Evidence explainerVitamin A (retinyl palmitate vs beta-carotene)

Smoked in the Past? Why Beta-Carotene Was Pulled From the Classic Eye-Vitamin Formula

Three large trials found more lung cancer when smokers or former smokers took high-dose beta-carotene. That finding reshaped a best-selling eye formula. Here is what each trial showed and how to read your label.

By Kymata Health editorial teamPublished October 9, 2026Last reviewed October 9, 2026

Medical review pending. Written by our editorial team from the studies cited below; a credentialed clinician has not reviewed it yet. Educational only, not medical advice.

Key takeaways

  • In 29,133 Finnish male smokers, 20 mg/day of beta-carotene for 5 to 8 years raised lung cancer incidence by 18% and total mortality by 8% [2].
  • In CARET, 30 mg/day of beta-carotene plus retinyl palmitate raised lung cancer risk by 28% and death from any cause by 17%, and the trial stopped 21 months early [3][1].
  • In the AREDS2 eye trial, more lung cancers occurred with beta-carotene than without (23 vs 11), mostly in former smokers [4].
  • Removing beta-carotene from the AREDS formula had no apparent effect on progression to advanced AMD, and lutein + zeaxanthin was suggested as the substitute [4].
  • The FNB advises against beta-carotene supplements for the general population, except as a source of vitamin A for people at risk of deficiency [1].

Safety at a glance

From our Vitamin A (retinyl palmitate vs beta-carotene) monograph. Published interactions and cautions only, each with its source.

Interactions

  • Oral retinoids. Taken with vitamin A supplements, these vitamin A-derived drugs can increase the risk of vitamin A toxicity.[1]
  • Orlistat. Lowers absorption of vitamin A, beta-carotene and other fat-soluble vitamins; the manufacturers advise a multivitamin with these vitamins.[1]

Who should be careful

  • Pregnancy. Preformed vitamin A above the UL can cause birth defects of the eye, skull, lungs and heart. Experts advise women who are or might be pregnant, and those breastfeeding, against supplements providing more than 3,000 mcg RAE (10,000 IU) a day.[1]
  • Smokers and former smokers. High-dose beta-carotene (20–30 mg/day) raised lung cancer and mortality in smokers and asbestos-exposed workers in two large trials, and more lung cancers were seen with beta-carotene in former smokers in AREDS2.[3][4][5]
  • High intakes. Chronic high intake of preformed vitamin A can cause dry skin, painful muscles and joints, fatigue, depression and abnormal liver tests; very large single doses cause headache, blurred vision, nausea and dizziness.[1]
  • Before you start. Talk to your pharmacist or clinician before adding this supplement, especially if you take prescription medicines, are pregnant or breastfeeding, or have a chronic health condition.[1]

Full Vitamin A (retinyl palmitate vs beta-carotene) safety section

The evidence, graded

Pulled from our monograph evidence tables. Grades follow our evidence-grading policy.

  • Grade BImprovedHarms in male smokers with beta-carotene (ATBC)Vitamin A (retinyl palmitate vs beta-carotene) · RCT · n=29,133 · 1994 · PMID 8127329Lung cancer incidence was 18% higher with beta carotene (95% CI 3 to 36 percent), and total mortality was 8% higher, mainly from lung cancer and ischemic heart disease.
  • Grade BImprovedHarms in smokers and asbestos-exposed workers (CARET)Vitamin A (retinyl palmitate vs beta-carotene) · RCT · n=18,314 · 1996 · PMID 8602180Lung cancer risk rose (RR 1.28; 95% CI 1.04 to 1.57), as did death from any cause (RR 1.17) and from lung cancer (RR 1.46). The trial was stopped 21 months early.
  • Grade CNo effectEye-condition progression when beta-carotene is removed from the AREDS formulaVitamin A (retinyl palmitate vs beta-carotene) · RCT · n=4,203 · 2013 · PMID 23644932Eliminating beta carotene had no apparent effect on progression to advanced AMD. More lung cancers occurred with beta carotene than without (2.0% vs 0.9%), mostly in former smokers.

