Benefits
Night vision and normal eyesight
Vitamin A forms rhodopsin, the light-sensitive pigment the retina uses in dim light, so night blindness is the first sign of deficiency. In children in low- and middle-income countries, supplements cut night blindness (RR 0.32) and Bitot's spots (RR 0.42). No trial cited here shows a vision gain in well-nourished adults, and beta-carotene with vitamins C and E alone did not significantly slow AMD in AREDS.
Immune function and mucosal barriers
Vitamin A is involved in immune function and in maintaining the linings of the airways and gut. In children in low- and middle-income countries, supplementation reduced diarrhea episodes (RR 0.85) and measles cases (2 trials, low certainty), but did not reduce respiratory infections. No trial cited here shows an immune benefit in well-nourished adults.
Child survival where vitamin A deficiency is common
A Cochrane review of trials in about 1.2 million children aged 6 months to 5 years, mostly in low- and middle-income countries, found 12% fewer deaths from all causes with vitamin A (RR 0.88). The largest single trial, in about 1 million Indian children, found no significant effect on its own. This applies to children where deficiency is common, not to well-nourished adults.
Cell growth and organ development
Vitamin A supports cell growth and differentiation and plays a key role in the normal formation and maintenance of the heart, lungs, eyes and other organs. These are roles of adequate vitamin A status; no trial cited here shows that extra vitamin A improves skin or organs in people who already get enough.
Reproduction and fetal development
Vitamin A is involved in male and female reproduction, and pregnant women need extra for fetal growth. Too much preformed vitamin A is harmful in pregnancy: in a study of 22,748 pregnancies, more than 10,000 IU a day from supplements was linked to a higher rate of birth defects. Pregnant women should stay under 3,000 mcg a day of preformed vitamin A.
Mechanism of action
Rhodopsin and the visual cycle
Vitamin A is an essential part of rhodopsin, the light-sensitive protein in the retina that responds to light entering the eye. Low vitamin A lowers rhodopsin, which is why night blindness is the first sign of deficiency.
Cornea and conjunctiva
Vitamin A supports the normal differentiation and functioning of the conjunctival membranes and cornea. Prolonged deficiency dries and damages the cornea (xerophthalmia), which can lead to permanent blindness.
Cell growth and differentiation
Through its active forms, vitamin A regulates cell growth and differentiation, which underlies its roles in immune function, organ formation and reproduction.
Carotenoid conversion
The body converts provitamin A carotenoids such as beta-carotene into vitamin A in the intestine through the BCMO1 enzyme. Conversion rates vary between people, partly because of common gene variants.
Liver storage
Because vitamin A is fat-soluble, the body stores excess amounts, mainly in the liver. Stores protect against short shortfalls, but regular high intakes of preformed vitamin A can build up to toxic levels.
Clinical trials
Cochrane systematic review and meta-analysis of 47 randomized trials of vitamin A supplementation, mostly in low- and middle-income countries; the 2022 update found no new trials. (Imdad et al. 2022, Cochrane Database Syst Rev)
About 1.2 million children aged 6 to 59 months.
All-cause mortality fell 12% (RR 0.88, 95% CI 0.83 to 0.93; 19 trials; high certainty) and diarrhea deaths 12% (RR 0.88). Supplements reduced diarrhea episodes (RR 0.85), measles cases (RR 0.45; 2 trials, low certainty), Bitot's spots (RR 0.42), night blindness (RR 0.32) and vitamin A deficiency (RR 0.71). There was no evidence of a difference for deaths from measles (RR 0.88, 95% CI 0.69 to 1.11) or respiratory disease, respiratory infections, meningitis, or hospital stays for diarrhea or pneumonia. Vomiting within 48 hours was more common (RR 1.97).
Cluster-randomized trial in north India: 200,000 IU retinyl acetate every 6 months for 5 years versus no vitamin A, across 72 blocks of village child-care centres; 25,000 deaths recorded at ages 1 to 6. (Awasthi et al. 2013, Lancet)
About 1 million preschool children in north India, where vitamin A deficiency is common.
