Vitamins

1. Vitamins

2. Definitions: • Vitamins are organic compounds required by the body in trace amounts to perform specific function, and can not be synthesized by humans, or can not be synthesized in adequate (sufficient) quantities to meet needs. • When present in inadequate quantities, deficiency states results leading to disease. • Modern views suggest that more quantities than RDIS might be needed to prevent some chronic diseases. • Provitaminsare precursors of vitamins that could be converted into vitamins inside the body e.g. Carotenes are provitamin A. • Vitamers:These are different forms of one vitamin e.g. Vitamin D has 2 vitamers; D2 &D3.

4. Water-soluble vitamins

5. Water-soluble vitamins They include the B-group vitamins and vitamin C. These are: • Not stored extensively. • Required regularly in the diet. • Generally non-toxic in excess (within reason). All B vitamins are coenzymes in metabolic pathways.

6. Thiamin (B1) • Co-factor or active form and Function • Co-factor active form: Thiamine pyrophosphate ( TPP). • TPP acts as cofactor in the following enzyme systems: -Pyruvate dehydrogenase (pyruvate acetyl CoA) -α-Ketoglutarate dehydrogenase (α-Ketoglutarate succinyl CoA) -Oxidative decarboxylation of α–keto acids derived from leucine, isoleucine, valine, threonine and serine. -Trans ketolase reaction in pentose phosphate pathway • TPP also supports normal appetite. And , • Is needed for normal brain and CNS function.

7. Deficiency • Decreased activity of the dehydrogenases , leading to -accumulation of pyruvate and lactate. -Decreased acetyl CoA and ATP formation , thus decreased acetylcholine and CNS activity. • Decreased HMP shunt results in low levels of NADPH , Hence decrease fatty acid synthesis necessary for myelin formation and causing peripheral neuropathy.

8. Deficiency:Severe Deficiencyleads to beri beri

10. Diagnosing deficiency • This is done by measuring the transketolase activity in RBCs , before and after the addition of TPP . A greater than 30% increase in activity indicates deficiency. • Requirement , sources and toxicity • RNI: 1.0mg/day for men; 0.8mg/day for women. Increased requirement in case of high carbohydrates diet. • Sources: Wholegrain cereals, liver, pork, yeast, dairy produce and legumes. • Toxicity: Rare but an excess causes headaches , insomnia and dermatitis.

11. Riboflavin ( B2) • Co-factor or active form and Function: • Co-factor or active form: Flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). • Function of active forms: FAD and FMN act as electron carriers in oxidoreduction reactions (usually tightly bound to the apoenzyme).

12. Deficiency

13. Diagnosis of deficiency • Erythrocyte glutathione reductase level is a good measurement of deficiency. • HPLC measurement of B2 in blood is used also for diagnosis of deficiency. • Requirement and sources • RNI: 1.3mg/day for men; 1.1mg/day for women. • Sources: Milk, eggs, liver. Riboflavin is readily destroyed by ultraviolet light.

14. Niacin ( B3) • Co-factor or active form • Co-factor or active form: NAD+ and NADP+ Nicotinamide-adenine dinucleotide and its phosphate. • A certain amount of NAD and NADP can be synthesized in the body from the amino acid tryptophan, in reactions requiring pyridoxal P

15. Functions and Deficiency

16. Requirement and sources • RNI: 17mg/day for men; 13mg/day for women. • Sources: Wholegrain cereals, meat, fish . It can be synthesized in the body from the amino acid tryptophan, but requires other B vitamins as co-factors ( Vit.B1, B2 &B6) ,and is not very efficient ( 60mg Tryp. To make 1mg of niacin)

17. Assessment of nutritional status • Measurement of urinary N-methylnicotiamide and 2-pyridone reflect nutritional status.

18. Pantothenic acid ( B5) • Co-factor or active form and function • Co-factor: Coenzyme A , ACP • Examples of enzyme systems needing CoA: - Pyruvate dehydrogenase - α-Ketoglutarate dehydrogenase - Oxidative decarboxylation of α-keto acids - Fatty acid activation - Generally, a carrier of acyl groups.

19. Functions and Deficiency Sources: Most foods but eggs, liver and yeast are very good sources.

20. Biotin Structure:

21. Functions and Deficiency

22. Sources -Most foods, especially egg yolk, offal, yeast and nuts. -A significant amount is synthesized by bacteria in the intestine.

