VITAMINS

Fayad Bin Abdus SalamDept. of PharmacyNUB

What is a Vitamin?

Vitamin is a naturally occurring organic molecule that is a normal constituent of diet.

It should be essential and required only in minute amounts.

And, it is required to maintain the normal cellular, biochemical and tissue integrity.

Properties of vitamin Vitamins Are Naturally Occurring.

But sometimes synthetic compound shows greater activity such as L- ascorbic acid is twice potent than naturally occurring racemic mixtures. Same as S-Biotin, D-Pantothenic acids.

Vitamins Are Essential Because They are Not Produced by Human Biochemical Pathways. With two exceptions, such as niacin which is derived from

conversion of an essential amino acid tryptophan. Vit D3- cholecalciferol also occurs by photochemical reaction on skin from 7-dehydrocholesterol.

Properties of vitamin

Vitamins are organic in nature. Trace elements such as Zinc, Iron, Magnesium,

Manganese, Chromium, Selenium are not called vitamins.

Vitamins Are normal constituent of diet Exception is cholecalciferol but some of the world

populations get it from protein of marine sources. Rest of the population get it from direct sunlight effects on cholesterol.

Properties of vitamin Vitamins Are required in minute amounts.

This is arbitrary, but ranges from 2.0 µg for cyanocobalamin to 90 mg for ascorbic acid.

Vitamins Are Required to Maintain Normal Biochemical Functions of the Tissues. Either as a hormone or chemical messenger (cholecalciferol), structural

component in some metabolic process (pantothenic acid), or a coenzyme (phytomenadione, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin).

Some vitamins have more than one biochemical role. E.g.Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation.

Causes of vitamin deficiencies

Inadequate ingestion due to poor diet Economic deprivation Self imposed reducing diet Diseases (loss of appetite due to chemotherapy, depression)

Inadequate absorption Disease at GIT (Crohn’s disease, parasites) Mineral oil laxatives (Vit A, D, E, K removes) Ion exchange resins ingestion (colestipol,

colestyramine) Cystic fibrosis causes less secretion of lipase enzyme

Causes of vitamin deficiencies Inadequate utilization

Genetic diseases Drug-vitamin reactions (isoniazid- pyridoxine, phenobarbitol-

cholecalciferol, methotrexate-folic acid)

Increased requirements of RDA(Recommended Dietary Allowance) Increased physical activity Medical needs (severe burns, illness, surgery,

malignancies, pregnancy) Chronic intake of alcohol

Ethyl alcohol interferes the uptake, processing, and storage of folic acid and thiamine.

Classification

Thiamine was the first vitamin (B1) whose structure was elucidated. It is an amine leading to the term vital amine and finally vitamin.

Classification

Fat soluble vitaminsVitamin A, D, E and KFound in the fats and oils of food.Absorbed into the lymph and carried in

blood with protein transporters = chylomicrons.

*Stored in liver and body fat and can become toxic if large amounts are consumed.

Classification

Water soluble vitaminsVitamin B and CFound in vegetables, fruit and grains, meat.Absorbed directly into the blood streamNot stored in the body and toxicity is rare.

Alcohol can increase elimination and smoking can cause decreased absorption.

Year of discovery Vitamin Food source

1913 Vitamin A (Retinol) Cod liver oil1910 Vitamin B1 (Thiamine) Rice bran1920 Vitamin C (Ascorbic acid) Citrus, most fresh foods1920 Vitamin D (Calciferol) Cod liver oil1920 Vitamin B2 (Riboflavin) Meat, eggs

1922 Vitamin E (Tocopherol)Wheat germ oil, unrefined vegetable oils

1926 Vitamin B12 (Cobalamins) liver, eggs, animal products1929 Vitamin K1 (Phylloquinone) Leafy green vegetables1931 Vitamin B5 (Pantothenic acid) Meat, whole grains,1931 Vitamin B7 (Biotin) Meat, dairy products, eggs1934 Vitamin B6 (Pyridoxine) Meat, dairy products1936 Vitamin B3 (Niacin) Meat, eggs, grains1941 Vitamin B9 (Folic acid) Leafy green vegetables

Vit RDA DeficiencyUpper intake overdose

Vit A 900 µgNight-blindness,Hyperkeratosis 3,000 µgHypervitaminosis A

Vit B1 1.2 mg Beriberi N/DDrowsiness or muscle relaxation

Vit B2 1.3 mg Ariboflavinosis N/D

Vit B3 16.0 mg Pellagra 35.0 mgLiver damage (doses > 2g/day)

Vit B5 5.0 mg Paresthesia N/DDiarrhea, nausea and heartburn.

