Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials

Our plain-English summary of Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials, by N. Druesne-Pecollo, P. Latino-Martel, T. Norat, et al (International Journal of Cancer, 2010).

The study

• Authors: N. Druesne-Pecollo, P. Latino-Martel, T. Norat, E. Barrandon, S. Bertrais, P. Galan, S. Hercberg
• Journal: International Journal of Cancer
• Published: 2010;127(1):172-84
• Type of article: Meta-analysis, Systematic review
• Cited by: 175 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The effect of beta-carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of beta-carotene supplementation on cancer incidence in randomized trials by cancer site, beta-carotene supplementation characteristics and study population. Relevant trials were retrieved by searching PubMed (up to April 2009). Authors involved in selected studies were contacted for additional information. Thirteen publications reporting results from 9 randomized controlled trials were included. Overall, no effect of beta-carotene supplementation was observed on the incidence of all cancers combined (RR, 1.01; 95% CI, 0.98-1.04), pancreatic cancer (RR, 0.99; 95% CI, 0.73-1.36), colorectal cancer (RR, 0.96; 95% CI, 0.85-1.09), prostate cancer (RR, 0.99; 95% CI, 0.91-1.07), breast cancer (RR, 0.96; 95% CI, 0.85-1.10), melanoma (RR, 0.98; 95% CI, 0.65-1.46) and non melanoma skin cancer (RR, 0.99; 95% CI, 0.93-1.05). The incidence of lung and stomach cancers were significantly increased in individuals supplemented with beta-carotene at 20-30 mg day(-1) (RR, 1.16; 95% CI, 1.06-1.27 and RR, 1.34; 95% CI, 1.06-1.70), in smokers and asbestos workers (RR, 1.20; 95% CI, 1.07-1.34 and RR, 1.54; 95% CI, 1.08-2.19) compared to the placebo group. Beta-carotene supplementation has not been shown to have any beneficial effect on cancer prevention. Conversely, it was associated with increased risk not only of lung cancer but also of gastric cancer at doses of 20-30 mg day(-1), in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta-carotene supplementation should not be recommended.

In plain English

This was a systematic review and meta-analysis. It pooled 9 randomized controlled trials (13 publications, 182,323 participants) that compared beta-carotene supplements, given alone or with other antioxidants, against placebo for cancer incidence. Asbestos appears only as a feature of the populations studied. In two trials (ATBC and CARET), all participants were smokers or asbestos workers, and the authors analyzed these two trials together; asbestos workers were not analyzed separately. Across all trials, supplementation had no statistically significant effect on all cancers combined (RR 1.01; 95% CI 0.98–1.04). It also had no significant effect on pancreatic, colorectal, prostate, breast or skin cancers. Lung cancer risk was higher in supplemented people overall (RR 1.13; 95% CI 1.04–1.24). In the two smoker/asbestos-worker trials, supplemented participants had higher risks of lung cancer (RR 1.20; 95% CI 1.07–1.34), stomach cancer (RR 1.54; 95% CI 1.08–2.19) and all cancers (RR 1.08; 95% CI 1.01–1.15). Doses of 20 mg per day and above were also associated with more lung and stomach cancer. The authors said they could not tell whether dose or smoking/asbestos exposure mattered more. They concluded that beta-carotene supplements should not be recommended for primary cancer prevention.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review and meta-analysis of published randomized controlled trials (PubMed search up to April 2009)
• Who was studied: 9 randomized controlled trials reported in 13 publications, with 182,323 participants in total; trial size ranged from 1,621 to 39,876 participants
• Exposure: Beta-carotene supplements (6 to 30 mg per day; most trials 20 to 30 mg per day), alone or combined with other antioxidants. Asbestos was a population characteristic only: in the ATBC and CARET trials all participants were former or current smokers or asbestos workers. No fiber types or asbestos exposure levels are given.
• Main results:
  • All trials combined (8 trials, 180,702 participants, 10,600 cancer cases): no statistically significant effect on all-cancer incidence, RR 1.01 (95% CI 0.98–1.04)
  • Lung cancer, all trials (8 trials, 180,702 subjects, 1,852 cases): significantly increased risk in supplemented subjects compared with placebo, RR 1.13 (95% CI 1.04–1.24)
  • Lung cancer in populations made up only of smokers or asbestos workers (ATBC and CARET; 47,447 subjects, 1,078 cases): RR 1.20 (95% CI 1.07–1.34)
  • Stomach cancer in populations of smokers or asbestos workers (ATBC and CARET; 47,447 subjects, 106 cases): significantly increased risk, RR 1.54 (95% CI 1.08–2.19)
  • All cancers combined in the ATBC and CARET trials (smokers and asbestos workers only; 47,447 subjects, 3,085 cases): RR 1.08 (95% CI 1.01–1.15)
  • Doses of 20 mg per day and above: lung cancer RR 1.16 (95% CI 1.06–1.27)
  • Doses of 20 mg per day and above: stomach cancer RR 1.34 (95% CI 1.06–1.70)
  • Stomach cancer, all trials (7 trials, 172,531 subjects, 808 events): not significantly different from controls, RR 0.99 (95% CI 0.86–1.13)
  • Stomach cancer with low doses (below 20 mg per day; Linxian and SU.VI.MAX trials): significantly decreased risk, RR 0.84 (95% CI 0.71–1.00), p = 0.047
  • Pancreatic, colorectal, prostate, breast and skin cancers: none of the meta-analyses gave a significant relative risk for supplemented subjects compared with controls
• The authors' conclusion: The authors concluded that their findings support an absence of any protective effect of beta-carotene supplementation against primary cancer. They suggested an increased risk of lung and stomach cancers at 20–30 mg per day and in smokers and asbestos workers, and stated that regular use of beta-carotene supplements should not be recommended for primary cancer prevention.
• Limitations the authors state:
  • In most trials, beta-carotene was given in combination with other antioxidants
  • Some meta-analyses were based on only a small number of trials
  • The lower stomach cancer risk at low doses rests almost entirely on the Chinese Linxian trial (539 of 543 events) and may not apply to other populations
  • The subgroup analyses could not separate whether the dose or the exposure to tobacco or asbestos was more important
  • The increased all-cancer risk in smokers and asbestos workers may be at least partly due to the high share of lung cancers in the ATBC and CARET trials

Topics

Medical terms in this study, explained in our Lexicon: Systematic Review, Colorectal Cancer, Stomach Cancer, Lung Cancer.

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