The result nobody expected

Beta-carotene was tested where lung cancer risk was highest. The ATBC study gave 29,133 male smokers aged 50 to 69 in Finland 20 mg/day of beta-carotene, vitamin E, both, or placebo for 5 to 8 years [2][1].

Instead of a benefit, lung cancer incidence was 18% higher with beta-carotene (95% CI 3 to 36 percent), and total mortality was 8% higher [2]. ODS notes the extra deaths were mainly from lung cancer and ischemic heart disease [1].

A second trial, the same direction

CARET enrolled 18,314 current and former smokers and asbestos-exposed workers aged 45 to 74 [1]. They took 30 mg of beta-carotene plus 25,000 IU of retinyl palmitate daily, or placebo [3].

After an average of 4.0 years, lung cancer risk was 28% higher (RR 1.28), death from lung cancer 46% higher and death from any cause 17% higher in the supplement group, and the trial was stopped 21 months earlier than planned [3][1].

For balance, ODS notes that three other trials found no link between vitamin A or beta-carotene and lung cancer, including one in 22,071 male physicians, most of whom did not smoke, given 50 mg of beta-carotene every other day for 12 years [1].

Why your eye vitamin changed

The original AREDS formula for age-related macular degeneration (AMD) contained beta-carotene. AREDS2, a 5-year trial of 4,203 people aged 50 to 85, tested the formula with and without it [4][1]. No current smokers received beta-carotene in that trial [1].

Removing beta-carotene had no apparent effect on progression to advanced AMD [4]. But more lung cancers occurred in the beta-carotene group (23, or 2.0%) than without it (11, or 0.9%), mostly in former smokers [4]. ODS reports that 31 of the 34 people affected were former smokers [1]. The authors suggested lutein + zeaxanthin as an appropriate carotenoid substitute [4].

How to check your label

Vitamin A in stand-alone supplements and most multivitamins comes as retinyl acetate, retinyl palmitate, beta-carotene or a combination, so check the ingredient line, not just the vitamin A total [1]. Labels list vitamin A in mcg RAE, and 1 mcg RAE equals 2 mcg of supplemental beta-carotene [1].

If you smoke or used to, it is worth asking your clinician or pharmacist whether any of your products contain beta-carotene, and in what amount. The trials above used 15 to 30 mg a day [1][2][3]. The difference between beta-carotene and preformed vitamin A is explained in how much vitamin A is too much, and all the evidence is on the vitamin A monograph.

Quick answers

Is beta-carotene from food a problem for smokers?

The harm signals came from high-dose supplements of 20 to 30 mg a day in ATBC and CARET [2][3]. Our sources do not show the same signal for beta-carotene from vegetables and fruit.

Does the current AREDS2 formula contain beta-carotene?

AREDS2 researchers suggested replacing beta-carotene with lutein + zeaxanthin because of the lung cancer finding in former smokers [4]. Check the label of the specific product you use.

Did the risk last after people stopped?

In CARET follow-up, differences in lung cancer risk were no longer statistically significant except in women, who had a 33% higher risk [1]. In AREDS2 follow-up, the higher lung cancer risk persisted 5 years after the trial [1].

Keep reading

Full monographs

Related articles

Browse the full Supplement & Nutrient Encyclopedia or all supplement articles.

References

  1. [1]Vitamin A and Carotenoids: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements, 2025.
  2. [2]The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med, 1994. PMID 8127329
  3. [3]Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med, 1996. PMID 8602180
  4. [4]Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA, 2013. PMID 23644932

Vitamin A (retinyl palmitate vs beta-carotene) and other dietary supplements are not intended to diagnose, treat, cure or prevent any disease, and these statements have not been evaluated by the FDA. Talk to your clinician or pharmacist before starting a supplement, especially if you take prescription medicines. This page has no product or affiliate links.

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