23. Pyridoxine Structure: Active form • All three forms can be converted to the active coenzymepyridoxal phosphate

24. Functions and Deficiency

25. Causes of Deficiency: • Deficiency is rare but can be seen in : - Newborn babies fed formula milk deficient in the vitamin. - Elderly people and alcoholics. - Women taking oral contraceptives. - Patients on isoniazid therapy for treatment of tuberculosis. Requirement and sources: • RNI: 1.4mg/day for men; 1.2mg/day for women. Increased requirement in case of high protein diet. • Sources: Whole grains (wheat or corn), meat, fish and poultry.

26. Toxicity • This is rare. • In fact vit.B6 is actually used in the treatment of PMT. However , neurological symptoms have been observed at intake >2g/day. • Improvement , but not complete recovery occurs when the vitamin is discontinued.

27. Folic acid • Active form and action: • Active form is 5,6,7,8-THF . • The function of THF derivatives is to carry and transfer various forms of one carbon units during biosynthetic reactions. The one carbon units are eithermethyl,methylene, methenyl,formylorformiminogroups.

28. Absorption and storage: • When stored in the liver or ingested folic acid exists in a polyglutamate form. • Intestinal mucosal cells remove some of the glutamate residues through the action of the lysosomal enzyme,conjugase. • The removal of glutamate residues makes folate less negatively charged (from the polyglutamic acids) and therefore more capable of passing through the basal lamenal membrane of the epithelial cells of the intestine and into the bloodstream. • Folic acid is reduced within cells to dihydrofolate and then tetrahydrofolate (principally in the liver where it is stored) through the action ofdihydrofolate reductase enzyme (DHFR), anNADPH requiring enzyme. • Malabsorption syndromes such as tropical sprue, celiac disease, and Crohn disease greatly affect the absorption of folate, also some drugs such as sulfasalazine may interfere with folate absorption. The most common circulating form of the vitamin is5-methyltetrahydrofolate.

29. Functions and Deficiency

30. Causes of deficiency • Decreased intake :Poor dietary habits as those of chronic alcoholics can lead to folate deficiency (for adult about 1 mg/day folate is considered enough for treatment of deficiency if there is no malabsorption). • The predominant causes of folate deficiency in non-alcoholics areimpaired absorptionor metabolismor anincreased demandfor the vitamin. • Increased demand:The most common condition requiring an increase in the daily intake of folate is pregnancy (it is recommended to give pregnant ladies 400 ug/day folate). • Drugs :Certain drugs such as anticonvulsants and oral contraceptives can impair the absorption of folate. • Others may interfere with its metabolism , e.g. dihydrofolate inhibitors. • Secondary to vitamin B12 deficiency.

32. Folate deficiency in pregnancy • The development of the neural tube in the fetus is dependant on the presence of folic acid. • Therefore , it is advisable for women planning a pregnancy to take prophylactic folate supplements to reduce the risk of neural tube defects such as spina bifida or anencephaly.

33. Requirement and sources • RNI: 200mg/day. • Sources: Green vegetables, liver and wholegrain cereals.

34. Vitamin B (cobalamin) • Absorption: • The vitamin must be hydrolyzed from protein in food in order to be absorbed. • Hydrolysis occurs in the stomach by gastric acid following consumption of animal meat. • The vitamin is then bound by intrinsic factor ( IF), a glycoprotein secreted by parietal cells of the stomach, and carried to the ileum where the complex is bound to receptors on the mucosal cells ,and vit.B12 is absorbed, the absorption is enhanced by calcium ions and pH >6.

35. Transport and Storage • Following absorption the vitamin is transported to the liver in the blood bound to carrier globulins; transcobalamin II. • About 2-3 g of the vitamin are stored in the liver ( enough for about 2 years requirement ) • Active Form: • Two active forms: - deoxyadenosyl cobalamin and - methyl cobalamin

36. Function • Till now there are only two known reactions in the body that require vitamin B12 as a cofactor: • The first one, during the catabolism of fatty acids with an odd number of carbon atoms ,and during the catabolism of amino acids valine, isoleucine and threonine . • One of the enzymes in this pathway,methylmalonyl-CoA mutase,requires vitamin B12 as a cofactor in the conversion ofmethylmalonyl-CoA to succinyl-CoA. • The 5'-deoxyadenosylcobalamin derivativeof cobalamin is required for this reaction. • The second reactionrequiring vitamin B12 (methylcobalmin) catalyzes the conversion of homocysteine to methionine and is catalyzed byhomocysteine methyl-transferase. • It requires methyl-tetrahydrofolate as cofactor ( as a carrier of the methyl group). • Therefore , in case of vit.B12 deficiency the THF is trapped as methyl-THF.

