Vitamin A: the supplement that increased cancer in a randomised trial

Vitamin A deficiency is one of the leading preventable causes of childhood blindness in the world, and vitamin A supplements are also the clearest case in nutrition of a pill that made healthy people worse. Both of those are true at once, and the difference between them is who is taking it and why.

What it does in the body

• Vitamin A is involved in immune function, cellular communication, growth and development, and male and female reproduction. — general adults Evidence E source

How much you need

• The RDA for vitamin A is 900 mcg RAE a day for adult men and 700 mcg RAE for adult women. — general adults Evidence E source
• The Tolerable Upper Intake Level for vitamin A is 3,000 mcg a day for adults aged 19 and over, and it applies only to preformed vitamin A from animal sources and supplements, not to carotenoids from plants. — general adults Evidence E source
• The unit printed on labels, mcg RAE, exists because the earlier unit was found to overstate what the body gets from plant food by about double. — American food labelling, all products Evidence E source

How well your body absorbs it

• Doubling the beta-carotene doubled the beta-carotene in the blood but raised the vitamin A made from it by only a third. The body throttles the conversion as the dose climbs. — 7 healthy adult volunteers, 4 men and 3 women Evidence B source
• When the conversion was measured directly in people eating a normal plate of rice, it came out at about 4 to 1 by weight, and it ranged from 2 to 1 to more than 6 to 1 between the five volunteers. — 5 healthy adults, 3 women and 2 men, each served 65 to 98 g of Golden Rice, that is 130 to 200 g cooked, with 10 g of butter Evidence B source
• Three scrambled eggs eaten with a raw vegetable salad raised the absorption of the salad's own carotenoids three to eight times over, and the eggs contributed almost none of those carotenoids themselves. — 16 healthy young men, each eating the same raw mixed-vegetable salad with 3 g canola oil and with no egg, 75 g of scrambled egg, or 150 g of scrambled egg Evidence B source
• Drying orange sweet potato keeps at least 60 per cent of its beta-carotene, and which variety you dry matters as much as how you dry it: one variety kept 99 per cent in the sun. — orange sweet potato in food technology and programme studies, not a human trial Evidence D source
• After cooking, what protects the carotene is the packet: temperature, oxygen and light do the damage during storage, not the cooking itself. — orange sweet potato, cooked and stored, and orange sweet potato flour Evidence D source
• Vitamin A is destroyed by air, and heat and light speed that up, which is why fortified oil is sold in sealed containers that keep the light out. — fortified edible oils and fats in public health programmes Evidence E source

What too little does

• Vitamin A deficiency damages the cornea and can end in permanent blindness, and it is one of the leading preventable causes of childhood blindness. — people with vitamin A deficiency, especially children Evidence E source
• Serum retinol, the test used to call someone vitamin A deficient, misses about nine deficiencies in ten when checked against isotope dilution. — individuals at risk of vitamin A deficiency of any age, sex or physiological state; 40 studies reporting 65 records, of which 25 compared serum retinol with retinol isotope dilution and 16 with liver vitamin A Evidence A source
• About one child in seven in low- and middle-income countries is vitamin A deficient, and the share is highest, nearly one in five, under the age of five. — children and adolescents up to 18 years in low- and middle-income countries; 116 articles from 40 countries, modelled out to 165 countries Evidence C source

Who is most likely to fall short

• Up to 90 per cent of people with cystic fibrosis cannot absorb fat properly, which puts them at risk of vitamin A deficiency. — people with cystic fibrosis Evidence E source

