Vitamins

Concept

Most of us have been told to take our vitamins, but few people know why, and despite all the talk about them in modern culture, vitamins remain something of a mystery. Vitamins are organic substances, essential for maintaining life functions and preventing disease among humans and animals and even some plants. They are found in very small quantities in food; certain health specialists recommend taking vitamin supplements to augment the supplies in food, while others insist that a well-balanced diet provides all the vitamins that an ordinary person needs. Some vitamins, such as vitamin C and the B complex, are water-soluble, which means that they are excreted easily and must be ingested every day. Others, such as vitamins A, D, E, and K, are fat-soluble and therefore are retained in the body's fatty tissues. With such vitamins, there may be a danger of taking too much, but in the case of most vitamins, the greatest harm comes from not receiving enough. Vitamin deficiencies can be the cause of rickets, pellagra, and other diseases that have plagued the poor in the Western world and the third world in the past and in the present.

How It Works

An Introduction to Vitamins

Once they were called vitamines, but for reasons that we address later, the "e" was dropped, and they became known as vitamins. There is also a reason for the strange alphabet of vitamins (A, B, C, D, E, K), which, like the change in spelling, came out of the early days of scientific research into the subject during the first third of the twentieth century. Though people did not know about vitamins per se until that time, folk wisdom certainly had taken account of the fact that certain foods are essential to the health and well-being of humans and animals.

Vitamins may be defined as organic substances, found in food, that are essential in very small quantities for the health of most animals and some plants. Organic substances, discussed in The Biosphere, are compounds (substances in which atoms of more than one element are chemically bonded to one another) containing hydrogen and carbon. Primarily, vitamins work with enzymes (protein materials that speed up chemical reactions in the bodies of plants and animals) in regulating metabolic processes—that is, processes that convert food to energy. They do not in themselves provide energy, however, and thus vitamins alone do not qualify as a form of nutrition.

Organisms require vitamins only in very small amounts: the total amount of vitamin mass a person needs in one day, for instance, is only about 0.0011 lb. (0.5 g). Yet vitamins are absolutely essential to the maintenance of health and for disease prevention, and most animals are not capable of synthesizing or manufacturing vitamins on their own. Nonetheless, most animals can produce vitamin C, though there are exceptions—humans included.

Animals depend on plants for their nutrition, either directly or indirectly (i.e., either by consuming the plant or by consuming an animal that has consumed the plant). Plants, on the other hand, are autotrophs, meaning that they can meet their nutritional needs with only sunlight, water, and a few chemical compounds. Among the nutrients plants produce are vitamins, which they pass on to animals that consume them directly or indirectly. (See Food Webs for more about autotrophs and the relationship of animal consumers to them.)

Classifying Vitamins

Numerous vitamin groups are necessary for the nutritional needs of humans, and though only minute amounts of each are required to achieve their purpose, without them life could not be maintained. Some vitamins, including A, D, E, and K, are fat-soluble, meaning that they are found in fattier foods and in body fat. Thus, they can be stored in the body; for this reason, it is not necessary to include them in the diet every day. In fact, it could be dangerous to do so, since it is possible that they would build up to toxic levels in the tissues. Other vitamins, the most notable of which are vitamin C and the many vitamins in what is known as the "B complex," are water-soluble. They are found in the watery parts of food and body tissue, and because they are excreted regularly in the urine, they cannot be stored by the body. Instead, they must be consumed on a daily basis. This difference in solubility is extremely important to the way the vitamins function within an organism and in the ways and amounts in which they are consumed.

The Names of Vitamins

Vitamins originally were classified in terms of their solubility in water or in fat, and these distinctions remain important for the reasons outlined above. Today, vitamins are known primarily by letters of the alphabet, a fact that harks back to a naming system developed as more and more vitamins were discovered in the early years of the twentieth century.

As scientists detected the existence of more vitamins, or what they thought were vitamins, they assigned to them successive letters of the alphabet: A, B, C, and so on. Eventually, however, they discovered that some substances originally thought to be vitamins were not vitamins, and they removed them from the roster. For example, what used to be called vitamin F is simply an essential fatty acid, a necessary component of the diet of a mammal but not the same thing as a vitamin. In other cases, what were once believed to be individual vitamins later were subsumed into the B complex. Among these substances are riboflavin, formerly termed vitamin G, and biotin, once called vitamin H. The result is that today the only alphabetical vitamin names are A, the B complex, C, D, E, and K.

Real-Life Applications

Fat-Soluble Vitamins

We are accustomed in modern life to being told that fat is bad for us, but to quote a much-cited line from the American composer George Gershwin's opera Porgy and Bess, "It ain't necessarily so." Fat is not inherently bad for people; in fact, a certain amount in the diet is essential. The problem in America today is the type of fat that people consume. There is a big difference between the healthy, natural, unsaturated fats one might find, say, in fresh salmon, and the highly processed and saturated fats in a bag of potato chips. (The term saturated means that every gap in which a hydrogen atom could fit in a string of carbon and hydrogen atoms has been filled. This helps make fats firm, for use in such products as shortening.)

Such fat is extremely harmful, because the body is not able to process it; even so, a certain amount of natural fat in the diet can be highly beneficial. This is true in large part because fat can serve as a medium for the fat-soluble vitamins A, D, E, and K, which are deposited in the body's fat cells. But as we noted earlier, it is important not to overdose on fat-soluble vitamins, because then what is inherently healthy can become extremely unhealthy.

Vitamin a

In 1596 the Dutch explorer Willem Barents (1550-1597) and his shipwrecked crew spent a grueling winter on the island of Novaya Zemlya in the Arctic Ocean north of Russia. They had sailed from Holland in search of the Northeast Passage, which, like the more famous Northwest Passage above Canada, offered the prospect of a short, relatively direct sea route from Europe to Asia and the Americas. The problem was that the ice made sailing the northern seas virtually impossible. It would be almost three centuries before a crew managed to negotiate the Northeast Passage, by which time the European powers had long since given up all hopes of using it as a viable sailing route. (The same was true of the Northwest Passage, which was not traversed until 1906.)

Barents and his men knew none of that, nor would they have cared in that miserable winter of 1596-1597. All they cared about was survival, the chances for which seemed slim—and not just because of the almost inhuman cold or the fact that their ship had been cracked to pieces by the ice. Men were dying of scurvy, a vitamin-deficiency disease we discuss later in the context of vitamin C, as well as from the cold. Yet there were a few blessings, mainly in the form of available wood for fuel and animals for food. The men killed polar bears and ate their meat, and no doubt they were thankful just to stay alive. They could not have guessed, however, that they were actually killing themselves with an overdose of vitamin A.

Just 1 lb. (0.454 kg) of polar bear liver contains about 450 times the recommended daily dose of vitamin A, and the men in Barents's expedition were absorbing far more of the vitamin than they should have. In time, they began to experience the effects of vitamin A poisoning: painful joints, bone thickening, peeling of the skin over the entire body, and chronic liver disease. When spring came, the men managed to make it off the island, but many of them—Barents included—never lived to see Holland again, in part because the side effects of vitamin A toxicity had weakened them.

So why take vitamin A at all? Because it is necessary for proper growth of bones and teeth, for the maintenance and functioning of skin and mucous membranes, and for the ability to see in dim light. There is some evidence that it can help prevent cataracts (a clouding of the lens in the eye) and cardiovascular disease, a condition of the heart and circulatory system. Furthermore, when taken at the onset of a cold, vitamin A can ward off the illness and fight its symptoms.

One of the first signs of vitamin A deficiency is "night blindness," in which the rods of the eye (necessary for night vision) fail to function normally. Extreme cases of vitamin A deficiency can lead to total blindness. Other symptoms include dry and scaly skin, problems with the mucous linings of the digestive tract and urinary system, and abnormal growth of teeth and bones. The bodies of healthy adults who have an adequate diet can store several years' supply of this vitamin, but young children, who have not had time to build up such a large reserve, suffer from deprivation much more quickly if they do not consume enough.

