Dietary Antioxidants, Supplements & Risk of Epithelial Ova Ca

Dietary Antioxidants, Supplements, and Risk of Epithelial Ovarian Cancer

Aaron T. Fleischauer, Sara H. Olson, Laura Mignone, Neal Simonsen, Thomas A. Caputo, and Susan Harlap

Abstract and Introduction


Several studies of dietary and serum antioxidant micronutrients (vitamins A, C, and E and beta-carotene) suggest that higher levels may be protective for ovarian cancer.

None of these has examined supplements. We used a food frequency questionnaire and additional questions on supplements to study 168 histologically confirmed epithelial ovarian cancer cases, 159 community controls, and 92 hospital-based controls. Antioxidant consumption from diet or supplements was calculated in milligrams or international units per day.

In multivariate analyses using only community controls, the highest levels of intake of vitamins C and E from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively.

Consumption of antioxidants from diet was unrelated to risk.

In analyses combining antioxidant intake from diet and supplements, vitamins C ( 363 mg/day) and E ( 75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and OR = 0.44 (95% CI = 0.21-0.94), respectively.

Results were similar, with some attenuation toward the null, in analyses combining both control groups. The levels of vitamins C and E associated with the protective effect were well above the current US Recommended Dietary Allowances.

These findings support the hypothesis that antioxidant vitamins C and E from supplements are related to a reduced risk of ovarian cancer.


Numerous case-control and cohort studies conducted in various populations over the years suggest that higher consumption of fruits and vegetables, foods rich in carotenoids and antioxidant vitamins and minerals, is related to a reduced risk of lung, colon, breast, and other cancers [1-3].

Few studies, however, have examined the relationship between consumption of antioxidants and ovarian cancer. The established risk factors for ovarian cancer are the increased risk associated with family history of ovarian and breast cancers and the protection associated with parity, use of oral contraceptives, hysterectomy, and tubal ligation [4,5].

The few studies of diet and ovarian cancer have consistently shown that higher consumption of antioxidant-rich vegetables offers protection against epithelial ovarian cancer [6-10]. Green leafy vegetables, a major source of antioxidant vitamins and minerals, appear to be associated with protection: reported relative risk estimates from three studies, for the highest categories of intake, range from 0.44 [6] to 0.62 [7].

Higher intake of carrots, a leading source of beta-carotene, has also been associated with a reduced risk [7,9]. Analyses of the association of ovarian cancer with micro-nutrient antioxidants from foods or from serum have shown contradictory results. Vitamin A from diet or in serum has been shown to be protective [10-13] or unrelated to risk [6,9,14.15]. beta-Carotene has been shown to be strongly protective [7,12], modestly protective [15], or unrelated to risk [6,9,13.14].

Vitamin C was found to be related to a reduced risk in two [11,12] of four (6,10-12) studies, whereas vitamin E from diet or serum has demonstrated no associations with ovarian cancer risk [6,13,14]. Although antioxidant supplements can be an important source of an individual's total daily intake of antioxidants [16], to our knowledge, no epidemiological studies have examined antioxidants from supplements and ovarian cancer risk.

The aim of this analysis was to investigate associations between ovarian cancer risk and reported intake of antioxidant micronutrients from diet and/or supplements. In addition, we address whether smoking status modifies these associations, and we examine the relationship between intake of antioxidants from supplements and from foods.

Nutr Cancer 40(2):92-98, 2002.

Case-Control Information

Method, Study, Subjects


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High intake of Vitamins C/E may reduce risk of ova ca

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