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American Journal of Clinical Nutrition, Vol. 80, No. 6, 1508-1520, December 2004
© 2004 American Society for Clinical Nutrition


Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts1,2,3

Paul Knekt, John Ritz, Mark A Pereira, Eilis J O'Reilly, Katarina Augustsson, Gary E Fraser, Uri Goldbourt, Berit L Heitmann, Göran Hallmans, Simin Liu, Pirjo Pietinen, Donna Spiegelman, June Stevens, Jarmo Virtamo, Walter C Willett, Eric B Rimm and Alberto Ascherio

1 From the National Public Health Institute, Helsinki (PK, PP, and JV); the Departments of Biostatistics (JR and DS), Nutrition (EJO, WCW, EBR, and AA), and Epidemiology (SL, DS, WCW, EBR, and AA), Harvard School of Public Health, Boston; the Harvard Center for Cancer Prevention, Boston (WCW); the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (WCW); the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (MAP); the Department of Medicine, Children’s Hospital, and the Department of Pediatrics, Harvard Medical School, Boston (MAP); the Department of Medical Epidemiology, Karolinska Institute, Stockholm (KA); the Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (SL); the Center for Health Research, Loma Linda University School of Medicine, Loma Linda, CA (GEF); the Section of Epidemiology and Biostatistics, Henry N Neufeld Cardiac Research Institute, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel (UG); the Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden (GH); the Research Unit for Dietary Studies at the Institute of Preventive Medicine, Copenhagen (BLH); the Research Centre for Prevention and Health, Glostrup, Denmark (BLH); the Glostrup University Hospital, Glostrup, Denmark (BLH); and the Departments of Nutrition and Epidemiology, School of Public Health, University of North Carolina, Chapel Hill (JS)

Background:Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear.

Objective:We studied the relation between the intake of antioxidant vitamins and CHD risk.

Design:A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline.

Results:Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P = 0.17) and 1.23 (1.04, 1.45; P = 0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend < 0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk.

Conclusions:The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.

Key Words: Antioxidant • carotenoids • cohort • coronary heart disease • diet • Pooling Project of Cohort Studies on Diet and Coronary Disease • vitamin C • vitamin E

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