Vitamins: An Overview

[icon name=”user” class=”” unprefixed_class=””] Ā Suchitra Chari, MS

overview-of-vitaminsVitamins are organic (carbon-containing) molecules that are required in amounts to promote one or more specific and essential biochemical reactions within the living cell. There are fourteen vitamins and they are essential for normal growth and health of humans. We get our vitamins from food, because the human body either does not produce enough or none at all. Lastly, insufficient amounts of vitamins in the diet may cause deficiency diseases.

The term “vitamin” is derived from the words “vital amine,” because the first vitamins to be discovered contained an amino group (-NR2, where R is a hydrogen or some carbon-containing functional group) in their molecular structure and because they are vital to life.

Brief History on Vitamins:

The 19th century was the period when nutritionists were studying what comprised a physiologically complete diet. It was assumed that our diet was only made up of proteins, carbohydrates, fats and inorganic salts. Vitamins had not been discovered yet. So, how did their discovery come along?

Evidences showed up as malnutrition problems with people who were usually away on long journeys at sea or working for the army or imprisoned.

Sailors who were out at sea for nearly 10-12 weeks and who consumed only dry, non-refrigerated foods developed symptoms of weakness, pain in the joints, loose teeth and blood spots all over the body. This is characteristic of a disease called scurvy, which we now know is caused by a deficiency of Vitamin C. Patients who were seriously ill, recovered, after receiving a diet of fresh fruits and salad greens when they reached the shore.

In the 1880s, a person called Christiian Eijkman while working for the army in the Dutch East Indies saw victims with symptoms of a disease called beriberi such as these: Weakness, fatigue, irritability, restlessness, loss of appetite, loss of feeling in the feet and legs and vague abdominal discomfort, followed by oedema of the trunk.1 The disease progressed to produce muscular atrophy and peripheral paralysis and death by heart failure. Beriberi was now one of the most common diseases in the region.

After a lot of work with chickens, Eijkman discovered that what he thought was a bacterium that caused the disease turned out to be a substance in the diet of the chickens used during the course of the experiment. This substance that happened to be present in the skin of the unpolished uncooked rice that cured the chickens when their diet changed from polished to unpolished rice.2 This was termed the anti-beriberi factor.

Eijkmanā€™s assistant, Gerrit Grijns who continued the studies was probably the first to propose that Beriberi was a deficiency disease caused by a nutritional deficiency, or the lack of a specific natural substance found in certain foods.

In 1912, Frederick Hopkins, the father of British biochemistry firmly established the existence of vitamins through one of his best known works: ā€œFeeding Experiments Illustrating the Importance of Accessory Factors in Normal Dietariesā€. Reasoning that an adequate diet contained more than just purified protein (casein), carbohydrate (starch) and fats (lard), with mineral salts and water, he concluded that there exists an unknown component in a basic synthetic diet. Young rats fed on such basic diets failed to grow and even lost weight unless they were given amounts of milk daily. Hence Hopkins reasoned out that ā€œmilk contained ā€œaccessory food factorsā€ that are required only in trace amounts but are indispensable for normal growth and maintenanceā€.3, 4

Going back to the milk factor, Elmer V. McCollum in Wisconsin found in 1914 he found that the activity remained in the ether-soluble fraction after the butter fat was saponified so that all the ordinary fat became water-soluble5. This was called factor “A” while “factor B” was the one in rice polishing. This was the origin of the system of naming of vitamins. Later on he found out at Johns Hopkins University that, a diet containing unbalanced proportions of calcium and phosphorus, a lack of certain animal fats produced a condition analogous to human rickets. The second fat-soluble factor to be named was “vitamin D as the active ingredient in the fat.” This factor was related to the sterols and that it could be formed by ultraviolet irradiation of crude cholesterol in vitro, or through the skin of living animals or humans.

Another chemist, Casimir Funk, regarded that there is a definite organic chemical substance, one of several whose inclusion in trace amounts in an otherwise adequate diet was responsible for the cure or prevention of deficiency diseases such as beriberi, scurvy, rickets, and pellagra. He wrongly assumed that a substance he had isolated was the active factor. Since this substance contained nitrogen in a basic form it was thought to be an amine. And since it appeared to be vital to life, he named it ā€œvitamineā€ or a ā€œvital amineā€. The name soon became synonymous with Hopkins’ “accessory factors”. Later on, although it was discovered that they were not amines the name was preserved as it been applied to a whole series of substances found in foods, independent of their chemical structure. Then in 1920, the final ā€œeā€ be dropped and the resulting word vitamin was formed.6

Also, the then used nomenclature of fat-soluble A, water-soluble B framed by McCollum was dropped, and the substances be referred to as vitamins A, B, C, etc., until their true nature was identified.

In 1924, a disease called ā€œpellagraā€ was common in the south of the United States characterised by severe skin eruptions on exposed body surfaces, diarrhoea and mental changes also death. An officer in the U.S. Public Health Service who was in charge of this epidemic called Joseph Goldberger discovered that yeast supplements were potent in countering this condition in dogs and in humans too. The active substance in yeast that fought pellagra was later identified as ā€œnicotinic acidā€ or ā€œniacinā€

All these mysterious vitamins that no one had seen so far were confirmed in 1926 when, two Dutch scientists working in Java finally obtained pure crystals from the fractional extraction of rice polishing. A hundredth of a milligram a day cured a deficient pigeon. Hopkins (for his academic approach) and Eijkman (for his clinical approach) shared the Nobel Prize in physiology or medicine n 1929 ā€œfor their discovery of the growth-stimulating vitamins.ā€

Several advances occurred in the field of nutrition. The American Institute of Nutrition was formed in 1933. Year by year, additional factors, many of them being growth factors needed by microorganisms, were discovered and shown to be necessary for prevention of one kind of disorder or another in humans or animals. Synthetic products that were identical in properties and physiological effect with the ā€œnaturalā€ vitamin were being produced in the laboratories and a new growth industry of ā€œnutritional supplementsā€ was created. At present this supplement theory is subject to much criticism and controversy.

Classifications of Vitamins:

Vitamins do not have any particular common structure or a common function. Hence their classification is based more on their biological and chemical activity. One way to classify vitamins that are present in the body is by the way they are stored in our body.

Thus fat-soluble (non polar) vitamins are so called because they are soluble in fat solvents and oils, are absorbed through the intestinal tract with the help of fats or lipids and stored in the fat tissues of the body, as well as the liver. Hence people with disease conditions like Celiac disease and Crohnā€™s disease that involve fat malnutrition can develop say Vitamin A ( a fat-soluble vitamin) deficiency over time. Examples are Vitamins A, D, E and K. They are present in minute amounts in various foods, are stored for longer periods of time than their water-soluble counterparts, sometimes even for months and are essential for maintaining normal metabolism and biochemical functions. They pose a greater risk for toxicity when consumed in excess than their water-soluble counterparts. Toxicity does not occur when eating a normal well-balanced diet but may occur when extra doses of these vitamins are taken as supplements since the body only needs amounts of any vitamin.

Water-soluble (polar) vitamins on the other hand do not get stored in the body for long – they soon get expelled through urine and hence need to be replaced more often than fat-soluble ones. Examples are Vitamins C and all the B Vitamins.

