15.2: Vitamin A
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Many of the earliest insights into nutritional deficiency concerned the fat-soluble vitamins. Among the first recorded references to the relationship between vitamin A-rich foods and night blindness are found in writings which are some 3,500 years old. Eber’s Papyrus, an Egyptian document from about 1500 B.C., defines the phenomenon of night blindness and suggests a cure of feeding patients the roasted livers of oxen or roosters. (The livers of virtually all animals are rich sources of vitamin A.)
Vision
Besides being one of the oldest accurate nutrition observations, the relationship between foods rich in vitamin A and vision is one of the best known. It’s a rare child who hasn’t been told to eat carrots in order to see better. Or who hasn’t heard that a lack of vitamin A can result in night blindness.
It’s less well known that such night blindness is far more than an inconvenience. It’s an extremely serious warning sign of a problem all too common among the world’s poor.
Night Blindness, a Deadly Omen
The night blindness which results from a deficiency of vitamin A is characterized by a difficulty of adjusting, from seeing in bright light to seeing in poor light. All of us have experienced this adjustment, when the bright light was especially intense and the succeeding low light especially weak—as when we drive from brilliant sunshine into a dark tunnel, or after a flash from a camera. A chemical change is demanded for our vision system to adjust, and it takes a little time to occur even when our vision is healthy.
Keep in mind that a reduced ability to see in dim light doesn’t necessarily mean a vitamin A deficiency. Eye changes related to aging, for example, can reduce one’s ability to accommodate from bright to dim light, and one’s ability to see in dim light. Again, if the problem isn’t caused by a vitamin deficiency, taking the vitamin won’t help.
The chemical involved in this change is rhodopsin. Vitamin A is the photosensitive part of the rhodopsin molecule, and this visual process begins when vitamin A is altered and released when light strikes it. This change sends an impulse from specialized cells at the back of the eyes, along the optic nerve to the brain (see Fig. 15-1).
This mechanism is perhaps the most basic phenomenon of seeing, for it enables us to tell the difference between more light or less. Thus do we see not only outlines but also the complex system of light and shadow that gives distinction to what we see—that enables us to distinguish the face of a friend from that of a stranger.
| Vitamin | Function | Source | Deficiency | Possible Toxicity |
| Vitamin A (retinol, retinoids, provitamin A carotenoids) | Vision, gene expression, maintain tissues, reproduction, immunity | Liver, carrots, spinach, winter squash, apricots, papaya, greens, tomatoes | Night blindness, xerophthalmia skin lesions | Fatigue, nausea, headache, hair loss, liver damage, birth defects |
| Vitamin D (calciferol) | Absorb calcium and phosphorus, mineralize bone | Fortified milk and breakfast cereals, fatty fish, sunshine on skin | Rickets, osteomalacia, osteoporosis | Fatigue, nausea, calcify soft tissue, kidney damage |
| Vitamin E (tocopherol) | Antioxidant | Vegetable oil, margarine, whole grains, egg yolk | Hemolytic anemia | Increased tendency to bleed. |
| Vitamin K | Blood clotting | Intestinal bacteria, liver, green leafy vegetables, milk, meat | Lessened ability of blood to clot | Jaundice in infants |
Table 15-1: Fat-Soluble Vitamins
The vitamin A portion must then be replaced before rhodopsin can be used again. So for continuing good vision, our eyes must be able to restore rhodopsin quickly. Otherwise, a bright light will leave us with too little rhodopsin for vision in dim light.
In 1958, George Wald discovered the action of vitamin A in vision; he was awarded the Nobel Prize in 1967.
When an insufficient amount of vitamin A is available in the eye, restoration of rhodopsin takes place very slowly. And during that time, to some extent, one is blinded. In other words, a shortage of vitamin A means a limitation on our ability to see. Conversely, we have no difficulty maintaining rhodopsin if we have sufficient vitamin A.
What Night Blindness Means
Recall that when vitamin deficiencies exist, there are shortages throughout the body, not just in one body system. True, some systems are more acutely dependent on the vitamin and show shortages sooner. But we may be certain that the rest of the body is also threatened with deficiency.
