin C status is impaired). ØProtection of folate and vitamin E from oxidation. ØInvolved 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 ØScurvy: Impaired connective tissue synthesis and fragility of blood subcutaneous hemorrhagic spots, inflamed and bleeding gums, joint stiffness and pain (due to bleeding into joints). ØImpaired wound healing. ØBuild-up of keratin in hair follicles producing rough “sandpaper skin”. ØWeakness, exhaustion, fatigue (due to impaired carnitine synthesis). ØImpaired immunity with increased risk of infection. ØDiminished 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 ØEnhance ability to fight infection: Vitamin C stimulates the activity and ability of WBCs to destroy bacteria and viruses. ØTreatment 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. Ø 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).

ØLarge 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. ØProtection from heavy metals: It absorption and detoxification and excretion of heavy metals. ØImproves healing of wounds and fractures in burns, trauma, and surgery. ØIron deficiency (by iron absorption from meals). ØPreventing and curing Scurvy.

Recommended Therapeutic Doses ØFor scurvy, 100 -250 mg once or twice daily. ØFor treating the common cold, 1 -3 g daily. ØDuring acute stress, 1 g (3 times daily) ØFor preventing sunburn, 2 g of vitamin C and 1000 IU vitamin E has been used.

Toxicity and Side Effects of Vitamin C ØVitamin C is generally regarded as safe in usual doses (up to 1000 mg). Dental erosion may occur from chronically chewing vitamin C tablets. ØHigh 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. ØVitamin 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 ØVitamin C chromium and aluminium absorption. Patients with renal failure who take (Al) compounds should avoid vitamin C in doses above the RDA. ØVitamin C can destroy dietary vitamin B 12 (so, it must be taken at least 2 hours after meals). Ø Acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels.

ØHigh doses of vitamin C can the response to warfarin, possibly by causing diarrhea and reducing Warfarin absorption Ø 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. ØEstrogens can vitamin C absorption or its breakdown.

Vitamin B Group 1. Vitamin B 1 (Thiamine) 5. Vitamin B 6 (Pyridoxine) 2. Vitamin B 2 (Riboflavin)6. Vitamin B 7 or Vitamin H (Biotin) 3. Vitamin B 3 (Niacin) 7. Vitamin B 9 or Vitamin M or (Folic acid) 4. Vitamin B 5 (Pantothenic 8. Vitamin B 12 acid) (Cyanocobalamin)

Water Soluble Vitamins Vitamin B Group Vitamin B 1 (Thiamine)

Vitamin B 1 (Thiamine) ØThe 1 st water-soluble B-vitamin family to be discovered. ØSince body reserve of thiamine is small (~30 mg), a steady dietary supply of it is important to avoid deficiency. ØBecause of its central role in energy production, most of thiamine is located in the muscles. ØOnce 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 v. RDA (Recommended Dietary Allowance )is based on the number of calories in diet: Vitamin B 1 requirement Energy requirement 1. 5 mg/day v. Adult male: 3000 k cal. 1. 1 mg/day v. Female: 2100 k cal 1 mg/day v. Children : 1700 -2000 k cal v. Daily requirement increases with high carbohydrate intake and for hard worker or athletes.

Stability of Thiamine ØStable in crystalline form but not so in solution. ØDestroyed by prolonged heat, baking soda (with heating), sulfite preservatives. ØUnstable in aqueous solutions with p. H > 5. 0. At p. H 8. 0 or above, thiamine turns yellow and is destroyed by a complex series of irreversible reactions. ØIn 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 B 1 in foods, pharmaceutical preparations, and biological fluids. Thiochrome

Functions of Vitamin B 1 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: 1. The pentose phosphate pathway to synthesize NADPH. 2. 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 B 1). § Thiaminase (found in raw fish destroys vitamin B 1). 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 B 1 deficiency A diagnosis test for B 1 deficiency can be determined by measuring transketolase levels of erythrocyte. Diseases of Vitamin B 1 deficiency Beriberi is the deficiency disease caused by lack of thiamine resulted from malnutrition, alcoholism or other causes. There are two major types of beri: A. Dry beri: affect the nervous system B. Wet beri: 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 B 1 deficiency (BERI-BERI)

People at high risk of Vitamin B 1 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 B 12 deficiency (with macrocytosis) that responds to thiamin. 1. 5. Disease caused by heavy alcohol consumption.

