Could eating grapefruit daily raise a woman's risk of breast cancer? Possibly, researchers from the University of Southern California report in the British Journal of Cancer (2007;97:440–445). The mechanism appears to be grapefruit's inhibition of CYP3A4, an isoenzyme that metabolizes estrogen. Although preliminary, the finding is one that warrants further investigation, they say.
“It's an interesting hypothesis, there's biological plausibility, and we want other researchers to look at it,” says lead study author Kristine R. Monroe, PhD, Research Associate in the Department of Preventive Medicine at the University's Keck School of Medicine.
Monroe's findings come from data on 46,080 naturally postmenopausal women taking part in the Hawaii-Los Angeles Multiethnic Cohort Study, a prospective study of people from 5 ethnic/racial groups in Los Angeles and Hawaii. Participants reported grapefruit or pomelo consumption as part of a comprehensive food frequency questionnaire. Only intake of whole grapefruit was examined in this analysis because grapefruit juice was combined with orange juice in the questionnaire.
Women in the highest intake category—60 grams or more per day, equal to slightly more than one-quarter grapefruit per day or half a grapefruit every other day—had a relative risk (RR) of breast cancer 30% higher than women who ate no grapefruit (RR = 1.30). The trend of increasing risk with increasing consumption was significant (P = 0.015) after adjusting for weight, exercise, use of postmenopausal hormone therapy, family history of breast cancer, and other factors that could impact risk.
The same association was evident for women who had never used postmenopausal hormone therapy (RR = 1.44; P = 0.038) and for those with a body mass index below 25, the cutoff for overweight (RR = 1.32; P = 0.011). Although risk also increased for women who were current or past users of hormone therapy (either estrogen-only or estrogen-progestin combination therapy) and for those with a higher body mass index, the differences were not statistically significant. This finding suggests grapefruit's effect on estrogen is greatest in women whose baseline levels are lower to begin with, Monroe says.
The results are consistent with a biological effect of grapefruit on estrogen metabolism. At least 2 previous studies have found higher estrogen levels in women consuming grapefruit or grapefruit juice, the authors note, and grapefruit is known to elevate serum concentrations of many drugs, including hormone replacement therapies. The US Food and Drug Administration requires hormone replacement products to carry warning labels stating that grapefruit juice may increase plasma concentrations of estrogen.
Monroe stresses, however, that there's not yet enough evidence to recommend women stop eating grapefruit as a means of lowering their breast cancer risk. And because premenopausal women and breast cancer survivors were not part of her cohort, it's not possible to know whether grapefruit would have similar effects on them.
“This needs to be confirmed in other studies,” she says. “I would use caution until further studies are done and a scientific conclusion can be reached.”
Other experts agree.
“Results from a single epidemiological study are insufficient as a basis for recommendations,” says Michael Thun, MD, American Cancer Society (ACS) Vice President of Epidemiology and Surveillance Research. “In this case, however, other studies have established that even modest consumption of grapefruit affects the action of many drugs. Women who have had estrogen receptor-positive breast cancer or are concerned for other reasons could consider substituting other fruit until this issue is clarified.”
Additional research is needed to determine whether grapefruit has any effect on the risk of recurrence or progression in breast cancer survivors and how that association might be influenced by the tumor's estrogen-receptor status, the patient's menopausal status, and her current or past treatment.
Until more is known, women would be well-advised to follow ACS nutrition guidelines for cancer prevention, says Marji McCullough, ScD, RD, ACS Strategic Director of Nutritional Epidemiology. The guidelines emphasize eating at least 5 daily servings of a wide variety of fruits and vegetables of different colors. A varied diet not only maximizes intake of beneficial plant nutrients, but could also limit the amount of potentially harmful substances from any single food. Further, eating fruits and vegetables helps to prevent excess weight gain in adulthood, a factor known to increase the risk of breast cancer. The full nutrition guidelines are available free online at http://CAonline.AmCancerSoc.org/cgi/content/full/56/5/310.
Monroe says future studies of grapefruit should not only seek to confirm her team's findings, but also to quantify grapefruit's effects by measuring estrogen levels before the fruit is eaten and afterward. Studies should also explore how long grapefruit's effect on estrogen lasts in the body, she says, as previous research has shown elevated levels of some drugs as many as 72 hours after drinking a single glass of grapefruit juice.