Each vitamin exists in several active forms called ā€œVitamersā€ that have similar molecular structures, and each of which shows a vitamin-activity in a vitamin deficient biological system. They are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well. For example Vitamins are organic (carbon-containing) molecules that are required in amounts to promote one or more specific and essential biochemical reactions within the living cell. There are fourteen vitamins and they are essential for normal growth and health of humans. We get our vitamins from food, because the human body either does not produce enough or none at all. Lastly, insufficient amounts of vitamins in the diet may cause deficiency diseases.

The term “vitamin” is derived from the words “vital amine,” because the first vitamins to be discovered contained an amino group (-NR2, where R is a hydrogen or some carbon-containing functional group) in their molecular structure and because they are vital to life.

Brief History on Vitamins:

The 19th century was the period when nutritionists were studying what comprised a physiologically complete diet. It was assumed that our diet was only made up of proteins, carbohydrates, fats and inorganic salts. Vitamins had not been discovered yet. So, how did their discovery come along?

Evidences showed up as malnutrition problems with people who were usually away on long journeys at sea or working for the army or imprisoned.

Sailors who were out at sea for nearly 10-12 weeks and who consumed only dry, non-refrigerated foods developed symptoms of weakness, pain in the joints, loose teeth and blood spots all over the body. This is characteristic of a disease called scurvy, which we now know is caused by a deficiency of Vitamin C. Patients who were seriously ill, recovered, after receiving a diet of fresh fruits and salad greens when they reached the shore.

In the 1880s, a person called Christiian Eijkman while working for the army in the Dutch East Indies saw victims with symptoms of a disease called beriberi such as these: Weakness, fatigue, irritability, restlessness, loss of appetite, loss of feeling in the feet and legs and vague abdominal discomfort, followed by oedema of the trunk.1 The disease progressed to produce muscular atrophy and peripheral paralysis and death by heart failure. Beriberi was now one of the most common diseases in the region.

After a lot of work with chickens, Eijkman discovered that what he thought was a bacterium that caused the disease turned out to be a substance in the diet of the chickens used during the course of the experiment. This substance that happened to be present in the skin of the unpolished uncooked rice that cured the chickens when their diet changed from polished to unpolished rice.2 This was termed the anti-beriberi factor.

Eijkmanā€™s assistant, Gerrit Grijns who continued the studies was probably the first to propose that Beriberi was a deficiency disease caused by a nutritional deficiency, or the lack of a specific natural substance found in certain foods.

In 1912, Frederick Hopkins, the father of British biochemistry firmly established the existence of vitamins through one of his best known works: ā€œFeeding Experiments Illustrating the Importance of Accessory Factors in Normal Dietariesā€. Reasoning that an adequate diet contained more than just purified protein (casein), carbohydrate (starch) and fats (lard), with mineral salts and water, he concluded that there exists an unknown component in a basic synthetic diet. Young rats fed on such basic diets failed to grow and even lost weight unless they were given amounts of milk daily. Hence Hopkins reasoned out that ā€œmilk contained ā€œaccessory food factorsā€ that are required only in trace amounts but are indispensable for normal growth and maintenanceā€.3, 4

Going back to the milk factor, Elmer V. McCollum in Wisconsin found in 1914 he found that the activity remained in the ether-soluble fraction after the butter fat was saponified so that all the ordinary fat became water-soluble5. This was called factor “A” while “factor B” was the one in rice polishing. This was the origin of the system of naming of vitamins. Later on he found out at Johns Hopkins University that, a diet containing unbalanced proportions of calcium and phosphorus, a lack of certain animal fats produced a condition analogous to human rickets. The second fat-soluble factor to be named was “vitamin D as the active ingredient in the fat.” This factor was related to the sterols and that it could be formed by ultraviolet irradiation of crude cholesterol in vitro, or through the skin of living animals or humans.

Another chemist, Casimir Funk, regarded that there is a definite organic chemical substance, one of several whose inclusion in trace amounts in an otherwise adequate diet was responsible for the cure or prevention of deficiency diseases such as beriberi, scurvy, rickets, and pellagra. He wrongly assumed that a substance he had isolated was the active factor. Since this substance contained nitrogen in a basic form it was thought to be an amine. And since it appeared to be vital to life, he named it ā€œvitamineā€ or a ā€œvital amineā€. The name soon became synonymous with Hopkins’ “accessory factors”. Later on, although it was discovered that they were not amines the name was preserved as it been applied to a whole series of substances found in foods, independent of their chemical structure. Then in 1920, the final ā€œeā€ be dropped and the resulting word vitamin was formed.6

Also, the then used nomenclature of fat-soluble A, water-soluble B framed by McCollum was dropped, and the substances be referred to as vitamins A, B, C, etc., until their true nature was identified.

In 1924, a disease called ā€œpellagraā€ was common in the south of the United States characterised by severe skin eruptions on exposed body surfaces, diarrhoea and mental changes also death. An officer in the U.S. Public Health Service who was in charge of this epidemic called Joseph Goldberger discovered that yeast supplements were potent in countering this condition in dogs and in humans too. The active substance in yeast that fought pellagra was later identified as ā€œnicotinic acidā€ or ā€œniacinā€

All these mysterious vitamins that no one had seen so far were confirmed in 1926 when, two Dutch scientists working in Java finally obtained pure crystals from the fractional extraction of rice polishing. A hundredth of a milligram a day cured a deficient pigeon. Hopkins (for his academic approach) and Eijkman (for his clinical approach) shared the Nobel Prize in physiology or medicine n 1929 ā€œfor their discovery of the growth-stimulating vitamins.ā€

Several advances occurred in the field of nutrition. The American Institute of Nutrition was formed in 1933. Year by year, additional factors, many of them being growth factors needed by microorganisms, were discovered and shown to be necessary for prevention of one kind of disorder or another in humans or animals. Synthetic products that were identical in properties and physiological effect with the ā€œnaturalā€ vitamin were being produced in the laboratories and a new growth industry of ā€œnutritional supplementsā€ was created. At present this supplement theory is subject to much criticism and controversy.

Classifications of Vitamins:

Vitamins do not have any particular common structure or a common function. Hence their classification is based more on their biological and chemical activity. One way to classify vitamins that are present in the body is by the way they are stored in our body.

Thus fat-soluble (non polar) vitamins are so called because they are soluble in fat solvents and oils, are absorbed through the intestinal tract with the help of fats or lipids and stored in the fat tissues of the body, as well as the liver. Hence people with disease conditions like Celiac disease and Crohnā€™s disease that involve fat malnutrition can develop say Vitamin A ( a fat-soluble vitamin) deficiency over time. Examples are Vitamins A, D, E and K. They are present in minute amounts in various foods, are stored for longer periods of time than their water-soluble counterparts, sometimes even for months and are essential for maintaining normal metabolism and biochemical functions. They pose a greater risk for toxicity when consumed in excess than their water-soluble counterparts. Toxicity does not occur when eating a normal well-balanced diet but may occur when extra doses of these vitamins are taken as supplements since the body only needs amounts of any vitamin.

Water-soluble (polar) vitamins on the other hand do not get stored in the body for long – they soon get expelled through urine and hence need to be replaced more often than fat-soluble ones. Examples are Vitamins C and all the B Vitamins.

