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

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 21 (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 21 , in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta-carotene supplementation should not be recommended.The use of dietary supplements has increased dramatically over the past years not only in the United States of America 1,2 but also in European countries 3-5 and Japan. 6 According to the third National Health and Nutrition Examination Survey, 37% of vitamin and mineral supplements contained beta-carotene. 7 Some study results supported a protective effect of beta-carotene supplementation against sunburn in humans, suggesting a potential benefit toward skin cancer risk. 8 However, in a randomized controlled trial (RCT) investigating the effect of an antioxidant supplementation containing beta-carotene, supplemented women had a significantly increased risk of skin cancer compared to women in the placebo group. 9 The effects of beta-carotene supplementation on mortality and cancer incidence have been investigated in several RCTs in different populations. A recent metaanalysis provided evidence of a significant increase of mortality in participants supplemented with beta-carotene. 10 The harmful effect of beta-carotene supplementation on lung cancer was also well established in smokers and asbestos workers supplemented with 20-30 mg of beta-carotene per day. [11][12][13] In contrast, RCTs provided divergent results for other cancer sites. If most of the RCTs did not show any significant effect of beta-carotene supplementation regard...

Associations of multiple carotenoid co-exposure with all-cause and cause-specific mortality in US adults: a prospective cohort study

“…With a larger sample size and more extended follow-up period than the previous study ( 14 ), we observed that, in addition to α-carotene and lycopene, low serum levels of β-carotene, β-cryptoxanthin, and lutein/zeaxanthin were also associated with increased risks of all-cause mortality. Despite indications from some interventional studies that supplementation with β-carotene may have null or harmful effects on mortality outcomes ( 16 , 36 ), higher circulating carotenoid levels did not correlate with elevated mortality risk in our study.…”

Associations of multiple carotenoid co-exposure with all-cause and cause-specific mortality in US adults: a prospective cohort study

“…With a larger sample size and more extended follow-up period than the previous study ( 14 ), we observed that, in addition to α-carotene and lycopene, low serum levels of β-carotene, β-cryptoxanthin, and lutein/zeaxanthin were also associated with increased risks of all-cause mortality. Despite indications from some interventional studies that supplementation with β-carotene may have null or harmful effects on mortality outcomes ( 16 , 36 ), higher circulating carotenoid levels did not correlate with elevated mortality risk in our study.…”

Serum carotenoid levels and risk of lung cancer death in US adults

“…The main focus of studies, from observational studies to randomized trials, of carotenoids and cancer prevention has been on beta-carotenoid intake or supplements. However, the protective effect of beta-carotenoids on lung cancer is not confirmed, (12,13) and the present study also failed to support the association. Consistent with our results, evidence is accumulating that the intake of or circulating levels of alpha-carotene and beta-cryptoxanthin are inversely associated with lung cancer risk.…”

Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression

“…Regarding the sex of the participants, beta-carotene supplementation was observed to have a significant negative effect in the RCTs with only male participants. This observation supports those obtained in a previous meta-analysis [ 12 ] based on trials “with a majority of men”. The reason for such an observation may be the fact that lung cancer is generally more common in men than in women [ 3 ], which is most likely due to the higher prevalence of cigarette smoking in men than women [ 21 ].…”

“…Moreover, the use of beta-carotene in the primary chemoprevention of lung cancer may increase the risk of lung cancer in some groups of people. These findings are in line with those obtained in a similar systematic review published a decade ago regarding beta-carotene supplementation in the primary prevention of various cancers [12].…”

Associations of multiple carotenoid co-exposure with all-cause and cause-specific mortality in US adults: a prospective cohort study

“…With a larger sample size and more extended follow-up period than the previous study ( 14 ), we observed that, in addition to α-carotene and lycopene, low serum levels of β-carotene, β-cryptoxanthin, and lutein/zeaxanthin were also associated with increased risks of all-cause mortality. Despite indications from some interventional studies that supplementation with β-carotene may have null or harmful effects on mortality outcomes ( 16 , 36 ), higher circulating carotenoid levels did not correlate with elevated mortality risk in our study.…”

Serum carotenoid levels and risk of lung cancer death in US adults

“…The main focus of studies, from observational studies to randomized trials, of carotenoids and cancer prevention has been on beta-carotenoid intake or supplements. However, the protective effect of beta-carotenoids on lung cancer is not confirmed, (12,13) and the present study also failed to support the association. Consistent with our results, evidence is accumulating that the intake of or circulating levels of alpha-carotene and beta-cryptoxanthin are inversely associated with lung cancer risk.…”

Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression

“…Regarding the sex of the participants, beta-carotene supplementation was observed to have a significant negative effect in the RCTs with only male participants. This observation supports those obtained in a previous meta-analysis [ 12 ] based on trials “with a majority of men”. The reason for such an observation may be the fact that lung cancer is generally more common in men than in women [ 3 ], which is most likely due to the higher prevalence of cigarette smoking in men than women [ 21 ].…”

“…Moreover, the use of beta-carotene in the primary chemoprevention of lung cancer may increase the risk of lung cancer in some groups of people. These findings are in line with those obtained in a similar systematic review published a decade ago regarding beta-carotene supplementation in the primary prevention of various cancers [12].…”

Associations of multiple carotenoid co-exposure with all-cause and cause-specific mortality in US adults: a prospective cohort study

“…With a larger sample size and more extended follow-up period than the previous study ( 14 ), we observed that, in addition to α-carotene and lycopene, low serum levels of β-carotene, β-cryptoxanthin, and lutein/zeaxanthin were also associated with increased risks of all-cause mortality. Despite indications from some interventional studies that supplementation with β-carotene may have null or harmful effects on mortality outcomes ( 16 , 36 ), higher circulating carotenoid levels did not correlate with elevated mortality risk in our study.…”

Serum carotenoid levels and risk of lung cancer death in US adults

“…The main focus of studies, from observational studies to randomized trials, of carotenoids and cancer prevention has been on beta-carotenoid intake or supplements. However, the protective effect of beta-carotenoids on lung cancer is not confirmed, (12,13) and the present study also failed to support the association. Consistent with our results, evidence is accumulating that the intake of or circulating levels of alpha-carotene and beta-cryptoxanthin are inversely associated with lung cancer risk.…”

Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression

“…Regarding the sex of the participants, beta-carotene supplementation was observed to have a significant negative effect in the RCTs with only male participants. This observation supports those obtained in a previous meta-analysis [ 12 ] based on trials “with a majority of men”. The reason for such an observation may be the fact that lung cancer is generally more common in men than in women [ 3 ], which is most likely due to the higher prevalence of cigarette smoking in men than women [ 21 ].…”

“…Moreover, the use of beta-carotene in the primary chemoprevention of lung cancer may increase the risk of lung cancer in some groups of people. These findings are in line with those obtained in a similar systematic review published a decade ago regarding beta-carotene supplementation in the primary prevention of various cancers [12].…”