Vitamin A // Retinol

Disease risk reduction

Cancer

Because of the possible roles of vitamin A in reversing tumor development and boosting immune function, it has been proposed that retinol might help reduce cancer risk.

While studies in animals have shown an efficacy for natural and synthetic vitamin A to reduce skin, breast, liver, colon, and prostate cancer (1), the results of human prospective studies examining the relationship between the consumption of preformed vitamin A (retinol) and cancer are less clear.

Most studies have failed to find significant associations between retinol intake and cancer risk. Presently, there is insufficient evidence that vitamin A is effective in preventing (or treating) cancer.

Lung cancer
Among ten prospective studies which compared blood vitamin A (retinol) levels among people who subsequently developed lung cancer and those who did not, only one found a significant effect of retinol in reducing lung cancer risk (9).

The results of the Beta-Carotene And Retinol Efficacy Trial (CARET) suggest that long-term high-dose supplementation of vitamin A (retinol) and beta-carotene should be avoided in people at high risk of lung cancer, such as smokers and people with asbestos exposure (10). About 9,000 people were assigned a daily regimen of 25,000 International Units (IU) of retinol and 30 milligrams of beta-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 compared to the placebo group. A possible explanation for such a finding is that the oxidative environment of the lung, created by smoke or asbestos exposure, gives rise to unusual carotenoid oxidation products, which interfere with normal retinoid signalling and are involved in cancer initiation and development.

Presently, it seems unlikely that increased vitamin A intake decreases the risk of lung cancer, although the effects of retinol may be different for non-smokers than for smokers (9).

Breast cancer
Although vitamin A has been found to reduce the growth of breast cancer cells in vitro, the majority of epidemiological studies have failed to find significant associations between retinol intake and breast cancer risk in women (12, 13, 14, 15).

One large prospective study found that increased intake of vitamin A reduced the risk of breast cancer in premenopausal women with a family history of breast cancer (16).

Due to homeostatic regulation of blood retinol levels, the do not reflect the intake of preformed vitamin A as well as provitamin A carotenoids like beta-carotene. Although a case-control study found increased blood retinol and antioxidant levels to be related to decreased risk of breast cancer (17), two prospective studies did not observe significant associations between blood retinol levels and subsequent risk of developing breast cancer (18, 19).

Presently, there is little evidence in humans that increased intake of preformed vitamin A reduces breast cancer risk (52).

Vitamin A supplementation in developing countries

In developing countries, vitamin A deficiency is one of the most widespread causes of blindness. Because vitamin A is required for the normal functioning of the immune system, even children who are only mildly deficient in vitamin A have a higher incidence of respiratory disease and diarrhea, as well as a higher rate of mortality from infectious diseases, than children who consume sufficient vitamin A.

Studies have shown that vitamin A supplementation given to children aged over 6 months reduces all-cause mortality by between 23% and 30% in low income countries. The beneficial effect is assumed to be due to the prevention of vitamin A deficiency.

Since vitamin A is stored in the liver, it is possible to build up a reserve in children by administration of high-potency doses: infants younger than 6 months of age receive a dose of 50,000 IU vitamin A, and children between six months and one year receive 100,000 IU every 4–6 months, while children older than 12 months of age receive 200,000 IU every 4–6 months.

A single dose of 200,000 IU given to mothers immediately after delivery of their child has been found to increase the vitamin A content of breast milk. However, caution is necessary when considering vitamin A therapy for breast-feeding women since this could endanger a co-existing pregnancy (see Safety). During pregnancy, a daily dose of 10,000 IU vitamin A should not be exceeded.

The high dose vitamin A supplementation was also debated in some reports and it was suggested that vaccination status and gender should be considered when evaluating the effects of vitamin A supplementation in early life (53).

Authored by Dr Peter Engel in 2010, reviewed by Dr. Adrian Wyss on 31.08.2017.