Among fat-soluble vitamins, a deficiency means that the body’s reserve has been exhausted. So when vitamin A shortage reaches a point at which the eyes can’t function optimally, other threats to health also exist.
What kinds of threats? For one, the night blindness indicates a condition known as xerophthalmia. The word derives from the Greek words for dry and eyes.
Indeed, the eyes of the vitamin A-deficient person do look dry. The whites of the eyes are especially flat and dull. The effect is much more than cosmetic. It means that eye tissue is beginning to dry out and die. Small ulcers can occur and result in little scars on the lens of the eye. Like the cataracts common in older people, these scars block areas of vision and can lead to permanent blindness.
The familiar trade name Xerox derives from the fact that its copies are dry—unlike the common office copier of the 1950s, which produced copies that literally had to be “hung out to dry.”
Another threat to health is that a vitamin-A deficiency impairs the immune system, leading to higher death rates in children with measles or severe diarrhea, for example.
How Common is Severe Vitamin A Deficiency?
Striking signs of vitamin A deficiency are rare in the U.S., but according to the World Health Organization (WHO) of the United Nations, about 254 million preschool children (half of them in Southeast Asia) are vitamin A deficient, based on clinical eye signs and/or very low vitamin A levels in the blood, and about 800,000 deaths worldwide can be attributed to vitamin A deficiency.1
Figure 15-1: Role of Vitamin A in Vision. When light strikes, vitamin A changes shape and is released. This sends an impulse to the brain. Vitamin A must be restored for rhodopsin to function in vision.
An estimated 250,000 to 500,000 vitamin-A deficient children become blind every year, and about half of these children die within a year of becoming blind.2
For those in developed countries, it seems incredible that such a huge and tragic health problem exists when its cure/prevention is an inexpensive vitamin. In fact, huge strides have been made in combating vitamin A deficiency, including providing vitamin A capsules to young children and fortifying various foods with vitamin A (e.g., sugar in Guatemala).
What is Vitamin A?
Vitamin A itself is found only in animals, not in plants. But plants contain substances (provitamin A) that our bodies can convert to vitamin A. Thus, we get vitamin A from food by eating provitamin A (vitamin A precursors) in plant foods or by eating vitamin A itself in animal foods or foods to which vitamin A has been added (e.g., fortified breakfast cereal).
The vitamin A that we get from animal foods originally came from carotenoids by conversion to vitamin A in an animal body.
The provitamin A in plants are among a group of pigments known collectively as carotenoids. The carotenoids bring color to life. They are a group of several hundred bright yellow, orange, and red pigments that are made in plants. They are found in fruits, vegetables, flowers, and foliage, giving leaves their beautiful fall colors.
Some of these carotenoids can be converted into vitamin A in the body (provitamin A carotenoids). Beta carotene, the most common and most potent of these, was first isolated from carrots in 1931, giving it its name.
Many animals can make vitamin A from carotenoids but cats can’t. So cats must get their vitamin A from meat or milk—a vegetarian diet doesn’t work for cats!
Carotenoids are found in yellow-orange fruits and vegetables. They are also found in dark-green vegetables—the green color of chlorophyll masks the yellow-orange color.
Carotenoids are only made in plants, but can be found in animal tissues when animals eat plants rich in them. The yellow-orange color of egg yolk is from carotenoids (only some of which have vitamin A value). In fact, poultry and egg producers routinely add carotenoid concentrates (e.g., from alfalfa or corn) to poultry feed so that the egg yolk and chicken skin will be more attractive to the consumer. Carotenoids are also added to margarine (otherwise, it would be white).
Although vitamin A itself isn’t found naturally in plants, processed plant foods (e.g., breakfast cereals) often have vitamin A and/or beta carotene added to them (“fortified with vitamin A”).
Like vitamin A, carotenoids are fat-soluble. Unlike vitamin A, however, they are fairly safe when consumed in large amounts. The body stores excesses, rather than converting the provitamin A carotenoids into toxic amounts of vitamin A.
The skin of people who eat a lot of carotenoids (e.g., drink carrot juice) looks yellow-orange because, as fat-soluble substances, carotenoids color the fat under the skin. Foods rich in carotenoids include sweet potato, mango, kale, pumpkin, carrots, cantaloupe, spinach, hot chili peppers, apricots, broccoli, and romaine lettuce.