Each vitamin exists in several active forms called ā€œVitamersā€ that have similar molecular structures, and each of which shows a vitamin-activity in a vitamin deficient biological system. They are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well. For example vitamin A has at least 6 vitamer chemicals that include the compounds retinal, retinol, and four known carotenoids. The term Vitamin A is called the ā€œgeneric descriptorā€ of the vitamin.

The roles that vitamins play can be as diverse as those with hormone-like functions where they are regulators of mineral metabolism (Vitamin D), or regulators of cell and tissue growth and differentiation (such as some forms of vitamin A), or as antioxidants to maintain structures within cells (e.g., vitamin E and sometimes vitamin C) and those like the b vitamins which are precursors for enzyme (proteins that catalyze or make reactions go faster without getting permanently changed) coenzymes (organic molecules belonging to the cofactor family that are required by certain enzymes to carry out catalysis).

Diseases and disease conditions could be caused by the lack of a single vitamin or a combination of vitamins. For example, pandemic deficiency disease is caused by a lack of five crucial vitamins (niacin, vitamin C, thiamin, vitamin D, and vitamin A) and is usually found in areas of widespread poverty and malnutrition.

Nowadays, vitamins are produced as inexpensive semi synthetic and synthetic-source multivitamin dietary and food supplements and additives. Study of structural activity, function and role of vitamins in maintaining health is called vitaminology.

Reference Values:

The National Institutes of Health (NIH) has categorized the amount of vitamins that humans of all ages should consume and what their upper limits of intake should be. For more details please refer to:

https://ods.od.nih.gov/Health_Information/Dietary_Reference_Intakes.aspx

Here is a definition of all the reference values as stated by the NIH:

DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:

Recommended Dietary Allowance (RDA): the average daily level of intake that is sufficient to meet the nutrient requirements of nearly all (97%-98%) healthy people. (This is specific to the United States but is used in other parts of the world too).

Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.

Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects and one that it recommends not be exceeded during any given day

The RDA is used to determine the Daily Value (DV) of foods which is a single reference number for simplicity. This number denotes the amount of a vitamin or nutrient that a person should get for optimum health from a 2,000 calories-a-day diet. It is printed on nutrition facts labels in the United States and Canada, and is regulated by the Food and Drug Administration (FDA) and Health Canada respectively.

Here is a table denoting all the vitamins, their names and their functions:

[custom_table]

Water Soluble Vitamins

Function

Vitamin B1 Thiamine Precursor of Coenzyme Thiamine Pyrophosphate (TPP)
Vitamin B2 Riboflavin Precursor of coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)
Vitamin B3 Niacin

Precursor of the coenzyme Nicotinamide Adenine Dinucleotide (NAD) and Nicotinamide Adenine Dinucleotide Phosphate (NADP)

Vitamin B5 Pantothenic acid

Precursor of Coenzyme A (CoA)

Vitamin B6 Pyridoxine Precursor of the coenzyme Pyridoxal phosphate
Vitamin B7 Biotin

Precursor of coenzyme Biotin

Vitamin B9 Folic Acid

Precursor of the coenzyme tetrahydrofolic acid

Vitamin B12 Cobalamine

Precursor of the coenzyme deoxyadenosyl cobalamine

Vitamin C

Co substrate in the hydroxylation of proline in collagen

Fat Soluble Vitamins
Vitamin A

Vision, growth and reproduction

Vitamin D

Regulation of calcium and phosphate metabolism

Vitamin E

Antioxidant

Vitamin K

Important for blood coagulation and calcium homeostasis

[/custom_table]

Now we talk in detail about the various vitamins, their main functions and their deficiencies:

Vitamin A:

Vitamin A is the name of a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters.

Two forms of vitamin A are available in the human diet: One is preformed vitamin A (retinol and its esterified form, retinyl ester) that comes from animal sources, including dairy products, fish, and meat (especially liver) and the other is provitamin A carotenoids that come from colorful fruits and vegetables. Beta-carotene is the most important carotenoid as it has the most significant provitamin A activity followed by alpha-carotene, gamma-carotene and beta-cryptoxanthin. The body converts these plant pigments into vitamin A. Both provitamin A and preformed vitamin A must be metabolized intracellularly to retinal and retinoic acid, the active forms of vitamin A.

Being fat-soluble, the various forms of vitamin A are solubilized into micelles in the intestinal lumen and absorbed by duodenal mucosal cells. Both retinyl esters and provitamin A carotenoids are converted to retinol, which is oxidized to retinal and then to retinoic acid. Most of the body’s vitamin A is stored in the liver in the form of retinyl esters.

Main Functions:

*It is needed in vision and in the proper functioning of the eyes. It is as an essential component of rhodopsin, a protein that absorbs light in the retinal receptors7. It also supports the normal differentiation and functioning of the conjunctival membranes and cornea.

* Gene transcription

* Essential for proper immune function

* Needed for normal embryonic and fetal development and reproduction

* Bone metabolism and growth

* Hematopoiesis

* Skin health

* Cellular communication

* Antioxidant activity

* Epithelial growth and repair

* Reproduction

* Cellular communication

The main deficiency due to lack of Vitamin A is impaired vision or childhood blindness in low-income countries. Another deficiency related to the eye is keratomalacia (an eye disorder that results in dry cornea). There is also impaired immunity (increased risk of ear infections, urinary tract infections, Meningococcal disease), hyperkeratosis (white lumps at hair follicles), skin diseases and enamel hypoplasia. Pregnant and breastfeeding women need to consume adequate amounts of the vitamin for normal fetal development in the body and through breast milk.

The best way to find out the level of Vitamin A consumed through fruits and vegetables is to measure the serum or plasma concentrations of carotenoids. The strongest dietary predictors of serum carotenoid concentrations are fruits (for sources of beta-cryptoxanthin), carrots and root vegetables (for sources of carotenes), and tomato products (for sources of trans-lycopene).

Foods rich in Vitamin A:

Liver, dairy products and fish, cod liver oil, carrot, broccoli, pumpkins, winter squash, sweet potato, apricots and dark green leafy vegetables like kale, spinach, dandelion greens, and collard greens.

The B Complex Vitamins:

The most talked about vitamins are the B vitamins. There are 8 of them. They are water-soluble and play important roles in cell metabolism. They are chemically distinct but coexist in the same foods. Being water soluble vitamins, excess B vitamins are generally readily excreted.

In general, whole unprocessed foods have more of the b vitamins than the processed sugar and white flour. ā€œEnriched Flourā€ is flour that is enriched with the b vitamins thiamine, riboflavin, niacin and folic acid. Please refer to the website http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=137.165 for more details.

Main Functions:

B vitamins aid enzymes in their work as catalysts in metabolism. In this role, vitamins may be tightly bound to enzymes as part of prosthetic groups: For example, biotin is part of enzymes involved in making fatty acids. They may also be less tightly bound to enzyme catalysts as coenzymes (detachable molecules that function to carry chemical groups or electrons between molecules). For example, folic acid may carry methyl, formyl, and methylene groups in the cell. Although these roles in assisting enzyme-substrate reactions are vitamins’ best-known function, the other vitamin functions are equally important.

