Incidence of Cancer and Mortality Following α-Tocopherol and β-Carotene Supplementation

Virtamo, Jarmo; Pietinen, Pirjo; Huttunen, Jussi K.; Korhonen, Pasi; Malila, Nea; Virtanen, Mikko; Albanês, Demetrius; Taylor, Phil R.; Albert, Paul

doi:10.1001/jama.290.4.476

Cited by 373 publications

(96 citation statements)

References 17 publications

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“…In contrast to the results of many observational studies and the current meta‐analysis, two large randomized controlled trials (RCT's), the ATBC and CARET, showed an increased risk of lung cancer with high‐dose supplemental β ‐carotene among smokers 14, 15, 16. The increased risk at high doses may be related to the prooxidant activity of β ‐carotene when administered as a supplement in high doses (5–10 times greater than normal dietary intake) to heavy smokers 6, 45, 46.…”

Section: Discussioncontrasting

confidence: 80%

“…By contrast, two large randomized double‐blind placebo‐controlled trials, the alpha‐tocopherol‐ β ‐carotene (ATBC) and the β ‐carotene and Retinol Efficacy Trial (CARET) showed an increased risk of lung cancer among high‐risk people supplemented with high doses of β ‐carotene and/or α ‐tocopherol 13, 14, 15, 16.…”

Section: Introductionmentioning

confidence: 98%

“…As part of the WCRF/AICR Continuous Update Project (CUP), we conducted an updated systematic review and meta‐analysis of cohort studies with the aim to clarify the relationship of blood carotenoids and lung cancer risk. Retinol was also included in this review because of the conflicting results of randomized controlled trials 13, 14, 15, 16.…”

Section: Introductionmentioning

confidence: 99%

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Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF–AICR systematic review of published prospective studies

et al. 2016

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Carotenoids and retinol are considered biomarkers of fruits and vegetables intake, and are of much interest because of their anti‐inflammatory and antioxidant properties; however, there is inconsistent evidence regarding their protective effects against lung cancer. We conducted a meta‐analysis of prospective studies of blood concentrations of carotenoids and retinol, and lung cancer risk. We identified relevant prospective studies published up to December 2014 by searching the PubMed and several other databases. We calculated summary estimates of lung cancer risk for the highest compared with lowest carotenoid and retinol concentrations and dose–response meta‐analyses using random effects models. We used fractional polynomial models to assess potential nonlinear relationships. Seventeen prospective studies (18 publications) including 3603 cases and 458,434 participants were included in the meta‐analysis. Blood concentrations of α‐carotene, β‐carotene, total carotenoids, and retinol were significantly inversely associated with lung cancer risk or mortality. The summary relative risk were 0.66 (95% confidence interval [CI]: 0.55–0.80) per 5 μg/100 mL of α‐carotene (studies [n] = 5), 0.84 (95% CI: 0.76–0.94) per 20 μg/100 mL of β‐carotene (n = 9), 0.66 (95% CI: 0.54–0.81) per 100 μg/100 mL of total carotenoids (n = 4), and 0.81 (95% CI: 0.73–0.90) per 70 μg/100 mL of retinol (n = 8). In stratified analysis by sex, the significant inverse associations for β‐carotene and retinol were observed only in men and not in women. Nonlinear associations were observed for β‐carotene, β‐cryptoxanthin, and lycopene, with stronger associations observed at lower concentrations. There were not enough data to conduct stratified analyses by smoking. In conclusion, higher blood concentrations of several carotenoids and retinol are associated with reduced lung cancer risk. Further studies in never and former smokers are needed to rule out confounding by smoking.

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Section: Discussioncontrasting

confidence: 80%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF–AICR systematic review of published prospective studies

et al. 2016

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“…Several studies have shown a direct correlation between a human diet rich in fruit, berries and vegetables containing high levels of carotenoids, and higher levels of serum carotenoids and lower risk of disease including several forms of cancer, cardiovascular and degenerative diseases (Virtamo et al, 2003;Wang et al, 2013;Fiedor and Burda, 2014). The ascribed health benefits of these natural foods cannot be unequivocally associated to the intake of carotenoids alone, since other antioxidant compounds present in the foods are ingested, such as vitamins, folate, and phenolic compounds (Virtamo et al, 2003;Voutilainen et al, 2006).…”

