Alpha-Tocopherol Beta-Carotene study

ALBANES D, HEINONEN O P, HUTTUNEN J K, TAYLOR P R, VIRTAMA J, EDWARDS B K, HAAPAKDSKI J, RAUTALATHI M, HARTMAN A M and PALMGREN J (1995) Effects of alpha-tocopherol and beta carotene supplements on cancer incidence in the alpha-tocopherol beta-carotene cancer prevention study , Am J Clin Nutr, 62, 1427S-30S. 

ALPHA-TOCOPHEROL BETA-CAROTENE (ATBC) CANCER PREVENTION STUDY GROUP (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers , New Engl J Med, 330, 1029. 

It is well known that excessive intake of P-carotene may lead to carotenodermia (yellow skin), and it is undoubtedly the case that some carotenoid is directly lost via the skin or through photo-oxidation in the skin. As far as is known the carotenoids are not cytotoxic or genotoxic even at concentrations up to 10 times the normal plasma concentration which may cause carotenodermia. However, they are associated with amenorrhoea in girls who may be consuming bizarre diets and, in long-term supplementation studies, with an increase in lung cancer (The Alpha-tocopherol, Beta-carotene Cancer Prevention Study Group, 1994). 

ATBC = Alpha Tocopherol Beta Carotene Prevention Study CARET = The Beta Carotene and Retinol Efficacy Trial PHYS = Physicians Health Study. 

ALBANES D, HEiNONEN o p, TAYLOR p R, et uL, (1996) a-tocopherol and P-carotene supplementation and Irmg cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study effect of base-line chacteristics and study compliance. J Natl Cancer Inst. 88 1560-70. 

Holick, C.N. et al., Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study, Am. J. Epidemiol., 156, 536, 2002. 

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, New Engl. J. Med., 330, 1029, 1994. 

The interaction of carotenoids with cigarette smoke has become a subject of interest since the results of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group 1994 (ATBC) and CARET (Omenn et al. 1996) studies were released. P-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. Thus, the autoxidation of P-carotene in the presence of cigarette smoke was studied in model systems (toluene) (Baker et al. 1999). The major product was identified as 4-nitro-P-carotene, but apocarotenals and P-carotene epoxides were also encountered. 

Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, Hartman AM, Palmgren J, Freedman LS, Haapakoski, J, Barrett MJ, Pietinen P, Malila N, Tala E, Liippo K, Salomaa ER, Tangrea JA, Teppo L, Askin FB, Taskinen E, Erozan Y, Greenwald P and Huttunen JK. 1996. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study effects of base-line characteristics and study compliance. J Natl Cancer Inst 88 1560-1570. 

Albanes D, Virtamo J, Taylor PR, Rautalahti M, Pietinen P and Heinonen OP. 1997. Effects of supplemental 3-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 66 366—372. 

Vitamin E is not recommended for the prevention of chronic disease, such as coronary heart disease or cancer. Clinical trials using vita min E supplementation have been uniformly disappointing. For example, subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study trial who received high doses of vitamin E, not only lacked cadiovascular benefit but also had an increased inci dence of stroke. 

I 90 Pietinen P Rimm EB, Korkonen R et al, Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Circulation 1996 94 2720-2727,... 

Ravnskov (1998) presented data for 28 cohorts from 21 prospective studies. In only three of these cohorts did the evidence show that saturated fat was associated with a statistically significant increased risk of CHD. CHD patients in three cohort studies had consumed significantly more polyunsaturated fat, and in only one cohort had CHD patients eaten less polyunsaturated fat than CHD-free participants. The cohorts included the Framingham Study and the large well-conducted Health Professionals Follow-up Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Since then, Hu et al. (1997) presented the 14-year follow-up data from the Nurses Health Study. After adjustment for confounding variables in multivariate analyses, no statistically significant associations were found between intake of total fat, animal fat, or saturated fat and the risk of CHD. 

Kritchevsky and Kritchevsky (2000) provided a summary of the evidence linking dietary cholesterol to the risk of CHD in 10 cohorts from eight large, well-conducted prospective studies that were reported since 1980, which included the Nurses Health Study, the Health Professionals Followup Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. In eight of the cohorts there was no statistical association between cholesterol intake and the risk of CHD. In one of the positive studies the association was established by simple univariate analysis and was not adjusted for other dietary variables. The other study adjusted only for fat intake. There is no compelling evidence from these epidemiological studies that dietary cholesterol is associated with the risk of CHD. 

Early studies of the relation between intake of TFAs and the occurrence of CHD also produced conflicting results. However, the large, well-conducted prospective studies showed positive associations between TFA intake and risk of CHD. The Nurses Health Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study produced statistically significant positive associations, whereas in the Health Professionals Followup Study the positive association did not attain statistical significance (Ascherio et al., 1999). There was also a significant positive association between TFA intake and CHD risk in the smaller Zutphen Elderly Study (Oomen et al., 2001). 

A case-control study (Ascherio et al., 1994), a cross-sectional study (Bolton-Smith et al., 1996) and three prospective studies the Nurses Health Study (Willett et al., 1993), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Pietinen et al., 1997), and the Zutphen Elderly Study (Oomen et al., 2001), separately assessed the effect of TFAs from hydrogenated vegetable oil and animal fat on the risk of CHD. With the exception of the small Zutpen Elderly Study (Oomen et al., 2001), the studies found that the positive association with the risk of CHD was explained entirely by the intake of TFAs from hydrogenated vegetable oil. 

H8. Hartman, T. J., Albanes, D., Rautalahti, M., Tangrea, J. A., Virtamo, J., etal., Physical activity and prostate cancer in the Alpha-tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (Finland). Cancer Causes Control 9, 11-18 (1998). 

Negative outcomes in several supplementation trials of beta-carotene, especially the results of the Finnish Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study (63) (SEDA-20, 363), have again revived discussion about the carcinogenic potential of beta-carotene. The ATBC trial showed that there was a statistically significant increase in the incidence of lung cancer in heavy smokers who took beta-carotene. 

Besides its hepatotoxic effects, beta-carotene supplementation can also cause cardiovascular complications in smokers and potentiate carcinogenicity. The Alpha-Tocopherol, Beta-Carotene and Cancer Prevention Study (ATBC) (72) and CARET (99) showed that supplementation of beta-carotene in smokers increased the incidence of death from coronary artery disease. Recent results suggest that beta-carotene participates as a prooxidant in the oxidative degradation of LDL, and that raised LDL concentrations may cancel the protective effect of alpha-tocopherol (102). 

Pietinen, P. A. Ascherio P. Kothonen A.M. Hartman W.C. Willett D. Albanes J. Virtamo. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men The alpha-tocopherol, beta-carotene cancer prevention study. Am. J. Epidemiol 1997, 145, 876—887. 

Acronyms and abbreviations PHSl, Physician s Health Study I CHAOS, Cambridge Heart Antioxidant Study ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Stirdy NHS, Nurses Healtli Study CVD, cardiovascular disease ALS, amyotrophic lateral sclerosis NMD A, A-methyl-D-aspartate glutamate receptors. 

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