Vitamins

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.

Provitamins are 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.

Water-soluble vitamins

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.

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.

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.

Deficiency:Severe Deficiencyleads to beri beri

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.

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).

Deficiency

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.

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

Functions and Deficiency

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)

Assessment of nutritional status

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

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.

Functions and Deficiency

Most foods but eggs, liver and yeast are very good sources.

Sources:

BiotinStructure:

Functions and Deficiency

Sources -Most foods, especially egg yolk, offal, yeast

and nuts.

-A significant amount is synthesized by bacteria in the intestine.

PyridoxineStructure:

All three forms can be converted to the active coenzyme pyridoxal phosphate

Active form

Functions and Deficiency

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.

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.

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 either methyl, methylene, methenyl, formyl or formimino groups. 

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 of dihydrofolate reductase enzyme (DHFR), an NADPH 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 is 5-methyltetrahydrofolate.

Functions and Deficiency

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 are impaired

absorption or metabolism or an increased demand for 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.

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.

Requirement and sourcesRNI: 200mg/day.

Sources: Green vegetables, liver and wholegrain

cereals.

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.

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

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 of methylmalonyl-CoA to succinyl-CoA.

The 5'-deoxyadenosylcobalamin derivative of cobalamin is required for this reaction.

The second reaction requiring vitamin B12 (methylcobalmin) catalyzes the conversion of homocysteine to methionine and is catalyzed by homocysteine 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.

Requirement and sourcesRNI: 1.5mg/day.

Sources: Only animal sources: liver, meat, dairy

foods; therefore vegans are at risk of deficiency.

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.

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.

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-CoA that

result from vitamin B12 deficiency.

Deficiency

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.

Requirement and sources RNI: 40mg/day.

Sources: Citrus fruit, tomatoes, berries and green

vegetables.

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.

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)

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)