Vitamin C supplement intake and postmenopausal breast cancer risk: interaction with dietary vitamin C

Am J Clin Nutr. 2016 Jul;104(1):228-34. doi: 10.3945/ajcn.115.126326. Epub 2016 May 18.


Background: Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk.

Objective: We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake.

Design: Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided.

Results: Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03).

Conclusions: We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation.

Keywords: breast cancer; diet; dietary supplements; interaction; prospective study; vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / adverse effects
  • Breast Neoplasms / etiology*
  • Diet*
  • Dietary Supplements / adverse effects*
  • Female
  • Humans
  • Middle Aged
  • Postmenopause
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires
  • Vitamins / administration & dosage*
  • Vitamins / adverse effects


  • Vitamins
  • Ascorbic Acid