Vitamin A is present in meats (mainly liver), fish oil, egg yolks, butter, and cheese. Although plants do not have vitamin A, dark green leafy vegetables and yellow fruits and vegetables (e.g., carrots, sweet potatoes, cantaloupe, corn, and peaches) contain a substance called beta-carotene, which is converted to vitamin A in the intestine and then absorbed by the body. It is nearly impossible to ingest beta-carotene in toxic amounts, unlike vitamin A from animal sources, since the body will not convert excess amounts to toxic levels of vitamin A.

Vitamin D

Vitamin D is actually two different substances, D₂ and D₃. (There was no D_1, since the substance designated thus at one time turned out to be a mixture of several compounds, including calciferol, or D₂) Both forms of vitamin D are activated, or made effective, by sunlight, and for this reason vitamin D often is called the sunshine vitamin. It is hard to suffer a vitamin D deficiency if one gets enough sunshine in combination with consuming such foods as eggs (specifically, the yolk), such fatty fish as salmon, and enriched milk. (Milk does not naturally contain vitamin D, but the vitamin is sometimes included as an additive.)

Vitamin D lets the body utilize calcium and phosphorus in bone and tooth formation, and a deficiency causes a bone disease called rickets. Under the influence of this physically debilitating and disfiguring disease, legs become bowed by the weight of the body, and the wrists and ankles thicken. The teeth are badly affected and, for a young child, take much longer to mature. Infants and children are most likely to suffer the effects of rickets, but since all milk and infant formulas have vitamin D added to them, the condition is seen rarely in the industrialized world today. In the brutal early days of the Industrial Revolution, however (i.e., in England ca. 1760-1830), crowded slum conditions in areas where there was little or no sunlight made possible many cases of rickets.

Whereas rickets primarily affects children, adults may suffer from a disease called osteomalacia, caused by a deficiency of vitamin D, calcium, and phosphorous. Sometimes seen in the Middle East and other parts of Asia, osteomalacia brings with it rheumatic pain and causes the bones to become soft and deformed. As with rickets, the treatment for osteomalacia is a combination of calcium, phosphorous, and vitamin D. On the other hand, as with all fat-soluble vitamins, a person may take in excessive amounts of vitamin D, which has its own ill effects: nausea, diarrhea, weight loss, and pain in the bones and joints. Damage to the kidneys and blood vessels also can occur as calcium deposits build up in these tissues.

Vitamin E

Composed of at least seven similar chemicals called the tocopherols, vitamin E is found in green leafy vegetables, wheat germ and other plant oils, egg yolks, and meat. The main function of this vitamin is to act as an antioxidant, to counteract the harmful effects oxygen can have on tissues. It may seem strange to speak of oxygen causing harm, since it is essential to life, but oxidation is an extremely powerful chemical reaction that, under various conditions, can manifest as rotting or putrefaction, rusting, or even combustion and explosion. When an apple turns brown a few minutes after you have cut it open, it is the result of oxidation.

Oxidation also may be linked to the effects of aging in humans as well as to other conditions, such as cancer, hardening of the arteries, and rheumatoid arthritis. It appears that oxygen molecules, which draw electrons to them, extract these electrons from the membranes in human cells. Over time, this can cause a gradual breakdown in the body's immune system. Antioxidants, such as vitamin E or beta carotene, therefore may be important in preserving human health and well-being.

Vitamin E is particularly important for counteracting oxidation in fats. When they are oxidized, fats form a highly reactive substance called peroxide, which is often very damaging to cells. Vitamin E is more reactive (i.e., more likely to form or break chemical bonds) than the fatty acid molecule, and, therefore, the vitamin reacts instead of the fat. Because cell membranes are composed partly of fat molecules, vitamin E is vitally important in maintaining the nervous, circulatory, and reproductive systems and in protecting the kidneys, lungs, and liver.

Because vitamin E is so common in foods, it is very difficult to suffer from a deficiency of this vitamin unless a person avoids consuming fats altogether—another example of why a no-fat diet is not a healthy one. The effects of vitamin E deficiency, all of which are apparently linked to the loss of its antioxidant protection, include cramping in the legs, fibrocystic breast disease (a condition that involves the formation of lumps and cysts in the breasts), and even muscular dystrophy. The seriousness of the latter two diseases only serves to highlight the importance of vitamin E to the body.

Vitamin K

Like vitamin D, vitamin K is composed of two groups of compounds, vitamins K₁ and K₂. There is also a substance called K₃, but this vitamin is actually menadione, a synthetic compound from which the other forms of K are derived. You can find vitamin K in many plants, especially green leafy ones such as spinach, and in liver. Vitamin K is also made by the bacteria that live in the intestine—the "good" bacteria that help make possible the processing of food through the body.

Vitamin K appears to be critical to blood clotting, thanks to its role in assisting the formation of a chemical called prothrombin in the liver. Deficiencies of this vitamin rarely occur as the result of an incomplete diet; instead, it is usually a consequence of liver damage and the blood's inability to process the vitamin. The deficiency manifests in unusual bleeding or large bruises under the skin or in the muscles. Adults in the West seldom experience vitamin K deficiencies, but newborn infants have been known to suffer from brain hemorrhage owing to a lack of this vitamin.

Water-Soluble Vitamins

B Vitamins

The two water-soluble vitamins, as we shall see, have played a major part in medical history. Actually, there are more than two water-soluble vitamins, because vitamin B is really a complex of about a dozen vitamins—hence, the name B complex. Among them are vitamin B₁ (thiamine), vitamin B₂ (riboflavin), vitamin B₆ (pyridoxine), and vitamin B₁₂ (cobalamin). A few others—for example, niacin (vitamin B₇) and pantothenic acid (vitamin B₃), are known better by names other than their "B names," while biotin and folate, or folic acid, are not known by "B names" at all.

Vitamin B₁, present in whole grains, nuts, legumes (e.g., peas), pork, and liver, helps the body release energy from carbohydrates. More than 4,000 years ago, the Chinese described a disease we know today as beriberi, which affects the nervous and gastrointestinal systems and causes nausea, fatigue, and mental confusion. The cause of beriberi is a deficiency of thiamine, or B₁, found in the husks or bran of rice and grains. White rice, which most people find more pleasing to the palate than brown rice, is the result of a milling and polishing process in which the husks—and along with them, this important nutrient—are removed. Manufacturers today produce "enriched" rice, flour, and other grain products by adding thiamine back in, but until scientists discovered the importance of thiamin in grain husks, many people, especially in the Far East, suffered the effects of beriberi. (Early research on beriberi will be discussed later.)

Vitamin B₂ helps the body release energy from fats, proteins, and carbohydrates. It can be obtained from whole grains, organ meats (e.g., liver), and green leafy vegetables. Lack of this vitamin causes severe skin problems. Vitamin B₆ is important in the building of body tissue as well as in protein metabolism and the synthesis of hemoglobin (an iron-containing pigment in red blood cells that is responsible for transporting oxygen to the tissues and removing carbon dioxide). A deficiency can cause depression, nausea, and vomiting. Vitamin B₁₂ is necessary for the proper functioning of the nervous system and in the formation of red blood cells. It can be obtained from meat, fish, and dairy products. Anemia (a lack of red blood cells, which produces a lethargic condition), nervousness, fatigue, and even brain degeneration, can result from vitamin B₁₂ deficiency.

Niacin is also highly important to human health, as we explain later in the context of the disease pellagra. Pantothenic acid helps release energy from fats and carbohydrates and is found in large quantities in egg yolks, liver, eggs, nuts, and whole grains. Deficiency of this vitamin causes anemia. Biotin, widely available from grains, legumes, and liver, plays a part in the release of energy from carbohydrates and in the formation of fatty acids. A lack of biotin causes dermatitis, or skin inflammation.

Vitamin C

The American chemist and peace activist Linus Pauling (1901-1994), winner of the Nobel Prize in chemistry (1954) and peace (1962), helped popularize vitamin C, also known as ascorbic acid. It was Pauling who originated the idea, now widespread in society, that massive doses of vitamin C can ward off the common cold. Pauling went further, by maintaining that vitamin C offers protection against some forms of cancer. While scientific studies have been unable to prove this theory, they do suggest that the vitamin can at least reduce the severity of the symptoms associated with colds.