Vitamin B 1 - Drug Interactions §Oral contraceptives, antibiotics, sulfa drugs, and certain types of diuretics may lower thiamine levels in the body. §Vitamin B 1 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 v. Thiamin is virtually nontoxic. v Doses > 200 mg may cause drowsiness in some people. v Rare, but severe, allergic reactions may be happened with injectable thiamin.

Vitamin B 2 (Riboflavin)

Vitamin B 2 (Riboflavin) v. Riboflavin is defined chemically as 7, 8 -Dimethyl 10 -[(2 S, 3 S, 4 R)-2, 3, 4, 5 -tetrahydroxypentyl] benzo [g] pteridine-2, 4 -dione and is a yellow to orange-yellow powder and soluble in water. v. 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 B 2 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 v. Riboflavin and its coenzymes are sensitive to alkali and acid but in the presence of light or UV light. v. Riboflavin is photodegraded to yield lumiflavin (7, 8, 10 trimethylisoalloxazine) under alkaline conditions and to lumichrome (7, 8 -dimethylalloxazine) under acidic conditions, and these products are biologically inactive. v. Therefore, phototherapy of neonatal jaundice and of certain skin disorders may promote systemic riboflavin deficiency.

Functions of Vitamin B 2 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 B 12, folate, vitamin B 6 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 ØMalnutrition. ØHealth conditions which affect intestinal absorption. ØIncrease of vitamin excretion from the body. Diagnostic testing for vitamin B 2 Deficiency A positive diagnostic test of serum riboflavin is by measuring glutathione reductase levels of erythrocytes.

Symptoms of vitamin B 2 deficiency (Ariboflavinosis) ØRed, scaly, painful, and itchy patches on sensitive skin (around nose, ears, mouth, labia majora (female), and the scrotum (male). ØPainful 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. ØMouth ulcers Red, scaly, painful skin angular stomatitis Cheilosis Mouth ulcers

ØRedness, burning, excessive tearing of eye. ØAnemia with decreased production of red blood cells. ØDeficiency of riboflavin typically produces symptoms of vitamin B 6 and niacin deficiency. Redness, burning, tearing of eyes Anemia Symptoms of niacin deficiency

People at high risk of vitamin B 2 deficiency ØChildren, and adolescent, athletes, as well as during pregnancy and lactation (cases with a high-energy output) need additional vitamin B 2. ØPeople under high stress ØDiabetics may have low level of riboflavin as a result of increased urinary excretion. ØThe elderly people (nutritional inadequacy and problems with absorption) ØPatients administering thyroid hormones, oral contraceptives, phenothiazines, barbiturates, probenacid, and Tricyclic antidepressant.

Use of Vitamin B 2 in Prevention and Therapy ØDetoxification: Riboflavin helps liver to detoxify pesticides, chemicals, and other environmental toxins. ØIncreasing the antioxidant capacity throughout the body and especially for lens of the eye. v. Ample intake of riboflavin help decrease the incidence of cataracts. v. As a cofactor of glutathione reductase, riboflavin with vitamin C increase body's level of glutathione (antioxidant). ØAmple riboflavin intake maintains healthy skin and mucous membranes. ØIt may be beneficial in stomatitis, cheilosis, and skin eruptions and rashes.

Vitamin B 2 – Drug interaction ØProbenecid (anti-gout) and propantheline bromide (antipeptic ulcers) both delays and impairs its absorption. ØPhenothiazines (antipsychotic drugs) increase the excretion of riboflavin, thus lowering serum levels. ØOral contraceptives may also decrease its serum levels. ØRiboflavin interferes with the absorption and effectiveness of anti-malarial (ex. chloroquine), tetracycline antibiotics and sulfa-containing drugs.

