- Retinoic acid
- Retinol palmitate
For Patients & Caregivers
Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.
What is it?
Vitamin A is essential for many bodily functions, and is best obtained from a varied diet. Overuse in the form of supplements can cause harmful effects including liver problems.
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. Therefore, vitamin A is best obtained from a varied diet, which is known to have overall protective effects against many chronic diseases.
What are the potential uses and benefits?
- 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 supplementation 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 a diet rich in nutrients is important, and unlikely to produce unwanted side effects. For cancer patients especially, any perceived vitamin deficiencies should be discussed and managed 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 may enhance the immune responses to certain vaccines.
What are the 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.
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. It also occurred in the case of a young patient who switched to self-treating with vitamin A for acne.
What else do I need to know?
Do Not Take if:
- You regularly consume alcoholic beverages: Taking supplemental vitamin A along with regular alcohol use, which should also be avoided, 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.
- Supplementation with doses greater than the recommended daily allowance may result in toxicity and patients may not realize that multivitamins commonly include vitamin A.
- Although rare in developed countries, vitamin A deficiency is the leading cause of preventable childhood blindness worldwide, usually from lack of proper food access from poor socioeconomic status.
- Certain restricted diets and conditions that lead to these restrictions, such as food allergies, mental disorders, or family dysfunction may also cause dietary inadequacies that lead to micronutrient deficiencies and complications.
- A few cases of vitamin A deficiency-related night blindness were reported several years after abdominal surgeries, which may cause a reduced ability to absorb nutrients. Patients experiencing vision problems should consult their healthcare practitioner.
For Healthcare Professionals
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 or dietary supplements to improve vision, skin conditions, immune function, growth and development in children, and to treat eczema (1) and hepatitis C (2).
In pediatric studies, supplementation appeared to benefit children (8) (9) (10), improve immune response to specific vaccines (11) (12), reduce recurring urinary tract (3) and parasitic infections (4), reduce clinical malaria episodes (5) and improve plasma retinol levels in extremely preterm infants (58). However, other trials yielded conflicting data (13) (14) (15) (16) (22), and also do not support maternal (21) or neonatal supplementation (17) (18) (19) (20).
In adults, preliminary findings suggest supplementation may inhibit progression of multiple sclerosis (6) and improve fatigue and depression (7) but evidence is lacking to support use of retinol-containing products to improve the appearance of aged skin (59).
In oncology settings, some studies reported 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, supplementation does not protect 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). Therefore it is best to obtain vitamin A from dietary sources, which can also protect against other chronic diseases. For instance, a meta-analysis found that having a diet rich in mixed carotenoids, which can then be converted to vitamin A in the body, benefits cardiometabolic health (51).
Vitamin A is fat-soluble and supplement overuse may cause accumulation in the body. Doses greater than the recommended Daily Value of 5,000 IU or in conjunction with certain medications or pre-existing conditions may also result in adverse effects or toxicity (30) (31). At the same time, vitamin A deficiency is the leading cause of preventable childhood blindness worldwide and often related to a lack of proper food access from poor socioeconomic status (52). Selective eating or restricted diet may also cause deficiencies and complications (53). In addition, a few cases of vitamin A deficiency-related retinopathy occurring years after abdominal surgeries have been possibly attributed to surgically-induced malabsorption: one related to multiple abdominal tumor resections (54), and another to bariatric surgery (55).
Purported Uses and Benefits
- Crohn’s disease
- Eye disorders
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).
Vitamin A competes with vitamin D for the same parathyroid hormone receptor (42).
- 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).
Increased atopy, wheezing: In neonate girls (44).
Complex presentations may include hepatotoxicity, bone and skin changes, and other nonspecific adverse effects (28).
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). Hepatotoxicity also occurred in a 27-year-old woman who was prescribed isotretinoin for acne, but switched to self-treatment with vitamin A purchased online and taken for 18 months (56).
Asymptomatic hypercalcemia: In an 18-year-old with burn injuries following treatment with steroids and Vitamin A. Calcium levels returned to normal after discontinuing Vitamin A (59).
- 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).