VITAMIN A
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITAMIN A (VITAMIN A).
Vitamin A (retinol) is converted to retinal and retinoic acid, which bind to nuclear receptors (RARs and RXRs) to regulate gene expression involved in cell growth, differentiation, and vision.
| Metabolism | Hepatic metabolism; retinol is oxidized to retinal by retinol dehydrogenases, then to retinoic acid by retinal dehydrogenases; conjugated with glucuronic acid and excreted in bile. |
| Excretion | Vitamin A is eliminated primarily via biliary excretion into feces as metabolites (approximately 80–90%), with renal excretion accounting for less than 10% of unchanged drug and metabolites. A small fraction undergoes enterohepatic circulation. |
| Half-life | The terminal elimination half-life of vitamin A is variable, ranging from 10 to 100 days due to extensive storage in the liver; in individuals with adequate hepatic stores, the half-life is approximately 50–100 days, but in deficiency states, it may be shorter (10–20 days). Clinically, this long half-life supports once-daily dosing for chronic therapy. |
| Protein binding | Approximately 95% bound to retinol-binding protein (RBP) in plasma; also binds to transthyretin (TTR) in a complex with RBP. |
| Volume of Distribution | Apparent volume of distribution is 0.05–0.2 L/kg, reflecting extensive storage in the liver (90% of body stores) and limited distribution in other tissues. This low Vd indicates sequestration in hepatic and fat stores. |
| Bioavailability | Oral: bioavailability of vitamin A from food sources is 70–90% when consumed with fat; for supplemental forms (retinyl palmitate or acetate), absorption is 70–90%. Topical: systemic absorption is negligible (<5%) with normal application. Intramuscular: not applicable; intravenous formulations are not used due to high toxicity. |
| Onset of Action | Oral: clinical improvement in deficiency symptoms (e.g., night blindness) occurs within 24–72 hours, with normalization of serum retinol levels at 1–2 weeks. Intramuscular (if applicable): not commonly used; topical: improvement in skin conditions may take 2–4 weeks. |
| Duration of Action | Duration of effect is weeks to months due to hepatic storage; a single large dose (e.g., 200,000 IU) can maintain adequate retinol levels for 4–6 months in deficiency. For continuous therapy, effects persist for the duration of treatment. |
| Molecular Weight | 286.45 |
Adults: 10000-50000 IU/day orally for deficiency; up to 100000 IU/day for severe deficiency short-term. Intramuscular: 50000 IU daily for 3 days, then 50000 IU weekly for 2-3 months.
| Dosage form | CAPSULE |
| Renal impairment | No specific GFR-based dose adjustment required; use caution in chronic kidney disease due to risk of hypervitaminosis A. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: reduce dose by 50% and monitor serum retinyl esters. |
| Pediatric use | Deficiency: 5000-10000 IU/kg/day orally for 2-4 weeks; maintenance: 3000-10000 IU/day depending on age. Prophylaxis: 1000-5000 IU/day. |
| Geriatric use | Use lowest effective dose; monitor for hepatotoxicity and bone mineral density loss; recommended daily allowance 700-900 mcg/day (2330-3000 IU/day). |
| 1st trimester | Avoid high doses (>5000 IU/day) due to teratogenic risk; low doses (≤5000 IU/day) may be used for deficiency. Vitamin A is essential for embryogenesis but high doses increase risk of congenital malformations. |
| 2nd trimester | Avoid high doses (>5000 IU/day) as risk of teratogenicity persists. Normal dietary intake is safe. |
| 3rd trimester | Avoid high doses (>5000 IU/day) near term; low doses safe. High doses may be associated with preterm birth. |
Clinical note
Comprehensive clinical and safety monograph for VITAMIN A (VITAMIN A).
| Placental transfer | Vitamin A crosses the placenta; retinol and retinyl esters are transferred. Excessive levels can accumulate and are associated with teratogenicity. |
| Breastfeeding | Vitamin A is excreted into breast milk; levels increase with maternal supplementation. Low doses (≤5000 IU/day) are considered safe; high doses may cause hypervitaminosis A in the infant. Single large postpartum doses are used in some settings to prevent deficiency. |
■ FDA Black Box Warning
No FDA boxed warning specific to vitamin A; however, high doses (>10,000 IU/day) are associated with teratogenicity.
| Common Effects | Injection site reactions pain swelling redness |
| Serious Effects |
Hypervitaminosis AAllergy to vitamin A or any component of the formulation
| Precautions | Hypervitaminosis A (toxicity) causing liver damage, intracranial hypertension, bone abnormalities; teratogenicity in pregnancy; avoid in patients with hyperlipidemia, renal impairment, or liver disease. |
| Food/Dietary | Taking with a fatty meal increases absorption. Avoid excessive alcohol intake as it may impair liver storage and contribute to toxicity. No specific food contraindications but note that some plant foods (e.g., carrots, sweet potatoes) contain provitamin A carotenoids which are safer. |
Loading safety data…
| Lactation Rating | L2 (Safer) for low doses; L3 (Moderately Safe) for high doses |
| Teratogenic Risk | Pregnancy category X. High-dose vitamin A (≥10,000 IU/day) is teratogenic in first trimester, causing CNS, cardiovascular, and craniofacial defects. Isotretinoin (metabolite) has established human teratogenicity. Therapeutic doses (≤5,000 IU/day) have minimal risk, but caution is advised throughout pregnancy. Third trimester: maternal toxicity at excess doses may affect fetus. |
| Fetal Monitoring | Monitor serum retinol levels if high-dose therapy is required. Assess for signs of toxicity (e.g., headache, nausea, hepatotoxicity). Fetal ultrasound for congenital anomalies if high dose exposure occurred in first trimester. |
| Fertility Effects | No adverse effects on fertility at recommended doses. Excess vitamin A may disrupt menstrual cycle; hypervitaminosis A can impair fertility in both sexes. |
| Clinical Pearls | Vitamin A is fat-soluble; administer with fatty meals to enhance absorption. Monitor for hypervitaminosis A with prolonged high doses (>10,000 IU/day), especially in elderly and renal impairment. Topical retinoids may cause photosensitivity. In pregnancy, avoid doses >5,000 IU/day due to teratogenicity. |
| Patient Advice | Take with food containing fat for best absorption. · Do not exceed recommended daily allowance unless prescribed for deficiency. · Report symptoms of toxicity: headache, blurred vision, bone pain, nausea. · Avoid taking additional multivitamins containing vitamin A. · Pregnant women should not exceed 5,000 IU daily. |