FAT SOLUBLE VITAMINS & THEIR SOLUTES Introduction

A vitamin is an organic compound required as a nutrient in tiny amounts by an organism.[1] In other words, an organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on the circumstances and on the particular organism. For example, ascorbic acid (vitamin C) is a vitamin for humans, but not for most other animals, and biotin and vitamin D are required in the human diet only in certain circumstances. By convention, the term vitamin does not include other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids (which are needed in larger amounts than vitamins), nor does it encompass the large number of other nutrients that promote health but are otherwise required less often.[2] Thirteen vitamins are universally recognized at present. Vitamins are classified by their biological and chemical activity, not their structure. Thus, each "vitamin" refers to a number of vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals is grouped under an alphabetized vitamin "generic descriptor" title, such as "vitamin A", which includes the compounds retinal, retinol, and four known carotenoids. Vitamers by definition are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well. Vitamins have diverse biochemical functions. Some have hormone-like functions as regulators of mineral metabolism (e.g., vitamin D), or

regulators of cell and tissue growth and differentiation (e.g., some forms of vitamin A). Others function as antioxidants (e.g., vitamin E and sometimes vitamin C).[3] The largest number of vitamins (e.g., B complex vitamins) function as precursors for enzyme cofactors, that help 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. Vitamins 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 carries various forms of carbon group methyl, formyl, and methylene in the cell. Although these roles in assisting enzymesubstrate reactions are vitamins' best-known function, the other vitamin functions are equally important.[4] Until the mid-1930s, when the first commercial yeast-extract and semi-synthetic vitamin C supplement tablets were sold, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) can alter the types and amounts of vitamins ingested. Vitamins have been produced as commodity chemicals and made widely available as inexpensive semisynthetic and synthetic-source multivitamin dietary supplements, since the middle of the 20th century. The term vitamin was derived from "vitamine," a combination word made up by Polish scientist Casimir Funk from vital and amine, meaning amine of life, because it was suggested in 1912 that the organic micronutrient food factors that prevent beriberi and perhaps other similar dietary-deficiency diseases might be chemical amines. This proved incorrect for the micronutrient class, and the word was shortened to vitamin.

History
The value of eating a certain food to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding liver to a patient would help cure night blindness, an illness now known to be caused by a vitamin A deficiency.[5] The advancement of ocean voyages during the Renaissance resulted in prolonged periods without access to fresh fruits and vegetables, and made illnesses from vitamin deficiency common among ships' crews.[6] In 1749, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, causing poor wound healing, bleeding of the gums, severe pain, and death.[5] 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 maintaining the morale of the crew while on board, rather than by a diet of fresh food.[5] 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.[5] During the late 18th and early 19th centuries, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Lipid from fish oil was used to cure rickets in rats, and the fat-soluble

nutrient was called "antirachitic A". Thus, the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called "vitamin A"; however, the bioactivity of this compound is now called vitamin D.[7] In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu in present-day Estonia.[8] 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."[8] 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) that still contained small amounts of vitamin B.

The Ancient Egyptians knew that feeding a patient liver (back, right) would help cure night blindness. In east Asia, where polished white rice was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was

endemic. In 1884, Takaki Kanehiro, a British trained medical doctor of the Imperial Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among officers who consumed a Western-style diet. With the support of the Japanese navy, he experimented using crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause of beriberi, but mistakenly believed that sufficient amounts of protein prevented it.[9] That diseases could result from some dietary deficiencies was further investigated by Christiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent beriberi in the chickens. The following year, Frederick Hopkins postulated that some foods contained "accessory factors" in addition to proteins, carbohydrates, fats etc. that are necessary for the functions of the human body.[5] Hopkins and Eijkman were awarded the Nobel Prize for Physiology or Medicine in 1929 for their discovery of several vitamins.[10] In 1910, the first vitamin complex was isolated by Japanese scientist Umetaro Suzuki, who succeeded in extracting a water-soluble complex of micronutrients from rice bran and named it aberic acid (later Orizanin). He published this discovery in a Japanese scientific journal.
[11]