Vit B61.3–1.7 mg

Anemia, peripheral neuropathy. 100 mg

nerve damage (> 100 mg/day)

Vit B7 30.0 µg Dermatitis, enteritis N/D

Vit RDA DeficiencyUpper intake overdose

Vit B9 400 µgMegaloblast, neural tube defects 1,000 µg

Vit B12 2.4 µg Megaloblastic anemia N/D Acne-like rash

Vit C 90 mg Scurvy 2,000 mgVitamin C megadosage

Vit D 10 µg Rickets, Osteomalacia 50 µg Hypervitaminosis D

Vit E 15 mgMild hemolytic anemia 1,000 mg

Increased congestive heart failure

Vit K 120 µg Bleeding diathesis N/D Increases coagulation

Fat Soluble Vitamins

Vitamin A (precursor – beta carotene) 3 forms: retinol (stored in liver), retinal, retinoic acid Roles in body:

Regulation of gene expression Retinol, a part of the visual pigment rhodopsin, maintains clarity

of cornea Required for cell growth and division - epithelial cells, bones and

teeth Promotes development of immune cells, especially “Natural Killer

Cells” Antioxidant Retinoic acid is required for the development of goblet mucous

cells.

Fat Soluble Vitamins

Vitamin ADeficiencies cause:

Night blindness, xerophthalmia (keratin deposits in cornea), macular degeneration.

Skin and mucous membrane dryness and infection, keratin deposits.

AnemiaDevelopmental defects – bones, teeth, immune

system, vision

Fat Soluble Vitamins

Vitamin AToxicities (single large doses of

supplements, eating excessive amounts of liver) cause:

Fragile RBCs, hemorrhageBone pain, fracturesAbdominal pain and diarrheaBlurred visionDry skinLiver enlargement

Fat Soluble Vitamins: A

Hypervitaminosis A fatigue, malaise, lethargy, abdominal comfort,

bone and joint pain, severe headache, insomnia, restlessness, dry and scaly skin, loss of body hair, brittle nails, constipation, and irregular menses.

Depending on the health of person's liver, there is risk of developing cirrhosis. There is a daily Tolerable Upper intake Level (UL) of 3000 µg for this vitamin.

Fat Soluble Vitamin A: Drugs

Due to retinol deficiency results in keratinization of epithelial tissue, so retinol was recommended for skin conditions including acne.

That is not proved yet but active form retinoic acid is targeted for treating acne, psoriasis and malignancy.

Retinoid and Retinoid-like Drugs Used in the Treatment of Acne

Fat Soluble Vitamin A: Retinoids

The first product introduced was tretinoin, which is a topical all-trans retinoic acid. It produces a complex response related to increasing the turnover of follicular epithelial cells. The result is decreased cohesiveness of follicular epithelial cells.

Tretinoin is also used as an antiwrinkle cream. There is an increase in epidermal cell turnover, shedding older cells and thickening the skin. Also the drug may combine with epidermal retinoic acid receptors, thereby decreasing keratin production. Keratin can contribute to skin wrinkling.

Fat Soluble Vitamin A: Adapalene

Although used topically, the nonretinoid,adapalene, a third generation drug, does bind to the retinoic acid nuclear receptor and does affect cell differentiation, keratinization, and inflammatory responses.

It is approved in 1996 by FDA for treatment of Acne. Available form is 0.1% cream and gel, 0.3% gel. Unlike tretinoin, adapalene has also been shown to

retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure.

Retinoid drugs:

Retinoid drugs:

Fat Soluble Vitamin D Vitamin D – precursor is cholesterol, converted by UV

from sunlight exposure, therefore is a “non-essential” vitamin.