Below we will talk about each of the 8 classes separately.

Vitamin B1: Thiamine

Vitamin B1 or Thiamine is a sulfur-containing vitamin and the first in line in the B complex. It is synthesized only in bacteria, fungi and plants and hence animals and humans must obtain it from them. Thiamine pyrophosphate (TPP), its phosphate derivative is produced by the enzyme thiamine diphosphokinase and is involved in many cellular processes. It was first discovered (as mentioned above) during the outbreak of the disease called ā€œBeriberiā€ (that affects the peripheral nervous system (polyneuritis) and / or the cardiovascular system). The other conditions that occur in mammals due to it deficiency are Korsakoff’s syndrome and optic neuropathy8. In birds, it causes a condition called ā€œpolyneuritisā€. TPP acts as a coenzyme in reactions like the catabolism of sugars and amino acids. In yeast, it is required in the first step of alcohol fermentation.

Cereal grains, specifically whole grains contain a lot of thiamine compared to refined grains, as thiamine is found mostly in the outer layers of the grain and in the germ (which are removed during the refining process). In the US, processed flour must be enriched with thiamine mononitrate (which is the stable and non-hygroscopic vitamer) along with niacin, ferrous iron, riboflavin, and folic acid to replace that loss in processing.

Main Functions and Deficiencies:

* It aids in converting carbohydrates into energy

* It is also necessary for the maintenance of healthy skin, the heart, and the nervous system

Since thiamine derivatives and thiamine-dependent enzymes are present in all cells of the body, a thiamine deficiency would seem to adversely affect all of the organ systems. However, the nervous system is particularly sensitive to thiamine deficiency, because of its dependence on oxidative metabolism.

Two main diseases caused by thiamine deficiency are Beriberi and Wernicke-Korsakoff syndrome.

1. Beriberi

Beriberi is a neurological and cardiovascular disease. The three major forms of the disorder are:

Dry Beriberi ā€“ characterized principally by peripheral neuropathy (tingling or numbness in the extremities) along with sensory, motor and reflex dysfunctions in the distal end.

Wet Berberi has all the characteristics of peripheral neuropathy along with edema, mental confusion, tachycardia and cardiomegaly and congestive heart failure.

Infantile Beriberi occurs when the nursing mother is thiamine-deficient. A well-known symptom is when the childā€™s moan emits no sound or a very faint one caused by nerve paralysis. Thiamine has to be administered promptly to save the life of the child.

2. Alcoholic brain disease

Nerve cells and other supporting cells (such as glial cells) of the nervous system require thiamine. Alcoholics have thiamine deficiency due to inadequate nutritional intake; decreased uptake of thiamine due to disturbed the GI tract, deficiency of magnesium (Mg helps bind thiamine to its enzymes) and other reasons. Examples of neurologic disorders that are linked to alcohol abuse include the following diseases as well as varying degrees of cognitive impairment.

Wernicke’s encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society. This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.

Korsakoff’s syndrome is, in general, considered to occur with deterioration of brain function in patients initially diagnosed with WE. It is characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.

Following improved nutrition and the removal of alcohol consumption, some impairment linked with thiamine deficiency are reversed, in particular poor brain functionality.

Foods that contain Thiamine:

Rice husk, Yeast, yeast extract, lean pork, unrefined cereal grains, bran, milk, chickpeas, beans, lentils, brown rice, peas, pecans, oatmeal, flax, sunflower seeds, brown rice, long grain rice, whole grain rye, asparagus, kale, cauliflower, potatoes, peas, oranges, pasta, watermelon and eggs

Vitamin B2

Riboflavin derives its name from the sugar ribose and flavin which is the ring-moiety and the one that gives the yellow color. This vitamin is yellow-orange in color with poor solubility in water. Its active forms are the two flavoproteins, Flavin mononucleotide (FAD) and flavin adenine dinucleotide (FMN) that act as cofactors in a variety of flavoprotein enzyme reactions including activation of other vitamins9. Both these coenzymes consist of a flavin mononucleotide unit that contains the reactive site. FAD has an additional sugar group and an adenine base which completes its structure. FAD and FMN react with two protons, as well as two electrons, in alternating between the reduced and the oxidized state.

The metabolic pathways they take part in include electron transport, DNA repair, nucleotide biosynthesis, beta-oxidation of fatty acids, amino acid catabolism, as well as synthesis of other cofactors such as CoA, CoQ and heme groups.

*They act as transient, intermediate storehouses of high-energy electrons in oxidation reduction reactions that finally produce ATP (Adenosine Triphosphate) or the energy source in the body. One such type of a crucial reaction that it participates in is in the Citric acid cycle or the TCA or Kreb’s cycle where an equivalent of 1.5 ATPs is produced.

*The primary coenzyme form of vitamin B6 (pyridoxal phosphate) is FMN dependent

*FAD is required to convert retinol (vitamin A) to retinoic acid via cytosolic retinal dehydrogenase

*FAD is required to convert tryptophan to niacin (vitamin B3)

Additional examples of FAD-dependent enzymes that regulate metabolism are glycerol-3-phosphate dehydrogenase (triglyceride synthesis) and xanthine oxidase involved in purine nucleotide catabolism. There are other noncatalytic roles that FAD can play a role in, such as structural roles, or involved in blue-sensitive light photoreceptors that regulate biological clocks and development and generation of light in bioluminescent bacteria.

Main Functions and Deficiencies:

* Aids in growth and reproduction

* It plays an important role in energy production and tissue repair

* helps the body make healthy red blood cells

Low levels of vitamin B2 can lead to bad skin and itchy eyes, ariboflavinosis and growth retardation.

Foods that contain Vitamin B2:

Milk, cheese, leafy vegetables, liver, kidneys, legumes, yeast, yeast extract, fish, eggs, mushrooms, almonds asparagus, bananas, persimmons, okra, chard, cottage yogurt, cereal, pasta, and green beans

Vitamin B3

Vitamin B3 or Niacin is a colorless, water-soluble derivative of pyridine, with a carboxyl group (COOH) hence also naming it as nicotinic acid. Other forms of vitamin B3 include the corresponding amide nicotinamide (“niacinamide“), Nicotinic acid and niacinamide are convertible to each other.

Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)10. Both NAD and NADP are based on a common structure consisting of the base adenine, two ribose sugars, linked by phosphate groups and a nicotinamide ring (reactive part of both molecules). NADP has an extra phosphate group. Both these coenzymes function as carriers of electrons and are involved in oxidation-reduction reactions where the nicotinamide ring accepts or donates electrons. NAD is mostly used in breakdown or catabolic reactions and NADP is used in biosynthetic or anabolic reactions. NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NADP and NAD are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes.

Main Functions and Deficiencies:

*NAD is mostly used in breakdown or catabolism reactions of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair

*NADP is mostly used in biosynthesis or anabolism reactions such as fatty acid and cholesterol synthesis.

* Niacin is involved in both DNA repair and the production of steroid hormones in the adrenal glands

* It aids in promoting a healthy digestive system by metabolizing fats (reduces cholesterol and triglycerides) and is thus used to treat high levels of ā€œbadā€ cholesterol.