Most animals can synthesize this vitamin in the liver, where glucose (a type of sugar that occurs widely in nature) is converted to ascorbic acid. This is not the case with at least four types of animal: monkeys, guinea pigs, Indian fruit bats, and humans, all of which must obtain vitamin C from their diets. Citrus fruits, berries, and some vegetables (e.g., tomatoes and peppers) are good sources of vitamin C. It is a fragile vitamin, one that is oxidized or destroyed easily. Food storage or food processing can render it ineffective; so, too, can soaking vitamin C-containing fruits and vegetables in water for long periods.

Vitamin Deficiencies and History

Most of the early history in the study of vitamins centered around what are now known as the water-soluble vitamins. Although vitamins as such were not discovered until early in the twentieth century, it was common knowledge long before that time that substances in certain foods were necessary for good health. An important turning point came in the mid-eighteenth century, with the work of the Scottish physician James Lind (1716-1794) on a vitamin deficiency condition that jeopardized England's vast merchant and military navies.

At a time when England had emerged as the world's leading sea power, even Her Majesty's sailing crews were at the mercy of a condition known as scurvy. Common among crews who had been at sea too long, scurvy could result in swollen joints, bleeding gums, loose teeth, and an inability to recover from wounds. Scientists today recognize scurvy as resulting from a deficiency of vitamin C, available in such citrus fruits as oranges. At the time, however, the concept of vitamins was unknown, and sailors at sea continued to live on a diet that consisted primarily of salted meats and hard biscuits—items that could be stored easily without spoilage in an era before refrigeration.

In 1746, Lind, a ship's doctor, observed that 80 of 350 seamen aboard his ship came down with scurvy during a 10-week cruise. Conducting a controlled experiment, he took 12 of the sailors in whom scurvy had developed and divided them into six groups. He gave each pair different substances, such as nutmeg, cider, seawater, and vinegar; the final pair was given lemons or oranges. The two men given the oranges and lemons both completely recovered in about a week. Not only was this a milestone in the history of vitamin research, but it also was the first example of a clinical trial, or the testing of a medication by careful and well-documented experimentation in which other variables or factors are kept unchanged.

It would be another half-century before the British navy adopted Lind's techniques. Another Scottish physician, Sir Gilbert Blane (1749-1834), had long fought for the adoption of Lind's methods, and finally, in 1796, he persuaded the navy to give each sailor a daily ration of lemons. At that time, the term lime was common for both lemons and limes, and, as a result, British sailors became known as limeys. Eventually, the treatment spread to the population as a whole, but outbreaks of scurvy continued until after World War I, when doctors isolated vitamin C as the controlling factor in scurvy prevention.

Beriberi in the Dutch East Indies

In 1897 the Dutch government sent the physician Christiaan Eijkman (1858-1930) as part of a government commission to the Dutch East Indies (now Indonesia), which had been long afflicted by a condition known as beriberi. There are various forms of this disease, including infant beriberi, which can kill a breast-feeding baby after the fifth month, as well as various juvenile and adult forms. In the childhood and adult versions of the disease, there is a preliminary condition of fatigue, loss of appetite, and a numb, tingling feeling in the legs. This condition can lead to either wet beriberi, characterized by the accumulation of fluid throughout the body and a rapid heart rate that can bring about sudden death, or dry beriberi, which is marked by a loss of sensation and weakness in the legs. The patient first needs to walk with the aid of a stick and then becomes bedridden and easy prey to infectious diseases.

Experimenting with birds, Eijkman noticed that some of the fowl experienced paralysis and polyneuritis (a disorder affecting several nerves at once), as in the dry form of beriberi. The director of the hospital had told Eijkman that he could not feed the birds with table scraps from the dining hall, where the diet was heavy in polished rice. The doctor thus was forced to feed his birds whole rice, and something amazing happened: the birds began to regain their ability to move and experienced no recurrence of paralysis.

Eijkman's colleagues rejected his claim that the birds had contracted some form of beriberi, though, in fact, he was correct. He was incorrect, however, in his supposition that the polished rice contained a toxin that was missing from the whole, unpolished rice. After Eijkman and the rest of the medical commission left the East Indies, another Dutch physician, Gerrit Grijns (1865-1944), stayed on to study the disease. He discovered that when the chickens were taken off the rice diet completely and fed meat instead, they did not show signs of the characteristic paralysis; if the meat was overcooked, however, the condition reappeared. In 1901, Grijns showed that beriberi could be cured by putting the rice polishings back into the rice. As it turned out, the husks and the meat contained vitamin B₁, also present in wheat germ, whole grain and enriched bread, legumes, peanuts, and nuts.

Pellagra in the Americas

A vitamin-deficiency disease often associated with poverty, pellagra produces symptoms known as the "three Ds": diarrhea, dermatitis, and dementia, or mental deterioration. It was first identified in 1762 by the Spanish physician Gaspar Casal (ca. 1680-1759), who wrote about the "mal de la rosa"—so called because of the reddened dermatitis that appeared around the back of the victim's neck—that afflicted sufferers in one particular region of Spain.

Casal was far ahead of his time in maintaining that inadequate nutrition caused pellagra, but for many centuries the belief persisted that the disease resulted from infection. The breakthrough came with the work of the American physician Joseph Goldberger (1874-1929), a member of the U.S. Public Health Service who studied the high numbers of pellagra cases among poor blacks and whites in the southern United States. Goldberger established that pellagra stems from insufficient niacin, which is required to release energy from glucose.

Niacin is present in whole grains, meat, fish, and dairy products. One of the foods from which niacin is not easily available is corn, and it so happened that corn products constituted a major part of the diet in areas suffering from high rates of pellagra. The poor of Spain and Latin America subsisted on a diet heavy in corn products, such as tortillas and polenta, while their counterparts in the southern United States survived on cornbread, grits, hominy, and other variants of corn. Although such foods made it possible to fill the stomach cheaply, this diet was killing people in large numbers because it was not delivering the essential B vitamin niacin.

Modern Knowledge of Vitamins

As it turned out, corn, in fact, does contain niacin, but to release the niacin from the large, fibrous molecules in corn, it is necessary to treat the corn with an alkaline solution, such as limewater. This is just one example of the vast knowledge that has accumulated since the time when the Polish-American biochemist Casimir Funk (1884-1967) coined the term vitamine in 1912. The first half of the word came from the Latin vita, or "life," and the second half reflected Funk's belief that all these substances belonged to a group of chemicals known as amines. Scientists later dropped the "e" when they discovered that not all vitamins contain an amine group.

In the director Stephen Spielberg's acclaimed 1987 film Empire of the Sun, one of the characters asks another, "Do you believe in vitamins?" The question reflects the relative newness of vitamins as an idea at the time when the movie was set, during World War II. After the war, interest in commercially produced vitamin supplements exploded, particularly among America's middle classes. Pauling's promotion of vitamin C, coming in the 1950s and 1960s, found a willing audience.

Although vitamin supplements remain a big business today, opinions vary as to the importance of enhancing one's diet with them. Many nutritionists insist that eating a well-balanced diet, consisting of the major food substances, is an effective and economical way to obtain nutrients for health. On the other hand, advocates of health foods and alternative medicine (medical practices that are not recognized officially by groups of university-trained and state-licensed medical doctors) insist that the recommended daily allowances established by the U.S. Food and Drug Administration do not provide sufficient vitamins for an average person.

The American Dietetic Association (ADA) recommends that nutrient needs come from a variety of foods taken from different dietary sources rather than from self-prescribed vitamin supplements. The organization makes allowances, however, for supplement usage by people who need extra doses of key vitamins and minerals. Examples include the use of iron supplements by women experiencing heavy menstrual bleeding as well as supplements of iron, folic acid, and calcium by pregnant women.

Where to Learn More

Apple, Rima D. Vitamania: Vitamins in American Culture. New Brunswick, NJ: Rutgers University Press, 1996.

