Vitamins A, D, E, K

ERNESTINE B. McCOLLUM AND ELMER V. McCOLLUM.

AN ALYSTS a half century ago used chemical methods, to estimate the proteins, fats, carbohydrates, mineral elements, and water in foods. They separated the substances in relatively pure form from such natural foods as milk, meat, and cereal grains. They fed mixtures of the purified nutrients to animals, which soon sickened and died. It became plain to the scientists that proteins, fats, carbohydrates, minerals, and water are not the only essential constituents of foods.

Animals grew well and remained healthy when small amounts of water-soluble material from yeast or wheat germ the embryo or heart of the wheat were added to the purified diets and when the right fat was included. All fats have essentially equal caloric value, but experiments on rats showed that some fats are superior to others for growth and the maintenance of health. Studies such as these led to the discovery of the vitamins.

We classify vitamins on the basis of their solubility. Vitamin C (ascorbic acid) and the vitamins of the B complex are water soluble. Vitamins A, D, E, and K in their natural forms are soluble in fats and such fat solvents as ether and chloroform. We call them the fat-soluble vitamins.

Elmer V. McCollum and Marguerite Davis, then of the University of Wisconsin, discovered in 1912 that the provision of something in butterfat or egg yolk fat made the difference between moderate success in the nutrition of young rats on certain diets and prompt nutritive failure. This something was vitamin A.

Some months later Thomas Burr Osborne and Lafayette Benedict Mendel, in investigations at Yale University, corroborated and extended Dr. McCollum's observations on the effects of a deficiency of vitamin A.

They described the condition as a "type of nutritive deficiency exemplified in the form of an infectious eye disease prevalent in animals inappropriately fed." They said it was alleviated speedily by adding butterfat to the diet.

They discovered first that young animals deprived of vitamin A fail to gain weight, an effect caused by a deficiency of any of the known essential nutrients.

An eye disease, xerophthalmia or dry eye, is a specific result of too little vitamin A, however. It occurs in human beings and in experimental animals. It was observed in infants in Japan in 1904 and among children in Denmark in 1917. It was attributed in both countries to scarcity of food fats.

A DEFICIENCY of vitamin A injures the epithelial tissues throughout the body. These cells form the outer layer of the skin and the mucous membranes that line the mouth and the digestive, respiratory, and genitourinary tracts. The secretory glands, such as the tear glands and digestive glands, are composed of specialized epithelial cells. Epithelial cells dry and flatten and slough off when vitamin A is lacking. The cells, instead of being soft and moist, become hard and dry like the scales of dry skin.

The mucous membranes are barriers against many kinds of bacterial invasion. Impairment of their structure and function when vitamin A is deficient lowers resistance to respiratory and other infections. Severe infections of the eyes, genitourinary tract, and mouth may occur.

This deficiency also is said to be the cause of much blindness among the populations of the Orient.

Vitamin A is necessary for vision. The retina of the eye contains a pigment, visual purple, which is composed of vitamin A and protein.

Visual purple is converted first to visual yellow and then to visual white when the eye is exposed to light. Vitamin A is lost in this conversion. Visual purple is regenerated if a fresh supply of the vitamin is available. Without this regeneration, vision in subdued light is impaired following exposure to bright light a condition known as night blindness.

Night blindness has a long medical history, in which it is associated with diet. It was common in Newfoundland among fishermen who worked in open boats in bright sunshine and exposed their eyes to the glare on the water. There was an old belief that if a man could not see at night, his vision would be restored by the next night if he ate the liver of a codfish or a sea gull.

Vitamin A profoundly influences the development of the teeth. When the tooth buds buried in the child's jaw are ready for the formation of enamel, certain epithelial cells from what later become gum tissue fold inward and form a cap over the part of the tooth that is to be enameled. These then become specialized as to function. Each cell forms a minute, six-sided prism of enamel substance. The prisms finally reach a length equal to the thickness of the enamel on the erupted tooth. The many enamel prisms are laid together so perfectly as to make a dense, thick, smooth enamel.

If the child gets too little vitamin A when his teeth are developing, the enamel-forming cells become abnormal and lose their effectiveness in forming enamel prisms. Some prisms in the finished enamel may be missing, and pits are formed. Such pits may later harbor food deposits, which may ferment and form acids that etch the enamel and lead to decay.

Vitamin A occurs only in foods of animal origin.

It is not found in any plant. All yellow and green plants, however, contain yellow pigments that can be converted by chemical cleavage into fragments, one of which is vitamin A.