What the evidence does and does not show

• A randomised trial of beta-carotene with vitamin A in smokers was stopped early because lung cancer rose 28 per cent and deaths from it 46 per cent. — smokers and asbestos-exposed adults in the CARET trial Evidence B source
• A Cochrane review pooling 19 trials in more than 1.2 million children aged six months to five years found vitamin A supplements cut deaths from any cause by 12 per cent. — children aged six months to five years living in the community, 19 trials in the mortality analysis Evidence A source
• In the same Cochrane review, vitamin A supplements cut new cases of night blindness by about two thirds and of Bitot's spots by more than half. — children aged six months to five years living in the community, 2 trials for night blindness and 5 for Bitot's spots Evidence A source
• The same review found no difference in deaths from measles or from respiratory disease, so the drop in overall child mortality does not run through those two causes. — children aged six months to five years, 6 trials for measles mortality and 9 for respiratory-disease mortality Evidence A source
• For preventing ordinary colds and other upper respiratory infections in young children, pooled trials show vitamin A supplements do nothing at all. — children up to seven years of age in six trials in lower-middle-income countries, three trials pooled for the main outcome Evidence A source
• In pregnancy, vitamin A supplements lower the risk of maternal night blindness by about a fifth where deficiency is common. — pregnant women in two trials reporting night blindness, out of 19 included trials Evidence A source
• In very premature babies, vitamin A cuts chronic lung disease by 17 per cent, one case avoided for every 16 treated, without changing how many survive. — infants born before 32 weeks' gestation or of very low birth weight; 17 studies qualitatively and 15 in the meta-analysis, 9 for the main outcome Evidence A source
• Pooling the Indian trials, vitamin A supplementation produced no reduction in deaths under five, unlike the global Cochrane estimate. — children aged six months to five years in India Evidence A source
• Across every randomised trial ever run, beta-carotene did not lower death from any cause, and it raised death from lung cancer by about 14 per cent. — adults with any health condition, in 31 randomised trials reported across 44 articles Evidence A source
• Whether modern gentle processing helps or hurts carotenoid absorption is genuinely unknown: the studies that exist contradict each other, and for some techniques there are no human data at all. — carotenoids and polyphenols in processed fruit and vegetable products Evidence E source

What too much does

• Intakes of preformed vitamin A above the Tolerable Upper Intake Level, and some retinoid medicines, can cause congenital birth defects. — general adults Evidence E source
• The same review found that a large dose of vitamin A roughly doubles the chance of vomiting in the two days after it is given. — children aged six months to five years, 4 trials Evidence A source
• In the ATBC trial of 29,133 male smokers in Finland, beta-carotene supplements raised lung cancer risk whatever the tar and nicotine content of the cigarettes. — male smokers aged 50 to 69 in south-west Finland Evidence B source
• Pooling prospective cohorts, a high intake of preformed vitamin A went with about 29 per cent more hip fractures, while beta-carotene showed no such link. — adults in 8 cohorts of vitamin A, retinol or beta-carotene intake and 4 cohorts with measured blood retinol Evidence C source
• Among 311 infants whose mothers took a median of 50,000 IU of vitamin A a day in the first nine weeks of pregnancy, major malformations were no more common than in the comparison groups. — women reporting 10,000 IU a day or more of vitamin A in the first nine weeks of gestation, followed by teratology information services across Europe Evidence C source
• Doses above the WHO recommendation raised respiratory infections by 13 per cent overall, and by 66 per cent in children who were already well nourished. — children in 26 randomised trials; subgroups defined by dose relative to WHO recommendations and by baseline nutritional status Evidence A source
• When vitamin A poisoning reaches a clinic, the commonest finding is a raised blood calcium, and in two cases out of three the source is a capsule, not food. — people with adverse effects or toxicity from hypervitaminosis A, described in 31 studies of which 26 were case reports and 3 case series Evidence C source
• Beta-carotene supplements raise the risk of lung cancer by about 16 per cent, and no dose was low enough to avoid it. — adults in eight randomised trials published to November 2021, including smokers and asbestos workers Evidence A source
• Vitamin A creams near the eye multiply complaints of pain more than sixfold, with prescription strengths driving the harm. — people applying topical vitamin A derivatives to the ocular surface or the skin around the eye, in 89 studies of which 55 were meta-analysed Evidence A source
• Europe kept its ceiling for preformed vitamin A at 3,000 mcg a day for adults in 2024, and set no ceiling at all for beta-carotene, because the data were not good enough to draw one. — European Union population, with a separate warning aimed at smokers Evidence E source

Medicines it interacts with

• The weight-loss drug orlistat reduces absorption of vitamin A and can leave blood levels low. — people taking orlistat Evidence E source

What to do with this

Which half of this page applies to you depends on where you live and what you eat.

