VITAMINS

B1 Thiamine

Vitamin B1, also called thiamine or thiamin, is one of 8 B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is "burned" to produce energy. These B vitamins, often referred to as B complex vitamins, also help the body metabolize fats and protein. B complex vitamins are necessary for healthy skin, hair, eyes, and liver. They also help the nervous system function properly.

Thiamine or thiamin, sometimes called aneurin, is a water-soluble vitamin of the B complex (vitamin B1), whose phosphate derivatives are involved in many cellular processes. The best characterized form is thiamine diphosphate (ThDP), a coenzyme in the catabolism of sugars and amino acids. In yeast, ThDP is also required in the first step of alcoholic fermentation. Thiamine is synthesized in bacteria, fungi and plants. Animals must cover all their needs from their food and insufficient intake results in a disease called beriberi affecting the peripheral nervous system (polyneuritis) and/or the cardiovascular system, with fatal outcome if not cured by thiamine administration. In less severe deficiency, nonspecific signs include malaise, weight loss, irritability and confusion. Today, there is still a lot of work devoted to elucidating the exact mechanisms by which thiamine deficiency leads to the specific symptoms observed. Finally, new thiamine phosphate derivatives have recently been discovered, emphasizing the complexity of thiamine metabolism and the need for more research in the field.

Like other B complex vitamins, thiamine is considered an "anti-stress" vitamin because it may strengthen the immune system and improve the body's ability to withstand stressful conditions. It is named B1 because it was the first B vitamin discovered.

Thiamine deficiency is rare, but can occur in people who get most of their calories from sugar or alcohol. People with thiamine deficiency have difficulty digesting carbohydrates. As a result, a substance called pyruvic acid builds up in their bloodstream, causing a loss of mental alertness, difficulty breathing, and heart damage (a disease known as beriberi).

• Beriberi
The most important use of thiamine is to treat beriberi, which is caused by not getting enough thiamine in your diet. Symptoms include swelling, tingling, or burning sensation in the hands and feet, confusion, difficulty breathing (from fluid in the lungs), and uncontrolled eye movements (called nystagmus).

• Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff syndrome is a brain disorder caused by thiamine deficiency; as with beriberi, it is treated by giving supplemental thiamine. Wernicke-Korsakoff is actually two disorders: Wernicke's disease involves damage to nerves in the central and peripheral nervous systems and is generally caused by malnutrition stemming from habitual alcohol abuse. Korsakoff syndrome is characterized by memory impairment and nerve damage. High doses of thiamine can improve muscle coordination and confusion, but only rarely improves memory loss.

• Cataracts
Some preliminary evidence suggests that thiamine -- along with other nutrients -- may lower risk of getting cataracts. People with plenty of protein and vitamins A, B1, B2, and B3 (niacin) in their diet are less likely to develop cataracts. Getting enough vitamins C, E, and B complex (particularly the B1, B2, B9 [folic acid], and B12 [cobalamin) may further protect the lens of your eyes from developing cataracts.

• Alzheimer's Disease
Lack of thiamine can cause dementia in Wernicke-Korsakoff Syndrome, it has been proposed that thiamin might help reduce severity of Alzheimer's disease.

Sources in the Diet

Most foods contain small amounts of thiamine. Large amounts can be found in pork and organ meats. Other good dietary sources of thiamine include whole-grain or enriched cereals and rice, wheat germ, bran, brewer's yeast, and blackstrap molasses.

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B2 Riboflavin

Riboflavin (E101), also known as vitamin B2, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a wide variety of cellular processes. Like the other B vitamins, it plays a key role in energy metabolism, and is required for the metabolism of fats, ketone bodies, carbohydrates, and proteins. Milk, cheese, leafy green vegetables, liver, kidneys, legumes such as mature soybeans, yeast, mushrooms and almonds [citation needed] are good sources of vitamin B2, but exposure to light destroys riboflavin.

The name "riboflavin" comes from "ribose" and "flavin".

Riboflavin in Food

Riboflavin is yellow or yellow-orange in color and in addition to being used as a food coloring, it is also used to fortify some foods. It is used in baby foods, breakfast cereals, pastas, sauces, processed cheese, fruit drinks, vitamin-enriched milk products, and some energy drinks. Regarding occurrence and sources of vitamin B2, Yeast extract is considered to be exceptionally rich in vitamin B2, and liver and kidney are also rich sources. Wheat bran, eggs, meat, milk, and cheese are important sources in diets containing these foods. Cereals grains contain relatively low concentrations of flavins, but are important sources in those parts of the world where cereals constitute the staple diet. Free riboflavin is naturally present in foods along with protein-bound FMN and FAD. It is difficult to incorporate riboflavin into many liquid products because it has poor solubility in water. Riboflavin is generally stable during the heat processing and normal cooking of foods if light is excluded. The alkaline conditions in which riboflavin is unstable are rarely encountered in foodstuffs.

Riboflavin Deficiency Further Information

• Ariboflavinosis Riboflavin is continuously excreted in the urine of healthy individuals making deficiency relatively common when dietary intake is insufficient.

• Riboflavin deficiency is always accompanied by deficiency of other vitamins.