Cholecalciferol is produced in the body from endogenously synthesized 7-dehydrocholesterol. Excess amounts of cholecalciferol can result in excess calcium uptake from the intestinal tract, leading to calcification of soft tissues.

Vitamin D Increases calcium absorption in bone, intestines, kidney. Promotes bone growth and maintenance.

Stimulates maturation of cells – heart, brain, immune system, etc.

Fat Soluble Vitamin D Exposure of human skin to sunlight of 295-300 nm

converts 7-dehydrocholesterol to previtamin D. The isomerization to cholecalciferol (vitamin D3) is

heat catalyzed. Continuous exposure to ultraviolet radiation from the sun results in the reversible formation of lumisterol and tachysterol.

Once the B ring of the steroids has been cleaved, the products should no longer be referred as steroid.

So Vitamin D is not a steroidal vitamin.

Calcium regulation: Role of Vit D

There are at least three hormones that regulate calcium metabolism, parathyroid (PTH), calcitonin, and 1,25(OH)2D3.

In response to low serum calcium levels, PTH stimulates the hydroxylation of 25(OH)D3 leading to formation of calcium transport protein and activation of osteoclast cells required to release calcium from bone. PTH also inhibits calcium excretion by the kidney.

In contrast, calcitonin (produced in the thyroid gland) acts when serum calcium levels are high. It promotes the deposition of calcium into bone by osteoblast cells and excretion of calcium by the kidney.

Function and deficiency:

One of the most important roles of vitamin D is to maintain skeletal calcium balance by promoting calcium absorption in the intestines, promoting bone resorption by increasing osteoclast number, maintaining calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels. 

Vitamin D deficiency can result in lower bone mineral density and an increased risk of reduced bone density (osteoporosis) or bone fracture because a lack of vitamin D alters mineral metabolism in the body. Deficiencies: rickets (children), osteomalacia (adults). Toxicities (5X RDA)

Loss of calcium from bone and deposition in soft tissues. Loss of appetite, nausea and vomiting, psychological depression.

Fat Soluble Vitamins

Vitamin DDaily Requirement – 5 micrograms/day for

ages 19-50, 10 for ages 51-70, 15 for ages >70.

Vitamin: E

Vitamin E includes both tocopherols and tocotrienols. Tocopherol and Tocotrienols are : *alpha-, beta -, gamma- and

delta- Most active form is alfa tocopherol. It is a fat-soluble antioxidant that stops the production

of reactive oxygen species formed when fat undergoes oxidation. Roles:

Antioxidant (protects polyunsaturated fats) Prevention of damage to lungs, RBCs, WBCs (immunity),

heart Necessary for normal nerve development

Vitamin E: Function As an antioxidant, vitamin E acts as a peroxy

radical scavenger, preventing the propagation of free radicals in tissues.

By reacting with them to form a tocopheryl radical which will then be oxidized by a hydrogen donor (such as Vitamin C) and thus return to its reduced state.

As it is fat-soluble, it is incorporated into cell membranes, which protects them from oxidative damage.

Vitamin E also plays a role in neurological functions, and inhibition of platelet aggregation.

Vitamin E protects lipids and prevents the oxidation of polyunsaturated fatty acids (PUFAs.)

Vitamin E: Function

Vitamin E also has an effect on gene expression.  Scavenger receptor CD36, is a class B scavenger receptor found

to be up-regulated by oxidized low density lipoprotein (LDL) and binds it.

Treatment with alpha tocopherol was found to down regulate the expression of the CD36 scavenger receptor gene and the scavenger receptor class A (SR-A)

Vitamin E deficiency and toxicity:

Deficiencies (decreased absorption of fats- liver disease, low fat diets)

Premature babies – fragile RBCs (hemolysis)Loss of muscle coordination, vision, impaired

immune functionsMyopathy, retinopathy, ataxia

Toxicities (more than 1000 milligrams/day) Increases the effects of anticoagulants

(Coumadin, Warfarin)

Fat Soluble Vitamins

Vitamin E15 milligrams/day (alpha-tocopherol)

Vitamin K: It was named Vitamin K for koagulation

vitamin. This may be the only vitamin that humans receive from bacteria in large intestine.Roles:

Promotes synthesis of blood clotting proteins (**Interferes with Coumadin)

Bone formation

Fat Soluble Vitamins There are two series for this vitamin. The vitamin K1

series (phylloquinone) is mostly obtained from green plants, whereas the K2 series (menaquinone) is the product of bacteria.