When the article was translated into German, the translation failed

to state that it was a newly discovered nutrient, a claim made in the original Japanese article, and hence his discovery failed to gain publicity. In 1912 Polish biochemist Casimir Funk isolated the same complex of micronutrients and proposed the complex be named "vitamine" (a portmanteau of "vital amine").[12] The name soon

became synonymous with Hopkins' "accessory factors", and, by the time it was shown that not all vitamins are amines, the word was already ubiquitous. In 1920, Jack Cecil Drummond proposed that the final "e" be dropped to deemphasize the "amine" reference, after researchers began to suspect that not all "vitamines" (in particular, vitamin A) has an amine component.[9] In 1931, Albert Szent-Gyrgyi and a fellow researcher Joseph Svirbely suspected that "hexuronic acid" was actually vitamin C, and gave a sample to Charles Glen King, who proved its anti-scorbutic activity in his long-established guinea pig scorbutic assay. In 1937, SzentGyrgyi was awarded the Nobel Prize in Physiology or Medicine for his discovery. In 1943, Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery of vitamin K and its chemical structure. In 1967, George Wald was awarded the Nobel Prize (along with Ragnar Granit and Haldan Keffer Hartline) for his discovery that vitamin A could participate directly in a physiological process.[10]

Fat-Soluble Vitamins
Quick Facts...

Small amounts of vitamins A, D, E and K are needed to maintain good health. Foods that contain these vitamins will not lose them when cooked. The body does not need these every day and stores them in the liver when not used. Most people do not need vitamin supplements. Megadoses of vitamins A, D, E or K can be toxic and lead to health problems.

Vitamins are essential nutrients your body needs in small amounts for various roles in the human body. Vitamins are divided into two groups: water-soluble (B-complex and C) and fat-soluble (A, D, E and K). Unlike water-soluble vitamins that need regular replacement in the body, fat-soluble vitamins are stored in the liver and fatty tissues, and are eliminated much more slowly than water-soluble vitamins. Because fat-soluble vitamins are stored for long periods, they generally pose a greater risk for toxicity than water-soluble vitamins when consumed in excess. Eating a normal, well-balanced diet will not lead to toxicity in otherwise healthy individuals. However, taking vitamin supplements that contain mega doses of vitamins A, D, E and K may lead to toxicity. Remember, the body only needs small amounts of any vitamin. While diseases caused by a lack of fat-soluble vitamins are rare in the United States, symptoms of mild deficiency can develop without

adequate amounts of vitamins in the diet. Additionally, some health problems may decrease the absorption of fat, and in turn, decrease the absorption of vitamins A, D, E and K. Consult your doctor about this. Table 1 lists sources of fat-soluble vitamins, their basic functions in the body, major deficiency symptoms caused by a lack of these vitamins, and symptoms of over-consumption.

Vitamin A
Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division and gene expression. Also, the skin, eyes and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. The best way to ensure your body gets enough vitamin A is to eat a variety of foods. Vitamin A is supplied primarily by certain foods of animal origin like dairy products, fish and liver. Some foods of plant origin contain beta-carotene, an antioxidant that the body converts to vitamin A. Beta-carotene, or provitamin A, comes from fruits and vegetables. Carrots, pumpkin, winter squash, dark green leafy vegetables and apricots are rich sources of beta-carotene. The recommendation for vitamin A intake is expressed as micrograms (mcg) of retinol activity equivalents (RAE). Retinol activity equivalents account for the fact that the body converts only a portion of betacarotene to retinol. One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene.

True vitamin A deficiency in the United States is rare. Night blindness and very dry, rough skin may indicate a lack of vitamin A. Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth. In the United States, toxic or excess levels of vitamin A are of more concern than deficiencies. The tolerable upper intake level for adults is 3,000 mcg RAE. It would be difficult to reach this level consuming food alone. But some multivitamin supplements contain high doses of vitamin A. If you take a multivitamin, check the label to be sure the majority of vitamin A provided is in the form of beta-carotene, which appears to be safe. Symptoms of vitamin A toxicity include dry, itchy skin, headache, nausea, and loss of appetite. Signs of severe overuse over a short period of time include dizziness, blurred vision and slowed growth. Vitamin A toxicity also can cause severe birth defects and may increase the risk for hip fractures. Physicians sometimes recommend that young infants take vitamin supplements that contain vitamin A. However, toddlers and children need protection from too much vitamin A due to their smaller body size. Typical foods eaten in large amounts by toddlers and children usually contain sufficient amounts of vitamin A. Provide a variety of foods for your children, and if in doubt, check with a pediatrician or Registered Dietitian.