• A deficiency of riboflavin can be primary - poor vitamin sources in one's daily diet - or secondary, which may be a result of conditions that affect absorption in the intestine, the body not being able to use the vitamin, or an increase in the excretion of the vitamin from the body.

• 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. The eyes may also become bloodshot, itchy, watery and sensitive to bright light.

• Riboflavin deficiency is classically associated with the oral-ocular-genital syndrome. Angular cheilitis, photophobia, and scrotal dermatitis are the classic remembered signs.

• In animals, riboflavin deficiency results in lack of growth, failure to thrive, and eventual death.

• During the deficiency state, dermatitis develops together with hair-loss. Other signs include corneal opacity, lenticular cataracts, hemorrhagic adrenals, fatty degeneration of the kidney and liver, and inflammation of the mucus membrane of the gastrointestinal tract.

• In children this deficiency results in reduced growth.

• Subclinical riboflavin deficiency has also been observed in women taking oral contraceptives, in the elderly, in people with eating disorders, and in disease states such as HIV, inflammatory bowel disease, diabetes and chronic heart disease. The fact that riboflavin deficiency does not immediately lead to gross clinical manifestations indicates that the systemic levels of this essential vitamin are tightly regulated.

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B3 Niacin

Niacin, also known as vitamin B3 or nicotinic acid, is an organic compound with the formula C5H4NCO2H. This colourless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters. The terms niacin, nicotinamide, and vitamin B3 are often used interchangeably to refer to any member of this family of compounds, since they have the same biochemical activity.

Niacin Deficiency

Niacin Deficiency is rarely seen in developed countries and is usually apparent in conditions of poverty and malnutrition and chronic alcoholism. Alcoholic patients typically experience increased intestinal permeability leading to negative health outcomes. Studies have indicated that in patients with alcoholic pellagra, niacin deficiency may be an important factor influencing both the onset and severity of this condition . Severe deficiency of niacin in the diet causes the disease pellagra. Pellagra is characterized by diarrhea, dermatitis and dementia as well as “necklace” lesions on the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, amnesia, delirium, and eventually death, if left untreated. Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression. Mild niacin deficiency has been shown to slow metabolism, causing decreased tolerance to the cold. Dietary niacin deficiency tends to occur in areas where people eat maize ("corn") as a staple food. Maize is the only grain low in niacin, and nixtamalization is needed to increase the bioavaiability of niacin during meal/flour production.

Pharmacological Uses

• Lipid Modifying Effects
Niacin has been proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, low-density lipoprotein, and increase high-density lipoprotein levels.

• Anti-Alzheimer's Symptomatic Effects
Vitamin B3 has been reported to prevent Alzheimer's-like symptoms in a mouse model of the disease.

• Oily Skin
Clinical trials using niacinamide topically have demonstrated a decrease in sebum output by the face epithelial cells, helping in the treatment of acne and related affections.

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B6 Group

Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Pyridoxal phosphate (PLP) is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen.

Seven forms of this vitamin are known

• pyridoxine (PN). - PN is the form that is given as vitamin B6 supplement.
• pyridoxine 5'-phosphate (PNP).
• pyridoxal (PL).
• pyridoxal 5'-phosphate (PLP). PLP is the metabolically active form.
• pyridoxamine (PM).
• pyridoxamine 5'-phosphate (PMP).
• 4-pyridoxic acid (PA). PA is the catabolite which is excreted in the urine.

All forms except PA can be interconverted.

Functions

Pyridoxal phosphate, the metabolically active form of vitamin B6, is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function and gene expression. Pyridoxal phosphate generally serves as a coenzyme for many reactions and can help facilitate decarboxylation, transamination, racemization, elimination, replacement and beta-group interconversion reactions. The liver is the site for vitamin B6 metabolism.

Metabolic functions The primary role of vitamin B6 is to act as a coenzyme to many other enzymes in the body that are involved predominantly in metabolism. This role is performed by the active form, pyridoxal phosphate. This active form is converted from the two other natural forms founds in food: pyridoxal, pyridoxine and pyridoxamine.

Vitamin B6 is involved in the following metabolic processes

• amino acid, glucose and lipid metabolism
• neurotransmitter synthesis
• histamine synthesis
• hemoglobin synthesis and function
• gene expression

Vitamin B6 Defficiency

• Skin disorder affecting the scalp, face, and trunk causing scaly, flaky, itchy, red skin. It particularly affects the sebum-gland rich areas of skin.

• Smooth tongue (also known as "Atrophic glossitis," "Bald tongue," "Hunter glossitis," and "Moeller glossitis") is a condition characterized by a smooth glossy tongue that is often tender/painful.

• Pediatric disease due to a lack of pyridoxine (or vitamin B6)

The disease presents with several key symptoms including seizures, irritability, cheilitis (inflammation of the lips), conjunctivitis and neurologic symptoms. It usually becomes noticeable within the first 12 months of life in infants with a lack of pyridoxine, a coenzyme responsible for numerous essential metabolic reactions in humans.

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B12 Cyanocobalamin

Cyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is chemically the most air-stable, and it is the easiest to crystallize and therefore easiest to purify after it is produced by bacterial fermentation. The cyanide is added to the molecule by activated charcoal columns in purification. Thus, the use of this form of B12 is the most wide-spread.