* Alleviates gastrointestinal disturbances

* Increases circulation and reduces blood pressure

* Prevents and eases the severity of migraine headaches

* Increases energy through proper utilization of food

* As part of the B team, B3 works with the other vitamins to keep the skin healthy and the nervous and digestive systems working right.

The most characteristic disease caused by Vitamin B3 deficiency is Pellagra. It is characterized by hyper pigmentation and thickening of the skin, digestive disturbances, amnesia, delirium, restlessness, anxiety and depression. The parts most susceptible to the deficiency are the high energy requiring brain and the high turnover rate organs like the gut and skin. Severe dermatitis is also caused by Vitamin B3 deficiency.

Foods that contain Vitamin B3:

liver, lean meat products (poultry), fish (tuna, salmon), whole wheat, wheat germ, milk, eggs, avocados, peanuts, dates, figs, prunes, tomatoes, leafy vegetables, broccoli, carrots, sweet potatoes, asparagus, nuts, legumes, mushrooms, and brewer’s yeast

Vitamin B5:

Vitamin B5 or Pantothenic acid is a water-soluble vitamin essential to all forms of life. It was discovered by Roger J. Williams in 1933. Many animals require it to synthesize coenzyme-A (CoA), a vital coenzyme that is required in chemical reactions that generate energy from food (proteins, carbohydrates, and fats) 11. Pantothenic acid is the amide between pantoic acid and Ī²-alanine. It is commonly found as its alcohol analog, the provitamin panthenol (pantothenol), and as calcium pantothenate.

Pantothenic acid in the form of CoA performs its actions through acylation and acetylation reactions. CoA may act as an acyl group carrier to form acetyl-CoA and other related compounds in a way to transport carbon atoms within the cell. Most proteins that have been acetylated in the body have their acetyl group donated by CoA. The protein function is altered due to this 3-dimensional structural change like in the case of peptide hormones.

Main Functions and Deficiencies:

CoA is required for the synthesis of essential fats, cholesterol and steroid hormones, the neurotransmitter acetylycholine and the hormone melatonin.

It is important in energy metabolism for pyruvate to enter the tricarboxylic acid cycle (TCA cycle) as acetyl-CoA, and for Ī±-ketoglutarate to be transformed to succinyl-CoA in the cycle.

It is required in the formation of Acyl-carrier protein (ACP) which is also required for fatty acid synthesis in addition to CoA.

Heme, a component of hemoglobin, requires a CoA-containing compound for its synthesis.

CoA is required for the metabolism of a number of drugs and toxins by the liver.

Protein acetylation plays a role in cell division and DNA replication and also affects gene expression by facilitating the transcription of mRNA.

The modifications in a number of proteins that are done by the attachment of long-chain fatty acids which are donated by CoA are known as protein acylation and appear to play a central role in cell signaling.

Due to low CoA levels,

*there is impaired energy production, (causing symptoms of irritability, fatigue, and apathy), *impairment of acetylcholine synthesis (causing neurological symptoms including numbness, paresthesia, and muscle cramps

*hypoglycemia or an increased sensitivity to insulin occurs

* Headache, fatigue, insomnia, intestinal disturbances, and numbness and tingling of their hands and feet

Most symptoms of pantothenic acid deficiency can be reversed with its return.

Foods rich in Vitamin B5:

High amounts found in meats, whole grains (milling may remove it), broccoli, avocados, royal jelly, fish ovaries, lentils, lentils, potatoes, chicken, eggs and yogurt

Vitamin B6:

The three major forms of Vitamin B6 are nitrogen-containing compounds. They are pyridoxine (the major form in plant and given as a B6 supplement), and the two most abundant forms in humans and animals, pyridoxal and pyridoxamine12. The metabolically active form of Vitamin B6 is Pyridoxal 5′-phosphate (PLP) that serves as a cofactor in many enzyme reactions in amino acid, glucose, and lipid metabolism. 4-Pyridoxic acid (4PA) is the end product of vitamin B6 catabolism.

Main Functions and Deficiencies:

As PLP, Vitamin B6 is used as a cofactor for nearly 200 biochemical reactions in the human body, mostly related to amino acid metabolism.

* Glucose metabolism ā€“ it is a required coenzyme of glycogen phosphorylase, the enzyme necessary for glycogenolysis to occur.

* Aminoacid metabolism ā€“ it is a cofactor in the synthesis of five important neurotransmitters, (serotonin, dopamine, epinephrine, norepinephrine and gamma-aminobutyric acid or GABA)

It is also used –

*in the conversion of tryptophan to niacin

*in the synthesis of hemoglobin, by serving as a coenzyme for the enzyme ALA synthase

*in histamine synthesis

*in facilitating the biosynthesis of sphingolipids and its breakdown

*in increasing or decreasing the expression of certain genes

*Anti-aging properties, prevents skin disorders

Deficiency is uncommon and symptoms do not appear immediately because ~80% of the vitamin B6 in the body is stored in muscle tissue and will remain stable until intake has been low for several weeks. But classic clinical syndrome results in seborrhoeic dermatitis (chronic, relapsing and usually mild dermatitis), atrophic glossitis (inflammation and soreness of the tongue) with ulceration, cheilosis or angular stomatitis (inflammation of one, or more commonly both, of the corners of the mouth), conjunctivitis, intertrigo (an inflammation (rash) of the body folds (adjacent areas of skin), effects on the central nervous system (including depression and somnolence), sideroblastic anaemia (a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells)and neuropathy.

Foods rich in Vitamin B6:

Best dietary sources include chicken, pork, beef, turkey, fish, eggs, chickpeas, garbanzo beans, bananas, baked potatoes, oatmeal, whole grains (highest amounts in the germ and aleuronic layer), vegetables, and pistachios. When milk is dried it loses about half of its B6. Freezing and canning can also reduce content.

Vitamin B7:

Vitamin B7, also called biotin, is a water-soluble vitamin and serves as a covalently bound coenzyme for five carboxylases in humans13. There are eight different forms of biotin, but only one of them ā€“ D-biotin ā€“ occurs naturally and has full vitamin activity. Biotin can only be synthesized by bacteria, moulds, yeasts, algae, and by certain plant species.

Main Functions:

* Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. Biotin assists in various metabolic reactions involving the transfer of carbon dioxide. It may also be helpful in maintaining a steady blood sugar level.

* It plays unique roles in cell signaling, regulation of genes and chromatin structure14.

Biotin deficiency is rare because, in general, intestinal bacteria produce biotin in excess of the body’s daily requirements. However, a number of metabolic disorders exist in which an individual’s metabolism of biotin is abnormal.

Mild deficiency symptoms are depression, lethargy, hallucination, and numbness and tingling of the extremities in adults. Severe deficiency results in Hair loss (alopecia), Conjunctivitis and dermatitis in the form of a scaly, red rash around the eyes, nose, mouth, and genital area.

Foods rich in Vitamin B7:

Egg yolk, milk, cheese, chocolate, bacon, chicken, liver and some vegetables.

Vitamin B9:

Vitamin B9 or folic acid is the synthetic form of folate that is found in supplements and added to fortified foods. Humans cannot synthesize folate and must consume it as part of their diet so as to meet their daily requirement. Folate is converted to dihydrofolate (dihydrofolic acid) and tetrahydrofolate (tetrahydrofolic acid) by humans.

