Vitamin A deficiency

Vitamin A deficiency arises when body stores of retinol are depleted, impairing the synthesis of retinal (for vision), retinoic acid (for gene regulation), and retinol esters (for storage). The liver stores ~80–90% of body vitamin A, and deficiency develops when dietary intake is chronically inadequate or absorption is compromised (e.g., in celiac disease, cystic fibrosis, or biliary obstruction).¹

Retinol is essential for the visual cycle: 11-cis-retinal binds to opsin to form rhodopsin in rod cells. In deficiency, dark adaptation fails, producing night blindness. Retinoic acid also regulates epithelial cell differentiation; without it, keratinizing metaplasia occurs in the cornea (xerophthalmia) and respiratory tract, increasing infection risk.²

VAD is most prevalent in sub-Saharan Africa and South Asia, where diets rely on starchy staples low in provitamin A carotenoids. The World Health Organization estimates that 250 million preschool children are deficient, with 250,000–500,000 going blind each year; half die within 12 months of losing sight.

Risk factors include poverty, food insecurity, maternal deficiency, and infections like measles and diarrhea that deplete vitamin A stores. In pregnant women, deficiency causes night blindness and increases maternal mortality. In developed countries, VAD is rare but occurs in individuals with malabsorption syndromes, strict vegan diets without supplementation, or liver disease.³

The earliest symptom is night blindness (nyctalopia), followed by conjunctival xerosis (dryness), Bitot's spots (foamy patches on the conjunctiva), and corneal xerosis. Advanced stages lead to keratomalacia (corneal melting) and irreversible blindness. These ocular signs are collectively termed xerophthalmia.

Beyond the eye, VAD compromises epithelial integrity in the respiratory, gastrointestinal, and urinary tracts, increasing susceptibility to infections, particularly measles and diarrhea. In children, severe deficiency is associated with growth retardation and increased mortality. In pregnancy, deficiency contributes to night blindness and may increase the risk of maternal death.⁴

Diagnosis is primarily clinical, based on ocular signs and dietary history. Laboratory tests include serum retinol <0.70 µmol/L (deficient) and <0.35 µmol/L (severe), but these are not always available in low-resource settings. The relative dose-response test and conjunctival impression cytology are more sensitive but rarely used in the field.¹

Treatment involves high-dose oral vitamin A: 200,000 IU for children over 12 months, 100,000 IU for infants 6–12 months, and 50,000 IU for infants under 6 months, given immediately upon diagnosis and repeated the next day and at 2–4 weeks. For xerophthalmia, treatment is urgent to prevent blindness. In cases of malabsorption, parenteral administration may be required.⁵

Prevention strategies include dietary diversification (promoting vitamin A-rich foods like liver, eggs, dairy, and orange-fleshed fruits and vegetables), food fortification (e.g., sugar, oil, and cereal flours), and periodic high-dose supplementation. The WHO recommends supplementation for children 6–59 months in areas with deficiency, and for postpartum women.

Biofortification, such as Golden Rice engineered to produce beta-carotene, has been developed but remains controversial due to regulatory and public acceptance issues. Vitamin A supplementation has been shown to reduce all-cause mortality in children by up to 24% in some meta-analyses, though recent trials have questioned the magnitude of benefit in settings with improved health care.⁶

Historically, vitamin A deficiency was recognized in ancient Egypt and China; night blindness was treated with liver, a practice documented in the Ebers Papyrus (c. 1550 BCE).

In the 1930s, the term 'xerophthalmia' was used to describe the condition, but it was not until the 1980s that global programs began. A notable figure is Dr. Alfred Sommer, whose research in Indonesia in the 1980s demonstrated that even mild deficiency increased child mortality, leading to the widespread adoption of supplementation programs.⁷

VAD also affects immune function by impairing antibody responses and mucosal immunity, which is why it is a risk factor for severe measles. In some cultures, VAD is exacerbated by dietary taboos that restrict consumption of vitamin A-rich foods during pregnancy and lactation. Additionally, vitamin A deficiency can cause follicular hyperkeratosis (phrynoderma), a skin condition characterized by rough, bumpy skin on the upper arms and thighs, which is often overlooked in clinical practice.

Xerophthalmia

A spectrum of ocular changes due to vitamin A deficiency, including night blindness, conjunctival xerosis, Bitot's spots, corneal xerosis, and keratomalacia.

Bitot's spots

Foamy, triangular patches on the conjunctiva, composed of keratinized epithelial cells and bacteria, indicative of vitamin A deficiency.

Keratomalacia

Corneal melting and ulceration leading to blindness, a severe manifestation of vitamin A deficiency.

Retinol

The animal form of vitamin A, essential for vision, immune function, and cellular differentiation.

Provitamin A carotenoids

Plant pigments such as beta-carotene that the body converts into retinol.