The effect of β-carotene on the mortality of male smokers is modified by smoking and by vitamins C and E: evidence against a uniform effect of nutrient

Abstract A previous analysis of the Alpha-Tocopherol Beta-Carotene (ATBC) Study on male smokers found that β-carotene supplementation increased the risk of pneumonia 4-fold in those who started smoking at the age of ≥21 years and smoked ≥21 cigarettes/d (a subgroup of 7 % of the study population). The present study hypothesised that β-carotene increases mortality in the same subgroup. The ATBC Study (1985–1993) recruited 29 133 Finnish male smokers (≥5 cigarettes/d) aged 50–69 years. Cox regression models were constructed to estimate the effect of β-carotene supplementation in subgroups. β-Carotene increased mortality (risk ratio 1·56; 95 % CI 1·06, 2·3) in those who started to smoke at ≥21 years and smoked ≥21 cigarettes/d. Within this subgroup, there was strong evidence of further heterogeneity. The effect of β-carotene supplementation was further modified by dietary vitamin C intake, fruit and vegetable intake (P = 0·0004), and by vitamin E supplementation (P = 0·011). Thus, harm from β-carotene was not uniform within the study population. Interactions between β-carotene and vitamins C and E were seen only within a subgroup of 7 % of the ATBC participants, and therefore should not be extrapolated to the general population. Heterogeneity of the β-carotene effect on mortality challenges the validity of previous meta-analyses that have pooled many diverse antioxidants for one single estimate of effect using the assumption that a single estimate equally applies to all antioxidants and all people. Trial registration: ClinicalTrials.gov NCT00342992.

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Vitamin E supplementation may transiently increase tuberculosis risk in males who smoke heavily and have high dietary vitamin C intake

British Journal Of Nutrition ◽

10.1017/s0007114508923709 ◽

2008 ◽

Vol 100 (4) ◽

pp. 896-902 ◽

Cited By ~ 24

Author(s):

Harri Hemilä ◽

Jaakko Kaprio

Keyword(s):

Vitamin E ◽

Vitamin C ◽

Alpha Tocopherol ◽

Dietary Vitamin ◽

Study Cohort ◽

Adjusted Risk ◽

Atbc Study ◽

Β Carotene ◽

Tuberculosis Risk ◽

Vitamin E Supplementation

Vitamin E and β-carotene affect the immune function and might influence the predisposition of man to infections. To examine whether vitamin E or β-carotene supplementation affects tuberculosis risk, we analysed data of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study, a randomised controlled trial which examined the effects of vitamin E (50 mg/d) and β-carotene (20 mg/d) on lung cancer. The trial was conducted in the general community in Finland in 1985–93; the intervention lasted for 6·1 years (median). The ATBC Study cohort consists of 29 023 males aged 50–69 years, smoking at baseline, with no tuberculosis diagnosis prior to randomisation. Vitamin E supplementation had no overall effect on the incidence of tuberculosis (risk ratio (RR) = 1·18; 95 % CI 0·87, 1·59) nor had β-carotene (RR = 1·07; 95 % CI 0·80, 1·45). Nevertheless, dietary vitamin C intake significantly modified the vitamin E effect. Among participants who obtained 90 mg/d or more of vitamin C in foods (n13 502), vitamin E supplementation increased tuberculosis risk by 72 (95 % CI 4, 185)%. This effect was restricted to participants who smoked heavily. Finally, in participants not supplemented with vitamin E, dietary vitamin C had a negative association with tuberculosis risk so that the adjusted risk was 60 (95 % CI 16, 81) % lower in the highest intake quartile compared with the lowest. Our finding that vitamin E seemed to transiently increase the risk of tuberculosis in those who smoked heavily and had high dietary vitamin C intake should increase caution towards vitamin E supplementation for improving the immune system.

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β-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine

Nicotine & Tobacco Research ◽

10.1093/ntr/nty115 ◽

2018 ◽

Vol 21 (8) ◽

pp. 1045-1050 ◽

Cited By ~ 10

Author(s):

Pooja Middha ◽

Stephanie J Weinstein ◽

Satu Männistö ◽

Demetrius Albanes ◽

Alison M Mondul

Keyword(s):

Lung Cancer ◽

Cancer Prevention ◽

Cancer Incidence ◽

Beta Carotene ◽

Alpha Tocopherol ◽

Lung Cancer Incidence ◽

Nicotine Content ◽

Increased Risk ◽

Atbc Study ◽

Β Carotene

Abstract Introduction The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated that β-carotene supplementation increases lung cancer incidence in smokers. Further, cigarettes with higher tar and nicotine content are associated with a higher risk of lung cancer. However, no studies have examined whether the increased risk associated with β-carotene supplementation in smokers varies by the tar or nicotine content of cigarettes. Methods The ATBC Study was a randomized, double-blind intervention trial conducted in southwest Finland. A total of 29 133 male smokers, aged 50–69 years, were enrolled and randomly assigned to one of four groups (α-tocopherol, β-carotene, both, or placebo). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by β-carotene trial assignment stratified by a priori categories of cigarette tar and nicotine content. Results The β-carotene supplementation group had significantly higher risk of developing lung cancer in all categories of tar content (yes vs. no β-carotene supplementation—ultralight cigarettes [≤7 mg tar]: HR = 1.31, 95% CI = 0.91 to 1.89; nonfiltered cigarettes [≥21 mg tar]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .91). Similarly, there was no interaction with nicotine content (yes vs. no β-carotene supplementation—ventilated cigarettes [≤0.8 µg nicotine]: HR = 1.23, 95% CI = 0.98 to 1.54; nonfiltered cigarettes [≥1.3 µg nicotine]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .83). Conclusion These findings support the conclusion that supplementation with β-carotene increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers should continue to avoid β-carotene supplementation. Implications Previous studies demonstrated that β-carotene supplementation increases risk of lung cancer in smokers. This study moves the field forward by examining the potential for modification of risk of lung cancer with different levels of tar and nicotine in cigarettes smoked, as interaction with carcinogens in these components of cigarette smoke is hypothesized to be the mechanism by which β-carotene increases risk. Our study provides evidence that the increased risk of lung cancer in smokers who take β-carotene supplements is not dependent upon the tar or nicotine level of cigarettes smoked and suggests that all smokers should continue to avoid β-carotene supplementation.