If your diet includes dairy, eggs, liver now and then, or orange and dark green vegetables, you are covered. Nothing to add. Beta-carotene from plants converts to vitamin A only as the body needs it, which is why plant sources do not carry the overdose risk that the preformed kind does.

Do not take high-dose preformed vitamin A on your own, and treat the retinoid medicines separately, because both can cause serious harm above the limit of 3,000 micrograms. If you smoke, avoid high-dose beta-carotene and vitamin A supplements outright: the trial that tested them in smokers was stopped early for increased lung cancer and death. And if you are pregnant or might become pregnant, any vitamin A supplement is a question for your doctor before it is a question for a shop.

Myth. Vitamin A does not keep young children from catching colds. Three trials in 22,668 children were pooled, and the number of upper respiratory infections over two weeks came out the same in both groups, a risk ratio of exactly 1.00. Certainty is low because the trials differed in dose and in what they counted, so what this rules out is a useful effect rather than every possible one.

Unsettled. A high intake of preformed vitamin A has been linked to broken hips. Across eight prospective studies covering 283,930 adults, the highest intakes went with about 29 per cent more hip fractures, while beta-carotene showed no such link. These are observational studies, and the curve was U-shaped, so low blood retinol carried risk too. No trial has tested it. That is why it sits here rather than in the safety limit.

Pregnancy has two findings worth holding at once. Where deficiency is common, vitamin A given during pregnancy cut maternal night blindness by about a fifth across two trials, although the same review found no effect on whether mothers or babies survived. The study most often quoted to say that high doses do no harm followed 311 babies whose mothers took a median of 50,000 IU a day in the first nine weeks. It was far too small to rule out anything short of a near tripling of risk. Neither result changes the answer, which is to ask a doctor first.

Two things have changed in what this page can promise. The first is the test. A 2025 Cochrane review found that serum retinol, the measurement behind nearly every statement about vitamin A status, picked up only 10 per cent of genuinely deficient people when checked against isotope dilution, and 53 per cent when checked against the liver itself. It stays negative in 92 per cent of people who have enough, so it is better at saying nothing is wrong than at finding what is. Read a vitamin A result as one piece of a picture rather than as the answer.

The second is the size of the benefit. Pooled worldwide, supplements cut deaths in children by 12 per cent. Pooled within India, they cut them by nothing at all, a risk ratio of 0.96. Both analyses are real and neither has been explained away. The place where vitamin A does something clear-cut is narrower than the headline. In babies born before 32 weeks, it lowered chronic lung disease by 17 per cent, one case avoided for every 16 treated, while the number who survived stayed the same. That decision belongs to a neonatal unit and has nothing to do with the supplement shelf.

On the capsule side the answer has hardened. Beta-carotene raised lung cancer by about 16 per cent across eight trials in 167,141 adults, with no dose low enough to escape it, and across 31 trials it did not lower death from any cause while raising death from lung cancer by 14 per cent.

The one thing here you can act on tonight is fat. Sixteen young men ate the same raw vegetable salad with no egg, with 75 g of scrambled egg and with 150 g. On the largest of those, the carotenoids from the salad came through three to eight times better, and most of them are not in egg at all. Oil, cheese, yoghurt or nuts would be doing the same work.

How much retinol a plate yields varies between people more than a table admits. Five adults eating 130 to 200 g of cooked Golden Rice converted beta-carotene to retinol at about 3.8 to 1 by weight, and across those five the ratio ran from 1.9 to 1 up to 6.4 to 1.

Cooking is kinder than people fear and storage is harsher. Drying orange sweet potato kept at least 60 per cent of its beta-carotene whatever the method, and the variety mattered as much as the method, with one keeping 99 per cent after solar drying. After that the packet decides, because temperature, oxygen and light are what take the carotene out during storage. The same chemistry is why fortified cooking oil comes in sealed containers that keep the light out.

