tuneTypical Dose
700-900 mcg RAE/day
Vitamin
Vitamin A
Retinol / Retinoic Acid
Evidence TierAWADA NOT PROHIBITED
watchEffect Window
Days to weeks for deficiency correction. Months for acne treatment.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Vitamin A is a fat-soluble vitamin essential for vision, immunity, and epithelial integrity. It is used to prevent deficiency-related night blindness and immune vulnerability, especially in low-intake populations.
Correcting deficiency prevents night blindness and supports immune and mucosal barrier function. In deficient regions, vitamin A programs reduce child morbidity and mortality. Minority evidence includes skin-related benefits, but many strong acne effects involve prescription retinoids rather than nutritional vitamin A. Excess intake is toxic and can increase liver and bone risks, so benefit depends on correcting deficiency within safe limits.
Retinal forms rhodopsin for scotopic vision. Retinoic acid regulates gene transcription via RAR/RXR nuclear receptors controlling cell differentiation, immune function, and epithelial maintenance.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Corrects night blindness and xerophthalmia in deficient populations
- Reduces childhood mortality from measles and diarrhea by 24%
- Isotretinoin achieves 80-90% remission of severe cystic acne
Secondary Outcomes
- Supports epithelial barrier integrity and immune cell function
- Beta-carotene does NOT prevent cancer and increases lung cancer risk in smokers
Safety
Contraindications and Interactions
Contraindications
- Pregnancy or planned pregnancy (high-dose preformed retinol)
- Lactation when considering high-dose preformed retinol without clinician oversight
- Liver disease or hepatic impairment
- Concurrent systemic retinoid therapy
- Current smokers (high-dose beta-carotene)
Side effects
- Nausea, vomiting, headache, or dizziness at high doses
- Abdominal fullness or GI upset
- Dry skin, chapped lips, erythema, or skin peeling (retinoid effects)
- Carotenodermia (yellow-orange skin discoloration from beta-carotene, generally harmless and reversible)
- Bulging fontanelle in infants at excessive dosing
- Hepatotoxicity risk with chronic excess preformed retinol (including fibrosis/cirrhosis at sustained high intake)
Interactions
- Tetracyclines - Additive risk of increased intracranial pressure (pseudotumor cerebri).
- Warfarin - May potentiate anticoagulant effect. Monitor for bleeding risk.
- Orlistat and cholestyramine - Reduce fat-soluble vitamin A absorption.
- Phenobarbital (Theoretical/Unknown) - May decrease blood vitamin A levels.
- Hepatotoxic drugs or supplements (Theoretical/Unknown, e.g., high-dose acetaminophen, statins) - Combined use may increase liver injury risk.
Avoid if
- Pregnant or planning pregnancy (preformed retinol above RDA)
- Current smoker or asbestos exposure (beta-carotene supplements)
- Active liver disease
- Lactation when considering high-dose preformed retinol without clinician oversight
Evidence
Study-level References
vitamin-a-SRC-001Clinical review
Sourceopen_in_newSommer A. "Vitamin A deficiency and clinical disease: an historical overview." J Nutr. 2008;138(10):1835-1839.
Population: Populations with endemic vitamin A deficiency
Dose protocol: Various supplementation regimens
Key findings: Severe vitamin A deficiency causes xerophthalmia (corneal drying and ulceration) and night blindness. Supplementation rapidly reverses these conditions and dramatically reduces mortality from infectious diseases in deficient populations. Established the causal link between vitamin A deficiency and preventable blindness.
Notes: Landmark historical review that established vitamin A supplementation as a global public health priority.
Paper content
Severe vitamin A deficiency causes xerophthalmia (corneal drying and ulceration) and night blindness. Supplementation rapidly reverses these conditions and dramatically reduces mortality from infectious diseases in deficient populations. Established the causal link between vitamin A deficiency and preventable blindness.
vitamin-a-SRC-002Systematic review and meta-analysis (43 trials, 215,633 children)
Sourceopen_in_newMayo-Wilson E, Imdad A, Herber K, Dean S, Bhutta ZA. "Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5." Cochrane Database Syst Rev. 2011;(8):CD008524.
Population: Children aged 6 months to 5 years in low- and middle-income countries
Dose protocol: 100,000-200,000 IU retinol every 4-6 months
Key findings: Vitamin A supplementation reduced all-cause mortality by 24% (RR 0.76, 95% CI 0.69-0.83), diarrhea-related mortality by 28%, and measles-related morbidity by 50%. One of the most cost-effective public health interventions identified.
Notes: Definitive Cochrane review. Forms the basis of WHO universal supplementation recommendations in high-risk regions.
Paper content
Vitamin A supplementation reduced all-cause mortality by 24% (RR 0.76, 95% CI 0.69-0.83), diarrhea-related mortality by 28%, and measles-related morbidity by 50%. One of the most cost-effective public health interventions identified.
vitamin-a-SRC-003Randomized controlled trial (29,133 male smokers, 5-8 years follow-up)
Sourceopen_in_newThe Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. "The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers." N Engl J Med. 1994;330(15):1029-1035.
Population: Male smokers aged 50-69 in Finland
Dose protocol: 20 mg/day beta-carotene, 50 mg/day alpha-tocopherol, or combination
Key findings: Beta-carotene supplementation at 20 mg/day increased lung cancer incidence by 18% (95% CI 3-36%) and total mortality by 8% in male smokers. This unexpected harm was replicated by the CARET trial (Omenn et al., 1996) showing 28% increased lung cancer in smokers/asbestos workers. Established that high-dose beta-carotene is contraindicated in smokers.
Notes: One of the most important negative findings in supplement research. Fundamentally changed beta-carotene supplementation recommendations.
Paper content
Beta-carotene supplementation at 20 mg/day increased lung cancer incidence by 18% (95% CI 3-36%) and total mortality by 8% in male smokers. This unexpected harm was replicated by the CARET trial (Omenn et al., 1996) showing 28% increased lung cancer in smokers/asbestos workers. Established that high-dose beta-carotene is contraindicated in smokers.
vitamin-a-SRC-004Randomized, single-blind, single-center controlled trial.
Sourceopen_in_newFu Q, Liu M, Zhang X, et al. A randomized controlled trial on the efficacy and safety of vitamin A supplementation in children with sepsis. Front Pediatr. 2025;13:1579006. doi:10.3389/fped.2025.1579006. PMID:40843069.
Population: Children diagnosed with sepsis.
Dose protocol: Vitamin A supplementation versus placebo in 156 children with sepsis
Key findings: No significant improvement in ICU length of stay or 28-day mortality. Favorable effects on lactate clearance (25% higher), day 3 lactate levels, and procalcitonin.
Notes: Supports immunomodulatory activity of vitamin A in acutely ill children without improving hard clinical outcomes. Consistent with the known role of retinoic acid in immune regulation.
Paper content
This single-blind RCT tested vitamin A supplementation versus placebo in 156 children with sepsis. The primary outcome (ICU length of stay) was not significantly different between groups, and 28-day mortality and ventilation duration were also similar. However, post hoc biomarker analysis showed that vitamin A improved lactate clearance by 25%, lowered day 3 lactate levels, and reduced procalcitonin and white blood cell counts on specific days. No adverse reactions were observed. The results suggest that vitamin A may favorably modulate inflammation and metabolic stress during sepsis without improving hard clinical outcomes, consistent with the known immunomodulatory role of retinoic acid.