Table 1: Vitamin facts. Physiological Vitamin A A, Source Functions Deficiency mucous blindness, and diarrhea, Overconsumption nausea, blurred growth of liver of pain, irritability, vision. Severe: retardation, enlargement and hair, spleen, bone loss (retinol) Vitamin such A: Helps to form skin Mild: night Mild:

(provitamin liver, beta carotene) and

vitamin and

as A fortified milk membranes products, butter, milk, egg thus

dairy keep them healthy, intestinal increasing infections, to impaired vision. whole resistance cheese, infections; yolk.

essential for night Severe: promotes inflammation and is tooth of an of skin

Provitamin A: vision; carrots, green vegetables, sweet potatoes, pumpkins, winter squash, apricots, cantaloupe. D Vitamin fortified products, fortified margarine, yolk. Synthesized by E sunlight action on skin. D- Promotes and increases leafy bones

increased pressure in

eyes, skull, skin changes. and

development. Beta keratinization carotene antioxidant may against cancer. and eyes. Blindness protect in children.

Severe: rickets Mild: nausea, weight children; loss, physical retardation, calcium from irritability. mental and growth kidney bones teeth, osteomalacia in Severe: the adults. of

dairy hardening of bones in

absorption

fish oils, egg calcium.

damage, movement of into soft tissues.

Vegetable oil, Protects vitamins A Almost margarine, butter, shortening, green and C and to fatty impossible cell without starvation; acids; damage prevents produce

Nontoxic under normal to conditions. Severe: digestive disorders. nausea, tract

and membranes.

leafy vegetables, wheat whole products, nuts, yolk, liver. K Dark leafy vegetables, liver; made intestine. also by egg germ, grain

Antioxidant.

possible anemia in low birth-weight infants.

green Helps blood to clot. Excessive bleeding.

None reported.

bacteria in the

Vitamin D
Vitamin D plays a critical role in the bodys use of calcium and phosphorous. It increases the amount of calcium absorbed from the small intestine and helps form and maintain bones. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth. The primary food sources of vitamin D are milk and other dairy products fortified with vitamin D. Vitamin D is also found in oily fish (e.g., herring, salmon and sardines) as well as in cod liver oil. In addition to the vitamin D provided by food, we obtain vitamin D through our skin which makes vitamin D in response to sunlight. An Adequate Intake (AI) for has been established for vitamin D (see Table 2). The AIs for vitamin D appear as micrograms (mcg) of cholecalciferol. Ten mcg of cholecalciferol equals 400 International Units (IU).

Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults is called osteomalacia, which results in muscular weakness and weak bones. These conditions are rare in the United States. The tolerable upper intake level for vitamin D is set at 50 mcg for people 1 year of age and older (see Table 3). High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning. Signs of vitamin D toxicity include excess calcium in the blood, slowed mental and physical growth, decreased appetite, nausea and vomiting. It is important that infants and young children do not consume excess amounts of vitamin D regularly. Children exposed to the sun for 5 to 10 minutes daily will produce enough vitamin D. However, if children live in inner cities, wear clothes that cover most of their skin or live in northern climates where little sun is seen in the winter, then vitamin D deficiency may occur. Rather than give children a supplement, add fortified foods to their diet, such as vitamin D fortified milk and other dairy products. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension and infectiouse disease. In the absence of adequate sun exposure, at least 800 to 1,000 IU of Vitamin D3 may be needed to reach the circulating level required to maximize Vitamin Ds beneficial health effects.

Table 2: Dietary Reference Intakes (DRI) for fat soluble vitamins.

Life

Vitamin Vitamin Vitamin Vitamin Vitamin Vitamin E (IU) A (IU)

1

Stage A Group (mcg ) Infants 0.00.5 0.51.0 Children 1-3 4-8 Males 9-13 500* 300 400 600 400*

D (mcg )
2

D (IU) 200

E (mg a-TE3) 4* 6

1333

5*

1666 1000 1333 2000 3000 3000 3000 3000 3000 2000 2333 2333 2333 2333 2333 2500 2566 4000 4333 4333

5* 5* 5* 5* 5* 5* 5* 10* 15* 5* 5* 5* 5* 10* 15* 5* 5* 5* 5* 5* 5*

200 200 200 200 200 200 200 400 600 200 200 200 200 400 600 200 200 200 200 200 200

5* 6 7 11 15 15 15 15 15 11 15 15 15 15 15 15 15 15 19 19 19

7.5 9 10.5 16.5 22.5 22.5 22.5 22.5 22.5 16.5 22.5 22.5 22.5 22.5 22.5 22.5 22.5 22.5 28.8 28.8 28.8

14-18 900 19-30 900 31-50 900 51-70 900 71+ Females 9-13 900 600

14-18 700 19-30 700 31-50 700 51-70 700 71+ Pregnant <18 700 750

19-30 770 31-50 770 Lactating <18 1,300 19-30 1,300 31-50 1,300 Allowance (RDA).
1

*Indicates an Adequate Intake (AI). All other values are Recommended Dietary As retinol activity equivalents (RAEs). 1 RAE = 1mcg retinol or 12 mcg betaAs cholecalciferol. 10 mcg cholecalciferol = 400 IU of vitamin D. As alpha-tocopherol equivalents. 1 mg of alpha-tocopherol = 1.5 IU of vitamin

carotene.
2 3

E.

