Vitamins

Vitamins are nutrients required in very small amounts for essential metabolic reactions in the body. The term vitamin does not encompass other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids. Nor does the term refer to the large number of other nutrients that promote health, but are not strictly essential.

Vitamins act both as catalysts and substrates in chemical reactions. When acting as a catalyst, vitamins are bound to enzymes and are called cofactors, for example vitamin K forms part of the proteases involved in blood clotting. Vitamins also act as coenzymes to carry chemical groups between enzymes, for example folic acid carries various forms of carbon groups (methyl, formyl or methylene) in the cell. Until the 1900's, vitamins were obtained solely through food intake. Many food sources contain different ratios of vitamins. Therefore, if the only source of vitamins is food, a seasonal, yearly or even daily change in diet also alters the ratio of ingested vitamins. Many vitamins can be stored by the body over a range of dosages and short term deficiencies (e.g. during a particular food growing season), do not always result in disease.

Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades allowing for consistent supplementation to dietary intake.

History
The value of eating certain foods to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding a patient liver would help cure night blindness, now known to be caused by a vitamin A deficiency. In 1747, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, and is characterized by poor wound healing, bleeding of the gums, and severe pain. In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname Limey for sailors of that organization. Lind's discovery, however, was not widely accepted by individuals in the Royal Navy's Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and by maintaining the morale of the crew while on board, rather than by a diet of fresh food. For these reasons, Arctic expeditions took with them all of the amenities of 'sophisticated' society, like silk sheets, spices, expensive food and drink, and almost nothing of any use beyond the Arctic Circle. As a result, Arctic expeditions continued to be plagued by scurvy and other deficiency diseases. In the early 20th century, when Robert Falcon Scott made his two expeditions to the Antarctic the prevailing medical theory was that scurvy was caused by "tainted" canned food.

In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu (in present day Estonia). He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely the proteins, fats, carbohydrates, and salts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that "a natural food such as milk must therefore contain, besides these known principal ingredients, small quantities of unknown substances essential to life". However, his conclusions were rejected by other researchers when they were unable to reproduce his results. One difference was that he had used table sugar (sucrose), while other researchers had used milk sugar (lactose) which still contained small amounts of vitamin B.

In 1905, William Fletcher discovered that eating unpolished rice instead of the polished variety helped to prevent the disease beriberi. The following year, Frederick Hopkins postulated that some foods contained "accessory factors"&mdash;in addition to proteins, carbohydrates, fats, etc.&mdash;that were necessary for the functions of the human body. Kazimierz Funk was the first to isolate the water-soluble complex of micronutrients, whose bioactivity Fletcher had identified, and Funk proposed the complex be named "Vitamine". The name soon became synonymous with Hopkins' "accessory factors", and by the time it was shown that not all vitamins were amines, the word was already ubiquitous. In 1920, Jack Cecil Drummond proposed that the final "e" be dropped, to deemphasize the "amine" reference, after the discovery that vitamin C had no amine component.

Throughout the early 1900s, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Initially, lipid from fish oil was used to cure rickets in rats, and the fat-soluble nutrient was called "antirachitic A". The irony here is that the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called vitamin A, the bioactivity of which is now called vitamin D, which is itself subject to the semantic debate that it is not truly a vitamin because it is a steroid derivative. What we now call "vitamin A" was identified in fish oil because it was inactivated by ultraviolet light. The group of water-soluble organic micronutrients we now recognize as the vitamin B complex was initially referred to as just one entity, "vitamin B".

Human vitamins
Vitamins are classified as either water soluble, meaning that they dissolve easily in water, or fat soluble, and are absorbed through the intestinal tract with the help of lipids. Each vitamin is typically used in multiple reactions and therefore, most have multiple functions.

In humans there are thirteen vitamins, divided into two groups; four fat-soluble vitamins (A, D, E and K), and nine water-soluble vitamins (eight B vitamins and vitamin C).

Vitamins in nutrition and disease
Vitamins are essential for normal growth and development. Using the genetic blueprint inherited from its parents, a fetus begins to develop, at the moment of conception, from the nutrients it absorbs.