Where to get it from food

The bottom line

Men need 900 micrograms RAE a day and women 700, with an upper limit of 3,000 micrograms for the preformed kind found in liver, supplements and animal foods. Deficiency damages the cornea and can end in permanent blindness, which is why supplementation programmes exist where diets are poor. In well-fed populations the picture inverts. A randomised trial of beta-carotene with vitamin A in smokers was stopped early because lung cancer rose by 28 per cent and deaths from it by 46 per cent. Both halves of that sentence are backed by large numbers. Where children are short of vitamin A, a Cochrane review of 19 trials in more than 1.2 million of them found supplements cut deaths from any cause by 12 per cent, and cut new cases of night blindness by about two thirds. The same review looked at what those children were dying of and found no drop in deaths from measles or from respiratory disease, so whatever is saving them is not running through those two causes. Two things have been added since about where those numbers come from. Europe went back over the upper level in 2024 and kept 3,000 micrograms RE a day for adults, grading it down to 600 for the youngest children. For beta-carotene the same review could not derive an upper level at all, on the ground that there are no adequate data to draw one, and it advises smokers to avoid supplements containing it. Set beside the pooled trials, where beta-carotene supplements raised lung cancer by about 16 per cent with no dose low enough to escape the effect, an absent ceiling is a hole in the evidence rather than a clean bill. The second thing is the unit on the label. RAE counts 6 micrograms of dietary beta-carotene as equal to 1 microgram of purified beta-carotene in a supplement, because dietary beta-carotene turned out to be absorbed about half as well as the older unit assumed.

