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Deficiency Disease- Night Blindness; Xerophalmia, hyperkeritosis
RDA-5000 IU (50% preformed and 50% pro-vitamin A); 1000 retinol equivalents
Supplement Recommendation 3000 IU (preformed); betacarotene up to 5,000 IU per day
Overdose: brain swelling with headache, drowsiness, and vomiting
Vitamin A is a set of biological activities produced by a family of molecules. Several substances contribute to the Vitamin A effect, including the fat-soluble retinol group (pre-formed) and the water soluble carotene group (Provitamin A).
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 principal Vitamin A that fills all the roles that Vitamin A plays metabolically. The activity of other members of the Vitamin A group is referred to retinol activity as an index of their biological potency (retinol equivalents). Beta carotene is converted to retinol. Under FAA/WHO recommendations for vitamin A activity, one retinol equivalent = 2 gm of retinol = 6 gm of beta carotene = 12 gm other carotenoids
The expression of total vitamin A activity in food and RDA recommendations of RDAs as international units (IU) can be confusing - for example 50,000 IU of Vitamin A could be considered toxic but if this measurement is an estimate of betacarotene content, then there is no concern about toxicity. A cup of sweet potato has over 50,000 IU of beta-carotene and “carotenoids in foods are not known to be toxic even when ingested in large amounts”.
A cousin of retinol, retinal, is the substrate for the production of the visual pigment, rhodopsin. Deficiency of rhodopsin 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, fat-soluble Vitamin A (retinols) are toxic in overdose. The source is usually an animal product such as mammalian or fish liver or supplements such as cod liver oil. A single megadose of 1,500,000 IU produces brain swelling with headache, drowsiness, and vomiting. Sustained Vitamin A (retinol) 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. High doses of betacarotene from food sources have no known toxicity, although high dose supplements (10,000 IU or greater per day) of betacarotene are not required and are not supported by existing research.
Betacarotene and related carotenoids are best ingested in fruits and vegetables. There is some concern that high intakes may aggravate osteoporosis in elderly women. Retinol (vitamin A) is known to have detrimental effects on bone at high doses. Long-term treatment with a synthetic retinoid etretinate, has been linked to decreased bone mineral density and osteoporosis. Retinol intake is negatively associated with BMD and positively associated with hip fracture risk in women.
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 treatment 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. 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. A review of Vitamin A activity stated: “The finding that retinoids may divert a cell from proliferation to differentiation may be a clue to a new approach for the prevention and treatment of cancer... Very many chemically or virally induced tumors are influenced by retinoids. It is possible to prevent or retard the development of tumors of various organ sites (e.g., skin, oral cavity, stomach, intestine, colon, pancreas, trachea, bronchus, urinary bladder, cervix, and breast) and induced by many different carcinogens. Some of the tumors even regress under treatment with retinoids."
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