The developing fetus requires certain vitamins and minerals to be present at certain times. These nutrients facilitate the chemical reactions that produce, among other things, skin, bone, and muscle. If there is serious deficiency in one or more of these nutrients, a child may develop a deficiency disease. Minor deficiencies also have the potential to cause permanent damage, and may be associated with reduced life expectancy. For the most part, vitamins are obtained through food sources. However, a few vitamins are obtained by other means: for example, microorganisms in the intestine - commonly known as "gut flora" - produce vitamin K and biotin, while one form of vitamin D is synthesized in the skin with the help of natural ultraviolet sunlight. Some vitamins can be obtained from precursors that are obtained in the diet. Examples include vitamin A, which can be produced from beta carotene and niacin from the amino acid tryptophan.

Once growth and development are completed, vitamins remain essential components of the healthy maintenance of the cells, tissues, and organs that make up the human body, and enable the body to efficiently use the calories provided by the food that we eat, and to help process proteins, carbohydrates, and fats.
 * Vitamin A, for example, protects the surface linings of the eyes and the respiratory, urinary, and intestinal tracts, and helps to maintain the barrier functions of the skin and mucous membranes. Vitamin A deficiency may cause those linings to break down, allowing bacteria to enter the body and cause infection.
 * Vitamin B6 is required for the production of hemoglobin, the component of red blood cells which transports oxygen to tissues, and like most of the other vitamins, is important in immune system function.
 * Vitamin B12 is necessary to maintain proper functioning of the nervous system.
 * Vitamin E is a powerful antioxidant (a chemical that neutralizes free radicals), which have been shown to be particularly beneficial for health. A buildup of free radicals can damage body cells and tissues, increasing the risks of disease. Studies have shown that diets rich in vegetables and fruits result in a lower incidence of some diseases, including cardiovascular diseases and certain cancers.

Vitamin deficiencies
An organism can survive for some time without vitamins, although prolonged vitamin deficits may result in often painful and potentially deadly diseases. Body stores for different vitamins can vary widely; an adult may be deficient in vitamin A and B12 for long periods of time before developing a deficiency condition, while vitamin B3 stores may only last a couple of weeks. Deficiencies of vitamins are classified as either primary or secondary. A primary deficiency occurs when you do not get enough of the vitamin in the food you eat. A secondary deficiency may be due to an underlying disorder that prevents or limits the absorption or use of the vitamin, or due to a “lifestyle factor”, such as smoking, excessive alcohol consumption, or the use of medications that interfere with the absorption or the body's use of the vitamin. Well-known vitamin deficiencies involve thiamine (beriberi), niacin (pellagra), vitamin C (scurvy) and vitamin D (rickets). In much of the developed world, such deficiencies are rare due to; an adequate supply of food and the addition of vitamins and minerals, often called fortification, to common foods.