The active vitamin is in the K2 series.

Menadione has sometimes been referred to as vitamin K3.

Escherichia coli found in the large intestine, can synthesize vitamin K2, but not vitamin K1.

Vitamin K deficiency: Three main causes are: Chronic obstructive jaundice that prevents the release of

bile salts into intestine and decreases absorption of vitamin K.

Surgery at intestine decreases bacterial flora and that decreases the production of vitamin K.

Infants born with a sterile intestinal tract may have hemorrhagic diseases. Until the flora are established, the infant will have to get vitamin K from the mother.

Toxicities: >1000 mg/day: rupture of RBCs and jaundice

Water Soluble Vitamins

Vitamin B complex: Tender Romance Never Fails with 6 to 12

Beautiful Pearls

T-Thiamin R-Riboflavin N-Niacin, F-Folate, B6, B12, B-Biotin P-Pantothenic acid

Vitamin B1  thiamine Vitamin B2  riboflavin Vitamin B3  niacin or niacinamide Vitamin B5  pantothenic acid Vitamin B6  pyridoxine Vitamin B7  biotin Vitamin B9  folic acid Vitamin B12  cyanocobalamin, mecobalamin

Water Soluble Vitamins Support and increase the rate of metabolism Maintain healthy skin, hair and muscle tone Enhance immune and nervous system function Promote cell growth and division, including that of the red blood

cells that help to prevent anemia Reduce the risk of pancreatic cancer All B vitamins are water-soluble, and are dispersed throughout

the body. Most of the B vitamins must be replenished regularly, since any excess is excreted in the urine. This can result in the urine produced being a bright green-yellow color.

B vitamins have also been hypothesized to reduce the symptoms of attention deficit hyperactivity disorder.

All Vitamin B acts as Cofactors? A cofactor is a non-protein chemical compound that is bound to a protein

enzymes and is required for the protein's biological activity. These cofactors can be considered "helper molecules" that assist in biochemical transformations.

Cofactors are either organic or inorganic. They can also be classified depending on how tightly they bind to an enzyme, with loosely-bound cofactors termed coenzymes and tightly-bound cofactors termed prosthetic groups.

An inactive enzyme, without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is the holoenzyme.

For example, the multienzyme complex pyruvate dehydrogenase at the junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: thiamine pyrophosphate (TPP), lipoamide and flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD+), coenzyme A (CoA), and a metal ion (Mg2+).

Thiamin: cofactors and roles

Thiamine produces TPP (thiamine pyrophosphate) coenzyme Thiamine kinase in the intestinal mucosa cell transfers a

pyrophosphate from the ATP to the propyl alcohol at position 5 of the thiazole ring, forming thiamine pyrophosphate (TPP).

The first role of TPP is the oxidative decarboxylation of a-keto acids. The two most common examples are pyruvate and a-ketoglutarate, oxidatively decarboxyated to acetyl CoA and succinyl CoA, respectively.

TPP is also the coenzyme in the transketolase reaction found in the pentose phosphate pathway that interconverts hexoses, pentoses, tetroses, and trioses.

Thiamine deficiency:

Beriberi is a nervous system ailment caused by a thiamine (vitamin B1) deficiency in the diet. 

Symptoms include weight loss, emotional disturbances, impaired sensory perception,  weakness and pain in the limbs, and periods of irregular heart rate, Edema(swelling of bodily tissues) are common.

It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause heart failure and death.

Dry beriberi and Wernicke-Korsakoff syndrome affect the peripheral and central nervous system respectively.

Wet beriberi affects the cardiovascular system, as well as other bodily systems.

Infantile beriberi affects mostly children in developing countries.

