Vitamin A

Mechanism of Action

In the liver, retinol is esterified to retinyl esters and stored in the stellate cells. Both retinol and beta-carotene are oxidized to retinal and retinoic acid in the tissues, which are essential for vision and gene regulation, respectively. These active metabolites bind nuclear receptors of the RAR family to control gene expression.[1][5][6][7]

Administration

Vitamin A supplementation may be administered orally or intramuscularly. Absorption of oral vitamin A enhanced by a fatty meal due to its lipophilic nature.[1]

Adverse Effects

Excess natural or synthetic vitamin A levels may result in a wide array of adverse effects. Vitamin A toxicity, also known as hypervitaminosis A, is more commonly associated with abuse of vitamin A supplements than with health intervention programs. Toxic reactions may also be provoked by consuming liver products rich in vitamin A or excess administration of vitamin A preparations. The amount of vitamin A required to cause toxicity among individuals varies depending on age and hepatic function.

Acute vitamin A toxicity may occur with a single ingestion of 25,000 IU/kg or more. Signs and symptoms include nausea, vomiting, diarrhea, dizziness, lethargy, drowsiness, increased intracranial pressure, and skin changes such as erythema, pruritus, or desquamation.

Chronic vitamin A toxicity may occur with excessive ingestion of 4000 IU/kg or more daily for 6 to 15 months. Signs and symptoms include low-grade fever, headache, fatigue, anorexia, intestinal disturbances, hepatosplenomegaly, anemia, hypercalcemia, subcutaneous swelling, nocturia, joint and bone pain, and skin changes like yellowing, dryness, alopecia, and photosensitivity. 

Vitamin A is highly teratogenic if taken during pregnancy. Retinoids affect the expression of the homeobox gene Hoxb-1, which regulates the axial patterning of the embryo. Birth abnormalities include craniofacial, cardiac, and central nervous system malformations. Therefore, treatment with vitamin A should be avoided in pregnant patients except in areas where vitamin A deficiency is prevalent. In this circumstance, supplementation should not exceed 10,000 IU daily.[8]

Of note, mild adverse effects have been observed with vitamin A given with immunization. Symptoms include loose stools, headache, irritability, fever, nausea, and vomiting. These side effects are rare and typically resolved within 24 to 48 hours.

Contraindications

Vitamin A is contraindicated in pregnancy, breastfeeding patients, and patients with hypersensitivity to this class of drugs. It should be prescribed with caution to patients with hepatic disease, renal disease, alcoholism, and acne vulgaris.[9]

Monitoring

Isotretinoin is an oral medication derived from vitamin A that is primarily used to treat severe acne. Its package insert recommends baseline lipid and hepatic panels followed by repeat testing weekly or biweekly until the response has been established. However, a recent meta-analysis demonstrated that increases in triglycerides or cholesterol levels typically occur within the first 8 weeks of therapy with minimal to no change after that. The data was not sufficient enough to conclude an early rise in liver function tests, although it was determined that elevated liver function values were rarely high risk. Based on these findings, evidence from the meta-analysis does not support monthly laboratory testing for standard doses of oral isotretinoin.[10]

Toxicity

Symptoms of toxicity may resolve within several weeks after discontinuing vitamin A and instituting supportive therapy. Patients with increased intracranial pressure may require lumbar punctures or medications such as mannitol and diuretics for therapy. Patients with hypercalcemia may require intravenous fluids and additional therapy such as calcitonin and corticosteroids.[8]

Congenital disabilities caused by vitamin A are irreversible. 

Enhancing Healthcare Team Outcomes

Interprofessional healthcare team members, including clinicians, nurses, dieticians, and pharmacists, should know that empirical dispensing of vitamin A is not recommended.  Unless there is a deficiency, patients should not be encouraged to take excess amounts of this vitamin as it is known to cause toxicity. Instead, patients should be urged to eat a healthy diet rather than rely on supplements. All interprofessional team members need to share open access to patient information to prevent vitamin A toxicity and deficiency, recognize signs of both conditions, and intervene appropriately to attain the best patient outcomes. [Level 5]