Beta-Carotene
Beta-carotene
TL;DR
Beta-carotene from food is fine. As a supplement it failed decisively: two large trials found it increased lung cancer incidence and mortality in smokers, and AREDS2 removed it from the eye formula for that reason.
Ideal For
- Erythropoietic protoporphyria, at high dose under specialist care
- Vitamin A repletion in non-smokers with poor vegetable intake
Avoid If
- Current smokers — increased lung cancer risk
- Former smokers and asbestos-exposed workers
- Heavy alcohol use
- Seeking eye protection — use lutein and zeaxanthin instead
Frequently Asked Questions
Overview
Beta-carotene is the canonical example of why a nutrient that looks protective in observational data can prove harmful when isolated and given at high dose. Epidemiology repeatedly found that people eating more carotenoid-rich vegetables had less lung cancer, so two large trials tested the pill. The ATBC trial in Finnish male smokers found 18% more lung cancer in the beta-carotene arm. CARET, testing beta-carotene with retinol in smokers and asbestos-exposed workers, was terminated early with 28% more lung cancer and 17% higher overall mortality. These are not ambiguous results. The proposed mechanism involves beta-carotene oxidation products in the high-oxygen, oxidant-rich smoker lung acting to promote rather than prevent carcinogenesis. The consequence is visible in the AREDS programme: the original AREDS eye formula contained beta-carotene, and AREDS2 replaced it with lutein and zeaxanthin, which performed at least as well without the cancer signal. Dietary carotenoids remain unambiguously good, and beta-carotene is still useful for erythropoietic protoporphyria and, at modest doses, as a vitamin A source in people who do not smoke. But as a general antioxidant supplement it should not be taken.
How It Works
- Converted to retinal by BCMO1, with feedback regulation
- Quenches singlet oxygen at low oxygen tension
- Becomes pro-oxidant at high oxygen tension, as in smoker lung
- Cleavage products disrupt retinoic acid signalling
Quick Facts
- ATBC: 18% more lung cancer in smokers
- CARET: stopped early, 28% more lung cancer, 17% higher mortality
- AREDS2 replaced it with lutein and zeaxanthin
- Food carotenoids remain entirely safe
Health Concerns Addressed
Supporting Research14 studies
Vitamin and mineral supplements for the primary prevention of cardiovascular disease and cancer: US Preventive Services Task Force review
O'Connor EA, Evans CV, Ivlev I +3 more
No consistent benefit was found for multivitamins or most single nutrients; beta-carotene increased lung cancer risk in high-risk groups.
Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life
Rutjes AWS, et al.
Cochrane review of 28 trials (about 83,000 cognitively healthy adults) found no evidence that vitamin or mineral supplementation - including B vitamins, antioxidant vitamins C and E, beta-carotene, selenium, zinc or multivitamins - preserves cognitive function in mid or late life; the only weak signals (beta-carotene and selenium after many years) were of doubtful clinical significance.
Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28
At 10 years, lutein/zeaxanthin substitution for beta-carotene was associated with reduced progression to late AMD and lower lung cancer risk.
Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3
AREDS2 Research Group, Chew EY, Clemons TE
In participants with the lowest dietary lutein/zeaxanthin intake, supplementation reduced progression to advanced AMD; lutein/zeaxanthin was a safer substitute for beta-carotene.
Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force recommendation statement
US Preventive Services Task Force
The evidence is insufficient to recommend multivitamins for preventing cardiovascular disease or cancer, and beta-carotene and vitamin E are recommended against.
Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial
Age-Related Eye Disease Study 2 Research Group, Chew EY, Clemons TE +8 more
In 4,203 participants at high risk of progression, adding lutein 10 mg + zeaxanthin 2 mg to the AREDS formulation did not significantly reduce progression to advanced AMD overall, but in secondary analyses lutein/zeaxanthin outperformed beta-carotene (HR ~0.82) and benefited participants with the lowest dietary lutein intake. Omega-3 (DHA+EPA) showed no effect. Beta-carotene raised lung cancer risk in former smokers.
Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease (CARET)
Omenn GS, Goodman GE, Thornquist MD +1 more
The trial was stopped early: participants receiving beta carotene plus retinyl palmitate had a 28% higher incidence of lung cancer and 17% higher death rate than placebo.
Beta-carotene, vitamins and skin photoprotection: meta-analysis of erythema studies
Kopcke W, Krutmann J
Beta-carotene protected against sunburn only after at least 10 weeks of supplementation
The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers
The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group
Male smokers receiving beta carotene had an 18% higher incidence of lung cancer and 8% higher total mortality than those not receiving it.
Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases
Bjelakovic G, Nikolova D, Gluud LL +2 more
Beta-carotene and vitamin E supplementation were associated with increased all-cause mortality in analyses of low-bias-risk trials.
The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up After Stopping Beta-Carotene and Retinol Supplements
Goodman GE, Thornquist MD, Balmes J +1 more
Excess lung cancer risk in the supplement arm diminished after supplementation stopped, though risks remained elevated among women.
Drugs for preventing lung cancer in healthy people
Cortés-Jofré M, Rueda JR, Asenjo-Lobos C +1 more
Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer.
Antioxidant vitamins and magnesium and the risk of hearing loss in the US general population
Choi YH, Miller JM, Tucker KL +2 more
High intakes of beta-carotene or vitamin C combined with high magnesium compared with low intakes of both nutrients were significantly associated with lower (better) PTAs at high frequencies.
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8
Age-Related Eye Disease Study Research Group
Antioxidants plus zinc reduced progression to advanced age-related macular degeneration by about 25% in higher-risk participants.
Safety Information
Potential Side Effects
Carotenodermia, a harmless yellow-orange skin discolouration, at high intake. The serious concern is not a side effect but an outcome: increased lung cancer incidence and mortality in smokers at supplemental doses.
Contraindications
Current or former smoking and asbestos exposure are effective contraindications to supplemental beta-carotene at doses of 20 mg/day or more.
Drug Interactions
- Statins and niacin — beta-carotene combinations blunted HDL response in one trial
- Orlistat and cholestyramine — reduced absorption
- Alcohol — may worsen hepatotoxic potential of retinoid pathways
Pregnancy & Breastfeeding
Pregnancy: likely_safe
Breastfeeding: likely_safe
Dosage Guidelines
Dosage Used in Studies
3-6 mg
Best Time to Take
With a fat-containing meal, if taken at all
Best Form
Dietary carotenoids from food; mixed carotenoids if supplementing
Bioavailability
Absorption from supplements is far higher than from raw vegetables; cooking and dietary fat substantially improve food-source absorption.
Forms Compared
Dietary beta-carotene
Synthetic beta-carotene
Mixed carotenoids
Lutein and zeaxanthin
Food & Timing
Fat-soluble — requires dietary fat for absorption.
Medical Disclaimer
The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.
Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.