- Retinoic acid
- Retinol palmitate
For Patients & Caregivers
Vitamin A is essential for many bodily functions. It is unclear if taking extra vitamin A can prevent cancer.
Vitamin A is best obtained from a well-balanced diet. Obtaining the recommended Daily Value (DV) of vitamin A (5,000 IU) is important because this vitamin is essential for a variety of bodily functions, including vision, embryonic development, maintenance of tissue integrity, and proper immune activation. Many fruits and vegetables are rich in vitamin A precursors, such as beta-carotene and cryptoxanthin, which are converted into the active form retinol, while dairy products, eggs, and fish are among the food sources containing vitamin A preformed as retinol. Too much retinol can cause a variety of side effects. Scientists are studying vitamin A byproducts that may be useful in cancer therapies, but these treatments are different from extra vitamin A taken in the form of supplements, the overuse of which can produce harmful effects including liver problems.
- To treat acne
Prescription forms of vitamin A have been shown to improve acne, but there is no proof that non-prescription forms can have the same effect.
- To prevent and treat cancer
A few large clinical trials show that vitamin A does not help prevent recurrence or prolong survival in patients with resected melanoma, head and neck cancer, or non-small cell lung cancer. However, overall nutritional status and diet of cancer patients is important, and a diet rich in nutrients is unlikely to produce unwanted side effects. For cancer patients especially, any perceived vitamin deficiencies should be discussed with their oncology healthcare professional.
- To treat Crohn’s disease
Although vitamin A supplementation does not treat Crohn’s disease, patients with this disorder can be malnourished. Therefore, symptoms such as night vision problems that may indicate a deficiency should be reported to and treated by your doctor.
- To enhance tissue strength
A diet containing adequate amounts of vitamin A is important in the maintenance of tissue strength, but human data are lacking.
- To treat eye disorders
Clinical trials have not definitively supported this use, although symptoms such as night vision problems that may be related to a deficiency should be reported to and treated by your doctor.
- To treat gastrointestinal disorders
No scientific evidence supports this use.
- To stimulate the immune system
This claim is not backed by clinical data.
- To treat infections
No scientific evidence supports this use.
- You regularly consume alcoholic beverages: Taking supplemental vitamin A along with regular alcohol use increases the risk for liver problems.
- You are pregnant: Doses of vitamin A 5000 IU or greater can cause birth defects.
- You take orlistat: This drug may reduce the absorption of vitamin A. Ask your doctor to see if you need to take a vitamin A supplement.
- You take retinoids (tretinoin, acitretin, bexarotene): Vitamin A may increase the adverse effects.
- You take warfarin (Coumadin®) or other blood thinners: Large doses of vitamin A may increase the risk of bleeding or bruising.
Nausea and vomiting, headache, blurred vision, muscular weakness, elevated liver function tests, liver toxicity
Chronic liver toxicity or vitamin A toxicity: Usually occurs with higher amounts of Vitamin A, although several cases have occurred with lower doses and among those who drink alcohol regularly.
For Healthcare Professionals
Derived from dietary sources and vitamin A precursors such as beta-carotene, alpha-carotene, and cryptoxanthin, vitamin A supplements are taken for eye conditions or acne, to improve immune function and growth and development in children, and to treat and prevent cancer. Vitamin A is necessary for normal differentiation of corneal, conjunctival, and retinal membranes, growth, development, and immune activation.
Clinical data suggest that vitamin A may be effective against growth retardation, acne, eczema (1), and hepatitis C (2). In children, vitamin A may also reduce recurring urinary tract infection (3), parasitic infections (4), and along with zinc, may reduce malaria-related morbidity (5). In developing countries, vitamin A supplementation reduced mortality in children (6)(7); however, its effects on infant mortality are conflicting (8)(9)(10), and maternal supplementation does not affect neonatal mortality (11). Vitamin A supplementation may also affect immune response to specific vaccines in children (12)(13), and was shown to be beneficial and safe in HIV-infected children (14). Studies to determine the proper dosage of vitamin A supplementation for children of varying demographics are still incomplete (15)(16)(17). Adults who may be malnourished, such as patients with Crohn’s disease, may also be vitamin A-deficient, and symptoms such as night vision problems should be assessed by physicians (18).