Brody, Jane E., and Denise Grady. The New York Times Guide to Alternative Health: A Consumer Reference. New York: Times Books/Henry Holt, 2001.

Duyff, Roberta Larson. The American Dietetic Association's Complete Food and Nutrition Guide. Minneapolis, MN: Chronimed Publishing, 1998.

Kiple, Kenneth F., and Kriemhild Coneé Ornelas. T he Cambridge World History of Food. New York: Cambridge University Press, 2000.

Nardo, Don. Vitamins and Minerals. New York: Chelsea House Publishers, 1994.

Reference Guide for Vitamins (Web site). <http://www.realtime.net/anr/vitamins.html>.

Snyder, Carl H. The Extraordinary Chemistry of Ordinary Things. New York: John Wiley and Sons, 1998.

Vitamins and Coenzymes. Indiana State University (Web site). <http://www.indstate.edu/thcme/mwking/vitamins.html>.

The Vitamin Collection. Molecular Expressions: Exploring the World of Optics and Microscopy, Florida State University (Web site). <http://micro.magnet.fsu.edu/vitamins/>.

Vitamin-Deficiency Diseases. Medic Planet (Web site). <http://www.medic-planet.com/MP_article/internal_reference/Vitamin-deficiency_diseases>.

Vitamins and Minerals Topic Page. Food and Nutrition Information Center National Agricultural Library, U.S. Department of Agriculture (Web site). <http://www.nal.usda.gov/fnic/etext/000068.html>.

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In present day Western society, the small print on packets of cereals and of citrus drinks is a ready source of information on the vitamins they provide, the quantity contained therein, and the fraction which that content provides of the recommended daily allowance (RDA). In many homes there is also a stock of packaged tablets or bottled syrups, swallowed mostly on the principle that if a little of these stuffs is necessary for health, then more must be better. In some instances this may possibly be so, but by no means to the extent that vitamin supplements are sold and bought. A vitamin is an organic substance that is necessary only in very small amounts (RDAs all less than 200 mg) for normal growth and health and which must be obtained from the diet because it cannot be synthesized by the body. But, as with many original definitions of this sort, exceptions have emerged with the progress of research.

There were three diseases that during the eighteenth and nineteenth centuries began to be linked in some way to the diet. The cure of scurvy in a ship's company by provision of citrus fruit dates back to 1754, to a historic, but initially neglected experimental observation: men with the disease were divided into pairs, and each pair given different additions to their rations; those, and only those, who received oranges and lemons recovered. The scurvy was successfully avoided with the issue of fruit and vegetables on Captain Cook's voyages in the 1770s, and official introduction of lemon juice into the Royal Navy diet followed before the end of the century. Understanding of the reason for this was to take more than a century. The occurrence of pellagra started to be associated from the mid 1700s with a poor diet of maize-meal without meat or milk in different parts of the world, and this link was still occurring in the US well into the twentieth century. The condition of beri-beri was prevalent in nineteenth-century Asian workers who lived mainly on rice that had been ‘improved’ by new machinery which removed the husks; also chickens who ate rice without its husks developed a peripheral nerve abnormality like that in the human disease. It was at first assumed that some toxin had been introduced by the cooking or polishing. But husks — or an extract made from them — were later shown to cure the condition in both people and chickens. Thus the notion gradually arose that diseases might be caused by an absence of something, rather than the presence of a poison or infection.

Substance(s)	Source	Deficiency effects	SEE ALSO
Fat-soluble vitamins
A retinol	Carotenes from	Night blindness.	vision
	plants. Animal/fish	Thickened cornea.
	fats and liver.
D calciferols	Animal fats.	Bone softening: rickets	bone, calcium,
	Fish liver oils.	in childhood,	skin, steroids,
	Skin and sun.	osteomalacia in adult.	sun, teeth
E tocopherols	Most foods.	Wide range proposed;
	Vegetable oils.	no clear evidence of
		specific effect.
K quinones	Plants. Also made	Slow blood clotting,	blood
	by gut flora.	tendency to bleed.
Water-soluble vitamins
B group
B1 thiamin	Grains and pulses.	Beri-beri = ‘extreme	disease
	Pork and offal.	weakness’; peripheral
		neuritis, oedema.
B2 riboflavin	Most foods.	Sore tongue and lips;
		visual impairment.
B6 pyridoxin	Most foods.	Skin lesions, convulsions.
B12 cobalamin	Animal products	Pernicious anaemia;	blood
	only. Requires	neurological disorder.	anaemia
	intrinsic factor for		stomach
	absorption.
Biotin	Liver, yeast, etc.	No specific syndrome.
Folic acid	Liver, greens,	Anaemia.	anaemia
	yeast.	Defective growth.	antenatal development
		Congenital CNS defects.
Niacin	Meat, liver, grains,	Pellagra = ‘rough skin’;
	pulses.	nerve, bowel, and mental
		abnormalities.
Pantothenic acid	Most foods	General illness;
		no specific syndrome.
C ascorbic acid	Fruit and	Scurvy: bruising and	collagen
	vegetables.	bleeding, impaired	wound healing
		healing.

The concept of necessary substances in the diet — in addition to the major energy-providers and minerals — whose absence led to disease, entered several minds, and led to many clinical and experimental studies in the early twentieth century. An early pioneer was the British biochemist Frederick Gowland Hopkins, later a Nobel prize winner. He, among others, found that a combination of all known nutrients was not sufficient to allow young animals to thrive. The word ‘vitamine’ was invented in 1911 by Funk, a biochemist also working in London, who believed, rightly, that he had isolated a vital dietary constituent from rice husks — and, wrongly, that it was by chemical nature an amine. Such extracts became known as vitamin B, and the original name without the ‘e’ came to be applied to the family of substances that emerged over the following decades as necessary for health, but required only in very small quantities. In the 1920s ‘vitamin B’ proved to be more than one substance; B₁ was identified as the anti-beri-beri factor, and others with comparable properties, equally essential, were later added to the group. Knowledge emerged, thanks to a young American physician, William Castle, of a vitamin (B₁₂) necessary for blood cell production, which needed a gastric secretion to allow its absorption — explaining the empirical observation that very large amounts of raw liver were needed to cure pernicious anaemia. Vitamin C — which prevented scurvy — was finally identified in lemon juice in 1932, was found to be readily destroyed by heat, was given the name of ascorbic acid, and became the first vitamin to be artificially synthesized. Meanwhile, some factor in fish oils and egg yolks became recognized as being necessary for growth and health, and was initially called vitamin A. Extracts proved effective against rickets, and this component was separately labelled vitamin D. Thus by the time of World War II the main vitamins had been identified, and their importance recognized; national programmes such as vitamin additions to staple foods and provision of enriched juices for infants and children supported wartime public health; vitamins had also become a major commercial proposition.

Each vitamin is a requisite for some essential metabolic function, and most cannot be synthesized in the body. The exceptions are vitamin D, which can be made in the skin in the presence of sunlight; vitamin A, which need not as such be in the diet, since it can be made from carotenes present in vegetables; and vitamin K, which can be made by bacteria in the gut.

The naming of the vitamins does not appear very logical, for various historical reasons. They are described in two categories — water-soluble and fat-soluble. The significance of this distinction relates to their sources, their absorption, storage, and excretion, and to the manner of their action.

The water-soluble vitamins comprise vitamin C and the ‘B group’ (see table). Vitamin C is necessary for collagen synthesis, the basis of connective tissue growth and maintenance. Those of the B group act by forming co-enzymes, essential for a range of vital, enzyme-dependent cellular processes. These include DNA synthesis, different components of the utilization of nutrients, and the respiratory and energy-releasing processes. Folic acid and B₁₂ specifically are essential for the formation of normal red blood cells. B₁₂ is unique in requiring the intrinsic factor secreted by glands in the stomach to enable it to be absorbed from the intestine, and also in being obtainable only from animal sources.