Vitamin side effects and overdose
Vitamins are classified as fat-soluble or water-soluble based on how they are absorbed by the body. Vitamins A, D, E, and K are fat soluble, while the water-soluble vitamins include vitamin C and the B-complex vitamins (thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), vitamin B6, vitamin B12, biotin and folate.  Fat-soluble vitamins (A, D, E and K) are often stored in the body and can cause toxicity when ingested in excess. With the exception of vitamin B12, which is stored in the liver, water-soluble vitamins are not stored in the body. All vitamins have documented side effects. Like side effects from drugs, vitamin side effects increase in severity with increasing dosage. At high enough dosages vitamins can cause extreme side effects such as nausea, diarrhea, and vomiting. Unlike side effects caused by drugs, vitamin side effects rarely cause any permanent harm.  There is no known toxic dose for the B-complex vitamins or for vitamin C. When vitamin side effects emerge, full and rapid recovery is accomplished by reducing the supplement dosage. Furthermore, the concentrations of vitamins an individual can tolerate vary widely, and appear to be related to age and state of health. The young, the old, and the sick have been reported to have higher tolerances than healthy young adults. The likelihood of consuming too much of any vitamin from food is remote, but overdosing from vitamin supplementation does occur. It is for this reason that physicians and scientists carefully review all the clinical data on supplement use in order to determine upper dosage thresholds for each vitamin that can be tolerated as a daily dose by the entire population without side effects. This dosage is known as the tolerable upper intake level (UL).
 * Because vitamin E can act as an anticoagulant and may increase the risk of bleeding problems many agencies have set an upper tolerable intake level (UL) for vitamin E at 1,000 mg (1,500 IU) per day.
 * Vitamin D toxicity can cause nausea, vomiting, poor appetite, constipation, weakness, and weight loss, and can raise blood levels of calcium, causing confusion or other mental status changes. High blood levels of calcium can also result in heart rhythm abnormalities and cause calcinosis, (a deposition of calcium and phosphate in the body's soft tissues such as the kidney). Therefore many governmental agencies have set the tolerable upper intake level (UL) for vitamin D at 25 μg (1,000 IU) for infants up to 12 months of age and 50 μg (2,000 IU) for children, adults, pregnant, and lactating women.
 * Although it is not stored in the body, ingestion of large quantities of vitamin C can cause intestinal gas and loose stool. Further increasing the dose causes painful cramping and diarrhea. In very rare cases, doses of vitamin C above 5,000 mg/day are known to cause kidney stones. However, this issue is still controversial, with evidence being presented for and against the possibility of this effect.


 * High levels of vitamin B6 can result in nerve damage to the arms and legs, which is reversible when supplementation is stopped.

The supplement controversy
Use of vitamin supplements is controversial. As the number of people who were taking vitamin supplements began to rise, a small group of physicians, specializing in the application of supplements, emerged. Many of these physicians categorize themselves as orthomolecular physicians, a term coined by two-time Nobel Prize winner Linus Pauling. A number of orthomolecular physicians are also obstetricians or pediatricians, who prescribe vitamin supplements to prevent and/or treat childhood physical and nervous disorders. Supplementation during pregnancy is often thought to be an important preventative measure. The credibility of orthomolecular physicians is buttressed by their use of vitamin C supplements to combat colds. At least 21 double-blind, placebo controlled clinical trials involving a total of over 6000 participants have been conducted. These trials were reviewed in the 1990's.  Reports from physicians have provided ample clinical confirmation that vitamin C reduces the duration and severity of colds (but not the frequency).

On the other hand, treating childhood obesity, neurological disorders, or most other health problems with vitamins is outside of mainstream practice, and the credibility of orthomolecular physicians is often harmed by their tendency to underplay the side effects of vitamins. Some vitamin tablets, prescribed by orthomolecular physicians, contain levels of vitamins many times higher, and in different forms, than one might ingest through food. Also unlike food, these contained vitamins are released rapidly. For these reasons, vitamin levels that are tolerated in food often cause side effects when consumed from supplements.

Governmental regulation of vitamin supplements
Most countries place dietary supplements in a special category under the general umbrella of "foods," not drugs. This necessitates that the manufacturer, and not the government, be responsible for ensuring that its dietary supplement products are safe before they are marketed. Unlike drug products that must implicitly be proven safe and effective for their intended use before marketing, there are often no provisions to "approve" dietary supplements for safety or effectiveness before they reach the consumer. Also unlike drug products, manufacturers and distributors of dietary supplements are not generally required to report any claims of injuries or illnesses that may be related to the use of their products. Some manufacturers of vitamin supplements claim that there are no side effects, and few, if any, provide warning labels. In reality, side effects have been reported for several types of supplements.

Names in current and previous nomenclatures
The reason the set of vitamins seems to skip directly from E to the rarely-mentioned K is that the vitamins corresponding to "letters" F-J were either reclassified over time, were discarded as false leads, or were renamed because of their relationship to "vitamin B", which became a "complex" of vitamins. The following table lists chemicals that had previously been classified as vitamins, as well as the earlier names of vitamins that later became part of the B-complex.