This fact has caused some people (usually from reading labels on packages and vitamin supplements, in which vitamin B12 is almost always listed last, since ingredients by law are listed in order of weight percentage), to infer that the correct chemical name of vitamin B12 actually is cyanocobalamin. In fact, vitamin B12 is the name for a whole class of chemicals with B12 activity, and cyanocobalamin is only one of these. Cyanocobalamin usually does not even occur in nature, and is not one of the forms of the vitamin which is directly used in the human body (or that of any other animal). However, animals and humans can convert it to active (cofactor) forms of the vitamin, such as methylcobalamin.

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B13 Orotic Acid

Orotic acid is a heterocyclic compound and an acid; it is also known as pyrimidinecarboxylic acid. It was once believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin but is instead manufactured in the body by intestinal flora.

It is primarily used for metabolization of folic acid and vitamin B12. It assists the absorption of essential nutrients especially calcium and magnesium and helps the production of genetic material. It may be beneficial after a heart attack and has been used in conditions such as multiple sclerosis and chronic hepatitis. It is also reported to prevent liver-related complications and premature aging.

Its salts, known as orotates, are sometimes used as mineral carriers in some dietary supplements, to increase their bioavailability. Lithium orotate is the most frequently used in this manner.

Orotic Acid Benefits

• Orotic acid improves the tolerance of the recently infarcted heart to global ischemia (rats).
• Orotic acid can improve the energy status of the recently infarcted myocardium (rat hearts).
• Orotic acid is recognized as a treatment for multiple sclerosis and is dispensed under the name of calcium orotate.
• Orotic acid may improve myocardial purine and pyrimidine levels by stimulating hepatic release of uridine into the bloodstream.

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Biotin

Also known as vitamin H or B7, is a water-soluble B-complex vitamin which is composed of an ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring. Biotin is a cofactor in the metabolism of fatty acids and leucine, and it plays a role in gluconeogenesis.

Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. It plays a role in the citric acid cycle, which is the process by which biochemical energy is generated during aerobic respiration. Biotin not only assists in various metabolic reactions, but also helps to transfer carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequently, it is found in many cosmetics and health products for the hair and skin.

Biotin Uses

• Hair Problems
Biotin supplements are often recommended as a natural product to counteract the problem of hair loss in both children and adults. The signs and symptoms of biotin deficiency include hair loss which progresses in severity to include loss of eye lashes and eye brows in severely deficient subjects. Some shampoos are available that contain biotin, but it is doubtful whether they would have any useful effect, as biotin is not absorbed well through the skin.

• Cradle Cap (seborrheic dermatitis)
Children with a rare inherited metabolic disorder called phenylketonuria often develop skin conditions such as eczema and seborrheic dermatitis in areas of the body other than the scalp.Increasing dietary biotin has been known to improve seborrheic dermatitis in these cases.

• Diabetes
Diabetics may also benefit from biotin supplementation. In both insulin-dependent and non-insulin-dependent diabetes, supplementation with biotin can improve blood sugar control and help lower fasting blood glucose levels, in some studies the reduction in fasting glucose exceeded 50 percent. Biotin can also play a role in preventing the neuropathy often associated with diabetes, reducing both the numbness and tingling associated with poor glucose control.

Biotin Deficiency

Biotin Deficiency is not due to inadequate biotin, but rather to a deficiency in the enzymes which process it. Deficiency rarely occurs among healthy people, since the daily requirement of biotin is low, many foods provide adequate amounts of it, intestinal bacteria synthesize small amounts of it, and the body effectively scavenges and recycles it from bodily waste. However, deficiencies can be caused by consuming raw egg whites over a period of months to years. Egg whites contain high levels of avidin, a protein that binds biotin strongly. When cooked, avidin is denatured and becomes entirely non-toxic.

Symptoms

Initial symptoms of biotin deficiency include:

• Dry skin • Seborrheic dermatitis • Fungal infections • Fine and brittle hair
• Rashes including red, patchy ones near the mouth (erythematous periorofacial macular rash)
• Hair loss or total baldness (alopecia)

If left untreated, neurological symptoms can develop, including:

• Mild depression, which may progress to profound lassitude and, eventually, to somnolence
• Changes in mental status
• Generalized muscular pains (myalgias)
• Hyperesthesias and paresthesias

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Choline

Choline is an organic compound, classified as a water-soluble essential nutrient and usually grouped within the Vitamin B complex. This natural amine is found in the lipids that make up cell membranes and in the neurotransmitter acetylcholine. Adequate intakes (AI) for this micronutrient of between 425 to 550 milligrams daily, for adults, have been established by the Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences.

Choline as a supplement

It is well established that supplements of methyl group transfer vitamins B6, B12, folic acid reduce the blood titer of homocysteine and so may prevent heart disease. Choline is a necessary source of methyl groups for methyl group transfer. Supplements of lecithin/choline were found to reduce heart disease in laboratory studies. The reduction in heart disease with lecithin supplements may however relate more to the cholesterol carrying capacity of lecithin than to the methyl group transfer role of choline.