Main Functions and Deficiencies:

*Folate functions as a coenzyme in single-carbon transfers in the metabolism of nucleic and amino acids.

*It is very important in rapid cell division and growth, during pregnancy and infancy.

*Used to synthesize DNA, repair DNA, and methylate DNA

*In children and adults folate is required to produce healthy red blood cells and prevent anemia.

Folic acid deficiency in early embryo development causes neural tube birth defects (NTDs) and it has been shown that supplementation effectively reduces the number of NTD15. Thus, women planning to become pregnant are usually encouraged to increase daily dietary folic acid intake and/or take a supplement. Also, since 1998, the U.S. Food and Drug Administration (FDA) has required the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products (U.S. Food and Drug Administration 1996). And the U.S. Centers for Disease Control and Prevention 1992) recommends at least 400 micrograms (Ī¼g) of folic acid each day. After the introduction of fortification, NTD rates have decreased by 36% (U.S. Centers for Disease Control and Prevention 2010).

Two national health objectives that relate to folate and maternal, infant, and child health are part of the objectives for Healthy People 2020: Objective MICH HP2020-14 (increase the proportion of women of childbearing potential with intake of at least 400 Ī¼g of folic acid from fortified foods or dietary supplements) and Objective MICH HP2020-15 (reduce the proportion of women of childbearing potential who have low red blood cell folate concentrations) (http://www.healthypeople.gov/HP2020/).

Foods rich in Vitamin B9:

The richest food sources of folate are dark-green leafy vegetables (such as spinach and turnip greens), whole-grain cereals, fortified grain products, animal products, legumes, liver, baker’s yeast, sunflower seeds, asparagus and peanuts. Folic acid is found in many vegetables and fruit juices. But if these foods are cooked too long, they lose a lot of B9.

Vitamin B12:

Vitamin B12 or Cobalamin is the largest and most structurally complicated vitamin in the B vitamin family. It cannot be produced by animals (including humans), fungi or plants. Only bacteria and archaea have the enzymes required to make it. We obtain it from foods that are intrinsically a natural source of bacterial symbiosis.

The term B12 may be properly used to refer to cyanocobalamin, the principal B12 form used in food additives, pharmaceuticals and nutritional supplements. Vitamin B12 consists of a class of chemically related compounds (vitamers), all of which have vitamin activity and contains the biochemically rare element cobalt sitting in the center of a planar tetra-pyrrole ring called a corrin ring.

The basic structure of the vitamin known as hydroxocobalamin is synthesized only by bacteria and archaea, and conversion between different forms of the vitamin can be accomplished in the human body. From the bacterial hydroxocobalamin is produced a common semi-synthetic form of the vitamin known as cyanocobalamin. In the body it is converted to the human physiological forms methylcobalamin and 5′-deoxyadenosylcobalamin, leaving behind a minimal concentration of cyanide ion.

Parietal cells of the stomach are responsible for secreting a protein called the intrinsic factor that is required for the normal absorption of B12 in the ileum. When these cells are destroyed (an autoimmune reaction by the body) absorption of B12 reduces causing a deficiency. This condition is known as pernicious anemia. Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to body tissues. There are many types of anemia.

Main Functions and Deficiencies:

* Vitamin B12 functions as a coenzyme for a critical methyl transfer reaction that converts homocysteine to methionine.

* Normally involved as a coenzyme in the metabolism of every cell of the human body, hence affects DNA synthesis and regulation, fatty acid metabolism, carbohydrate metabolism and amino acid metabolism.

* Helps to form and regenerate red blood cells preventing anemia

* Promotes growth and increase appetite in children

* Improves concentration, memory and balance

Deficiency results mostly from poor intake, including strict veganism but can also result from malabsorption (due to absence of intrinsic factor as mentioned above), certain intestinal disorders like gastric or ilial disease, low presence of certain binding proteins and use of certain medications. It causes pernicious anaemia in the elderly and strict vegetarians. Megaloblastic anaemia occurs when both Vitamin B12 and folate are deficient16.

Subtly reduced cognitive function like depression and poor memory results from early vitamin B12 deficiency. Severe vitamin B12 deficiency can cause permanent nerve damage and dementia.

A deficiency in vitamin B12 may impact the production and function of those neurotransmitters since is a co-substrate of various cell reactions involved in methylation synthesis of nucleic acid and neurotransmitter.

Foods rich in Vitamin B12:

Found naturally in animal derived foods, including fish (salmon, shellfish, and tuna), meat (beef, pork) especially liver, and poultry, eggs, milk, and milk products.

Sources of B12 for vegetarians and vegans are fortified breakfast cereals; fortified soy products fortified energy bars and fortified nutritional yeast.

Vitamin C:

Vitamin C, a water-soluble vitamin, is also known as ascorbic acid. Since humans are incapable of synthesising their own vitamin C, it must be obtained through their diet. It acts as a cofactor in hydroxylation reactions, which are required for collagen synthesis.

Main Functions and Deficiencies:

*Plays major role in growth and tissue repair, helps make collagen, a sticky protein substance in skin, cartilage, tendons, ligaments and blood vessels that keeps the bones and muscles together,

*Involved in non-heme iron absorption

*Helps healing wounds

*Hormone synthesis

*Aids in preventing bacterial and viral infections

*Required for normal energy-yielding metabolism

*Helps in the normal functioning of the immune system and the nervous system

*Offers protection against cancer producing agents

*Helps counteracts the formation of nitrosamines

*Acts as a natural laxative

*Prevents scurvy

*Lowers incidence of blood clots in veins

*Acts as an antioxidant along with vitamin E and beta carotene to fight free radicals thus protecting cell constituents from oxidative damage

* Shortens the length of a cold

*Reduction of tiredness and fatigue

Vitamin C and Common Cold:

Linus Pauling stimulated a lot of public interest with his theory that consuming Vitamin C greater than 1 gram a day will prevent the common cold17. Out of 53 placebo-controlled trials that have been evaluated for the effect of vitamin c supplementation on the incidence, duration and severity of the common cold, it was observed that while regular supplementation with vitamin c (0.25 to 2 grams a day) did not reduce the incidence of colds in the general population (23 trials), it halved the incidence of colds in participants undergoing heavy physical stress (e.g., marathon runners, skiers, or soldiers in subarctic conditions) 18. There was also a benefit of regular vitamin C supplementation, seen in the duration of colds, with a greater benefit in children than in adults. And finally, no significant effect of vitamin C supplementation (1-8 grams/day) was observed when it was given after cold symptoms occurred.

Signs of vitamin deficiency include dry and splitting hair, inflammation of the gums, bleeding gums, rough, dry, scaly skin, decreased wound-healing rate, easy bruising, nosebleeds, and a decreased ability to ward off infection.

A severe form of vitamin C deficiency is known as scurvy. Scurvy is a particularly deadly disease in which collagen is not properly formed, causing bruising and poor wound healing, bleeding of the gums, severe pain, and death.

It has been proposed that a sufficient vitamin C intake may reduce the risk of developing a number of cardiovascular disorders, including heart disease, hypertension, stroke, and atherosclerosis, as well as some cancers.