Section: Relevance Of Carotenoids To Human Healthmentioning

confidence: 99%

“…The ascribed health benefits of these natural foods cannot be unequivocally associated to the intake of carotenoids alone, since other antioxidant compounds present in the foods are ingested, such as vitamins, folate, and phenolic compounds (Virtamo et al, 2003;Voutilainen et al, 2006). Epidemiological evidence shows that people who ingest more dietary carotenoids exhibit a reduced risk for cancer, yet results from intervention trials indicate that the supplemental β-carotene does not prevent cardiovascular diseases or cancer (Chatterjee et al, 2012;Karppi et al, 2012;Wang et al, 2013), and may enhance lung cancer incidence and mortality among smokers (Omenn et al, 1996;Russell, 2002;Virtamo et al, 2003). The inefficient use of β-carotene as chemopreventive agent has been tentatively linked to cell-specific effects of the carotenoid in in vitro cultures: absence of effect on gap junctional intercellular communication (GJIC), Cx43 expression and growth of non-transformed or neoplastic murine lung epithelial cells, and enhanced GJIC, Cx43 expression and reduced growth of murine fibroblasts (Banoub et al, 1996).…”

Section: Relevance Of Carotenoids To Human Healthmentioning

confidence: 99%

Carotenoids in Aquatic Ecosystems and Aquaculture: A Colorful Business with Implications for Human Health

2017

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The colorful carotenoid pigments are known as biological active compounds that have beneficial effects on the metabolism of animals and humans. Carotenoids provide protection against several stressors, including UV radiation, reactive oxygen species and free radicals, have important roles in vision, and act as precursors of transcription regulators and in the immune system. Studies on human nutrition point to the relevance of consuming functional foods instead of supplementing the human diet with the desired nutrients. This stresses the importance of obtaining dietary items with high quality nutritional value for human consumption. The various biological roles of carotenoids in aquatic animals ascribes them a major role in aquaculture where they are routinely added to ensure the development and health of fish such as salmon, trout and red porgy, and of shellfish like shrimp and lobster. In aquaculture, it is widely recognized that fish larvae dramatically increase their survival rate when reared on live feeds (e.g., rotifers, Artemia sp. and copepods) containing carotenoids. Ultimately, pigmentation provided by carotenoids is one of the relevant quality attributes of the aquatic animal for consumer acceptability and market value. Appropriate feeds for aquaculture are thus required to provide the carotenoids necessary for the desired pigmentation. In this review, we discuss the role of carotenoids in aquatic food webs, both in the wild and in aquaculture, and its relevance for human health.

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A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men<subtitle>The Physicians' Health Study II</subtitle>

Grodstein

Kang²,

Glynn³

et al. 2007

Arch Intern Med

167

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Background: Oxidative stress contributes to brain aging. Antioxidant treatment, especially over the long term, might confer cognitive benefits. Methods: We added cognitive testing to the Physicians' Health Study II (PHSII), a randomized trial of beta carotene and other vitamin supplements for chronic disease prevention. The PHSII is a continuation of the Physicians' Health Study (PHS), which had randomized male participants to low-dose aspirin and beta carotene. Participants include those continuing their original beta carotene assignment from the PHS, begun in 1982, and newer recruits randomized as of 1998. The beta carotene arm (50 mg, alternate days) was terminated; follow-up is ongoing for the remaining arms. Near the close of the beta carotene arm, we interviewed 5956 participants older than 65 years to assess general cognition, verbal memory, and category fluency. The primary end point was a global score averaging all tests (using z scores); the secondary end point was a verbal memory score combining results of 4 tests. We compared mean cognition among those assigned to beta carotene vs placebo. We separately examined new recruits and continuing participants. Results: Among 1904 newly recruited subjects (mean treatment duration, 1 year), cognition was similar across treatment assignments. Among 4052 continuing participants from the PHS (mean treatment duration, 18 years), the mean global score was significantly higher in the beta carotene group than in the placebo group (mean difference in z scores, 0.047 standard units; P=.03). On verbal memory, men receiving long-term beta carotene supplementation also performed significantly better than the placebo group (mean difference in z scores, 0.063; P=.007). Conclusion: We did not find an impact of short-term beta carotenesupplementationoncognitiveperformance,butlongterm supplementation may provide cognitive benefits.

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Incidence of Cancer and Mortality Following α-Tocopherol and β-Carotene Supplementation

Cited by 373 publications

References 17 publications

Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF–AICR systematic review of published prospective studies

Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF–AICR systematic review of published prospective studies

Carotenoids in Aquatic Ecosystems and Aquaculture: A Colorful Business with Implications for Human Health

A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men<subtitle>The Physicians' Health Study II</subtitle>

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