Choline is a chemical precursor or "building block" needed to produce the neurotransmitter acetylcholine, and research suggests that memory, intelligence and mood are mediated at least in part by acetylcholine metabolism in the brain. The compound's quaternary amine renders it lipid insoluble which might suggest it would be unable to cross the blood-brain barrier. However, despite choline's lipid insolubility, a choline transporter exists that allows transport across the blood-brain barrier.

Physiology

Choline metabolism. (Choline is green box at left, second from the bottom.) Choline and its metabolites are needed for three main physiological purposes: structural integrity and signaling roles for cell membranes, cholinergic neurotransmission (acetylcholine synthesis), and as a major source for methyl groups via its metabolite, trimethylglycine (betaine) that participates in the S-adenosylmethionine synthesis pathways. When choline is metabolized by the body, it may form trimethylamine, a compound with a fishy odor. Hence, when large amounts of choline are taken the person may suffer from a fishy body odor.

Choline and Anxiety

Despite its importance in the central nervous system as a precursor for acetylcholine and membrane phosphatidylcholine, the role of choline in mental illness has been little studied. In a large population-based study, choline concentrations were negatively associated with anxiety symptoms in subjects aged 46–49 and 70–74 years who had valid information on plasma choline concentrations and symptoms of anxiety.

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Folic Acid

Folic acid (also known as vitamin B9 or folacin) and folate (the naturally occurring form), as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B9. Folic acid is itself not biologically active with its biological importance being due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver.

Vitamin B9 (folic acid and folate inclusive) is essential to numerous bodily functions ranging from nucleotide biosynthesis to the remethylation of homocysteine. It is especially important during periods of rapid cell division and growth. Both children and adults require folic acid to produce healthy red blood cells and prevent anemia. Folate and folic acid derive their names from the Latin word folium (which means "leaf"). Leafy vegetables are a principle source, although in Western diets fortified cereals and bread may be a larger dietary source.

A lack of dietary folic acid leads to folate deficiency (FD). This can result in many health problems, most notably neural tube defects in developing embryos.

Health Issues

• Heart Disease
Adequate concentrations of folate, vitamin B12, or vitamin B6 may decrease the circulating level of homocysteine, an amino acid normally found in blood.

• Stroke
Folic acid appears to reduce the risk of stroke.

• Cancer
The association between folate and cancer appears to be complex.[34] It has been suggested that folate may help prevent cancer, as it is involved in the synthesis, repair, and functioning of DNA, and a deficiency of folate may result in damage to DNA that may lead to cancer.

• Antifolates
Folate is important for cells and tissues that rapidly divide.[10] Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer.

• Fertility
Folate is necessary for fertility in both men and women. In men, it contributes to spermatogenesis. In women, on the other hand, it contributes to oocyte maturation, implantation, placentation, in addition to the general effects of folic acid and pregnancy.

Folic Acid and Masking of B12 Deficiency

There has been concern about the interaction between vitamin B12 and folic acid. Folic acid supplements can correct the anemia associated with vitamin B12 deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage could theoretically occur if vitamin B12 deficiency is not treated. Therefore, intake of supplemental folic acid should not exceed 1000 micrograms (1000 µg or 1 mg) per day to prevent folic acid from masking symptoms of vitamin B12 deficiency.

Health Risk of Too Much Folic Acid

The risk of toxicity from folic acid is low. The Institute of Medicine has established a tolerable upper intake level (UL) for folate of 1 mg for adult men and women, and a UL of 800 µg for pregnant and lactating (breast-feeding) women less than 18 years of age. Supplemental folic acid should not exceed the UL to prevent folic acid from masking symptoms of vitamin B12 deficiency.

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Inositol

Inositol is needed for health at cellular level and a fair concentration is found in the lens of the human eye as well as the heart.
Itl plays an important part in the health of cell membranes especially the specialized cells in the brain, bone marrow, eyes and intestines. The function of the cell membranes is to regulate the contents of the cells, which makes effective functioning possible. Inositol is said to promote healthy hair, hair growth, and helps in controlling estrogen levels and may assist in preventing breast lumps. It may also be of benefit in reducing blood cholesterol levels.Inositol is available from both plant and animal sources. The plant form in which inositol is available is phytic acid, which can bind with minerals and so affect their absorption negatively. The body is also able to manufacture this factor. Inositol is available from wheat germ, brewers yeast. bananas, liver, brown rice, oat flakes, nuts, unrefined molasses, raisins and vegetables.

Function

Inositol as the basis for a number of signaling and secondary messenger molecules, is involved in
a number of biological processes, including:

• Insulin signal transduction
• Cytoskeleton assembly
• Nerve guidance (Epsin)
• Intracellular calcium (Ca2+) concentration control{inositol Intracellular calcium (Ca2+) concentration control
• Cell membrane potential maintenance
• Serotonin activity modulation
• Breakdown of fats and reducing blood cholesterol
• Gene expression

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Pantothenic Acid

Pantothenic acid, also called vitamin B5 (a B vitamin), is a water-soluble vitamin required to sustain life (essential nutrient). Pantothenic acid is needed to form coenzyme-A (CoA), and is critical in the metabolism and synthesis of carbohydrates, proteins, and fats. In chemical structure, it is the amide between D-pantoate and beta-alanine. Its name is derived from the Greek pantothen meaning "from everywhere" and small quantities of pantothenic acid are found in nearly every food, with high amounts in whole-grain cereals, legumes, eggs, meat, and royal jelly. It is commonly found as its alcohol analog, the provitamin panthenol, and as calcium pantothenate.