The fat-soluble vitamins are A, D, E, and K. Fat-solubility means not only that their sources are in fats in the diet, but also that they can be stored in adipose tissue and can have actions on cells by dissolving in the lipid cell membranes. Deficiency may occur not only in malnutrition, but also in any condition that interferes with fat absorption, including liver disease because of the role of bile. Unlike water-soluble vitamins, their storage means that signs of deprivation are delayed — and also that over-dosage can become toxic.

For many of the vitamins there are distinctive abnormalities related to their deficiency, which can be reversed by an adequate intake. Deficiencies occur in undernourished or malnourished communities or individuals; in alcoholism, poverty, and neglect in the aged in any society; and in strict vegetarians. Apart from the treatment of deficiency conditions, the question remains open, and the subject of research, as to whether there is any advantage to be gained from supplements in excess of the minimal adequate amounts. Since the relatively recent understanding of the damaging effect of free radicals, the counteracting antioxidant action of vitamins A, C, and E has been recognized; the fat-soluble and water-soluble vitamins may combine to protect against free radical damage particularly to cell membranes, and thus to diminish processes such as arteriosclerosis and others associated with ageing. Some of the B vitamins (folic acid and B12) may have a role in protecting from heart disease. There has been contradictory evidence concerning protection from the common cold or alleviation of its symptoms by large doses of vitamin C. On the other hand, there can be serious ill-effects from overdose of the fat-soluble vitamins and also of vitamin C.

— Sheila Jennett

Bibliography

• Carpenter, K. J. (1986). The history of scurvy and vitamin C. Cambridge University Press.
• Roe, D. A. (1973). A plague of corn: the social history of pellagra. Cornell University Press, Ithaca NY

See also biochemistry; enzymes.

Water-Soluble and Fat-Soluble Vitamins

Vitamins are among the nutrients found to be essential for life. Unlike other classes of nutrients, vitamins serve no structural function nor do they provide significant energy. Their various uses tend to be highly specific. Common food forms of most vitamins require some metabolic activation into a functional (active) form. Although vitamins share these general characteristics, they show few close chemical or functional similarities. For example, some vitamins function as coenzymes, others function as antioxidants, and two vitamins, A and D, function as hormones.

Fourteen substances are now generally recognized as vitamins. Vitamins are frequently described according to their solubility; they may be either fat-soluble or watersoluble. This method of classification dates back to the history of their discovery as labeled by McCollum as "fatsoluble A" and "water-soluble B."

Other sections in this encyclopedia describe the chemistry, biochemistry, and physiology of the vitamins. This article provides additional information that is focused on dietary requirements, upper levels (to avoid toxicity from supplementation), and food sources. (See sidebar for definition of terms, and see Appendix for a complete chart of vitamins.)

Water-Soluble Vitamins

Thiamin. Thiamin was the first vitamin to be identified. In modern times, thiamin deficiency is seen most commonly in association with chronic alcoholism. Only a small percentage of large doses are absorbed, and elevated serum levels result in its active urinary excretion. After an oral dose of the vitamin, peak excretion occurs in about two hours (Davis et al., 1984). Total body thiamin content in adults is approximately 30 milligrams with a half-life of 9 to 18 days (Ariaey-Nejad et al., 1970).

The recommended dietary allowance (RDA) for thiamin in adult women is 1.1 mg/day and in adult men it is 1.2 mg/day. The RDA for pregnancy and lactation is 1.4 mg/day (FNB, 1998). It should be noted that increased needs exist in persons being treated with hemodialysis or peritoneal dialysis, individuals with malabsorption syndrome, women carrying more than one fetus, and women nursing more than one infant.

There are no reports of adverse effects from the consumption of excess thiamin consumed in food or supplements. No upper level (UL) can be set due to the lack of reported findings associated with adverse effects. Supplements that contain up to 50 mg/day are available over-the-counter with no reported problems.

Food sources from which most of thiamin in the United States is derived include enriched, fortified, or whole-grain products, such as bread, bread products, mixed foods that contain grain, and ready-to-eat cereals. Foods that are especially rich in thiamin include yeast, lean pork, and legumes. Thiamin is absent from fats, oils, and refined sugars. Milk, milk products, seafood, fruits, and vegetables are not good sources.

Riboflavin. The second vitamin discovered was named vitamin B₂ or riboflavin. Most dietary riboflavin is consumed as a complex of food protein. Signs of riboflavin deficiency are sore throat, redness, and edema of the throat and oral mucous membranes, cheilosis (cracking of the skin around the mouth), and glossitis (red tongue). Vitamin B₂ deficiency most often occurs in combination with other nutrient deficiencies. The B vitamins are quite interrelated; for example, niacin requires riboflavin for its formation from the amino acid tryptophan, and vitamin B₆ requires riboflavin for conversion to the active coenzyme form (McCormick, 1989).

The RDA for riboflavin has been set at 1.3 mg/day for men and 1.1 mg/day for women through age seventy years and older. For pregnancy, the RDA for riboflavin is set at 1.4 mg/day and it is 1.6 mg/day for lactation (FNB, 1998).

When riboflavin is absorbed in excess, very little is stored in the body tissues. Excess is excreted via the urine, and the amount varies with intake, metabolic events, and age (McCormick and Greene, 1994). No adverse effects associated with riboflavin consumption from food or supplements have been reported. No adverse effects were reported from a single dose of up to 60 milligrams and 11.6 milligrams of riboflavin given as a single intravenous (IV) dose (Zempleni et al., 1996).

The greatest contribution of riboflavin from the diet comes from milk and milk drinks, followed by bread products and fortified cereals. Especially good food sources of riboflavin are eggs, lean meats, milk, broccoli, and enriched breads and cereals. Recall that riboflavin loss occurs when it is exposed to light, so store milk in opaque containers or away from the light.

Niacin. The term "niacin" refers to nicotinamide and nicotinic acid. The coenzymes, the active form of niacin in the body, are synthesized in all tissues of the body. The amount of niacin in the body is the result of absorbed nicotinic acid and nicotinamide, as well as conversion of the amino acid tryptophan (60 milligrams of tryptophan = 1 milligram of niacin; Horwitt et al., 1981). Excess niacin is excreted through the urine.

Pellagra is the classical manifestation of niacin deficiency. Pellagra has been seen in areas where corn (low in niacin and tryptophan) is the dietary staple. Enrichment and fortification of grain has virtually eliminated pellagra from the United States and Europe.

The RDA for adult men is 16 mg/day of niacin equivalents, and the RDA for women aged nineteen to over seventy is 14 mg/day. In pregnant women the RDA is 18 mg/day of niacin equivalents and in lactating women it is 17 mg/day (FNB, 1998).

Niacin, given as nicotinic acid in doses from 4 to 6 g/day, is one of the oldest drugs used in the treatment of hyperlipidemia, which consists of elevated blood levels of triglycerides and cholesterol. Niacin lowers low-density lipoprotein (LDL) cholesterol and triglyceride concentration. This therapeutic effect is not seen with nicotinamide. Nicotinic acid in therapeutic doses can cause flushing and headache in some people. These side effects are not harmful.

An upper limit for niacin was set at 35 mg/day for adults, if the niacin is obtained from supplements, not foods. Individuals who take over-the-counter niacin to "self-medicate" may exceed the UL on a chronic basis. The UL is not intended to apply to those receiving niacin under medical supervision.

Dietary intake of niacin comes mainly from mixed dishes containing meat, poultry, or fish, followed by enriched and whole-grain breads, and fortified cereals. Significant amounts of niacin are found in red meat, liver, legumes, milk, eggs, alfalfa, cereal grains, yeast, and fish.

Vitamin B_6. Vitamin B₆ is a coenzyme for more than 100 enzymes involved in the metabolism of amino acids, glycogen, and nerve tissues (FNB, 1998). Microcytic anemia, reflecting decreased hemoglobin synthesis, can be seen in deficiency states. The interaction of vitamin B₆ and folate (another B vitamin discussed below) has been shown to reduce the plasma concentrations of homocysteine and decrease the incidence of cardiovascular disease (CVD) risk (Rimm et al., 1998). Subjects with the highest intake of folate and vitamin B₆ had a twofold reduction in CVD as compared to the group with the lowest intake.