Thiamine deficiency:

Dry beriberi Dry beriberi causes partial paralysis resulting from damaged

peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:

Difficulty in walking Tingling or loss of feeling (sensation) in hands and feet

(numbness) Loss of muscle function or paralysis of the lower legs Mental confusion/speech difficulties Pain Involuntary eye movements (nystagmus) Vomiting

Thiamine deficiency:

Wet beriberi It affects the heart; it is sometimes fatal, as it causes a

combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. It is also characterized by:

Vasodilation Peripheral edema Paroxysmal nocturnal dyspnea Increased heart rate Swelling of the lower legs

Thiamine deficiency

Alcohol reduces the active transport of the vitamin. This form of thiamine deficiency is called Wernicke-Korsakoff syndrome.

Riboflavin

Most dietary riboflavin is eaten as the FAD (Flavin adenine diphosphate) or FMN (Flavin Mononeucleotide) coenzymes

Riboflavin coenzymes are required for most oxidations of carbon- carbon bonds. Examples include the oxidation of succinyl CoA to fumarate in the Krebs cycle and introduction of α,β-unsaturation in β-oxidation of fatty acids.

Riboflavin is also required for the metabolism of other vitamins, including the reduction of 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate and interconversion of pyridoxine-pyridoxal phosphate- pyridoxamine, retinal to retinoic acid, tryptophan to niacin etc.

Reduction of the oxidized form of glutathione (GSSG) to its reduced form (GSH) is also FAD dependent

Riboflavin deficiency:

Riboflavin deficiency is always accompanied by deficiency of other vitamins.

In humans, signs and symptoms of riboflavin deficiency (ariboflavinosis) include cracked and red lips, inflammation of the lining of mouth and tongue, mouth ulcers, cracks at the corners of the mouth (angular cheilitis), and a sore throat.

A deficiency may also cause dry and scaling skin, fluid in the mucous membranes, and iron-deficiency anemia.

Niacin:

Niacin is also named as nicotinic acid because of presence of carboxylic acid in 3-position of pyridine. The corresponding amide that is nicotinamide is the vitamin that has amide group in that position.

Niacin is a precursor to NAD+/NADH and NADP+/NADPH, which play essential metabolic roles in living cells.

Niacin is involved in both DNA repair, and the production of steroid hormones in the adrenal gland.

Niacin:

NAD is the primary coenzyme required for oxidation/reduction of carbon-oxygen bonds and is required for oxidative catabolism (glycolysis, β-oxidation, Krebs cycle)

NADP is the coenzyme in biosynthetic routes (fatty acid and cholesterol synthesis) and will be part of oxidation/reduction reactions involving both carbon-oxygen and carbon-carbon bonds

Niacin: deficiency

Niacin deficiency, manifested as pellagra, is characterized by the four Ds: dermatitis, diarrhea, depression, and death.

The dermatitis is characterized by a pigmented rash developing on skin exposed to heat.

Changes in the gastrointestinal tract can lead to vomiting, constipation, or diarrhea.

Depression is one of the neurological symptoms that can include apathy, headache, fatigue, and memory loss.

Pellagra

Pantothenic acid: Its name derives from the Greek pantothen meaning "from everywhere"

and small quantities of pantothenic acid are found in nearly every food. Pantothenic acid is used in the synthesis of coenzyme A (CoA).

Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell.

CoA is important in energy metabolism for pyruvate to enter the tricarboxylic acid cycle (TCA cycle) as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine.

CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively.

Pyridoxine

The vitamin B6 family consists of pyridoxine, pyridoxal, pyridoxamine, pyridoxine phosphate, pyridoxal phosphate (PLP), and pyridoxamine phosphate.

The commercial form is pyridoxine. Pyridoxal phosphate is the coenzyme form.

Pyridoxal phosphate (PLP) is required for amino acid metabolism and reactions involving amino acids.

Pyridoxine

The most common of the PLP-catalyzed reactions are transaminations.

One-half of all transamination reactions involve a-ketoglutarate as the acceptor of the amine group forming glutamic acid. Alternatively, glutamic acid donates the amine group and an a-keto acid is the acceptor forming a new amino acid.