Foods rich in Vitamin C:

Leafy, green vegetables, broccoli, cauliflower, brussel sprouts, peppers, citrus fruits (blackcurrants), tomatoes, strawberries, grapefruit, cantaloupes, guava, kiwi, oranges, mangoes and mainly The Kakadu plum and the camu fruit have the highest vitamin C contents of all foods. Liver also has vitamin C.

Vitamin D:

Vitamin D is a hormone precursor that is present in 2 forms, Ergocalciferol or vitamin D2 (present in plants and some fish) and Cholecalciferol or vitamin D3 (synthesized in the skin by sunlight). So, our daily Vitamin D requirement is obtained either by ingesting vitamin D or being exposed to the sun for enough time to produce adequate amounts19. Vitamin D3 can be manufactured in the skin by way of ultraviolet (UV) B rays and the amount the hormone that the skin needs to produce adequate vitamin D depends on the strength of the UVB rays (which part of the world we stay in), the length of time spent in the sun, and the amount of pigment in the skin.

Vitamin D3 is normally made in animals by the deposition of 7-dehydrocholesterol (a derivative of cholesterol commonly referred to as 7-D) in the skin. This Vitamin D3 is transported to the liver by a protein that binds to it. Here it undergoes hydroxylation to 25-hydroxyvitamin D3 (25(OH) D) (the inactive and major circulating form of vitamin D). Then it goes to the kidneys via the blood where it is hydroxylated by the enzyme 1-hydroxylase to 2 metabolites. The more active form is 1,25-dihydroxyvitamin D3 (1,25(OH)D), its active form and the less active form 24,25-dihydroxyvitamin D3 that appears to have a physiological role as well but is less well studied. The half-life of vitamin D in the liver is approximately 3 weeks, which underscores the need for frequent replenishment of the bodyā€™s supply.

For simplicity, we refer to 1, 25-dihydroxyvitamin D3 as vitamin D.

Main Functions and Deficiencies:

* Vitamin D acts as a steroid hormone, with effects on calcium absorption in the intestine, phosphorous homeostasis, bone turnover, and multiple other tissues.

* It works with parathyroid hormone to mediate skeletal mineralization and maintain calcium homeostasis in the bloodstream.

* It also helps keep the immune and nervous systems working well.

Vitamin D levels and multiple disease states have been linked, probably due to its anti-inflammatory and immune-modulating properties and possible affects on cytokine levels.

Vitamin D deficiency is associated with rickets in children. In adults, it could lead to secondary hyperparathyroidism, bone loss, osteopenia, osteoporosis, and increased fracture risk.

A low vitamin D level is an established risk factor for osteoporosis but it has to work together with calcium to have an effect on curing fractures. Elderly people tend to have fewer falls when consuming Vitamin D supplements. there is evidence that host factors such as genetic polymorphisms strongly influence fracture risk and may determine the host response to vitamin D. Dark-skinned people are at higher risk of deficiency (although at lower risk of fracture overall), as are those with little exposure to sunlight. The addition of calcium may be required to realize the beneficial effects of vitamin D in preventing fracture risk.

Other studies have shown a relationship between Vitamin D and blood pressure, coronary artery calcification, and existing cardiovascular disease, cancer prevention and survival. A role of vitamin D in the homeostasis of glucose metabolism and the development of type 1 and type 2 diabetes mellitus (DM) has been shown in animal models and humans.

Food and other sources of Vitamin D:

Vitamin D may also be ingested in the diet in the form of vitamin D3, a prohormone. Food sources include fortified milk, saltwater fish, shiitake mushrooms and fish-liver oil.

Vitamin E:

Vitamin E refers to a family of eight related, fat-soluble molecules that include both tocopherols and tocotrienols20. The major chemical forms of vitamin E (based on the location of a methyl group) are the tocopherols Ī±, Ī², Ī”, and Ī³. The well-known ones among these are

1. Ī³-tocopherol which is the most common form of Vitamin E in the North American diet is found in corn oil, soybean oil, margarine, and dressings

2. Ī±-tocopherol, which is the most biologically active form of vitamin E, is the second-most common form of vitamin E in the diet and is most abundant in the human body. This variant can be found most abundantly in wheat germ oil, sunflower, and safflower oils.

Main Functions and Deficiencies:

*As an antioxidant it stops the production of reactive oxygen species formed when fat undergoes oxidation. Being fat-soluble it is incorporated into cell membranes and protects the cell constituents, tissues and organs from oxidative damage due to ā€œfree radicalsā€ which are responsible for the aging process (Free radicals may cause various health conditions such as heart disease, cancer, and inflammatory conditions).

*inhibits damaging blood clotting, potentially blocking blood flow

*regulates the opening of blood vessels, important for unhindered blood flow.

*enzymatic activities, gene expression, neurological functions (as an antioxidant can protect against Alzheimerā€™s disease that is caused doe to oxidative stress), inhibition of platelet aggregation

*protects lipids and prevents the oxidation of polysaturated fatty acids

* Aids in immune function

*cell signaling

*helps make red blood cells and keeps the nervous and immune systems healthy.

* Both Ī±- and Ī³-tocopherol may be associated with prostate cancer reduction.

Deficiency is rare. It may cause mild hemolytic anemia in newborns. Symptoms of vitamin E deficiency include muscle weakness, loss of muscle mass, abnormal eye movements, impaired vision, and unsteady gait. Chronic deficiency may also cause problems with kidney and liver function. In addition, severe vitamin E deficiency can be associated with serial miscarriages and premature delivery in pregnant women.

On the other hand, doses higher than 1200 mg/d may result in headache, fatigue, nausea, diarrhoea, cramping, weakness, blurred vision, and gonadal dysfunction.

Foods rich in Vitamin E:

Vegetable oils (olive, soya beans, palm, corn, safflower, sunflower), margarine, kiwi fruit, almonds, peanuts, avocado, eggs, milk, nuts, leafy green vegetables, legumes, tomatoes, unheated vegetable oils, wheat germ, and whole grains.

Vitamin K:

Vitamin K refers to a group of structurally similar, fat-soluble vitamins required by the body for the clotting or coagulating of blood. It serves as an essential cofactor for a carboxylase that catalyzes carboxylation of glutamic acid residues (forming gamma-carboxyglutamic acid) 21 on vitamin K-dependent proteins. This makes the protein biologically active. The key vitamin K-dependent proteins include the coagulation proteins – factors II (prothrombin), VII, IX and X, the anticoagulation proteins – proteins C, S and Z and others like the bone proteins osteocalcin and matrix-Gla protein (needed to manipulate binding of calcium in bone and other tissues), and certain ribosomal proteins. Vitamin K undergoes a cycle of oxidation and reduction that allows its reuse.

It is stored in fat tissue and liver. The two naturally occurring vitamers of vitamin K are vitamin K1 and vitamin K2. They are both quinone derivatives. Three synthetic types of vitamin K are known: vitamins K3, K4, and K5. Although the natural K1 and all K2 homologues and synthetic K4 and K5 have proven nontoxic, the synthetic form K3 (menadione) has shown toxicity.

Vitamin K1, also known as phylloquinone, phytomenadione, or phytonadione, is synthesized by plants, and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis.

