Multivitamin Use and Breast Cancer: Protective or Harmful?

Nick Mulcahy

April 27, 2010

April 27, 2010 (Washington DC) — Use of multivitamins was associated with a decreased risk for breast cancer in women, according to a case–control study of 725 women from Puerto Rico presented at the American Association for Cancer Research (AACR) 101st Annual Meeting.

However, in the same week these data were presented, an observational study of 35,329 women from Sweden reported the opposite — that multivitamin use is associated with an increased risk for breast cancer.

So which is it? Are multivitamins harmful or helpful?

A definitive answer cannot come from these types of studies, which are not randomized controlled trials and, suggest both sets of authors, are subject to confounding factors.

About 40% of US women reported using multivitamins.

Still, the authors of both studies had supporting ideas about why their findings were biologically plausible.

Both studies have possible public health implications of considerable scope, because "about 40% of US women reported using multivitamins in 1999-2000," write the Swedish researchers in their paper, which appears in the May issue of the American Journal of Clinical Nutrition.

Multivitamins Boost DNA Repair Capacity

The study with the positive findings, led by Jamie Matta, MD, from the Ponce School of Medicine in Puerto Rico, involved 268 women with recently diagnosed untreated breast cancer and 457 women without breast cancer who acted as control sunjects. The majority of the women in the study were 41 to 60 years of age.

All of the women in the study completed an 8-page family history, medical history, lifestyle questionnaire, which included 3 sections on vitamin and dietary supplement intake over the previous 5 years.

The study found a 33% decrease in breast cancer risk associated with multivitamin use and a 41% decrease associated with calcium use.

The 2 effects were independent of each other.

The authors also measured the women's DNA repair capacity, which is a mechanism that helps prevent damaged normal cells from turning into cancer cells, including those in the breast.

DNA repair capacity was measured with a validated assay, using blood samples previously taken from all study participants.

They found that "a higher DNA repair capacity was associated with multivitamin intake and calcium intake," said Dr. Matta.

"Our paper is the first to show that DNA repair capacity can be modified by multivitamin and/or calcium intake," he said. Previous research has suggested that DNA repair capacity is "genetically fixed," he explained.

They also found that a decreased DNA repair capacity was associated with breast cancer. Specifically, for each decreasing percent unit of DNA repair capacity, the odds of having breast cancer increased 1.9 times.

In addition, the researchers had more conventional findings: a family history of breast cancer meant 2.2-fold greater odds of having breast cancer. Advancing age, increasing body mass index, and not breastfeeding also statistically significantly increased the risk for breast cancer.

Notably, when the researchers included DNA repair capacity in their risk analysis (logistic regression model), the protective effect of calcium was no longer statistically significant, "suggesting that DNA repair capacity is responsible for the association we found," they write in their AACR abstract.

In contrast, the association of multivitamin intake and breast cancer was unaffected when they adjusted for higher levels of DNA repair capacity, suggesting that multivitamins are an "independent protective factor," write Dr. Matta and colleagues.

Also of note was the fact that taking single supplements of each vitamin (A, E, C, and beta-carotene alone) was not associated with a significant reduction in breast cancer risk, reported Dr. Matta.

Vitamins have been shown to work better collectively in their antioxidant effect.

"This is not so weird because vitamins have been shown to work better collectively in their antioxidant effect," he said about taking isolated versions of these standard ingredients in multivitamins.

"Take your multivitamin," Dr. Matta told Medscape Oncology. "It's a cheap insurance policy."

Do Multivitamins Promote Breast Density?

An oppositive conclusion comes out of the Swedish study, which spanned 10 years and involved 35,329 women with an average age of about 61 years.

"We observed a 19% increased risk of breast cancer associated with multivitamin use after adjustment for other breast cancer risk factors," write the authors, led by Susanna Larsson, PhD, and colleagues from the Karolinska Institute in Stockholm.

The Swedish authors note that previous "epidemiologic studies of the association between multivitamin use and breast cancer risk yielded inconsistent results."

Their findings are much like "those of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort, in which an 18% increased risk of breast cancer was observed among users of multivitamins [relative risk, 1.18; 95% confidence interval, 0.95 - 1.48] who were followed up from 1993 to May 2003," they note.

"The possibility that multivitamin use may increase the risk of breast cancer is biologically plausible," explain the Swedish investigators. However, unlike the study from Puerto Rico, the plausibility relates to findings from outside the new research.

Namely, Dr. Larsson and her coauthors cite a recent study that showed that the current use of multivitamins and minerals in premenopausal women was associated with a statistically significant 5.3% higher mean mammographic breast density (Am J Clin Nutr. 2008;87:1400-1404).

Breast density is "strongly and positively related to breast cancer risk," write Dr. Larsson and colleagues.

Folic acid in supplements could also increase the risk for breast cancer, they add. "High doses of folic acid from supplements or fortified foods are of concern because synthetic folic acid is more bioavailable than folate from natural food sources and, hence, potentially more potent in promoting cancer growth," they write.

If folic acid is responsible for the observed association between multivitamin use and the risk for breast cancer, the association might not be seen in the American population, the authors posit. Why?

"Because breakfast cereals and grain products have been fortified with folic acid since 1998 in the United States." This would complicate the detection of the influence of folic acid.

There is no mandatory folic acid fortification in Sweden, they add.

Dr. Larsson and her coauthors believe their findings are a matter of "concern" and in need of further research.

Dr. Larsson's study was supported by research grants from the Swedish Cancer Foundation and the Swedish Research Council for Infrastructure. The authors have disclosed no relevant financial relationships.

American Association for Cancer Research (AACR) 101st Annual Meeting: Abstract 4568. Presented April 18, 2010.

Am J Clin Nutr. 2010;91:1268-1272. Abstract

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