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Unraveling the vitamin A mystery.


Until the recent flurry of excitement was generated by retinoic acid's apparent ability to reduce or remove wrinkles in aging skin, its precursor, vitamin A, was just one of those good things to have in one's diet. However, there was some additional evidence that retinoic acid might also be a factor in the development of lung cancer in persons whose diets were deficient in beta-carotene, which the body converts to vitamin A. There had also been a more disturbing recent finding that retinoic acid was capable of producing serious birth defects when pregnant women used the antiacne drug Accutane, of which retinoic acid is the active ingredient.

From a large number of recent studies published in a host of medical and scientific journals, it now appears that the lowly vitamin A has been elevated to the ranks of the most elite compounds in molecular biology--those critical conductors of the biological orchestra that produce the body's organs. From the single cell of a fertilized human egg, the human embryo begins to develop as an undifferentiated mass of cells that then go on to form the multitude of organs and their component structures. Contained in every cell are the genes that determine an organ's eventual form and function, but these genes remain dormant until, at the appropriate time, something arouses them to do their thing. Vitamin A, it now appears, is one such "something."

At critical points in the development process, vitamin A seems to turn on groups of genes that in turn arouse other dormant genes--a kind of domino effect that results in the finished product. One of the foremost researchers on retinoic acid, Dr. Gregor Eichele of the Harvard Medical School in Boston, declares, "It's a good bet that this [retinoic acid] is one of the body's master molecules." Another Harvard biologist, Dr. Lorraine Gudas, adds, "I think this is going to be one of the most exciting molecules in respect to embryogenesis that exists. It's a master regulator that can send a very loud signal at critical points throughout development."

Retinoic acid appears to be responsible for the development of a wide range of structures, including parts of the brain and spinal column; the face, arms and legs; the skeleton; the heart; and, of course, the skin. This, then, would explain the mystery of the congenital defects found in babies born to mothers who used Accutane for acne during pregnancy. Presumably the excess supply of retinoic acid delivered to the body from the drug, in addition to that derived from the normal intake of beta-carotene, upsets the delicate biological balance required for normal development. The result has been a horrendous array of defects: hydrocephalus, facial defects, missing ear canals, heart defects, hormone deficiencies, and brain and spinal cord malformations. The pattern of these birth defects suggests that retinoic acid is very specific in its regulatory action during the earliest stages of fetal development, and its effect is far-reaching. It also appears that retinoic acid continues to play a vital role throughout life in the growth and well-being of the epithelial cells that form most of the skin, the breasts and the linings of other organs, including the lungs and the intestinal tract. Further studies of retinoic acid may reveal why some cells go berserk and become cancerous as others shrivel and die.
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Publication:Medical Update
Date:Jun 1, 1990
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