Although vitamin A derivatives are used as chemotherapeutic agents for cancer, a review of 14 clinical trials showed that supplementation with antioxidants beta-carotene, vitamin A, vitamin C, and vitamin E does not seem to prevent gastrointestinal cancer and may actually increase overall mortality (19). Higher serum retinol was also associated with elevated risk of prostate cancer, with prolonged high exposure resulting in increased risk (20)(21). Other large clinical trials have shown that vitamin A supplementation does not help to prolong survival for melanoma patients (22), prevent recurrence of head and neck cancer (23), or reduce the risk of non-small cell lung cancer (24), although a reduction in melanoma risk was associated with supplemental retinol but not carotenoid intake, particularly for women, in a large epidemiological study (25). At the same time, higher retinol intakes are associated with significant direct trends for risk of oral and pharyngeal cancers (26) and may also negatively impact high-dose vitamin D protection against colon cancer risk (27) as well as vitamin D involvement in calcium uptake in the bone (28), increasing the risk for hip fractures (29).
In assessments of nutritional status among in cancer patients, one study noted significantly lower serum retinol and beta-carotene levels in stage III versus earlier-stage breast cancer patients and also in patients after radiotherapy (30). Another study found human papillomavirus positive (HPV+) head and neck cancer patients who have diets richer in micronutrients including vitamin A may have better immune functioning and prognosis (31).
Deficiencies of vitamin A are rare in developed countries (29). Supplementation of vitamin A with doses greater than the recommended Daily Value of 5,000 IU or in conjunction with certain medications or pre-existing conditions may result in adverse effects or toxicity (32)(33). Vitamin A is therefore best obtained from a variety of dietary sources.
Vitamin A is essential for many aspects of ocular metabolism, including conjunctival and corneal epithelial maintenance, retinal phototransduction, and retinal pigment epithelial cell viability (34). Nuclear receptor transcription factors are central to vitamin A activity, and most transcriptional actions require the retinoic acid receptor/retinoid x receptor (RXR/RAR) heterodimer (35). Transcriptional changes are linked to epigenetic changes in histones and DNA via recruitment of epigenetic modifying enzymes (36). All-trans retinoic acid (ATRA) has been identified as the most important active metabolite in vitamin A for tissue homeostasis in adults and segmentation control in developing organisms (37). As such, retinoids that include ATRA along with natural and synthetic derivatives exhibit anticancer properties linked to their ability to induce cellular differentiation and growth suppression (36)(37).
In animal models of melanoma, ATRA in combination with epigallocatechin-3-O-gallate (EGCG) from green tea enhanced 67-kDa laminin receptor expression and increased EGCG-induced cell growth inhibition (38). In estrogen receptor-negative breast cancer cells, ATRA halts telomerase activity and exerts antitumor effects via a rapid decrease of H3-K9 acetylation at the hTERT promoter (39). The protective effect of supplemental retinol against melanoma may be mediated by sunlight exposure (25).
Vitamin A competes with vitamin D for the same parathyroid hormone receptor (29).
- Women who are pregnant should not consume vitamin A supplements due to possible teratogenicity (29).
- Pre-existing conditions such as chronic alcohol consumption, liver lesions, and concurrent medications with liver toxicity profiles may increase the risk of developing hepatotoxicity with vitamin A supplementation (33).
Chronic toxicity or hypervitaminosis A: Usually associated with chronic intake of more than 30,000 IU of vitamin A (44), although there have been several cases of significant hepatotoxicity with vitamin A doses as low as 20,000 IU and in regular alcohol consumers (33)(45).
Complex presentations may include hepatotoxicity, bone and skin changes, and other nonspecific adverse effects (20).
Alcohol: Ethanol can compete with retinol for alcohol dehydrogenase, leading to reduced levels of retinol oxidation to retinaldehyde and retinoic acid (45).
Orlistat: May reduce the absorption of vitamin A. Patients taking orlistat should take a multivitamin containing vitamins D, E, K, and beta-carotene once a day at least 2 hours before or after the administration orlistat (46).
Retinoids (tretinoin, acitretin, bexarotene): May increase risks of adverse effects. Avoid vitamin A supplements in excess of minimum recommended daily allowances when on these medications (47).
Warfarin: Large doses of vitamin A may increase the anticoagulant effects of warfarin (48).