Absorption

Within most foods, pantothenic acid is in the form of CoA or Acyl Carrier Protein (ACP). In order for the intestinal cells to absorb this vitamin it must be converted into free pantothenic acid. Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4'-phosphopantetheine. 4'-phosphopantetheine is then dephosphorylated into pantetheine. Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid.

Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system. At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be absorbed via passive diffusion. However, as intake increases 10-fold, absorption rate decreases to 10%

Patothenic Acid Uses

• Testicular Torsion
Testicular Torsion can severely affect fertility if it occurs. Pantothenic acid has the ability to spare reduced glutathione levels. Reactive oxygen species play a role in testicular atrophy, which the glutathione can 'fight' against.

• Diabetic Ulceration
Foot ulceration is a problem commonly associated with diabetes, which often leads to amputation. A preliminary study completed by Abdelatif, Yakoot and Etmaan indicated that perhaps a royal jelly and panthenol ointment can help cure the ulceration

• Hypolipidemic Effects
Pantothenic acid derivatives, panthenol, phosphopantethine and pantethine, have also been seen to improve the lipid profile in the blood and liver.

• Wound Healing
Pantothenic acid has an effect on wound healing in vitro.

• Hair Care
Skin irritation and loss of hair color as possible results of severe pantothenic acid deficiency. As a result, the cosmetic industry began adding pantothenic acid to various cosmetic products, including shampoo. These products, however, showed no benefits in human trials. Despite this, many cosmetic products still advertise pantothenic acid additives.

Pantothenic Acid Deficiency

Symptoms of deficiency are similar to other vitamin B deficiencies.

• There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue, and apathy.

• Acetylcholine synthesis is also impaired, therefore, neurological symptoms can also appear in deficiency.

• They include numbness, paresthesia, and muscle cramps.

• Deficiency in pantothenic acid can also cause hypoglycemia, or an increased sensitivity to insulin.

• Insulin receptors are acylated with palmitic acid when they do not want to bind with insulin. Therefore, more insulin will bind to receptors when acylation decreases, causing hypoglycemia.

• Additional symptoms could include, restlessness, malaise, sleep disturbances, nausea, vomiting, and abdominal cramps. In a few rare circumstances more serious (but reversible) conditions have been seen, such as adrenal insufficiency and hepatic encephalopathy.

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Rutin

Also called rutoside, quercetin-3-rutinoside and sophorin, is a citrus flavonoid glycoside found in buckwheat, the leaves and petioles of Rheum species, and asparagus. Rutin is also found in the fruit of the Fava D'Anta tree (from Brazil), fruits and fruit rinds (especially citrus fruits (orange, grapefruit, lemon, lime)) and berries such as mulberry and cranberries. Its name comes from the name of Ruta graveolens, a plant that also contains rutin.

Rutin is the glycoside between the flavonol quercetin and the disaccharide rutinose.

Health Effects

• Rutin has anti-inflammatory activity.
• Rutin inhibits aldose reductase activity.
• It helps prevent a common unpleasant-looking venous edema of the legs.
• Rutin inhibits platelet aggregation, making the blood thinner and improves circulation.
• Rutin also strengthens the capillaries, and, therefore, can reduce the symptoms of haemophilia.
• Rutin,as ferulic acid, can reduce the cytotoxicity of oxidized cholesterol and lower the risk of heart disease.

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Vitamin C

Vitamin C or L-ascorbic acid is an essential nutrient for humans, in which it functions as a vitamin. Ascorbate (an ion of ascorbic acid) is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms; notable mammalian exceptions are most or all of the order chiroptera (bats), and the entire suborder Anthropoidea (Haplorrhini) (tarsiers, monkeys and apes). It is also needed by guinea pigs and some species of birds and fish. Deficiency in this vitamin causes the disease scurvy in humans. It is also widely used as a food additive.

The pharmacophore of vitamin C is the ascorbate ion. In living organisms, ascorbate is an anti-oxidant, since it protects the body against oxidative stress and is a cofactor in several vital enzymatic reactions.

Biological Significance

Ascorbic acid Vitamin C is purely the L-enantiomer of ascorbate; the opposite D-enantiomer has no physiological significance. Both forms are mirror images of the same molecular structure. When L-ascorbate, which is a strong reducing agent, carries out its reducing function, it is converted to its oxidized form, L-dehydroascorbate. L-dehydroascorbate can then be reduced back to the active L-ascorbate form in the body by enzymes and glutathione. During this process semidehydroascorbic acid radical is formed. Ascorbate free radical reacts poorly with oxygen, and thus, will not create a superoxide. Instead two semidehydroascorbate radicals will react and form one ascorbate and one dehydroascorbate. With the help of glutathione, dehydroxyascorbate is converted back to ascorbate. The presence of glutathione is crucial since it spares ascorbate and improves antioxidant capacity of blood. Without it dehydroxyascorbate could not convert back to ascorbate.