The commonest of these pigments is carotene, so called because it was first prepared from carrots. There are three carotenes. One of them can be converted into two molecules, and the others into one molecule of vitamin A.

The yellow pigment of corn, cryptoxanthine, also can be converted into vitamin A in the body.

The conversion of carotene into vitamin A is thought to take place in the intestinal mucosa.

Because carotene can be converted into vitamin A, it is often called provitamin A.

Experiments generally have shown that carotene is utilized less efficiently than vitamin A. Individuals differ in their ability to convert it into the vitamin.

An example is the difference in the yellowness of milks of a Jersey cow, a Holstein cow, a ewe, a goat, and a sow that graze on the same green grass. The milk of the Jersey is yellower than that of the Holstein. The milks of the other three species are nearly white.

The yellow color of milk and cream is due to carotene. Vitamin A is almost colorless. Animals with great ability to convert carotene to the vitamin produce white or slightly yellow milk. Those that are not so efficient put more carotene and less vitamin A into their milk.

The total vitamin A value of milk, cream, butter, and eggs is the sum of the vitamin A and the carotene present, but one cannot estimate the vitamin A value of such foods on the basis of their color alone.

The biologic activities of vitamin A and carotene are expressed in I.U. (International Units) or U.S.P. units (United States Pharmacopoeia). These units have the same value, and the terms are used interchangeably. They are defined in terms of standardized, pure, crystalline vitamin A or beta-carotene. Three-tenths of a gamma of crystalline vitamin A or six-tenths of a gamma of pure beta-carotene is equal to one unit. A unit is very small. There are 1 million gamma in a gram and about 30 grams in an ounce. An ounce of the pure, crystalline vitamin equals 30 million units. This is enough to meet the needs of one person for almost 30 years!

We estimate that two-thirds of the vitamin A activity in the average American diet comes from carotene and related compounds. One-third is provided by the vitamin itself present in foods of animal origin.

Not all of the carotene present in the food eaten is converted into vitamin A. Some passes through the digestive tract and is excreted as such. Some circulates in the blood, and some is changed in the intestine or liver. The amount of ingested carotene that is converted into vitamin A varies with different foods and with methods used in preparing them. Other substances present in foods or served with them may also affect the body's ability to take up carotene from the intestinal tract and convert it into vitamin A.

Feeding experiments on human beings indicated that cooked carrots put through some blender (Waring Blender, Osterizer, or similar device) were more than twice as good a source of carotene as cooked carrots that were sliced or mashed. When cooked spinach was compared with carrots prepared in the two ways described, it was found to be equal in carotene value to the blended carrots.

Other dietary factors also influence the requirement for vitamin A. Vitamin E protects carotene and vitamin A against oxidative destruction within and outside the body. The livers of animals deprived of vitamin E are depleted rapidly of vitamin A. The store of vitamin A in the liver can increase when vitamin E is provided again.

Mineral oil reduces the absorption of carotene and vitamin A. It is undesirable to combine mineral oil with the food. Anybody who uses it should take it on rising or long enough after a meal to prevent interference with the utilization of the fat-soluble vitamins.

The National Academy of Sciences-National Research Council has recommended a daily intake of 5 thousand I.U. of vitamin A. This allowance is approximately twice that required to meet the minimum needs of the average healthy adult on a good diet. It assumes that two-thirds of the total vitamin A is provided by carotene present in the yellow and green, leafy vegetables and yellow fruits, like kale, spinach, collard greens, mustard greens, carrots, pumpkin, yellow sweetpotatoes, apricots, yellow peaches, and cantaloup. Foods from animal sources, like whole milk, butter, eggs, liver, kidney, and some fish, contain the vitamin itself.

Vitamin A accumulates in the liver. A well-nourished individual is likely to have a sufficient store to last for months even if his food is completely devoid of the vitamin and carotene.

Overdosing with vitamin A may cause serious injury to health. Self-administration of highly potent concentrates is likely to result in hypervitaminosis A, a serious condition from which recovery is slow. It has been observed in children who were given excessive intakes of 75 thousand units or more daily for some time.

The recommended allowance for vitamin A can be met by including yellow and green, leafy vegetables, such as collards, turnip greens, kale, carrots, squash, and sweetpotatoes in the diet every day. Yellow peaches, apricots, cantaloups, and papayas are also good sources. Liver of all animals is an excellent source. A 2-ounce serving of cooked beef liver provides more than 30 thousand I.U. of the vitamin.