Vitamin A and Body Chemistry
Vitamin A plays crucial roles in many other body functions besides vision, but the chemistry of its action in these roles is not as well understood. Possibly, the broadest and most important function of vitamin A is to maintain epithelial tissues—our skin, and skin-like structures (such as the tissues that line our respiratory and digestive tracts).
Beta-carotene is “clipped” to form two vitamin A molecules.
The word epithelium comes from the Greek, and it’s instructive to look at its roots. The prefix epi is the same as in such words as epidemic or epicenter, meaning on, upon, or over. The thelium part refers to the nipple. Then why use it to describe the outer and inner protective tissues of the body? Because these tissues protect not only by covering but also by secreting important substances. When there is a vitamin A deficiency, the skin, intestinal lining, and other such tissues lose some of their integrity and their ability to secrete.
Vitamin A values are standardized as micrograms (µg) of Retinol Activity Equivalents (RAE), e.g., 1 µg RAE = 12 µg beta-carotene or 3.3 International Units (IU) vitamin A.
When there’s a shortage of vitamin A, the eyes take on a dry look because the tissues are, in fact, dry. These tissues are among the first to be affected when there’s a vitamin A deficiency. Eventually, tissues of the respiratory system and digestive tract are also affected. The normal cleansing and protective mechanisms of the body don’t work as well.
Infectious organisms which are normally swept away, remain, and infections are harder to combat. Infections of the eyes, nose, throat, lung, and digestive tract become much more common. Vitamin A deficiency also reduces the effectiveness of white blood cells that fight infection—compromising further the ability to overcome infection.
A vitamin A deficiency can mean the difference between life and death in fighting infection. Measles epidemics, for example, regularly take the lives of many of the world’s vitamin-A-deficient children.
Vitamin A in Foods
Liver, the main storage organ for vitamin A, is the main high-density food source of vitamin A itself. Other organ meats, eggs, butterfat, and the foods to which we add (fortify with) vitamin A, such as milk and many breakfast cereals, are also key sources.
The vitamin A used to fortify foods or used in dietary supplements is often listed as vitamin A palmitate, retinyl palmitate, vitamin A acetate, etc. Vitamin A is manufactured in these combinations to make it more stable.
We get the rest of our vitamin A indirectly through carotenoids, mainly from plants. As was mentioned earlier, color—particularly yellow-orange and dark green—provides a good clue as to the amount in plants. However, unlike vitamin A, which is readily absorbed and already in usable form, carotenoids vary a lot in how well they are absorbed, and in the extent to which they can be converted to vitamin A.
How many carrots does it take for Sue to meet her RDA for vitamin A? The RDA for adult females is 700 µg RAE (see above). The carotenoids in a medium carrot provide about 1,400 µg RAE. Thus, Sue only needs a half a carrot to meet her RDA for vitamin A.
When diets are very low in fats—as they are in many of the poorer nations of the world— carotenoids are less readily absorbed. It then becomes important to pay particular attention to the quantity and quality of the available yellow-orange and dark green fruits and vegetables. Vitamin A deficiency can be a major concern when there are severe seasonal problems, as when cold weather cuts off the harvest of plant foods. Remember, most poorer nations can’t count as we do upon canned, frozen, and imported fruits and vegetables.
The possibilities of vitamin A shortage become great among such people. Their low fat consumption often means that there’s also a shortage of vitamin A itself, compounding the deficiency problem. We saw such a case in tales of the fat shortages among the Athabascans of the far north. Winter had eliminated fresh fruits and vegetables, and forage conditions had been poor for the animals they hunted. Since the game consumed by the Athabascans were less well fed, they weren’t only less fat, but could be expected also to have provided less vitamin A and carotenoids.
Cooking increases the amount of carotenoids absorbed from food, as does fat in the meal.
In many parts of the world, vitamin A depletion occurs with appalling frequency. When vitamin A intake is reduced—as in the case of strict vegetarian diets or when animal sources of food are scarce—the carotenoid intake must be substantial to avoid depleting liver stores of the vitamin.