In the 1970s there was quite a bit of discussion about the status of vitamin B₆ in women using oral contraceptives. This was probably an artifact of hormonal stimulation of tryptophan catabolism rather than vitamin B₆ deficiency. At the time these studies were conducted, estrogen concentrations were three to five times higher in contraceptive agents than they are today.

The RDA for vitamin B₆ is 1.3 mg/day for adult men and women up to age fifty years. The RDA for people over fifty years of age is 1.7 mg/day for men and 1.5 mg/day for women. For pregnant women the RDA is set at 1.9 mg/day and for lactating women, 2.0 mg/day (FNB, 1998).

No adverse effects have been associated with intakes of vitamin B ₆ from food. However, large doses of pyridoxine used to treat carpal tunnel syndrome and premenstrual syndrome have been associated with sensory neuropathy (Schaumburg and Berger, 1988). These findings were noted with dosages from 2 to 6 g/day. It appears that the risk of developing sensory neuropathy decreases quite rapidly at dosages below 1 g/day. Thus, the UL for adults is set at 100 mg/day of vitamin B₆ as pyridoxine.

Food sources of vitamin B₆ include fortified, ready-to-eat cereals; mixed foods with meat, fish, or poultry as the main ingredient: white potatoes, starchy vegetables, and noncitrus fruits. Vitamin B₆ is widely distributed in foods; good sources are meats, whole-grain products, vegetables, and nuts.

Folate. Folate is a B vitamin that exists in many chemical forms (Wagner, 1996). Folic acid, the most stable form of folate, occurs rarely in food, but is the form used in supplements and fortified food products. Folate coenzymes are involved in numerous reactions that involve DNA synthesis, purine synthesis, and amino acid metabolism. The most well known is the conversion of homocysteine to methionine. It is this reaction that reduces the concentration of homocysteine in the plasma, and may lower the risk of cardiovascular disease (Rasmussen et al., 1996).

The metabolic interrelationship between folate and vitamin B₁₂ may explain why a single deficiency of either vitamin leads to the same hematological changes. In either folate or vitamin B₁₂ deficiency, megaloblastic changes occur in the bone marrow and other replicating cells.

Pregnant women are at risk for developing folate deficiency because of the heightened demands imposed by increased synthesis of DNA. Low folate status is associated with poor pregnancy outcome, low birth weight, and fetal growth retardation (Scholl and Johnson, 2000). Because of the possible incidence of neural tube defects (NTDs) during the preconception period (that is, just before and during the first 28 days of conception), the Food and Nutrition Board recommends that women who are capable of becoming pregnant should consume 400

Recommendations for intake of folate are dependent on variation in bioavailability. Supplemental folate is nearly 100 percent absorbed, while absorption of folate found in foods is only about 50 percent. Fortified foods approach the level of bioavailability of folate found in supplements. This has led to the term Dietary Folate Equivalents or DFEs. Thus, dietary recommendations for folate intake are based on "folate equivalents." One

No adverse effects have been associated with the consumption of normal folate-fortified foods. However, the risk of neurological effects that result from vitamin B₁₂ deficiency that are masked with high doses of folate caused the FNB to set a UL. The UL for adults, nineteen years and older, is set at 1,000

Folates are found in nearly all natural foods. Protracted cooking or processing may destroy folate. Foods with the highest folate content include yeast, liver, other organ meats, fresh green vegetables, and some fruits (oranges, for example). Most of the dietary intake of folate in the United States comes from fortified ready-to-eat breakfast cereals followed by a variety of beans and peas, fresh and dried. As of 1 January 1998, all enriched cereal grains, pasta, flour, and rice are required to be fortified with folate at 1.4 mg/kg of grain.

Vitamin B_12. Cyanocobalamin is the compound we call vitamin B₁₂. This is the only vitamin B₁₂ preparation used in supplements. An adequate supply of vitamin B₁₂ is essential for normal blood formation and neurological function. The absorption of vitamin B₁₂ is dependent on several physiological steps. In the stomach, food-bound vitamin B₁₂ is dissociated from proteins in the presence of stomach acid. Vitamin B₁₂ then binds with protein and in the intestine the vitamin B₁₂ binds with intrinsic factor for absorption. If there is a lack of sufficient acid in the stomach or intrinsic factor in the intestine, malabsorption occurs and the resulting condition caused is pernicious anemia.

The anemia of vitamin B₁₂ deficiency (completely reversed by addition of B₁₂) is indistinguishable from that seen with folate deficiency. Because up to 30 percent of people older than fifty are estimated to have atrophic gastritis with low stomach acid secretion, older adults may have decreased absorption of B₁₂ from foods. Thus, it is recommended that most of the vitamin B₁₂ consumed by adults greater than fifty-one years of age be obtained from fortified foods or supplements.

The RDA of vitamin B₁₂ for men and women is 2.4 12 intake from food or supplements. After reviewing the literature, the FNB found insufficient evidence for determining a UL.

Vitamin B₁₂ is present in all forms of animal tissues. It is not present in plants and thus does not occur in fruits or vegetables. Because a generous intake of animal foods is customary in the United States, B₁₂ intake from foods is usually adequate. People who avoid eating animal products may obtain most of their requirement through fortified foods.

Vitamin C. Ascorbic acid (the chemical name for vitamin C) is a potent antioxidant in animals and plants. Vitamin C is important in the synthesis of collagen. Some evidence indicates that vitamin C reduces virus activity by inhibiting viral replication (Johnston, 2001). Many anecdotal reports support a role for vitamin C supplementation to reduce the severity of cold symptoms.

Some epidemiological evidence indicates that supplemental vitamin C protects against risk for myocardial infarction. However, large-scale epidemiological studies do not suggest a benefit of vitamin C supplementation on cardiovascular health risks (Kushi et al., 1996).

Non-heme iron absorption from food is enhanced two-to threefold in the presence of 25 to 75 mg of vitamin C, presumably because of the ascorbate-induced reduction of ferric iron to ferrous iron, which is less likely to form insoluble complexes in the intestine. However, vitamin C has no effect on increasing iron absorption from heme iron (Johnston, 2001). Unlike most animal species, humans lack the ability to synthesize ascorbic acid; thus, the diet is the sole source for this vitamin.

The current requirement of vitamin C is 90 mg/day for adult men and 75 mg/day for adult women. During pregnancy the RDA is 85 mg/day, and 120 mg/day during lactation. The UL for vitamin C was set at 2 g/day (FNB, 2000). This level was set as a guideline for people using dietary supplements and was based on reports of gastrointestinal symptoms reported when too much vitamin C was taken.

Almost 90 percent of vitamin C in the diet comes from fruits and vegetables, with citrus fruits, tomatoes, tomato juice, and potatoes being the major contributors. It is also added to some processed foods as an antioxidant.

Pantothenic acid. Pantothenic acid was named after the Greek, meaning "from everywhere," because it is so widespread in foods. Pantothenic acid is essential in the diet because of the inability of animals and humans to synthesize the pantoic acid moiety of the vitamin. Pantothenic acid plays a primary role in many metabolic processes, such as oxidative metabolism, cell membrane formation, cholesterol and bile salt production, energy storage, and activation of some hormones (Miller et al., 2001).

Pantothenic acid deficiency in humans is rare because of its ubiquitous distribution in foods. Many health claims are made regarding the role of pantothenic acid in ameliorating rheumatoid arthritis, lowering cholesterol, enhancing athletic performance, and preventing graying of hair (Miller et al., 2001). However, sufficient information is lacking at this time and so firm recommendations may not be made. No reports of adverse effects of oral pantothenic acid in humans have been reported.

The Food and Nutrition Board (1998) established an adequate intake level (AI) for pantothenic acid of 5.0 mg/day for adult men and women, 6.0 mg/day during pregnancy, and 7.0 mg/day during lactation. As mentioned above, pantothenic acid is found in a wide variety of both plant and animal foods. Because of its thermal lability and susceptibility to oxidation, significant amounts are lost during processing. Rich food sources include chicken, beef, liver, and other organ meats, whole grains, potatoes, and tomato products.