Assay of Vitamin B 2 Lumiflavin method: Riboflavin solution or biological sample is irradiated in alkaline medium to yielded a chloroformsoluble lumiflavin, measured by fluoremetry.

VITAMIN B 3 (NIACIN & NIACINAMIDE)

Vitamin B 3 (Niacin & Niacinamide) ØTwo main forms of Vitamin B 3 are found in foods: nicotinic acid (niacin) and nicotinamide (niacinamide). ØNiacin can be partially satisfied by intake of tryptophan, which is converted by the liver into niacin. Ø 60 mg of tryptophan can be converted into about 1 mg of niacin. Ø Dietary requirements for niacin are described in terms of niacin equivalents (NEs): 1 NE = 60 mg of tryptophan = 1 mg of niacin RDA: 13 - 20 mg/day

Sources of Vitamin B 3 Nicotinic acid or Niacin Meat Rice bran Nicotinamide or Niacinamide Fish Sheep liver Groundnuts Chilgozas Yeast Prawns Turnip Cow’s milk Beet greens Bran

Pharmacokinetics of Vitamin B 3 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 B 1, B 2, and B 6 (60 mg of Tryptophan 1 mg of niacin). Bacteria in the gut may also perform the conversion but are inefficient.

Functions of Vitamin B 3 1. It acts as a co-enzyme in oxidation reduction reactions: v. Catabolic Rxn: in form of NAD+/NADH v. 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 B 3 Deficiency Diseases 1. Milder deficiency of niacin (as well as tryptophan) can cause: v Glossitis (inflammation of the tongue leading to purplish discoloration) v. Dermatitis around the mouth and rashes v. Fatigue v. Irritability v. Poor appetite v. Indigestion v. Weight loss v. Headache Glossitis Dermatitis around mouth Fatigue Poor appetite Indigestion Headache

2. Severe deficiency leads to Pellagra: Characterized by v. Inflamed mouth (painful swollen tongue and fissured lips) and GIT. v. Diarrhea v. Dermatitis in the exposed skin of hands, face, neck (Casal’s necklace) v. Dementia and mental disorders v. 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). Inflamed mouth Diarrhea Dermatitis of exposed skin Mental disorders Death.

People at high risk of vitamin B 3 deficiency ØPeople with very poor nutrition (or niacin or tryptophan- deficient food e. g corn). ØPeople with deficiencies in vitamin B 6 or riboflavin (conversion of tryptophan to niacin is reduced niacin stores in the body is reduced). ØPeople with inflammatory bowel disease and other digestive disorders malabsorption of niacin. ØHeavy alcohol consumption interferes with absorption and metabolism of niacin. ØPeople under high stress, chronic illnesses, liver disease.

Uses in prevention and Therapy ØMental illness e. g. schizophrenia: Niacinamide can be effective with traditional medical treatment. ØAtherosclerosis 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. ØArthritis: Niacin helps in treatment of osteoarthritis. ØDiabetes: Niacinamide slow down the development of nephropathy in diabetes and delay need for insulin therapy in juvenile diabetes.

ØProtection against environmental toxins: The antioxidant function of niacin help protect liver against damage from pesticides, chemicals, alcohol, and drugs. ØHeadache: Niacin help in prevention of headache. ØTreatment of Pellagra.

Toxicity and side effects of vitamin B 3 v. Large doses (500 mg) of niacin (but not niacinamide) can cause dilation of capillaries tingling and flushing of the skin. v. Flushing of the skin is usually worse if nicotinic acid is taken on an empty stomach, therefore it should be taken just after meals. v. Niacin in the form of niacinamide does not produce these side effects. v. 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 B 3 – Drug Interactions ØNiacin with antihypertensive drugs severe hypotension. ØExtra niacin may be required in case of people taking Isoniazid (Inhibits biotransformation of tryptophan to niacin ), by women taking oral contraceptives. ØBile acid sequesterants e. g. Cholestyramine and cholestipol should be taken at a different time than niacin (not niacinamide) otherwise they will reduce its absorption.

ØCarbamazepine may cause toxicity with niacin. ØThe 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