Sources

1. vita-01 · Position of an expert body · expert body statement
   Vitamin A is involved in immune function, cellular communication, growth and development, and male and female reproduction.
   NIH Office of Dietary Supplements, VitaminA - Health Professional Fact Sheet · checked 2026-09-16 · extracted
2. vita-02 · Position of an expert body · expert body statement
   900 mcg RAE for adolescent and adult men; 700 mcg RAE for adult women (value from the source's table, not a sentence)
   NIH Office of Dietary Supplements, VitaminA - Health Professional Fact Sheet · checked 2026-09-16 · extracted
3. vita-03 · Position of an expert body · expert body statement
   3,000 mcg for adults age 19 and older, applying only to products from animal sources and supplements (value from the source's table, not a sentence)
   NIH Office of Dietary Supplements, VitaminA - Health Professional Fact Sheet · checked 2026-09-16 · extracted
4. vita-e2-03 · Position of an expert body · regulatory rule preamble
   RAEs consider 6 mcg of dietary [beta]-carotene to be equivalent to 1 mcg of purified [beta]-carotene in supplements (i.e., a carotene:retinol equivalency ratio of 6:1) because more recent evidence suggests that the bioavailability of [beta]-carotene is approximately half of what was previously considered for setting mcg RE.
   Food Labeling: Revision of the Nutrition and Supplement Facts Labels (proposed rule), FDA, 2014, section on units of vitamin A activity · checked 2026-09-18 · independently re-checked
5. vita-e2-01 · Randomised controlled trial(s) · randomised crossover controlled trial
   The plasma AUC for beta-carotene-d8 increased 2-fold from the 20-mg dose to the 40-mg dose. The plasma AUC for ROH-d4 increased 36% from the 20-mg dose to the 40-mg dose.
   Novotny et al., The Journal of Nutrition, 2010 · checked 2026-09-18 · independently re-checked
6. vita-e2-02 · Randomised controlled trial(s) · controlled human isotope feeding study
   Thus, the conversion factor of Golden Rice beta-carotene to retinol is 3.8 +/- 1.7 to 1 with a range of 1.9-6.4 to 1 by weight, or 2.0 +/- 0.9 to 1 with a range of 1.0-3.4 to 1 by moles.
   Tang et al., American Journal of Clinical Nutrition, 2009 · checked 2026-09-18 · independently re-checked
7. vita-e2-04 · Randomised controlled trial(s) · randomised crossover controlled trial
   The TRL AUC(0-10h) of lutein and zeaxanthin increased 4-5-fold (P < 0.001), and the TRL AUC(0-10h) of carotenoid not present in eggs, including α-carotene, β-carotene, and lycopene, increased 3-8-fold (P < 0.01) for the HE meal compared with the control meal.
   Kim et al., American Journal of Clinical Nutrition, 2015 · checked 2026-09-18 · independently re-checked
8. vita-e2-05 · Mechanistic or laboratory data · systematic review of food retention studies
   Drying methods retained at least 60% of ATBC or BC but varied by variety
   Nature Food, 2023 · checked 2026-09-18 · independently re-checked
9. vita-e2-06 · Mechanistic or laboratory data · systematic review of food retention studies
   Studies showed that packaging types along with other variables such as temperature, oxygen and light levels are critical to consider to maximize BC retention during storage
   Nature Food, 2023 · checked 2026-09-18 · independently re-checked
10. vita-e2-07 · Position of an expert body · WHO guideline, technical section
    Vitamin A is sensitive to oxidation by air. Loss of activity is accelerated by heat and exposure to light.
    WHO Guideline on fortification of edible oils and fats with vitamins A and D for public health, World Health Organization, 2025 · checked 2026-09-18 · independently re-checked
11. vita-05 · Position of an expert body · expert body statement
    Xerophthalmia also affects the cornea and can eventually lead to permanent blindness; vitamin A deficiency is one of the top causes of preventable blindness in children
    NIH Office of Dietary Supplements, Vitamin A - Health Professional Fact Sheet · checked 2026-09-16 · extracted
12. vita-r3-01 · Meta-analysis or systematic review · Cochrane systematic review of diagnostic test accuracy
    SR pooled sensitivity against RID at the 0.1 μmol/g cutoff was 10% (95% confidence interval (CI) 2 to 38; 23 studies, 385 participants; very low-certainty evidence), and specificity was 92% (95% CI 85 to 96; 23 studies, 1110 participants; low-certainty evidence)...SR pooled sensitivity against liver vitamin A at the 0.1 μmol/g cutoff was 53% (95% CI 30 to 75; 16 studies, 192 participants; very low-certainty evidence) and specificity was 83% (95% CI 63 to 93; 16 studies, 370 participants; moderate-certainty evidence).
    Cochrane Database of Systematic Reviews, 2025 · checked 2026-09-17 · independently re-checked
13. vita-r3-02 · Observational data · systematic review and modelling analysis of prevalence data