Biotin. In mammals, biotin serves as a coenzyme for reactions that control such important functions as fatty acid metabolism and gluconeogenesis. Biotin is recycled upon degradation of enzymes to which it is bound. Biotin from pharmaceutical sources is 100 percent bioavailable. Deficiency is rare but has been seen in patients on parenteral nutrition without biotin supplementation (Zempleni and Mock, 1999). Lipoic acid and biotin have structural similarities, thus competition potentially exists for intestinal or cellular uptake. This may be of concern in settings where large doses of lipoic acid are administered or taken as supplements (Zempleni et al., 1997).

The Food and Nutrition Board established an AI for biotin due to insufficient data to set an RDA. Adult men and women have an AI of 30

Biotin is distributed widely in natural foods. Those rich in biotin include egg yolk, liver, and some vegetables. It is estimated that individuals in the United States consume between 35 and 70

Choline. Choline has been considered a nonessential nutrient because humans can synthesize sufficient quantities. However, when hepatic function is compromised, hepatic choline synthesis is decreased and thus choline is now considered "conditionally" essential. In a 1998 report from the Food and Nutrition Board, choline is considered an essential nutrient (FNB, 1998). The Food and Nutrition Board noted that additional studies on the essentiality for human nutrition are needed. Specifically, the 1998 Food and Nutrition Board study suggested that graded doses of choline intake be studied regarding their effects on organ function, plasma cholesterol, and homocysteine levels.

Choline functions as a precursor for phospholipids and acetylcholine, and betaine. The AI for adult men was set at 550 mg/day and for women at 425 mg/day. For pregnancy, the AI was increased to 450 mg/day and during lactation, to 550 mg/day (FNB, 1998). Due to reports of hypotension (low blood pressure) from excess intake, a UL was set at 3.5 g/day for persons nineteen years and older. Choline and choline-containing lipids, mainly phosphatidylcholine, are abundant in foods of both plant and animal origin. Rich sources include muscle and organ meats and eggs. To date there are no nationally representative estimates of choline intake from food or supplements.

Fat-Soluble Vitamins

Vitamin A. The active forms of vitamin A participate in three essential functions: visual perception, cellular differentiation, and immune function. A number of food sources are available for vitamin A. Preformed vitamin A is abundant in animal foods and provitamin A carotenoids are abundant in dark-colored fruits and vegetables. With a 2001 report from the Food and Nutrition Board (FNB 2001), there has been recognition of a change in equivalency values of various carotenoids to vitamin A. Retinol activity equivalents (RAEs) for dietary provitamin A carotenoids—beta-carotene, alpha-carotene, and betacryptoxanthin—have been set at 12, 24, and 24

A number of factors affect the bioavailability of carotenoids (Castenmiller and West, 1998). Percent absorption decreases as the amount of dietary carotenoids increases, and the relative carotene concentration absorbed increases when consumed with oil or associated with plant matrix material. That is part of the plant vitamin source, not separated out as a supplement. The presence of dietary fat stimulates the secretion of bile acids and improves the absorption of carotenoids.

Table 1

Dietary forms of vitamin A and provitamin A carotenoids
Consumed	Absorbed	Bioconverted
Dietary or supplemental Vitamin A (1 μg)	Retinol	Retinol (1 μg)
Supplemental beta-carotene (2 μg)	beta-carotene	Retinol (1 μg)
Dietary beta-carotene (12 μg)	beta-carotene	Retinol (1 μg)
Dietary alpha-carotene or beta-cryptoxanthin (24 μg)	alpha-carotene or beta-cryptoxanthin	Retinol (1 μg)
SOURCE: Adapted from FNB 2001

Recommended dietary allowance for men is 900

Based on the literature review, the FNB used liver abnormalities as the critical adverse effect for setting the UL for adults. Issues of carcinogenicity were considered for women of childbearing age. The UL varies slightly with age between 2,800 and 3,000

The richest sources of vitamin A are fish oils, liver, and other organ meats. Whole milk, butter, and fortified margarine and low-fat milks are also rich in the vitamin. In the United States carrots, fortified spreads, and dairy products are the leading contributors of vitamin A to the diet.

Vitamin D. Vitamin D is essential for life in higher animals. It is one of the most important regulators of calcium homeostasis and was historically considered the "anitrachitic" factor. The biological effects of vitamin D are achieved only by its hormonal metabolites, including two key kidney-produced metabolites: 1,25(OH)₂ vitamin D and 24,25(OH) vitamin D. In addition to its role in calcium metabolism, research has identified that vitamin D plays an important role in cell differentiation and growth of keratinocytes and cancer cells and has shown that it participates in the process of parathyroid hormone and insulin secretion (Bouillon et al. 1995).

Vitamin D₃, the naturally occurring form of the vitamin, is produced from the provitamin, 7-dehydrocholesterol, found in the skin under the stimulation of ultraviolet (UV) irradiation or UV light. Vitamin D₂ is a synthetic form of vitamin D that is produced by irradiation of the plant steroid ergosterol. A requirement for vitamin D has never been precisely defined because vitamin D is produced in the skin after exposure to sunlight. Therefore, humans do not have a requirement for vitamin D when sufficient sunlight is available. The fact that humans wear clothes, live in cities where tall buildings block the sunlight, use synthetic sunscreens that block UV rays, and live in geographical regions of the world that do not receive adequate sunlight contributes to the inability of the skin to synthesize sufficient vitamin D (Holick, 1995). Exposure to the sun sufficient for humans to obtain enough UV radiation to synthesize adequate vitamin D can be as little as three weekly exposures of the face and hands to ambient sunlight for 20 minutes (Adams et al., 1982).

A substantial proportion of the U.S. population is exposed to suboptimal levels of sunlight during the winter months. Under these conditions, vitamin D becomes a true vitamin and must be supplied regularly in the diet. The Food and Nutrition Board recommend an AI or adequate intake of vitamin D at 200 IU/day (5

To prevent life-threatening hypercalcemia, an upper level (UL) for vitamin D has been set at 2,000 IU/day (50 2 vitamin D for treatment of hypoparathyroidism, vitamin D–resistant rickets, renal osteodystrophy, osteoporosis, and psoriasis opens the door for potential toxicity because this form of the vitamin is much more toxic and the body's metabolic controls are bypassed. When this medication is being used, careful monitoring of plasma calcium concentrations is required.

Salt-water fish are good unfortified sources of vitamin D. Small quantities are derived from eggs, beef, butter, and vegetable oils. Fortification of milk, butter, margarine, cereals, and chocolate mixes help in meeting the dietary requirements. Excessive amounts of vitamin D are not available in usual dietary sources. However, excessive amounts can be obtained through supplements that result in high plasma levels of 25(OH) vitamin D.

Vitamin E. Vitamin E (also called tocopherol) is found in cell membranes and fat depots. Because of their chemical structure, there are eight stereoisomers of each of the tocopherols. In addition to each of the stereoisomers, each occur in alpha, beta, gamma, and delta forms (FNB, 2000).

Its most recognized function is to protect polyunsaturated fatty acids (PUFA) from oxidation. PUFAs are particularly sensitive to oxidative damage, and the protective role of vitamin E is supported by a similar antioxidant protection from vitamin C and selenium. One tocopherol molecule can protect 100 or more PUFA molecules from autoxidative damage (Pryor, 2001).

The various forms of vitamin E have different biological activity, with the natural source isomer—R,R,R,-alpha-tocopherol—being the most active. In supplements you may see this isomer called by its former name, d-alpha-tocopherol. Synthetic vitamin E is called all-rac-alpha-tocopherol or dl-alpha-tocopherol in supplements. Biological activities of vitamin E are given in the older international units (IU) or alpha-tocopherol equivalents (alpha-TE). Because of the many forms of vitamin E in plants and available synthetically, the relative activities of each form is complex. Current evidence indicates that vitamin E from natural sources has approximately twice the bioactivity in humans that the all-rac (synthetic) vitamin does (Burton et al., 1998).