37. Requirement and sources • RNI: 1.5mg/day. • Sources: Only animal sources: liver, meat, dairy foods; therefore vegans are at risk of deficiency.

38. Vitamin B12 deficiency: • The liver can store up to 2-3 years of vitamin B12, hence deficiencies of this vitamin are rare. • Reduced intake , as in total vegetarians , could cause deficiency. • There are many causes that may affect the absorption of vitamin B12 such as: - achlorhydria, - total gastrectomy - gastric atrophy (as in aging and pernicious anemia), , - impaired pancreatic function , and - production of antibody against the intrinsic factor (pernicious anemia) .The commonest cause of deficiency. - Some drugs (anticonvulsant, neomycin, paraaminosalicylic acid, Cholestyramine and alcohol) also cause vitamin B12 deficiency. - Diseases of terminal ileum , e.g. Crohn’s disease or tuberculosis. - Blind – loop syndrome: parasites compete for B12.

39. Vitamin B12 deficiency(continue) • Deficiency can cause two main problems: -Pernicious anemia which is a megaloblastic anemia The anemia resulting from impaired DNA synthesis due to a block in purine and thymidine biosynthesis. • The block in nucleotide biosynthesis is a consequence of the effect of vitamin B12 on folate metabolism. When vitamin B12 is deficient essentially all of the folate becomes trapped as the N5-methyltetrahydrofolate derivative and cannot participate in nucleotide biosynthesis.

40. Vitamin B12 deficiency(continue) • Neurological complications (subacute combined degeneration of the spinal cord of lateral {motor} and posterior {sensory} columns and peripheral neuritis leads to numbness tingling and weakness of extremities) also are associated with vitamin B12 deficiency and result from a progressive demyelination of nerve cells. • The demyelination is thought to result from the increase in methylmalonyl-CoAthat result from vitamin B12 deficiency.

41. Deficiency

42. Ascorbate (Vitamin C) • Active form and function: • Active form is ascorbate • Functions : 1-Important antioxidant, inactivates free oxygen radicals , and protects other antioxidant vitamins A and E. 2- Essential for iron absorption , reducing F3+ to F2+. 3 - It has mild anti-histamine effect. 4- important for the immune system (antibodies and white blood cells), strengthening resistance to infection. 5- Coenzyme in hydroxylation reactions : - Collagen formation (essential for formation of hydroxylysine and hydroxyproline. - Formation of corticosteroid hormones in the adrenal gland. -It is important for formation of adrenaline and noradrenaline.

43. Requirement and sources • RNI: 40mg/day. • Sources: Citrus fruit, tomatoes, berries and green vegetables.

44. Deficiency • Defective collagen synthesis causes scurvy which is characterized by bleeding gum, bruises. • Hypochromic microcytic anemia may take place due to decreased iron absorption. • Low levels of this important antioxidant may increase risk of minor infections and heart disease. • Diagnosis of deficiency is by measuring vitamin C level in blood.

45. Effect of mega dose and toxicity • It is thought that large doses of 1-4 g/day can : - decrease the severity of symptoms of cold (but not decrease the incidence ) - decrease the incidence of CHD and certain cancers by scavenging free radicals. • Chronic intake of large doses may lead to formation of kidney stones ( ascorbate is metabolized to oxalate in the body – uric acid excretion is also increased)

46. Assessment of nutritional status • Vitamin C (ascorbate ) can be measured in serum. • Normal Level is .4 – 1.2 mg/dl • .1-.2 mg/dl indicate moderate deficiency • <0.1 mg/dl indicate severe deficiency (high risk of scurvy) • Vitamin C load test: • Mega dose of Vitamin C is given orally, and urinary excretion is measured. • Most of the dose is excreted within hours if status is adequate • No or little ascorbate appear in urine in case of deficiency (tissue de-saturation)