Vitamin A
Common Names
- Retinol
- Retinal
- Retinoic acid
- Retinoid
- Retinol palmitate
- How It Works
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 of vitamin A (DV: 5,000 IU) is essential for a variety of bodily functions, including vision, embryonic development, 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. Dairy products, eggs, and fish are among the foods containing vitamin A already 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.
- Purported Uses
- 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 melanoma, head and neck cancer, or non-small cell lung cancer. It may also increase risk of prostate cancer. However, overall nutritional status and diet of cancer patients is important, and a diet rich in nutrients rather than from supplements 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 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 stimulate the immune system
Vitamin A can enhance the immune responses to certain vaccines.
- To treat acne
- Do Not Take If
- 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.
- Side Effects
Nausea and vomiting, headache, blurred vision, muscular weakness, elevated liver function tests, liver toxicity
Increase in allergies: In newborn girls who received supplements.
Case Reports
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. - Special Point
- Supplementation with doses greater than the recommended daily allowance may result in toxicity; therefore patients should be monitored accordingly.
- Multivitamins commonly include vitamin A.
- Deficiencies of vitamin A are rare in developed countries.
- Clinical Summary
Vitamin A is a group of nutrient compounds available from dietary sources including fruits, vegetables, eggs, dairy products, and fish. Vitamin A and its analogs such as beta-carotene, alpha-carotene, and cryptoxanthin are used as prescription drugs and as dietary supplements to improve vision, skin condition, immune function, or growth and development in children, and to treat and prevent cancer, 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).
Preliminary studies suggest Vitamin A supplementation may inhibit progression of multiple sclerosis (6) and improve fatigue and depression (7).
Vitamin A supplementation was thought to benefit children (8) (9) (10) and affect immune response to specific vaccines (11) (12). However, other studies yielded conflicting results (13) (14) (15) (16), and more recent large trials do not support neonatal supplementation (17) (18) (19) (20). Maternal supplementation also did not affect neonatal mortality (21) or improve intelligence, memory, or motor function in children (22).
Some studies found that late-stage breast cancer patients have lower serum vitamin A levels (23), and that diets richer in micronutrients including vitamin A can improve immune functioning and prognosis in head and neck cancer patients (24), and reduce the risk of oral and pharyngeal cancers (25). However, vitamin A supplementation does not have a protective effect against non-small cell lung cancer (26) or prolong survival for melanoma patients (27), and may actually elevate the risk of prostate cancer (28) (29).
Vitamin A is fat-soluble and overuse may cause accumulation in the body. Supplementation 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 (30) (31).
- Food Sources
- Purported Uses
- Acne
- Cancer prevention and treatment
- Crohn’s disease
- Eye disorders
- Immunostimulation
- Mechanism of Action
Vitamin A is essential for many aspects of ocular metabolism, including conjunctival and corneal epithelial maintenance, retinal phototransduction, and retinal pigment epithelial cell viability (33). 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 (34). Transcriptional changes are linked to epigenetic changes in histones and DNA via recruitment of epigenetic modifying enzymes (35).
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 (36). 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 (35) (36).
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 (37). 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 (38). The protective effect of supplemental retinol against melanoma may be mediated by sunlight exposure (39).
In multiple sclerosis patients, vitamin A supplementation as retinyl palmitate upregulated TGF-beta and FoxP3 gene expression (40) and decreased IFN-gamma and T-bet gene expression (41).
Vitamin A competes with vitamin D for the same parathyroid hormone receptor (42).
- Contraindications
- 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 (31).
- Women who are pregnant should not consume vitamin A supplements due to possible teratogenicity (42).
- Adverse Reactions
Nausea, vomiting, headache, blurred vision, muscular weakness, elevated liver function tests, hepatotoxicity (9) (30) (43).
Increased atopy, wheezing: In neonate girls (44).
Complex presentations may include hepatotoxicity, bone and skin changes, and other nonspecific adverse effects (28).
Case reports
Chronic toxicity or hypervitaminosis A: Usually associated with chronic intake of more than 30,000 IU of vitamin A (45), although there have been several cases of significant hepatotoxicity with vitamin A doses as low as 20,000 IU and in regular alcohol consumers (31) (46). - Herb-Drug Interactions
- Alcohol: Ethanol can compete with retinol for alcohol dehydrogenase, leading to reduced levels of retinol oxidation to retinaldehyde and retinoic acid (46).
- Warfarin: Large doses of vitamin A may increase the anticoagulant effects of warfarin (47).
- 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 (48).
- 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 (49).
- References
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