Homologues of Vitamin K2, the main storage form in animals are called menaquinones

The third kind of Vitamin K is Vitamin K3 or menadione that is widely used in animal husbandry. It is a synthetic compound and is a provitamin that needs to be converted to menaquinone-4 (MK-4) to be active.

Main Functions and Deficiencies:

Blood clotting: Vitamin K is needed for the complete synthesis of certain proteins needed for blood coagulation. Vitamin K is one of the factors that work together with other substances to clot blood. Without vitamin K, a cut could bleed for a long time and a bruise could turn into a big one.

Indeed, many commercially-available rodent poisons are compounds that interfere with vitamin K and kill by inducing lethal haemorrhage.

Vitamin K also plays an important role in bone health and for bone metabolism.

A vitamin K deficiency is rare since apart from being found in leafy green foods, the bacteria in your intestines can make it. However, it could occur due to inadequate intake or altered vitamin K synthesizing intestinal bacteria. This results in clotting disorders with excessive bleeding. Blood coagulation is seriously impaired and haemorrhage could set in. Newborn infants are also at risk because of poor placental transfer of vitamin K, lack of intestinal bacteria, and low content in breast milk. This deficiency in Vitamin K in the liver results in haemorrhage or permanent brain damage or death. For this reason, they receive intramuscular vitamin K supplements at birth.

Low levels of vitamin K also weaken bones and promote calcification of arteries and other soft tissues. There is an increased risk of fractures and reduced bone mineral density (BMD) due to its necessary role in production of bone proteins such as osteocalcin22. Vitamin K supplementation, on the other hand, has been shown to improve the bone turnover profile and decrease the level of circulating ucOC.

Foods rich in Vitamin K:

Vitamin K1 is found chiefly in dark-green leafy greens (like spinach), broccoli, peas, brussel sprouts, cauliflower, lettuce, coleslaw, parsley, avocado, kiwi and liver. Absorption is greater when accompanied by fats such as butter or oils. However, the chief source of vitamin K is synthesis by bacteria in the large intestine as these colonic bacteria synthesize a significant portion of humans’ vitamin K needs. Since vitamin K is a fat-soluble vitamin, both dietary and microbial vitamin K is absorbed into intestinal lymph along with other lipids. The foetus obtains vitamin K from its mother by transplacental transfer. Newborns often receive a vitamin K shot at birth to tide them over until their colons become colonized at five to seven days of age from the consumption of their mother’s milk.

Controversy about taking vitamin supplements:

Letā€™s finish off with this note.

In a a forum at the American Association for Cancer Research (AACR) Annual Meeting 2015 by University of Colorado Cancer Center, investigator Tim Byers, MD, MPH quotes ā€œWe found that the supplements were actually not beneficial for their health. In fact, some people actually got more cancer while on the vitamins,ā€ explains Byers23.

The effects of beta carotene supplements in a particular trial showed that taking more than the recommended dosage increased the risk for developing both lung cancer and heart disease by 20 percent. Folic acid, which was thought to help reduce the number of polyps in a colon, actually increased the number in another trial.

ā€œThis is not to say that people need to be afraid of taking vitamins and minerals,ā€ says Byers. ā€œIf taken at the correct dosage, multivitamins can be good for you. But there is no substitute for good, nutritional food.ā€

This and a lot of research produce contradicting theories about consumption of supplements. It would be wise to stick to natural foods except in cases where there is an underlying problem and only consume vitamin supplements when they are advised or prescribed.

References:

1. Beriberi, White Rice, and Vitamin B: A disease, a cause, and a cure. By Kenneth J. Carpenter. 282 pp., illustrated. Berkeley, University of California Press, 2000

2. “Christiian Eijkman – Nobel Lecture: Antineuritic Vitamin and Beriberi”. Nobelprize.org. Nobel Media AB 2014. Web. 13 Jul 2015

3. Hopkins FG. Feeding experiments illustrating the importance of accessory factors in normal dietaries. J Physiol. 1912; 49:425ā€“60

4. Ann Nutr Metab 2012; 61:192ā€“198 On the ā€˜Discoveryā€™ of Vitamin A SembaĀ R.D.

5. McCollum EV, Davis M. The essential factors in diet during growth. J Biol Chem. 1915; 23:231ā€“54

6. Jack Cecil Drummond. The Nomenclature of the so-called accessory food factors (vitamins). From the Institute of Physiology, University College, London. (Received August 12th, 1920)

7. Fridericia L. S. & Holm, E. (1925) Experimental contribution to the study of the relation between night blindness and malnutrition. Am. J. Physiol. 73, 63ā€“78

8. Aviva Fattal-Valevski. Thiamine (Vitamin B1). Journal of Evidence-Based Complementary & Alternative Medicine – SAGE – March 9 2011

9. McCormick DB. Two interconnected B vitamins: riboflavin and pyridoxine. Physiol Rev. 1989; 69(4):1170-1198.

10. Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry. New York: Worth Publishers.

11. Tahiliani AG, Beinlich CJ. Pantothenic acid in health and disease. Vitam Horm. 1991; 46:165-228

12. Kathleen M. Fairfield, MD, DrPH; Robert H. Fletcher, MD, MSc. Vitamins for Chronic Disease Prevention inĀ Adults:Ā Scientific ReviewAuthor Affiliations: Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School (Dr Fairfield); Department of Ambulatory Care and Prevention, Harvard Medical School/Harvard Pilgrim Health Care, and Department of Epidemiology, Harvard School of Public Health (Dr Fletcher), Boston, Mass JAMA. 2002; 287(23):3116-3126.

13. Janos Zempleni, Subhashinee S.K. Wijeratne and Yousef I. Hassan. Biotin. Article first published online: 18 FEB 2009

14. J. Zempleni. Uptake, localization, and noncarboxylase roles of biotin. Annu. Rev. Nutr., 2005

15. MilunskyĀ A, JickĀ H, JickĀ SS. Ā et al.Ā Ā Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects.Ā Ā JAMA.1989; 262:2847-2852.

16. Sally P. Stabler, M.D. Vitamin B12 Deficiency. N Engl J Med 2013; 368:149-160

17. Pauling LC. Vitamin C and the Common Cold. San Francisco: W. H. Freeman; 1970.

18. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane database of systematic reviews. 2013; 1

19. Teresa Kulie, MD, Amy Groff, DO, Jackie Redmer, MD, MPH, Jennie Hounshell, MD, and Sarina Schrager, MD, MS Vitamin D: An Evidence-Based Review. JABFM Novemberā€“December 2009 Vol. 22 No. 6, 698

20. Brigelius-FlohĆ© R, Traber MG; Traber (1999). Vitamin E: function and metabolism. FASEB J. 13 (10): 1145ā€“1155.

21. Shearer MJ: Vitamin K. Lancet 345:229, 1995

22. BĆ¼gel S. Vitamin K and bone health in adult humans. Vitam Horm. 2008; 78:393-416

23. MartĆ­nez ME, Jacobs ET, Baron JA, Marshall JR, Byers T. Dietary supplements and cancer prevention: balancing potential benefits against proven harms. J Natl Cancer Inst. 2012 May 16; 104(10):732-9.
Epub 2012 Apr 25.

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