Based on the literature review, FNB used hemorrhagic (bleeding) effects for the criteria to set the UL. For adults nineteen years and older the UL is 1,000 mg (2,326 mol)/day of any form of supplementary alpha-tocopherol. There is no evidence of adverse effects from intake of vitamin E naturally occurring in foods.

The RDA for vitamin E is 15 mg/day of naturally occurring alpha-tocopherol for adults above nineteen years of age (FNB, 2000). During pregnancy 15 mg/day is recommended and 19 mg/day for lactation.

The tocopherol content of foods varies widely depending on storage, processing, and preparation. The best sources of vitamin E are the common vegetable oils and products made from them. However, most of the tocopherols may be removed in processing. Wheat germ and walnuts also have high amounts of tocopherols.

Vitamin K. Vitamin K was named after the first letter of the German word Koagulation. For many years blood coagulation was assumed to be the sole physiological role for vitamin K. We now know that vitamin K plays an essential role in the synthesis of proteins including prothrombin and the bone-forming protein, osteocalcin (Vermeer et. al., 1995).

Dietary vitamin K absorption is enhanced by dietary fat and is dependent on bile and pancreatic enzymes. The human gut contains large amount of bacterially produced vitamin K, but its contribution to the maintenance of vitamin K status has been difficult to assess (Suttie, 1995). The vitamin K produced by bacteria in the gut is less biologically active even though it is stored in the liver and present in blood. Current understanding supports the view that this vitamin K source may partially satisfy the human requirement but that the contribution is much less than previously thought.

The drug warfarin, widely prescribed as an anticoagulant, functions through inhibition of vitamin K. As a result, alterations in vitamin K intake can influence the efficacy of warfarin. The effective dose of warfarin varies from individual to individual, as does the dietary intake of vitamin K. The best solution appears to be to establish the necessary dose of warfarin and urge patients to maintain a constant intake of foods high in vitamin K in their diets. Only a small number of food items contribute substantially to the dietary vitamin K.

The recommended intake is based on an AI or adequate intake of 120

Collards, spinach, and salad greens are high in vitamin K. Broccoli, Brussels sprouts, cabbage, and Bib lettuce contain about two-thirds as much, and other green vegetables contain even less. Vitamin K is also found in plant oils and margarine, with soybean and canola oils having the highest amounts. U.S. food intake surveys indicate that spinach, collards, broccoli, and iceberg lettuce are the major contributors of vitamin K in the diet.

Dietary Reference Intakes

See Appendix for full chart of Dietary Reference Intakes.

Recommended Dietary Allowance (RDA)—the dietary intake level that is sufficient to meet the nutrient requirement of nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group.

Adequate Intake (AI)—a recommended intake value based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of healthy people that are assumed to be adequate—used when an RDA cannot be determined.

Tolerable Upper Intake Level (UL)—the highest level of nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals in the general population. As intake increases above the UL, the risk of adverse effects increases.

SOURCE: Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes (FNB, 2000, p. 3).

Bibliography

Adams, J. S., T. L. Clemens, J. A. Parrish, and M. F. Holick. "Vitamin D-Synthesis and Metabolism after Ultraviolet Irradiation of Normal and Vitamin-D-deficient Subjects." New England Journal of Medicine 306 (1982): 722–725.

Bouillon, R., W. H. Okamura, and A. W. Norman. "Structure-Function Relationships in the Vitamin D Endocrine System." Endocrine Reviews 16 (1995): 200–257.

Burton, G. W., M. G. Traber, R. V. Acuff, W. Walters, H. Kayden, L. Hughes, and Ku Ingold. "Human Plasma and Tissue Alpha-Tocopherol Concentrations in Response to Supplementation with Deuterated Natural and Synthetic Vitamin C." American Journal of Clinical Nutrition 67 (1998): 669–684.

Castenmiller, J. J., and C. E. West. "Bioavailability and Conversion of Carotenoids." Annual Reviews of Nutrition 18 (1998): 19–38.

Davis, R. E., G. C. Icke, J. Thom, and W. J. Riley. "Intestinal Absorption of Thiamin in Man Compared with Folate and Pyridoxal and Its Subsequent Urinary Excretion." J Nutritional Science and Vitaminology (Tokyo) 30 (1984): 475–482.

Food and Nutrition Board (FNB). Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, D.C.: National Academy Press, 1997.

Food and Nutrition Board (FNB). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press, 1998.

Food and Nutrition Board (FNB). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C.: National Academy Press, 2000.

Food and Nutrition Board (FNB). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press, 2001.

Holick, M. F. "Environmental Factors That Influence the Cutaneous Production of Vitamin D." American Journal of Clinical Nutrition 61 (Suppl) (1995): 638S–645S.

Horwitt, M. K., A. E. Harper, and L. M. Hendersen. "Niacin-Tryptophan Relationships for Evaluating Niacin Equivalents." American Journal of Clinical Nutrition 34 (1981): 423–427.

Johnston, C. S. "Vitamin C." In Present Knowledge of Nutrition, 8th ed., edited by B. A. Bowman and R. M. Russell, pp. 175–183. Washington, D.C.: ILSI Press, 2001.

Kushi, L. H., A. R. Folsom, R. J. Prineas, P. J. Mink, Y. Wu, and R. M. Bostick. "Dietary Antioxidant Vitamins and Death from Coronary Heart Disease in Postmenopausal Women." New England Journal of Medicine 334 (1996): 1156–1162.

McCormick, D. B. "Two Interconnected B Vitamins: Riboflavin and Pyridoxine." Physiological Reviews 69 (1989): 1170–1198.

McCormick, D. B. "Riboflavin." In Modern Nutrition in Health and Disease, edited by M. E. Shils, J. E. Olson, and M. Shike, pp. 366–375. Philadelphia: Lea & Febiger, 1994.

Miller, J. W., L. M. Rogers, and R. B. Rucker. "Pantothenic Acid." In Present Knowledge of Nutrition, 8th ed., edited by B. A. Bowman and R. M. Russell, pp. 253–260. Washington, D.C.: ILSI Press, 2001.

Pryor, W. A. "Vitamin E." In Present Knowledge of Nutrition, 8th ed., edited by B. A. Bowman and R. M. Russell, pp. 156–163. Washington, D.C.: ILSI Press, 2001.

Rasmussen, K., J. Moller, M. Lyngbak, A.-M. Pedersen, and L. Dybkjaer. "Age-and Gender-Specific References Intervals for Total Homocysteine and Methylmalonic Acid in Plasma before and after Vitamin Supplementation." Clinical Chemistry 43 (1996): 630–636.

Rimm, E. B., W. C. Willett, F. B. Hu, L. Sampson, G. A. Colditz, J. E. Manson, C. Hennekens, and M. J. Stampfer. "Folate and Vitamin B6 from Diet and Supplements in Relation to Risk of Coronary Heart Disease among Women." Journal of the American Medical Association 279 (1998): 359–365.

Schaumberg, H. H., and A. Berger. "Pyridoxine Neurotoxicity." In Clinical and Physiological Applications of Vitamin B6, pp. 403–414. New York: Alan R. Liss, 1988.

Scholl, T. O., and W. J. Johnson. "Folic Acid: Influence on the Outcome of Pregnancy." American Journal of Clinical Nutrition 71 (Suppl) (2000): 295S–303S.

Suttie, J. W. "The Importance of Menaquinones in Human Nutrition." Annual Review of Nutrition 15 (1995): 399–417.

Vermeer, C., K.-S. G. Jie, and M. H. J. Knapen. "Role of Vitamin K in Bone Metabolism." Nutrition 15 (1995): 1–22.

Wagner, C. "Symposium on the Subcellular Compartmentation of Folate Metabolism." Journal of Nutrition 126 (1996): 1228S–1234S.

Zempleni, J., J. R. Galloway, and D. B. McCormick. "Pharmacokinetics of Orally and Intravenously Administered Riboflavin in Healthy Humans." American Journal of Clinical Nutrition 63 (1996): 54–66.

Zempleni, J., and D. M. Mock. "Biotin Biochemistry and Human Requirements." Journal of Nutritional Biochemistry 10 (1999): 128–138.

—Ann M. Coulston