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Abstract LB-30: Metabolomic profile of response to β-carotene supplementation reveals potential for pharmacologic interactions with β-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

10.1158/1538-7445.am2013-lb-30 ◽

2013 ◽

Author(s):

Alison M. Mondul ◽

Steven C. Moore ◽

Joshua N. Sampson ◽

Stephanie J. Weinstein ◽

Edward D. Karoly ◽

...

Keyword(s):

Cancer Prevention ◽

Beta Carotene ◽

Alpha Tocopherol ◽

Metabolomic Profile ◽

Atbc Study ◽

Β Carotene

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Family history of prostate cancer and prostate cancer risk in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study

International Journal of Cancer ◽

10.1002/ijc.23591 ◽

2008 ◽

Vol 123 (5) ◽

pp. 1154-1159 ◽

Cited By ~ 15

Author(s):

Jiyoung Ahn ◽

Roxana Moslehi ◽

Stephanie J. Weinstein ◽

Kirk Snyder ◽

Jarmo Virtamo ◽

...

Keyword(s):

Prostate Cancer ◽

Family History ◽

Cancer Risk ◽

Cancer Prevention ◽

Prostate Cancer Risk ◽

Beta Carotene ◽

Alpha Tocopherol ◽

History Of ◽

Atbc Study

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Metabolomic profile of response to supplementation with β-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

American Journal of Clinical Nutrition ◽

10.3945/ajcn.113.062778 ◽

2013 ◽

Vol 98 (2) ◽

pp. 488-493 ◽

Cited By ~ 19

Author(s):

Alison M Mondul ◽

Joshua N Sampson ◽

Steven C Moore ◽

Stephanie J Weinstein ◽

Anne M Evans ◽

...

Keyword(s):

Cancer Prevention ◽

Beta Carotene ◽

Alpha Tocopherol ◽

Metabolomic Profile ◽

Prevention Study ◽

Β Carotene

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Vitamin E and the risk of pneumonia: using the I2 statistic to quantify heterogeneity within a controlled trial

British Journal Of Nutrition ◽

10.1017/s0007114516003408 ◽

2016 ◽

Vol 116 (9) ◽

pp. 1530-1536 ◽

Cited By ~ 6

Author(s):

Harri Hemilä

Keyword(s):

Vitamin E ◽

Cancer Prevention ◽

Treatment Effect ◽

Leisure Time ◽

Controlled Trial ◽

Beta Carotene ◽

Alpha Tocopherol ◽

Nutritional Epidemiology ◽

Atbc Study ◽

Vitamin E Supplementation

AbstractAnalyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50–69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I2 statistic. The I2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.

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Comparison of two frequency questionnaires for quantifying fruit and vegetable intake

Public Health Nutrition ◽

10.1079/phn200094 ◽

2001 ◽

Vol 4 (2) ◽

pp. 233-239 ◽

Cited By ~ 31

Author(s):

Soumela Amanatidis ◽

Dorothy Mackerras ◽

Judy M Simpson

Keyword(s):

Vegetable Intake ◽

Vegetable Consumption ◽

Beta Carotene ◽

Fruit And Vegetable Intake ◽

Fruit And Vegetable ◽

Seasonal Differences ◽

Food Frequency ◽

The Family ◽

Study Population ◽

Colposcopy Clinic

AbstractObjectiveThe effect on individual rankings and total intakes of nutrients of correcting total fruit and vegetable frequencies from a long food frequency questionnaire (FFQ) using the responses to two summary questions was examined in a group of women.MethodsThe performance of a self-administered FFQ in ranking individual levels of intake and estimating absolute levels of nutrient and energy intake was compared with the performance of the questionnaire when it was corrected for fruit and vegetable intake reported using the Block summary questions.SubjectsThe study population included 123 women, aged between 18 and 54 years, who were recruited from the Family Planning Association Colposcopy Clinic in Sydney.ResultsSubstantial and significant differences (P<0.001) were found in fruit and vegetable intakes between the FFQ and the summary questions. Intake frequency by the FFQ was more than double that by the summary questions. When the FFQ was corrected for fruit and vegetable intakes using the summary questions, the intakes of beta-carotene, vitamins A and C, and dietary fibre were more than 20% lower (P<0.001) than the uncorrected results. However, this had little effect on ranking individuals. This study also examined seasonal differences in vegetable intakes and differences in nutrient intakes when either summer or winter vegetable consumption was substituted for seasonal vegetable intake in the FFQ. Although there were seasonal differences for some foods, the substitution had little effect on intake of nutrients.ConclusionThese results indicate that important differences in intakes are observed when two methods, which appear to yield the same results, are used. Further work is needed to determine which, if either, of the two methods yields intakes that can be compared quantitatively with national references for assessing the adequacy of population intakes.

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