Blood retinol rose and Bitot's spots fell from 3.5% to 1.4%, but deaths did not differ significantly (mortality ratio 0.96, 95% CI 0.89 to 1.03, P=0.22). Pooled with eight earlier trials, the authors estimated an 11% average reduction in child deaths (95% CI 5 to 16%).
Systematic review and meta-analysis of five randomized trials in Africa (four in hospitals) comparing vitamin A with placebo in children with measles. (D'Souza et al. 2002, J Trop Pediatr)
923 children aged 6 months to 13 years (445 vitamin A, 478 placebo).
Pooled across all five trials, the 39% lower death rate was not statistically significant. In hospitalized children in high case-fatality areas, 200,000 IU on two consecutive days was linked to fewer deaths (RR 0.36) and fewer pneumonia deaths (RR 0.33); a single dose was not (RR 1.25). This is supervised treatment of active measles, not a consumer supplement use.
Community trial in northern Sumatra: 450 villages randomly assigned to a vitamin A capsule program (229) or to serve as controls for one year (221); children over 1 year received 200,000 IU, repeated 6 months later. (Sommer et al. 1986, Lancet)
25,939 preschool children examined at baseline and again after 11 to 13 months.
Among children aged 12 to 71 months, deaths were 7.3 per 1,000 in control villages versus 4.9 per 1,000 in supplemented villages (P<0.05). The authors suggested supplements may reduce deaths in deficient populations by as much as 34%. Villages, not children, were randomized, and the much larger DEVTA trial did not reproduce an effect of this size.
11-center, double-masked, randomized, placebo-controlled trial: antioxidants (vitamin C 500 mg, vitamin E 400 IU, beta-carotene 15 mg), zinc 80 mg with copper 2 mg, both, or placebo; average follow-up 6.3 years. (Age-Related Eye Disease Study Research Group 2001, Arch Ophthalmol)
3,640 adults aged 55 to 80 with various stages of age-related macular degeneration.
Antioxidants plus zinc reduced the odds of developing advanced AMD versus placebo (OR 0.72, 99% CI 0.52 to 0.98). Antioxidants alone (OR 0.80, 99% CI 0.59 to 1.09) and zinc alone (OR 0.75) were not significant. The trial tested a multi-nutrient formula and does not show an eye benefit for beta-carotene or vitamin A on their own.
Epidemiologic follow-up of the AREDS2 randomized trial from December 2012 to December 2018, comparing participants originally assigned beta-carotene or lutein/zeaxanthin. (Chew et al. 2022, JAMA Ophthalmol)
3,882 AREDS2 participants (mean age 72; 57.7% women).
At 10 years the odds of lung cancer were raised for those assigned beta-carotene (OR 1.82, 95% CI 1.06 to 3.12) but not for lutein/zeaxanthin (OR 1.15, 95% CI 0.79 to 1.66), even though all participants took a beta-carotene-free formula during follow-up. Compared directly with beta-carotene, lutein/zeaxanthin was linked to less progression to late AMD (HR 0.85).
Multicenter, randomized, double-blind, placebo-controlled prevention trial of beta-carotene 30 mg plus 25,000 IU retinyl palmitate (preformed vitamin A) a day; mean follow-up 4 years. (Omenn et al. 1996, N Engl J Med)
18,314 smokers, former smokers and asbestos-exposed workers.
The supplement group had more lung cancer (RR 1.28, 95% CI 1.04 to 1.57) and higher death from any cause (RR 1.17, 95% CI 1.03 to 1.33). The trial was stopped 21 months early.
Randomized, double-blind, placebo-controlled 2 x 2 factorial trial of alpha-tocopherol 50 mg, beta-carotene 20 mg, both, or placebo daily; follow-up 5 to 8 years. (The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group 1994, N Engl J Med)
29,133 male smokers aged 50 to 69 in Finland.
Men given beta-carotene had 18% more lung cancer (95% CI 3 to 36%) and 8% higher total mortality (95% CI 1 to 16%) than men not given it, mainly from lung cancer and ischemic heart disease. Neither supplement reduced lung cancer.