Vitamin A

What it is

Vitamin A is a group of fat-soluble compounds that the body needs for normal vision and immune function, and the liver stores most of the body's reserves [1]. Preformed vitamin A (retinol and its esters) comes almost entirely from animal foods such as liver and is well absorbed (about 74%); plant foods supply provitamin A carotenoids such as beta-carotene, which the body converts to retinol and absorbs less efficiently (about 16%) [2][3]. In adults, serum retinol normally runs from about 0.3 to 1.2 mg/L [1]. Public-health analyses flag retinol intakes above 3,000 µg a day in women and above 600 µg a day in young children as above the tolerable upper intake level [4]. Vitamin A deficiency is still common in low- and middle-income countries, affecting about 190 million children under five [5]. In high-income countries, deficiency and its eye condition xerophthalmia turn up mainly in children on restrictive diets or with conditions such as autism [6].

How it might work

Proposed mechanisms: vitamin A compounds are needed for normal vision and immune defence, and deficiency is linked to eye damage and higher child mortality [1][5]. In deficient children, supplements lower night blindness and diarrhoea deaths, which fits with restoring those functions [5]. For bones, researchers note that high vitamin A intakes affect bone remodelling in animal studies and set out to test whether long-term intake raises fracture risk in people [7].

What the research says

Eyes. In low- and middle-income countries, giving children vitamin A cut night blindness by about two-thirds: in a Cochrane review of two trials with 22,972 children, the risk ratio was 0.32 (95% CI 0.21 to 0.50) [5]. The same review found fewer Bitot's spots (RR 0.42, 0.33 to 0.53 across five trials) and less vitamin A deficiency (RR 0.71, 0.65 to 0.78) [5]. An earlier BMJ meta-analysis of 43 trials found the same pattern for night blindness (rate ratio 0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45) [8]. In pregnancy, a Cochrane review found vitamin A reduced maternal night blindness (RR 0.79, 0.64 to 0.98 across two trials) [9], and in a Bangladesh trial of 125,257 pregnant women weekly vitamin A lowered gestational night blindness from 9.2% to 7.1% [10]. Deficiency eye disease still occurs in rich countries: a 2026 review of 61 paediatric cases found most were linked to restrictive eating patterns [6].

Child deaths. Vitamin A supplementation lowers child deaths in low-income countries, though how large the benefit is remains contested. The 2022 Cochrane review pooled 19 trials with 1,202,382 children: all-cause mortality was 12% lower with vitamin A (RR 0.88, 95% CI 0.83 to 0.93, high-certainty evidence), and diarrhoea deaths were also 12% lower (RR 0.88, 0.79 to 0.98); there was no clear effect on deaths from measles or respiratory disease [5]. A 2017 analysis of 17 trials (1,180,718 children) found a 22% mortality reduction that did not depend on how often, how long or in what total dose supplements were given [11]. However, DEVTA, a cluster-randomised trial in about 1 million north Indian children, found no significant effect on mortality (ratio 0.96, 0.89 to 1.03), and combining it with eight earlier trials gave an 11% reduction (5 to 16) [12]. A 2022 trial synthesis reported that well-concealed trials gave RR 0.91 (0.85 to 0.97) but trials published since 2000 gave only RR 0.96 (0.89 to 1.03), with a funnel-plot suggestion of publication bias [13].

Beta-carotene and lung cancer in smokers. The best-documented harm comes from high-dose beta-carotene in people who smoke or have been exposed to asbestos. In the ATBC trial, 29,133 male smokers took 20 mg of beta-carotene a day for 5 to 8 years: lung cancer incidence was 18% higher (95% CI 3 to 36%) and total mortality 8% higher (1 to 16%) [14]. CARET gave 18,314 smokers, former smokers and asbestos-exposed workers 30 mg of beta-carotene plus 25,000 IU of retinol a day; lung cancer risk rose 28% (RR 1.28, 1.04 to 1.57), deaths from lung cancer rose 46% and deaths from any cause 17%, and the trial stopped early [15]. A meta-analysis of eight trials (167,141 participants) found lung cancer risk 16% higher overall and 21% higher in smokers and asbestos workers [16]; a 2023 analysis of eight trials found the same pattern (RR 1.19, 1.08 to 1.32) [17]. The 2020 Cochrane review rated the smoker/asbestos finding high-certainty: lung cancer incidence RR 1.10 (1.01 to 1.20), lung cancer mortality RR 1.18 (1.01 to 1.38) and all-cause mortality RR 1.09 (1.05 to 1.13) [18]. Beta-carotene at 20 to 30 mg a day was also linked to stomach cancer in smokers and asbestos workers (RR 1.54, 1.08 to 2.19) [19]. Across 31 trials, beta-carotene did not change overall mortality but lung cancer deaths were 14% higher (RR 1.14, 1.02 to 1.27) [20].

