Vitamin A | Supplementopedia

Overview

Vitamin A refers to a group of fat-soluble compounds—including retinol, retinal, retinoic acid, and provitamin A carotenoids (e.g., β-carotene)—that are essential for vision, cellular differentiation, and immune function. In the body it acts primarily as a regulator of gene expression, enabling the body to maintain healthy epithelial tissues, support visual phototransduction, and modulate immune responses.

Benefits

Vision: Retinal combines with opsin to form rhodopsin, enabling scotopic (low-light) vision; deficiency leads to night-blindness (WHO, 2022).
Immune function: Retinoic acid promotes differentiation of T-helper and regulatory T cells, enhancing mucosal immunity and reducing infection risk (Mason et al., 2021).
Cellular differentiation & skin health: Vitamin A drives keratinocyte maturation, reducing keratinization disorders and supporting wound healing (Klein, 2020).
Reproductive health: Adequate levels support spermatogenesis and embryonic development; deficiency is linked to congenital malformations (WHO, 2022).
Antioxidant activity: Provitamin A carotenoids act as free-radical scavengers, protecting ocular and skin tissues from oxidative damage (García-López, 2023).
Metabolic regulation: Retinoic acid modulates adipogenesis and insulin sensitivity, influencing body-weight regulation (Huang & Liu, 2021).

How It Works

Process: Vitamin A functions primarily through its active metabolite, all-trans-retinoic acid (ATRA).
Pathway: ATRA binds nuclear retinoic acid receptors (RARα, β, γ) and retinoid X receptors (RXR), forming heterodimers that bind retinoic-acid-response elements (RAREs) in DNA. This transcriptional complex modulates expression of >500 genes involved in cell-cycle control, differentiation, and apoptosis.
Visual Cycle: In the visual cycle, retinal (the aldehyde form) combines with 11-cis-retinal to form rhodopsin; photon absorption triggers isomerization to all-trans-retinal, initiating the phototransduction cascade.
Provitamin A Conversion: Provitamin A carotenoids are enzymatically cleaved by β-carotene 15,15′-dioxygenase to yield retinal, which can be reduced to retinol for storage in hepatic stellate cells as retinyl esters.
Mobilization: Retinol is mobilized via retinol-binding protein (RBP) and delivered to peripheral tissues where it is oxidized to retinal or retinoic acid as needed.

Dosage

The Recommended Dietary Allowance (RDA) for adults is 900 µg RAE (retinol activity equivalents) for men and 700 µg RAE for women (≈3,000 IU).
Upper tolerable intake for adults is 3,000 µg RAE (≈10,000 IU) per day to avoid hypervitaminosis A.
Typical supplement formulations provide 2,500–5,000 IU of retinyl acetate or palmitate; β-carotene supplements are often 5–15 mg (≈3,000–9,000 IU).
For therapeutic use (e.g., xerophthalmia) WHO recommends 200,000 IU oral dose for 2–3 days, then 25,000 IU daily for 2 weeks.
Fat-soluble vitamins are best taken with a meal containing 5–10 g of dietary fat to improve absorption.
Pregnant women should not exceed 2,500 µg RAE/day due to teratogenic risk; prenatal supplements usually contain 2,500–5,000 IU (≈800–1,600 µg RAE) of pre-formed vitamin A.

Safety & Side Effects

Acute toxicity (>25 mg RAE/kg) can cause nausea, headache, and hepatic dysfunction; chronic intake >10 mg RAE/day may lead liver fibrosis, bone demineralization, and teratogenic effects (neural-tube defects) in pregnancy.
Contraindications include pregnancy, chronic liver disease, and hyperlipidemia when high-dose retinyl esters are used.
Drug interactions: retinoids increase serum levels of warfarin, tetracyclines, and some antiretrovirals; isotretinoin and vitamin A have additive teratogenic risk.
Populations at risk of deficiency (e.g., children in low-income settings) require supplementation, but monitoring is essential to avoid excess.
Patients on cholesterol-lowering agents (e.g., statins) should be cautioned, as retinoids can increase serum triglycerides.
Chronic alcohol consumption potentiates hepatic toxicity.

Chemistry

Vitamin A is a family of C₁₈ isoprenoid compounds.
The most biologically active form, retinol, has the molecular formula C₂₀H₃₀O and an IUPAC name (2E,4E,6E,8E)-3,7-dimethyl-2,4,6,8,10‑dodecapentaen-1‑ol.
Retinal (C₂₀H₂₈O) differs by a terminal aldehyde group, while retinoic acid (C₂₀H₂₈O₂) contains a carboxylic acid.
Key structural features: a β-ionone ring, a polyunsaturated hydrocarbon chain with conjugated double bonds (conjugated triene system) essential for light absorption, and a terminal hydroxyl (retinol) or aldehyde (retinal) or acid (retinoic acid) functional group that determines its biochemical role.
The molecule is lipophilic (log P ≈ 6), poorly soluble in water, and stable under low-light, neutral-pH conditions, but susceptible to oxidation and isomerization upon exposure to light, heat, or oxygen.

Sources & Quality

Natural vitamin A is sourced from animal liver (beef, cod liver) and dairy (butter, cheese) as retinyl esters; plant sources (carrots, sweet potatoes, leafy greens) provide provitamin A carotenoids such as β-carotene, α-carotene, and β-cryptoxanthin.
Commercially, retinyl acetate/palmitate is synthesized chemically from β-ionone through a series of condensation and reduction steps, yielding high-purity retinoids for pharmaceutical use.
Carotenoid extracts are obtained by supercritical CO₂ or solvent extraction from carrots or algae, then saponified to yield β-carotene.
Quality considerations include verification of RAE conversion factor (β-carotene: 2 µg RAE = 1 µg retinol), absence of oxidation products (e.g., retinyl esters > 90 % purity), and compliance with GMP and USP/Ph. Eur. standards.
For clinical use, pharmaceutical-grade retinyl acetate is preferred for its stability and predictable bioavailability.