Vitamins >> Vitamin A for Disease Prevention

Cancer
Studies in cell culture and animal models have documented the capacity for natural and synthetic retinoids to reduce carcinogenesis significantly in skin, breast, liver, colon, prostate, and other sites. However, the results of human studies examining the relationship between the consumption of preformed vitamin A and cancer are less clear.

Lung cancer:
At least ten prospective studies have compared blood retinol levels at baseline among people who subsequently developed lung cancer and those who did not. Only one of those studies found a statistically significant inverse association between serum retinol and lung cancer risk. The results of the Beta-Carotene And Retinol Efficacy Trial (CARET) suggest that high-dose supplementation of vitamin A and b-carotene should be avoided in people at high risk of lung cancer. About 9,000 people (smokers and people with asbestos exposure) were assigned a daily regimen of 25,000 IU of retinol and 30 milligrams of b-carotene, while a similar number of people were assigned a placebo. After four years of follow up the incidence of lung cancer was 28% higher in the supplemented group. Presently, it seems unlikely that increased retinol intake decreases the risk of lung cancer, although the effects of retinol may be different for nonsmokers compared to smokers.

Breast cancer: Retinol and its metabolites have been found to reduce the growth of breast cancer cells in the test tube, but observational studies of dietary retinol intake in humans have been less optimistic. The majority of epidemiologic studies have failed to find significant associations between retinol intake and breast cancer risk in women, although one large prospective study found total vitamin A intake to be inversely associated with the risk of breast cancer in premenopausal women with a family history of breast cancer. Blood levels of retinol reflect the intake of both preformed vitamin A and provitamin A carotenoids like b-carotene. Although a recent case-control study found serum retinol levels and serum antioxidant levels to be inversely related to the risk of breast cancer, two recent prospective studies did not observe significant associations between blood retinol levels and the subsequent risk of developing breast cancer. Presently, there is little evidence in humans that increased intake of preformed vitamin A or retinol reduces breast cancer risk.

DISEASE TREATMENT

Pharmacologic doses of retinoids
It is important to note that treatment with high doses of natural or synthetic retinoids overrides the body's own control mechanisms, and therefore carries with it risks of side effects and toxicity. Additionally, all of these compounds have been found to cause birth defects. Women who have a chance of becoming pregnant should avoid treatment with these medications. Retinoids tend to be very long acting; side effects and birth defects have been reported to occur months after discontinuing retinoid therapy. The retinoids discussed below are prescription drugs, and should not be used without medical supervision.

Retinitis pigmentosa
Retinitis pigmentosa describes a broad spectrum of genetic disorders that result in the progressive loss of photoreceptor cells (rods and cones) in the eye's retina. Early symptoms of retinitis pigmentosa include impaired dark adaptation and night blindness, followed by the progressive loss of peripheral and central vision over time. The results of a randomized controlled trial in more than 600 patients with common forms of retinitis pigmentosa indicated that supplementation with 4,500 mcg (15,000 IU)/day of preformed vitamin A (retinol) significantly slowed the loss of retinal function over a period of 4-6 years. In contrast, supplementation with 400 IU/day of vitamin E increased the loss of retinal function by a small but significant amount, suggesting that patients with common forms of retinitis pigmentosa may benefit from long term vitamin A supplementation but should avoid vitamin E supplementation at levels higher than those found in a typical multivitamin. Up to 12 years of follow-up in these patients did not reveal any signs of liver toxicity as a result of excess vitamin A intake. High dose vitamin A supplementation to slow the course of retinitis pigmentosa requires medical supervision and must be discontinued if there is a possibility of pregnancy (see Safety).

Acute promyelotic leukemia
Normal differentiation of myeloid stem cells in the bone marrow gives rise to platelets, red blood cells, and white blood cells, which are important for the immune response. Altered differentiation of those stem cells results in the proliferation of immature leukemic cells, giving rise to leukemia. A mutation of the retinoic acid receptor RAR has been discovered in patients with a specific type of leukemia called acute promyelotic leukemia (APL). Treatment with all-trans retinoic acid or high doses of all-trans retinyl palmitate restores normal differentiation, and leads to improvement in some APL patients.

Diseases of the skin
Both natural and synthetic retinoids have been used as pharmacologic agents to treat disorders of the skin. Etretinate and acitretin are retinoids that have been useful in the treatment of psoriasis, while tretinoin (Retin-A) and isotretinoin (Accutane) have been used successfully to treat severe acne. Retinoids most likely affect the transcription of skin growth factors and their receptors.