No cancer benefit in well-nourished adults. A 2023 meta-analysis of eight randomised trials found overall cancer incidence essentially unchanged (RR 1.02, 95% CI 0.99 to 1.05), with the lung-cancer harm in smokers as the exception (RR 1.19, 1.08 to 1.32) [17]. An earlier meta-analysis of nine trials reached the same conclusion (all cancers RR 1.01, 0.98 to 1.04) [19], as did the Women's Health Study, in which 39,876 women took 50 mg of beta-carotene on alternate days with no change in cancer (RR 1.03, 0.89 to 1.18) [21]. The US Preventive Services Task Force review of 84 studies concluded that vitamin and mineral supplements offer little or no benefit for preventing cancer or heart disease, and noted harm signals including hip fracture with vitamin A and higher lung-cancer and cardiovascular-death risk with beta-carotene [22]. One review reported a borderline 16% higher cancer risk with vitamin A supplements (RR 1.16, 95% CI 1.00 to 1.35) [23].

No heart-disease benefit. The Women's Health Study found no differences in heart attacks (42 vs 50), strokes (61 vs 43), cardiovascular deaths (14 vs 12) or the combined endpoint over a median 4.1 years [21]. CARET's cardiovascular deaths were 26% higher with beta-carotene plus retinol (RR 1.26, 0.99 to 1.61) [15], and the USPSTF pooling found cardiovascular mortality 10% higher with beta-carotene (with or without vitamin A; OR 1.10, 1.02 to 1.19) [22]. The 2012 Cochrane review of antioxidant trials found beta-carotene increased deaths (RR 1.05, 1.01 to 1.09 in low-bias trials), while the pooled vitamin A result (RR 1.07, 0.97 to 1.18) was not statistically significant; higher vitamin A doses were associated with higher mortality [24].

Bones. High long-term intakes of preformed vitamin A are linked to hip fractures. A 2014 meta-analysis of eight intake studies (283,930 participants) and four blood-level studies (8,725 participants) found hip-fracture risk 29% higher with high vitamin A intake (adjusted RR 1.29, 1.07 to 1.57) and 40% higher with high retinol intake (1.40, 1.03 to 1.91); beta-carotene intake was not linked to fractures [25]. In the Nurses' Health Study, 72,337 postmenopausal women were followed for 18 years: the highest total vitamin A intake (at least 3,000 µg a day) carried 48% higher hip-fracture risk than the lowest (RR 1.48, 1.05 to 2.07), and high retinol intake (at least 2,000 vs under 500 µg a day) was linked to an 89% higher risk (RR 1.89, 1.33 to 2.68) [7]. In Swedish men followed for 30 years, the highest serum retinol levels were linked to more fractures (any fracture RR 1.64, 1.12 to 2.41; hip fracture RR 2.47, 1.15 to 5.28) [26]. The meta-analysis also found a U-shaped pattern in blood levels, with both low and high serum retinol carrying higher hip-fracture risk [25].

Toxicity at high doses. A 2026 systematic review of 31 case-based reports of hypervitaminosis A found chronic cases most often involved liver and biliary problems (22.6%), musculoskeletal symptoms (19.4%) and high blood calcium (29.0%); acute overdoses caused headache, double vision and raised pressure inside the skull, and treatment ranged up to liver transplantation [27]. A meta-analysis of 259 published cases found chronic hypervitaminosis A after about 2 mg of retinol per kg per day in oil-based form for months, while water-miscible, emulsified or solid forms were roughly 10 times as toxic, causing the same condition at about 0.2 mg/kg a day within weeks [28]. A separate review describes liver injury progressing from fatty liver to fibrosis and cirrhosis [1]. In pregnancy, more than 10,000 IU a day of supplemental preformed vitamin A in the first trimester was linked to cranial-neural-crest birth defects (prevalence ratio 4.8, 95% CI 2.2 to 10.5 versus 5,000 IU or less), with an apparent threshold near 10,000 IU a day and about 1 in 57 exposed infants estimated to have an attributable malformation [29]. An earlier review notes that osteoporosis and hip fracture have been associated with preformed vitamin A intakes only twice the recommended allowance [3].

