| Editor's note: This is part one of a two-part article on vitamin A. Part one discusses general features, functions and health benefits of vitamin A; part two, which will appear in the July 16 issue, discusses toxicity, supplementation, drug-nutrient reactions and potential contraindications.
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Vitamin A is a vital, but often-ignored nutrient for health optimization and disease prevention. It is important in the prevention of cancer, night blindness and infection. More than 50 percent of Americans do not meet the daily requirement of vitamin A intake, while other Americans ingest excess vitamin A from supplements, which increases the risk of vitamin A toxicity, birth defects and osteoporosis. The daily ingestion of vitamin A is a delicate balancing act between taking in enough of the vitamin to derive its beneficial effects, while at the same time avoiding problems mitigated by excess consumption. This article highlights important physiological and clinical aspects of vitamin A that health practitioners should be aware of when making recommendations to their patients about optimizing vitamin A status and using supplements containing vitamin A.
General Features
Preformed Vitamin A is a fat-soluble group of related compounds. The most common preformed version present in food is retinol; others are retinal (retinaldehyde) and retinoic acid. Retinol can be reversibly oxidized to retinal, which is required for night vision. Oxidation of retinal produces retinoic acid, which does not participate in the visual cycle and cannot be converted back to the aldehyde form (retinal). However, retinoic acid does support growth and normal differentiation of epithelial tissue, but does not support reproductive function, as do other forms of vitamin A.
In general, vitamin A serves at least five major functions in the body:
- It helps cells reproduce normally and undergo complete differentiation to fully developed adult cells. (Cells that have not properly differentiated are more likely to undergo precancerous changes.)
- It is required for vision. One of the first symptoms of vitamin A deficiency is night blindness.
- It is required for normal growth and development of the embryo and fetus, influencing genes that determine the sequential development of organs in embryonic development.
- It may be required for normal reproductive function, with influences on the function and development of sperm, ovaries and placenta.
- It is a powerful fat-soluble antioxidant. Vitamin A is vital to health optimization and health maintenance, as studies show that vitamin A-deprived animals not only go blind, but also die shortly thereafter. Due to its diverse effects on epithelial cells, including growth, replication, differentiation and antioxidant function, animal studies have shown that vitamin A reduces the risk of cancer development in epithelial cells in the presence of certain carcinogens.
Absorption and Metabolism
Preformed vitamin A is absorbed in the gastrointestinal tract, enters the lymphatic system within chylomicrons and then enters into general circulation, which ultimately delivers vitamin A to the liver, the main storage site (90 percent) for vitamin A (which also is stored to a lesser degree in the kidneys, adipose tissue, and adrenal glands). It is released from the liver in the form of retinol, and bound to retinol-binding protein (RBP).
Between 80 percent and 90 percent of vitamin A typically is absorbed from the gut, demonstrating excellent bioavailability. Retinoic acid from food is absorbed from the gut and transported in the blood bound to albumin. It normally does not accumulate within the liver or other tissues in any real appreciable amounts.
Once delivered to the cells via the bloodstream, vitamin A is extracted from the bloodstream and binds to intracellular proteins known as CRBP (cellular retinal-binding protein) and CRABP (cellular retinoic acid-binding protein). Within the cells of the body, vitamin A modulates many biochemical reactions that promote growth, replication, differentiation, and provide additional antioxidant protection.
Functions
- Vision. Within the retina, the 11-cis isomer of vitamin A aldehyde (retinal) is combined with the protein opsin (rhodopsin in the rods and iodopsin in the cones). Light changes the 11-cis configuration to the all-trans form of retinal, which causes visual excitation. When there is a deficiency of vitamin A, the rods and cones cannot adjust to light changes. Night blindness is an early consequence when these cells, especially the rods, are deprived of vitamin A.
- Growth and bone development. Through its effects on protein synthesis and differentiation, vitamin A is necessary for growth and development of bones and soft tissues. It also is required for enamel-forming epithelial cells in the development of teeth. Retinoic acid appears to be the most important form of vitamin A for these purposes.
- Epithelial cell and mucous membrane development and maintenance. Retinoic acid is required for the development of mucous epithelial cells that line the respiratory tract, the alimentary canal and the urinary tract. Vitamin A deficiency results in keratinization (drying and hardening) of these tissues, which lowers the protective barrier of the tissues against infection. Suboptimal vitamin A status also may render these tissues more susceptible to cancerous changes.
- Immune function. Vitamin A influences both humoral and cell-mediated immunity. The circulating number of T-lymphocytes, as well as their response to mitogens, is reduced in vitamin A deficiency. Vitamin A also is known as the anti-infective vitamin, due to its effects on mucous membranes, helping to create a barrier to infection.
- Reproduction. Animal studies provide evidence that retinal is required for normal reproduction and lactation.
- Antioxidant. Vitamin A is a potent fat-soluble antioxidant, which appears to have important implications in regards to the prevention of epithelial cancers.
Retinol Equivalents (RE)
In addition to preformed vitamin A, which is present in animal foods, orange-yellow fruits and vegetables and dark green vegetables contain precursors to vitamin A synthesis, which occurs in the body (e.g., beta-carotene). In North America, approximately 50 percent of vitamin A is derived from vitamin A precursors via the consumption of fruits and vegetables. The following chart outlines the retinal equivalent values of various carotenes as well as preformed vitamin A.
1 retinol equivalent (RE):
= 1 ug retinal
= 6 ug beta-carotene
= 12 ug other provitamin A carotenoids
= 3.33 IU vitamin A activity from retinol
= 10 IU vitamin A activity from beta-carotene
Recommended Daily Allowance
| Group | RDA |
| Adult males | 1,000 retinol equivalents (RE) |
| Adult women | 800 RE or 4,000 IU |
| Pregnancy | 1,000 RE (5,000 IU) |
| Lactation | 1,200 RE (2,000-5,000 IU) |
| Children | 400-1,000 RE (2,000-5,000 IU); amount increases from infancy to 14 years. |
Overt Deficiency of Vitamin A
- Night blindness (nyctalopia).
- Xerophthalmia or xerosis conjunctivae. This is a progressive disorder of the eye leading to blindness and involving dryness, thickening, wrinkling and pigmentation of the conjunctiva, Bitot's spots, dryness and keratinization of the cornea, and (finally) ulceration, softening of the cornea and possibly perforation and iris prolapse and infection.
- Follicular hyperkeratosis (toad skin). Goose-flesh appearance known as xeroderma. In follicular hyperkeratosis, the hair follicles are blocked with plugs of keratin from the epithelial lining. The result is rough, dry, scaly skin, beginning with the forearms and thighs and progressing to full-body involvement.
- Other potential consequences of vitamin A deficiency include growth inhibition; skeletal abnormalities; decreased resistance to infection; taste bud keratinization and loss of sense of taste; and loss of appetite.1
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