L-ascorbate is a weak sugar acid structurally related to glucose which naturally occurs either attached to a hydrogen ion, forming ascorbic acid, or to a metal ion, forming a mineral ascorbate.

Antioxidant

Ascorbic acid is well known for its antioxidant activity. Ascorbate acts as a reducing agent to reverse oxidation in aqueous solution. When there are more free radicals (Reactive oxygen species) in the body versus antioxidant, a human is under the condition called Oxidative stress. Oxidative stress induced diseases encompass cardiovascular diseases, hypertension, chronic inflammatory diseases and diabetes.

Pro-Oxidant

Ascorbic acid behaves not only as antioxidant but also as pro-oxidant. Ascorbic acid reduced transition metals, such as cupric ions (Cu2+) to cuprous (Cu1+) and ferric ions (Fe3+) to ferrous (Fe2+) during conversion from ascorbate to dehydroxyascorbate In Vitro. This reaction can generate superoxide and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper is bound to diverse proteins.

Vitamin C Deficiency

Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, the synthesised collagen is too unstable to perform its function. Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth and, eventually, death. The human body can store only a certain amount of vitamin C, and so the body soon depletes itself if fresh supplies are not consumed.

It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of vitamin C in the blood.

Therapeutic Uses

• Vitamin C is necessary for the treatment and prevention of scurvy.
• Vitamin C's effect on the common cold has been extensively researched
• High doses of vitamin C may have "protective effects" on lead-induced nerve and muscle abnormalities, especially in smokers.

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Vitamin D

Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol). Vitamin D obtained from sun exposure, food, and supplements, is biologically inert and must undergo two hydroxylation reactions to be activated in the body. Calcitriol (1,25-Dihydroxycholecalciferol) is the active form of vitamin D found in the body. The term vitamin D also refers to these metabolites and other analogues of these substances.

Calcitriol plays an important role in the maintenance of several organ systems. However, its major role is to increase the flow of calcium into the bloodstream, by promoting absorption of calcium and phosphorus from food in the intestines, and reabsorption of calcium in the kidneys; enabling normal mineralization of bone and preventing hypocalcemic tetany. It is also necessary for bone growth and bone remodeling by osteoblasts and osteoclasts

Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Deficiency can arise from inadequate intake coupled with inadequate sunlight exposure; disorders that limit its absorption; conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders; or, rarely, by a number of hereditary disorders. Vitamin D deficiency results in impaired bone mineralization and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis.

Vitamin D plays a number of other roles in human health including inhibition of calcitonin release from the thyroid gland. Calcitonin acts directly on osteoclasts, resulting in inhibition of bone resorption and cartilage degradation. Vitamin D can also inhibit parathyroid hormone secretion from the parathyroid gland, modulate neuromuscular and immune function and reduce inflammation.

Vitamin D Deficiency

Hypovitaminosis D Deficiency of vitamin D can result from a number of factors: inadequate intake coupled with inadequate sunlight (UVB) exposure, disorders that limit its absorption from the gastrointestinal tract, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders and body characteristics such as skin color and body fat. Rarely, deficiency can result from a number of hereditary disorders. Deficiency results in impaired bone mineralization, and leads to bone softening diseases[33] including:

• Rickets
A childhood disease characterized by impeded growth, and deformity, of the long bones.

• Osteomalacia
A bone-thinning disorder that occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility. The effects of osteomalacia are thought to contribute to chronic musculoskeletal pain.

• Osteoporosis
A condition characterized by reduced bone mineral density and increased bone fragility.

Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases, such as high blood pressure, tuberculosis, cancer, periodontal disease, multiple sclerosis, chronic pain, seasonal affective disorder, peripheral artery disease, cognitive impairment which includes memory loss and foggy brain, and several autoimmune diseases including type 1 diabetes

Role In Immunomodulation

The hormonally active form of vitamin D mediates immunological effects by binding to nuclear vitamin D receptors (VDR) which are present in most immune cell types including both innate and adaptive immune cells. The VDR is expressed constitutively in monocytes and in activated macrophages, dendritic cells, NK cells, T and B cells. In line with this observation, activation of the VDR has potent anti-proliferative, pro-differentiative, and immunomodulatory functions including both immune-enhancing and immunosuppressive effects.

Role in cancer Prevention and Recovery

The vitamin D hormone, calcitriol, has been found to induce death of cancer cells in vitro and in vivo. The anti-cancer activity of vitamin D is thought to result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. These effects may be mediated through vitamin D receptors expressed in cancer cells.

Role in Cardiovascular Disease

Prevention Research indicates that vitamin D may play a role in preventing or reversing coronary disease. Vitamin D deficiency is associated with an increase in high blood pressure and cardiovascular risk. When researchers monitored the vitamin D levels, blood pressure and other cardiovascular risk factors of 1739 people, of an average age of 59 years for 5 years, they found that those people with low levels of vitamin D had a 62% higher risk of a cardiovascular event than those with normal vitamin D levels. Low levels of vitamin D have also been implicated in hypertension, elevated VLDL triglycerides, and impaired insulin metabolism.