Vitamin E

Vitamin E acts as an antioxidant, protecting vitamins A and C, red blood cells and essential fatty acids from destruction. Research from a decade ago suggested that taking antioxidant supplements, vitamin E in particular, might help prevent heart disease and cancer. However, newer findings indicate that people who take antioxidant supplements are not better protected against heart disease and cancer than nonsupplement users. On the other hand, there are many studies that show a link between regularly eating antioxidant-rich fruits and vegetables and a lower risk for heart disease, cancer and several other diseases. The RDA for vitamin E is based on the most active and usable form called alpha-tocopherol (see Table 2). One milligram of alphatocopherol equals to 1.5 International Units (IU).About 60 percent of vitamin E in the diet comes from vegetable oil or products made with vegetable oils. Therefore, good food sources of vitamin E include vegetable oils and margarines. Vitamin E is also found in fruits and vegetables, grains, nuts, seeds and fortified cereals. Vitamin E deficiency is rare. Cases of vitamin E deficiency only occur in premature infants and people unable to absorb fats. The tolerable upper intake levels for vitamin E are shown in Table 3. Large doses of vitamin E pose a hazard to people who take bloodthinning medications. People taking statin drugs are also not advised to take supplemental vitamin E because it may interfere with how the medication works.

Vitamin K
Naturally produced by the bacteria in the intestines, vitamin K plays an essential role in normal blood clotting and helps promote bone health.

Good food sources of vitamin K are green vegetables such as turnip greens, spinach, cauliflower, cabbage and broccoli, and certain vegetables oils including soybean oil, cottonseed oil, canola oil and olive oil. Animal foods, in general, contain limited amounts of vitamin K. To help ensure people receive sufficient amounts of vitamin K, an Adequate Intake (AI) has been established for each age group Without sufficient amounts of vitamin K, hemorrhaging can occur. Deficiencies may appear in infants, or in people who take anticoagulants or antibiotic drugs. Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week. People on anticoagulant drugs (blood thinners) may become deficient in vitamin K, but should not change their vitamin K intake without consulting a physician because the effectiveness of the drug may be affected. People taking antibiotics may lack vitamin K temporarily because intestinal bacteria are sometimes killed as a result of long-term use of antibiotics. Also, people with chronic diarrhea may have problems absorbing sufficient amounts of vitamin K through the intestine and should consult their physician to determine if supplementation is necessary. Although a tolerable upper intake level has not been established for vitamin K, excessive amounts can cause the breakdown of red blood cells and liver damage. Large doses are not advised.
Table 3. Tolerable upper intake levels (UL)*. Life Stage Vitamin Group Infants Children 0.0-0.5 0.5-1.0 1-3 4-8 600 600 600 900 Vitamin D Vitamin E (mg a-TE) ND1 ND 200 300 25 25 50 50 A (mcg) (mcg)

Males/Females 9-13 14-18 19-70 >71

1,700 2,800 3,000 3,000

50 50 50 50

600 800 1,000 1,000

Pregnant & Lactating

<18 19-50

2,800 3,000

50 50

800 1,000

*A UL for vitamin K was not established.

1

ND = not determinable due to insufficient data.

Standards for Measuring Intake

Vitamin requirements are expressed in small units. Most are given in milligrams (mg) or micrograms (mcg). When comparing vitamin amounts on labels, note whether values are in micrograms (mcg), milligrams (mg) or International Units (IU). Make sure you compare the same units. Dietary Reference Intakes (DRI) are dietary standards for desirable and/or safe vitamin intake levels published by the Food and Nutrition Board of the National Academy of Sciences National Research Council. DRIs include three sets of values: recommended dietary allowances (referred to as RDAs) which are intended to meet the nutrient needs of

healthy individuals; tolerable upper intake levels (UL) which are designed to help people avoid harmful effects caused by consuming too much of a nutrient; and adequate intakes (AI), which are established when there is not enough scientific evidence to set an RDA and are based on diets known to be nutritionally adequate for U.S. and Canadian populations. Table 2 lists the recommended amounts of fatsoluble vitamins that individuals in the United States need daily for good health.