One saving aspect is the liver’s ability to store any surplus of vitamin A. This gives health-care workers the opportunity to provide vitamin A less frequently in doses high enough for liver storage. This stored vitamin A can then be used later as needed.
Ironically, countries in which vitamin A deficiency is common often have plenty of inexpensive, leafy sources of carotene. But it’s hard to change eating habits. And even if the parents understand and try to cooperate, it’s hard to generate much affection for greens among small youngsters.
Golden Rice was produced as a way to provide vitamin A to deficient populations where rice provides as much as 80% of calories. Carotenoids aren’t normally made in rice, so the necessary genes to do this (one of them from a daffodil!) were inserted. The resulting beta-carotene gives the rice its golden color.
We face the same challenge with eating habits in our own country, but our children are better protected. They have greater access to such popular vitamin A sources as milk, butter, cheese, eggs, ice cream, and the like, as well as many sweet, carotene-rich fruits and fruit juices.
Figure 15-2: Vitamin A toxicity and deficiency.
In addition, we have widespread vitamin A fortification, particularly in such foods as milk and ready-to-eat breakfast cereals.
The Toxicity of Excess
Large doses of vitamin A are dangerous, unless current intakes and liver stores are low. Toxic effects are most commonly the result of excess vitamin A supplementation. Particularly vulnerable is the unborn child, susceptible to malformations when large doses of vitamin A supplements are taken during pregnancy.
Vitamin A poisoning brings on a wide variety of symptoms. They range from dry, itchy skin to swellings over the bones, and can include blurred vision, irritability, lost appetite, hair loss, headaches, diarrhea, nausea, liver damage, and neurological problems, including brain damage. Efforts to use vitamin A therapeutically, especially to correct skin and hair problems have generally proven futile. Indeed, much of what we know about vitamin A toxicity comes from misguided attempts to correct skin problems.
Vitamin A, Carotenoids, and Vitamin-A Analogs as Medicine
Vitamin A deficiency has been associated with an increased risk of lung cancer, leading some enthusiasts to interpret this as a call for vitamin A supplementation for cancer protection. Since vitamin A is needed to maintain the epithelial tissue that lines the lungs, it’s logical to suppose that a vitamin A deficiency will make lung tissue more vulnerable to the assaults of cancer-causing substances, such as those in tobacco smoke. But, again, supplementation can help only where there is a deficiency.
Beta-carotene may have a protective effect against cancer that’s separate from its role in providing vitamin A, e.g., it can act as an antioxidant (the role of antioxidants in possibly reducing cancer risk will be discussed in the section on vitamin E).
Observational studies have shown that smokers who ate more beta-carotene-containing food had less lung cancer, and it was plausible that beta-carotene was protective. However, randomized, double-blind studies (see Chap. 1) of smokers taking pills of either beta-carotene or a placebo had a shocking result—the beta-carotene group got more lung cancer than the placebo group.3 A randomized double-blind study of non-smokers, however, didn’t show a harmful (or beneficial) effect of taking beta-carotene.
This reinforces the view that it’s better to get our carotenoids from a normal diet that regularly includes yellow-orange and dark-green vegetables and fruit, i.e., food, rather than supplements. People who eat more foods containing certain carotenoids have been found to have lower risk of some diseases. So people take lutein supplements to prevent macular degeneration (an eye disease occurring mostly in people over age 65), and lycopene supplements to prevent prostate cancer. (Neither lutein nor lycopene have vitamin A value.) But the lesson of the smokers and beta-carotene pills is that taking carotenoid supplements is not the same as eating carotenoid-rich foods. (Spinach is a rich source of lutein; tomato products are a rich source of lycopene—put more catsup on those fries!)
Vitamin A analogs (lab-produced drugs that are similar in structure to vitamin A) have been produced as prescription drugs for specific medicinal roles. The vitamin A analog isotretinoin (Accutane), for example, has been used successfully in the treatment of severe acne and in preventing the recurrence of head and neck cancers. Unfortunately, isotretinoin has some toxic effects in common with vitamin A. Those being treated with this drug are carefully monitored for toxicity symptoms, including liver damage. Strict measures are taken to avoid pregnancy while being treated with isotretinoin, because normal doses of the drug can cause birth defects.