Role in All-Cause Mortality

Among many factors that may be responsible for vitamin D's apparent beneficial effect on all-cause mortality is its effect on telomeres and its potential effect on slowing aging. Shortening of leukocyte telomeres is a marker of aging. Leukocyte telomere length (LTL) predicts the development of aging-related disease, and length of these telomeres decreases with each cell division and with increased inflammation (more common in the elderly) Research indicates that vitamin D is a potent inhibitor of the proinflammatory response and slows the turnover of leukocytes. Higher vitamin D levels were also associated with longer leukocyte telomere length, indicating that vitamin D sufficiency may be play a role in preventing age-related diseases.

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Vitamin E

Vitamin E is a generic term for tocopherols and tocotrienols. Vitamin E is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation. Of these, Alpa-tocopherol has been most studied as it has the highest bioavailability.

It has been claimed that Alpa-tocopherol is the most important lipid-soluble antioxidant, and that it protects cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This would remove the free radical intermediates and prevent the oxidation reaction from continuing. The oxidised Alpa-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol. However, the importance of the antioxidant properties of this molecule at the concentrations present in the body are not clear and it is possible that the reason why vitamin E is required in the diet is unrelated to its ability to act as an antioxidant. Other forms of vitamin E have their own unique properties. For example, alpa-tocopherol (also written as gamma-tocopherol) is a nucleophile that can react with electrophilic mutagens.

However, the roles and importance of all of the various forms of vitamin E are presently unclear, and it has even been suggested that the most important function of vitamin E is as a signaling molecule, and that it has no significant role in antioxidant metabolism. So far, most studies about vitamin E have supplemented using only the synthetic alpha-tocopherol, but doing so leads to reduced serum gamma- and delta-tocopherol concentrations. Moreover, a 2007 clinical study involving synthetic alpha-tocopherol concluded that supplementation did not reduce the risk of major cardiovascular events in middle aged and older men. For more info, read article tocopherol. Compared with tocopherols, tocotrienols are poorly studied. Less than 1% of PubMed papers on vitamin E relate to tocotrienols. Current research direction are starting to give more prominence to the tocotrienols, the lesser known but more potent antioxidants in the vitamin E family. Tocotrienols have specialized roles in protecting neurons from damage, cancer prevention and cholesterol reduction by inhibiting the activity of HMG-CoA reductase; Alpa-tocotrienol blocks processing of sterol regulatory element-binding proteins (SREBPs).

Oral consumption of tocotrienols is also proven to protect against stroke-associated brain damage in vivo. Disappointments with outcomes-based clinical studies testing the efficacy of Alpa-tocopherol need to be handled with caution and prudence recognizing the untapped opportunities offered by the other forms of natural vitamin E. Toxicity studies of a specific form of tocopherol in excess should not be used to conclude that high-dosage “vitamin E” supplementation may increase all-cause mortality. Such conclusion incorrectly implies that tocotrienols are toxic as well under conditions where tocotrienols were not even considered.

Vitamin E Deficiency

Vitamin E deficiency causes neurological problems due to poor nerve conduction. These include neuromuscular problems such as spinocerebellar ataxia and myopathies. Deficiency can also cause anemia, due to oxidative damage to red blood cells.

Vitamin E deficiency is very rare in humans and is almost never caused by a poor diet. Instead, there are three specific situations when a vitamin E deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3.5 pounds), and is seen in individuals with rare disorders of fat metabolism.

Individuals who cannot absorb fat may require a vitamin E supplement because some dietary fat is needed for the absorption of vitamin E from the gastrointestinal tract. Anyone diagnosed with cystic fibrosis, individuals who have had part or all of their stomach removed, and individuals with malabsorptive problems such as Crohn's disease, liver disease or pancreatic insufficiency may not absorb fat and should discuss the need for supplemental vitamin E with their physician. People who cannot absorb fat often pass greasy stools or have chronic diarrhea and bloating.

Very low birth weight infants may be deficient in vitamin E. A neonatologist, a pediatrician specializing in the care of newborns, typically evaluates the nutritional needs of premature infants.

Abetalipoproteinemia is a rare inherited disorder of fat metabolism that results in poor absorption of dietary fat and vitamin E. The vitamin E deficiency associated with this disease causes problems such as poor transmission of nerve impulses, muscle weakness, and degeneration of the retina that can cause blindness. Individuals with abetalipoproteinemia may be prescribed special vitamin E supplements by a physician to treat this disorder. In addition, there is a rare genetic condition termed isolated vitamin E deficiency or ataxia with isolated with vitamin E deficiency, caused by mutations in the gene for the tocopherol transfer protein. These individuals have an extremely poor capacity to absorb vitamin E and develop neurological complications that are reversed by high doses of vitamin E.

Vitamin E and Health

Many claims have been made about vitamin E’s potential to promote health and prevent and treat disease. The mechanisms by which vitamin E might provide this protection include its function as an antioxidant and its roles in anti-inflammatory processes, inhibition of platelet aggregation, and immune enhancement.

