Vitamin A

Vitamin A is  range of biological activity not a single molecule. Several different substances contribute to the Vitamin A effect, including the fat soluble retinol group and the water soluble carotene group. The fat soluble group is strictly a product of animal metabolism, and must be obtained from animal-source foods. Liver is generally known as a good source, and fish-liver oils are the standard Vitamin A supplements.

Retinol is the principle Vitamin A, and fills all the roles that Vitamin A plays metabolically. The activity of other members of the Vitamin A group are referred to retinol activity as an index of their biological potency (retinol equivalents). Beta carotene has half the activity of retinol.

A cousin of retinol, retinal, is the substrate for the production of the visual pigment, rhodopsin. Deficiency of rhodoposin leads to night blindness, the best recognized symptom of vitamin A deficiency. Another cousin, retinoic acid, and its derivatives have become important drug-like Vitamin A used in the treatment of the skin conditions, cystic acne and psoriasis.

Many Vitamin A effects are hormone-like, influencing the growth and differential of cells. Vitamin A may also be considered a biological response modifier. This effect is most noticeable in the skin where Vitamin A activity reduces the tendency of surface cells to pile up, producing thickened scaly skin. This "hyperkeritinizing" effect is characteristic of skin diseases such as psoriasis, acne, lichen planus, and dry-scaly skin (ichthyosis).

Naturally occurring Vitamin A is also toxic in overdose. A single megadose of 1,500,000 IU produces brain swelling with headache, drowsiness, and vomiting. Sustained Vitamin A doses over 50,000 IU may be toxic. In children, overdose results in loss of appetite, itching, irritability, swelling and tenderness of bones, and failure to gain weight. In adults other effects include sore mouth, brittle nails, increased blood calcium, liver enlargement, low-grade fever and headache. Clearly Vitamin A intake should fit into an optimal range to achieve all its benefits, without its toxicity.

Over 1500 Synthetic Vitamin A analogues or retinoids have been developed. Isoretinoin (13-cis-retinoic acid) has been marketed as "Accutane" for the treatment of severe acne. While this vitamin-drug is effective, it is so biologically potent that a pregnant woman taking accutane is assured of a malformed fetus. A woman suffering severe acne can only take the drug if she takes adequate precautions to avoid pregnancy. Etretinate is similarly effective in the treament of psoriasis and has benefits in the treatment of skin cancers. The toxicity of these compounds limits their use. 

Tretinoin or Vitamin A acid has been marketed as a skin cream or gel for the treatment of acne. Recent observations suggest that tretinoin reduces sun damage to skin, and reduces facial skin wrinkling. Topical application of tretinoin in concentrations of 0.01 to 0.05% may produce redness and peeling of the skin; reduced concentration and frequency of application limit the side effects of this cream. Tretinoin may be the first effective anti-skin -aging substance.

Changes in the growth patterns of cells are characteristic of cancer, and Vitamin A activity seems to protect against cancer development. Each Vitamin A component may have different abilities as anti-cancer agents. The water soluble plant pigment, beta-carotene is receiving the most intense study in this role.

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