    In 2019, VAD and mVAD affected 333.95 million (95% CI = 253.00-433.74) and 556.13 million (95% CI = 388.83-767.94) children and adolescents in 165 LMICs, respectively, corresponding to a prevalence of 14.73% (95% CI = 11.16-19.14) and 24.54% (95% CI = 17.15-33.88). The prevalence of both VAD and mVAD was the highest in children aged 0-5 years at 19.53% (95% CI = 15.03-24.91) and 28.22% (95% CI = 20.00-38.24), respectively
    Journal of Global Health, 2023 · checked 2026-09-17 · independently re-checked
14. vita-06 · Position of an expert body · expert body statement
    Up to 90% of people with cystic fibrosis have pancreatic insufficiency, which increases their risk of vitamin A deficiency due to difficulty absorbing fat
    NIH Office of Dietary Supplements, Vitamin A - Health Professional Fact Sheet · checked 2026-09-16 · extracted
15. vita-08 · Randomised controlled trial(s) · review of trials cited by expert body
    The trial was ended prematurely after a mean of 4 years, partly because the supplements were unexpectedly found to have increased lung cancer risk by 28% and death from lung cancer by 46%; the supplements also increased the risk of all-cause mortality by 17%
    NIH Office of Dietary Supplements, Vitamin A - Health Professional Fact Sheet · checked 2026-09-16 · extracted
16. vita-t1 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence).
    Imdad et al., Cochrane Database of Systematic Reviews, 2022 · checked 2026-09-16 · independently re-checked
17. vita-t4 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.45, 95% CI 0.30 to 0.69; 2 studies, 1,982 children; low-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence).
    Imdad et al., Cochrane Database of Systematic Reviews, 2022 · checked 2026-09-17 · independently re-checked
18. vita-t5 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis.
    Imdad et al., Cochrane Database of Systematic Reviews, 2022 · checked 2026-09-17 · independently re-checked
19. vita-t6 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence).
    Cheng et al., Cochrane Database of Systematic Reviews, 2024 · checked 2026-09-17 · independently re-checked
20. vita-t8 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    Vitamin A supplementation reduces the risk of maternal night blindness (RR 0.79, 95% CI 0.64 to 0.98; two trials).
    McCauley et al., Cochrane Database of Systematic Reviews, 2015 · checked 2026-09-17 · independently re-checked
21. vita-r3-03 · Meta-analysis or systematic review · systematic review and meta-analysis of randomised trials
    Moderate-certainty evidence suggested a beneficial effect of vitamin A for decreasing the risk of BPD at 36 wk postmenstrual age (RR: 0.83; 95% CI: 0.74, 0.93; numbers needed to treat for an additional beneficial outcome: 16; 95% CI: 9, 53; 9 studies, n = 1752; P = 0.002)...Vitamin A supplementation did not have adverse effects and did not alter mortality before discharge (12 studies, n = 1917) or neurodevelopmental outcomes at 18-22 mo (1 study, n = 538).
    American Journal of Clinical Nutrition, 2021 · checked 2026-09-17 · independently re-checked
22. vita-r3-05 · Meta-analysis or systematic review · meta-analysis of trials in a single country
    There was no reduction in risk of all-cause mortality with VAS (RR=0.96; 95% CI: 0.89, 1.03). When regressing mortality on VAD in high or low VAD prevalence states, the regression coefficients were discordant.
    Indian Pediatrics, 2022 · checked 2026-09-17 · independently re-checked
23. vita-r6-03 · Meta-analysis or systematic review · systematic review and meta-analysis of randomised controlled trials
    In a random-effects meta-analysis of all 31 trials, beta-carotene supplements were found to have no preventive effect on mortality (risk ratio 1.02, 95% confidence interval 0.98-1.05, I 2 = 42%). Further, the analysis showed no preventive effect on cancer, cardiovascular, cerebrovascular, and other mortality causes. Instead, beta-carotene supplementation significantly increased the risk of lung cancer mortality (RR 1.14, 95% CI 1.02, 1.27, I 2 = 3%) but decreased the risk of human immunodeficiency virus-related mortality (RR 0.55, 95% CI 0.33, 0.92, I 2 = 0).
    Gallicchio et al., Frontiers in Medicine, 2022 · checked 2026-09-17 · independently re-checked
24. vita-e2-09 · Position of an expert body · expert position paper
    Considering bioaccessibility, studies have mainly focused on the effect of high pressure processing on carotenoids, with contradictory results.
    Bohn et al., Molecular Nutrition & Food Research, 2015 · checked 2026-09-18 · independently re-checked
25. vita-04 · Position of an expert body · expert body statement
    Total intakes of preformed vitamin A that exceed the UL as well as some retinoid medications can cause congenital birth defects.