A primary barrier to characterizing the roles of vitamin E in health is the lack of validated biomarkers for vitamin E intake and status to help relate intakes to valid predictors of clinical outcomes

• Coronary Heart Disease
Evidence that vitamin E could help prevent or delay coronary heart disease (CHD) comes from several sources. In vitro studies have found that the nutrient inhibits oxidation of low-density lipoprotein (LDL) cholesterol, thought to be a crucial initiating step for atherosclerosis. Vitamin E might also help prevent the formation of blood clots that could lead to a heart attack or venous thromboembolism

• Cancer
Antioxidant nutrients like vitamin E protect cell constituents from the damaging effects of free radicals that, if unchecked, might contribute to cancer development. Vitamin E might also block the formation of carcinogenic nitrosamines formed in the stomach from nitrites in foods and protect against cancer by enhancing immune function. Human trials and surveys that attempted to associate vitamin E intake with cancer incidence have generally been inconclusive.

• Eye Disorders
Age-related macular degeneration (AMD) and cataracts are among the most common causes of significant vision loss in older people. Their etiologies are usually unknown, but the cumulative effects of oxidative stress have been postulated to play a role. If so, nutrients with antioxidant functions, such as vitamin E, could be used to prevent or treat these conditions.

• Cognitive Decline
The brain has a high oxygen consumption rate and abundant polyunsaturated fatty acids in the neuronal cell membranes. Researchers hypothesize that if cumulative free-radical damage to neurons over time contributes to cognitive decline and neurodegenerative diseases, such as Alzheimer's disease, then ingestion of sufficient or supplemental antioxidants (such as vitamin E) might provide some protection. This hypothesis was supported by the results of a clinical trial in 341 patients with Alzheimer's disease of moderate severity who were randomly assigned to receive a placebo, vitamin E (2,000 IU/day dl-alpha-tocopherol), a monoamine oxidase inhibitor (selegiline), or vitamin E and selegiline. Over 2 years, treatment with vitamin E and selegiline, separately or together, significantly delayed functional deterioration and the need for institutionalization compared to placebo.

Health Risks from Excessive Vitamin E

Research has not found any adverse effects from consuming vitamin E in food. However, high doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation. Two clinical trials have found an increased risk of hemorrhagic stroke in participants taking alpha-tocopherol; one trial included Finnish male smokers who consumed 50 mg/day for an average of 6 years and the other trial involved a large group of male physicians in the United States who consumed 400 IU every other day for 8 years. Because the majority of physicians in the latter study were also taking aspirin, this finding could indicate that vitamin E has a tendency to cause bleeding.

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Vitamin K

Vitamin K (K from "Koagulations-Vitamin" in German and Scandinavian languages) denotes a group of lipophilic, hydrophobic vitamins that are needed for the posttranslational modification of certain proteins, mostly required for blood coagulation. Chemically they are 2-methyl-1,4-naphthoquinone derivatives. Vitamin K1 is also known as phylloquinone or phytomenadione (also called phytonadione). Vitamin K2 (menaquinone, menatetrenone) is normally produced by bacteria in the Large Intestine, and dietary deficiency is extremely rare unless the intestines are heavily damaged, are unable to absorb the molecule, or due to decreased production by normal flora, as seen in broad spectrum antibiotic use[3]. There are three synthetic forms of vitamin K, vitamins K3, K4, and K5, which are used in many areas including the pet food industry (vitamin K3) and to inhibit fungal growth (vitamin K5)

Physiology

Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues). The modified residues are often (but not always) situated within specific protein domains called Gla domains. Gla-residues are usually involved in binding calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins.

At this time 14 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes:

• Blood coagulation: (prothrombin (factor II), factors VII, IX, X, protein C, protein S, and protein Z).
• Bone metabolism: osteocalcin, also called bone Gla-protein (BGP), and matrix gla protein (MGP).
• Vascular biology.

Function

• Aids in reducing excessive menstrual flow
• Aids the absorption of calcium in bone
• Essential for normal liver functioning
• Essential for synthesis of four proteins that act in coagulation
• Important in maintaining vitality and longevity
• Necessary for formation of prothrombin which is required for effective blood clotting
• Involved in electron transport mechanism and oxdative phosphorylation

Vitamin K Uses

• Anticoagulant drug overdose
• Reduces excessive menstral flow
• Essential for blood clotting/haemorrhage and bleeding
• Hemorrhagic disease in newborn babies
• Inhibiting some cancer tumors
• Overcoming inability to absorb vitamins
• Overcoming effects of antibiotics on intestinal bacteria
• Protection against osteoporosis

SYMPTOMS OF DEFICIENCY

• Excessive bleeding and hemorrhage

In Babies:
• Bleeding from the stomach, intestines, umbilical cord site

DEFICIENCY CAUSED BY

In Babies
• Low levels in human breast milk
• Poor transfer across placenta
• Sterile intestine with no bacteria

In Adults
• As a consequence of sprue
• Celiac's Disease
• Destruction of intestinal bacteria by antibiotics
• Lack of bile salts
• Liver conditions, such as viral hepatitis
• Surgical removal of intestines
• Prolonged ingestion of liquid paraffin

Deficiency Leads to
• Inability of blood to coagulate

Symptoms of Toxicity

None reported

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