Another PLP-catalyzed reaction is decarboxylation of amino acids. These are part of the biosynthesis of neurotransmitters, including histamine from histidine; serotonin from tryptophan, dopamine, norepinephrine, and epinephrine from dihydroxyphenylalanine (dopa) II and y-aminobutyric acid from glutamic acid, two reactions in biosynthesis of cysteine from methionine.

Biotin:

Biotin consists of two 5-membered rings cis-fused to each other that can be drawn either as the keto (urea) or enolic form.

Biotin picks up carbon dioxide that has been activated by combining with an ATP-donated phosphate, producing the mixed anhydride of phosphoric and carbonic acids.

The biotin enolate receives the carbon dioxide, producing the keto carbon dioxide-releasing coenzyme.

There are four biotin-dependent carboxylation reactions, three of which are in the mitochondria.

Biotin:

1. Pyruvate carboxylase: This reaction, which converts pyruvate to oxalaceetate.

2. Acetyl CoA carboxylase: This reaction, found mostly in the cytosol, is the committed step in the synthesis of fatty acids

3. Propionyl CoA carboxylase: Propionyl CoA is the product from the catabolism of valine, isoleucine, methionine, and odd-numbered fatty acids. The carboxylation reaction, found in the mitochondria, produces methyl malonyl CoA.

4. Β-Methylcrotonyl CoA carboxylase. This mitochondrial reaction permits the final steps in the catabolism of the branched-chain amino acid leucine. The final products, acetoacetate and acetyl CoA, either are oxidative metabolized to carbon dioxide and water or enter other reactions in lipid metabolism.

Folic acid:

The commercial form of the vitamin is folic acid . It consists of a pteridine ring attached to a p-aminobenzoic acid that is attached to the amine of glutamic acid.

Two biosynthetic changes must occur before it is active. First, it must be reduced to tetrahydrofolate by

dihydrofolate reductase in a two-step reduction. Second, a polyglutamate chain must be attached to the

y-carboxyl of the parent glutamic acid The most common polyglutamate found in food is 5-

methyltetrahydrofolate polyglutamate

Folic acid:

It is obvious that folic acid is a very important vitamin for biosynthetic reactions, particularly those required for the biosynthesis of purines, methylation of deoxyuridylic acid, and regeneration of methionine from homocysteine.

Folic acid deficiency:

The main deficiency is a characteristic megaloblastic anemia attributed to a shortage of nucleotides required for the production of erythrocyte precursor cells.

Another clinical sign of folic acid deficiency is neural tube defects, including spina bifida and anencephaly (absence of a major portion of the brain, skull, and scalp).

A third indication of inadequate folic acid is elevated blood homocysteine levels, with attendant increased risk of cardiovascular disease.

Cobalamin:

Vitamin B-12, also called cobalamin, plays a key role in the normal functioning of the brain and nervous system, and for the formation of blood.

It is normally involved in the metabolism of every cell of the human body, especially affecting DNA synthesis and regulation, but also fatty acid synthesis and energy production.

A common synthetic form of the vitamin, cyanocobalamin, does not occur in nature, but is used in many pharmaceuticals and supplements, and as a food additive, because of its stability and lower cost.

In the body it is converted to methylcobalamin and adenosylcobalamin.

Vitamin B12 was discovered from its relationship to the disease pernicious anemia (red blood cell count is low).

Cobalamin:

since B12 is used to regenerate folate in the body. Most vitamin B12 deficiency symptoms are actually folate deficiency symptoms, since they include all the effects of pernicious anemia and megaloblastosis, which are due to poor synthesis of DNA when the body does not have a proper supply of folic acid for the production of thymine.

vitamin B12-dependent enzymes are Methylmalonyl Coenzyme A mutase, and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase.

Water Soluble Vitamins

Vitamin C, ascorbic acidRoles:

Connective tissue development, collagenAntioxidantPromotes iron absorptionProtects vitamin E

Water Soluble Vitamins

Vitamin C Deficiency – Scurvy (skin and mucous membrane

damage), anemia. DRI : 75 – 90 milligrams/day. Increased for

smokers. Toxicity (> 2grams/day) – pro-oxidant, activates

oxidizing agents. Notes: can interfere with diagnostic tests for

diabetes, and blood clotting