    NIH Office of Dietary Supplements, VitaminA - Health Professional Fact Sheet · checked 2026-09-16 · extracted
26. vita-t2 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies, 10,541 children; moderate-certainty evidence).
    Imdad et al., Cochrane Database of Systematic Reviews, 2022 · checked 2026-09-16 · independently re-checked
27. vita-t3 · Randomised controlled trial(s) · randomised controlled trial
    These findings support the conclusion that supplementation with β-carotene increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked.
    Middleton et al., Nicotine & Tobacco Research, 2019 · checked 2026-09-16 · independently re-checked
28. vita-t7 · Observational data · meta-analysis of prospective cohort studies
    Eight vitamin A (or retinol or beta-carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included...High intake of vitamin A and retinol were shown to increase risk of hip fracture (adj.RR [95% CI] = 1.29 [1.07, 1.57] and 1.40 [1.03, 1.91], respectively), whereas beta-carotene intake was not found to increase the risk of hip fracture (adj.RR [95% CI] = 0.82 [0.59, 1.14]).
    Wu et al., Journal of Bone and Mineral Research, 2014 · checked 2026-09-17 · independently re-checked
29. vita-t9 · Observational data · prospective controlled cohort study
    The presence of major structural malformations, excluding chromosomal and genetic diseases, was evaluated in 311 infants exposed to a median daily dose of vitamin A of 50,000 IU per day (range, 10,000-300,000 IU per day; interquartile range, 25,000-60,000 IU per day)...When the birth prevalence rate of major malformations in the study group was compared with two internal control groups of infants exposed to: 1) "high" vitamin A exposure later in pregnancy, and 2) nonteratogenic agent exposures, the rate ratio was, respectively, 0.28 (CI 95% interval, 0.06, 1.23) and 0.50 (CI 95% interval, 0.14, 1.76).
    Mastroiacovo et al., Teratology, 1999 · checked 2026-09-17 · independently re-checked
30. vita-r3-04 · Meta-analysis or systematic review · systematic review and meta-analysis of randomised trials
    There was no significant association of VAS with the incidence of ARTI compared with the placebo (RR 1.03, 95% CI 0.92 to 1.15). Subgroup analyses showed that VAS higher than WHO recommendations increased the incidence of ARTI by 13% (RR 1.13, 95% CI 1.07 to 1.20), and in the high-dose intervention group, the incidence rate among well-nourished children rose by 66% (RR 1.66, 95% CI 1.30 to 2.11).
    Nutrients, 2021 · checked 2026-09-17 · independently re-checked
31. vita-r6-01 · Observational data · systematic review of case reports and case series
    Various sources of vitamin A toxicity were reported, most commonly vitamin A capsules or tablets (n = 21, 67.7%). The most common adverse effect was hypercalcemia (n = 9, 29.0%), followed by gastrointestinal manifestations (n = 8, 25.8%), neurological manifestations (n = 7, 22.6%), hepatobiliary manifestations (n = 7, 22.6%), musculoskeletal manifestations (n = 6, 19.4%), and dermatological manifestations (n = 5, 16.1%).
    Kumar, Clinica Chimica Acta, 2026 · checked 2026-09-17 · independently re-checked
32. vita-r6-02 · Meta-analysis or systematic review · systematic review and meta-analysis of randomised controlled trials
    The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06-1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08-1.35) and non-medics (RR = 1.18, 95% CI = 1.07-1.29).
    Wysocka et al., Nutrients, 2022 · checked 2026-09-17 · independently re-checked
33. vita-r6-04 · Meta-analysis or systematic review · systematic review and meta-analysis
    Eighty-nine studies (10,794 participants) met inclusion criteria; 55 were included in meta-analysis. Compared with controls, topical vitamin A derivatives increased odds of pain (OR = 6.37), dryness (OR = 2.69), burning (OR = 2.44), and any harm (OR = 1.71). Serious adverse events were uncommon and not significantly increased (OR = 1.21).
    Alanazi et al., Investigative Ophthalmology and Visual Science, 2026 · checked 2026-09-17 · independently re-checked
34. vita-e2-08 · Position of an expert body · expert body statement
    β-Carotene(c) No adequate data to derive a UL
    Overview on Tolerable Upper Intake Levels as derived by the EFSA NDA Panel, European Food Safety Authority, 2024 · checked 2026-09-18 · independently re-checked
35. vita-07 · Position of an expert body · expert body statement
    Orlistat (Alli, Xenical), a weight-loss treatment, can decrease the absorption of vitamin A, other fat-soluble vitamins, and beta-carotene, resulting in low plasma levels in some patients
    NIH Office of Dietary Supplements, Vitamin A - Health Professional Fact Sheet · checked 2026-09-16 · extracted