Doses used in studies

Child-mortality trials used WHO-style schedules, typically 200,000 IU of retinyl acetate in oil every six months, as in DEVTA [12]; across 17 trials, dosing ranged from every 3 months to every 2 years over 4 to 60 months, and the mortality benefit did not vary with frequency or total dose [11]. Most trials in the Cochrane review ran about a year [5]. The Bangladesh pregnancy trial gave weekly 7,000 µg of retinol equivalents (retinyl palmitate) or 42 mg of beta-carotene from the first trimester through 12 weeks after giving birth [10]. Cancer-prevention trials used 20 mg of beta-carotene a day (ATBC) [14], 30 mg of beta-carotene plus 25,000 IU of retinol a day (CARET) [15] or 50 mg of beta-carotene on alternate days (Women's Health Study) [21]. For the harm studies: birth defects appeared above about 10,000 IU a day of supplemental preformed vitamin A [29]; fracture associations in the Nurses' Health Study were seen in the highest intake groups (at least 3,000 µg a day total, at least 2,000 µg a day of retinol) [7]; chronic hypervitaminosis A followed roughly 2 mg per kg a day of oil-based retinol for months [28].

Safety and interactions

Common side effects. In children, high-dose vitamin A supplements increased vomiting in the first 48 hours (RR 1.97, 95% CI 1.44 to 2.69 across four trials) [5], and vitamin A supplements cause yellowing of the skin and minor gut symptoms [18]. Acute hypervitaminosis A causes headache, double vision and raised pressure inside the skull, while chronic high intake more often causes liver and biliary problems, bone and muscle pain and high blood calcium [27].

Upper limits and toxic doses. Public-health analyses treat retinol intakes above 3,000 µg a day in women and above 600 µg a day in young children as exceeding the tolerable upper intake level [4]. Chronic hypervitaminosis A has been reported at daily doses around 2 mg of retinol per kg of body weight in oil-based form for months, with water-miscible, emulsified or solid forms about 10 times as toxic [28], and osteoporosis and hip fracture have been associated with preformed intakes only twice the recommended allowance [3].

Interactions. Alcohol increases the liver toxicity of retinol, and vitamin A, alcohol and some drugs share liver enzyme pathways, so a review recommends caution with high intakes in drinking populations [30]. People taking synthetic retinoid medicines, which are chemically similar to vitamin A and are themselves teratogenic, should ask a doctor before adding vitamin A supplements [29]. No trials of other specific medicine interactions with vitamin A supplements were found in the records reviewed.

Pregnancy and breastfeeding. More than 10,000 IU a day of supplemental preformed vitamin A in early pregnancy was linked to birth defects, with an apparent threshold near that dose, so women who are pregnant or may become pregnant should talk to a doctor before taking preformed vitamin A supplements [29]. Vitamin A is still needed in pregnancy: deficiency is common in some regions and supplementation reduced maternal night blindness in trials, without a clear effect on maternal or newborn mortality [9]. For breastfeeding, a 2006 review notes that dosing regimens for large vitamin A doses in lactating women have not been systematically evaluated [3].

Relevant conditions. People with liver disease or heavy alcohol use, and older adults whose bones may already be fragile, are the groups the harm evidence points at; they should get medical advice before high-dose vitamin A supplements [1][30][25].

Caveats and open questions

Child-mortality evidence is the most contested part of this page: the 1-million-child DEVTA trial found no significant effect, newer well-concealed trials give smaller estimates, and publication bias has been suggested, which is why that claim is graded B rather than A [12][13]. The eye-benefit evidence is rated moderate-certainty in the Cochrane review, and the benefits are shown for deficient populations; they do not establish benefit for well-nourished people taking supplements [5]. Cancer- and heart-prevention evidence comes mostly from beta-carotene trials, and fewer large trials have tested retinol alone in well-nourished adults [16][22]. Fracture evidence is observational, so it cannot prove cause and effect, and the blood-level association is U-shaped, with low retinol also linked to fractures [25]. The birth-defect finding comes from one large cohort rather than a randomised trial [29]. A recruiting trial in Burkina Faso is testing a simplified method for measuring vitamin A status in at-risk populations.