Cancer
Does grapefruit intake raise breast cancer risk?
By David Liu, Ph. D.
Mar 31, 2008 - 2:59:17 PM

MONDAY March 31, 2008 (Foodconsumer.org) -- The following is what we found in the literature showing that there is a good possibility that grapefruit or its juice when consumed in large quantity for a long term may increase risk of breast cancer.  

The study by Dr. Kristine Monroe from University of Southern California showed that those who consumed the largest amounts were at a 30% increased risk of breast cancer, the increased risk equivalent to the effect observed in those who received hormone replacement therapy.

Dr. Kim from Harvard Medical School on the other hand published a letter in the same journal saying their study proved the opposite.  It is unknown how Dr. Kim’s group conducted their study and how they came to the conclusion, but the data were derived from the Nurse Health’s Study.

Our position is that laboratory work has provided some evidence showing some grapefruit compound may have an effect on estrogen production although other studies generated controversial results.  We tend to believe that the effect of grapefruit (juice) on breast cancer is likely. Of course this is our opinions only.

Regardless, we should error on the side of safety, meaning that it’s better not to consume too much grapefruit (juice).  Early studies have found certain compounds in grapefruit juice could disrupt metabolism of many drugs, raising the drug-poisoning risk.

For the effect of grapefruit (juice) on breast cancer risk, read the following summaries of studies.


Nutr Cancer. 1996;26(2):167-81.
Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices.
So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK.
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.

The researchers tested orange and grapefruit juice concentrates, two citrus flavonoids, hesperetin and naringenin found in oranges and grapefruit and four noncitrus flavonoids, baicalein, galangin and quercetin to see how they affect proliferation and growth of a human breast carcinoma cell line, MDA-MB-435.

They found orange juice has anticancer properties and citrus flavonoids inhibit effectively human breast cancer cell proliferation in vitro, particularly when used along with quercetin.

Adv Exp Med Biol. 1998;439:227-36.
Inhibition of mammary cancer by citrus flavonoids.
Guthrie N, Carroll KK.
Department of Biochemistry, University of Western Ontario, London, Canada.

This study found orange juice may be better in inhibiting mammary tumorigenesis as tested in rats than grapefruit juice.  The researchers speculated that this is because hesperetin retains its effectiveness in vivo better than naringenin. It is also possible that orange juice contains other types of anticancer compounds, which may work alone or synergistically with hesperetin.

The researchers said citrus flavonoids can inhibit both estrogen receptor-negative MDA-MB-435 and estrogen receptor-positive MCF-7 human breast cancer cell in vitro.

Altern Med Rev. 2002 Aug; 7(4):336-9.Click here to read Links
Calcium-D-glucarate.

The study found calcium-D-glucarate or glucaric acid in many fruits and vegetables, particularly in oranges, grapefruit and cruciferous vegetables, may fight a variety of cancer. Oral supplementation of calcium-D-glucarate was found inhibiting beta-glucuronidase produced by colonic microflora and involved in Phase II liver detoxification.  High levels of beta-glucuronidase were associated with an increased risk for various cancers, particularly those hormone-dependent cancers such as breast, prostate, and colon cancers.

Breast Cancer Res Treat. 2004 May;85(2):103-10.
Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: a mechanism for impaired cellular proliferation.
Harmon AW, Patel YM.
Department of Nutrition, University of North Carolina School of Public Health, Chapel Hill, NC 27599, USA.

This study found naringenin in grapefruit inhibits insulin-stimulated glucose uptake in proliferating and growth-arrested MCF-7 breast cancer cells.  The flavanone was found to inhibit the activity of phosphoinositide 3-kinase and also the p44/p42 mitogen-activated protein kinase. The compound reduces the glucose uptake by 60 percent.  Decrease in availability of glucose by lowering the glucose concentration of the culture medium inhibits proliferation. The findings suggest that naringenin inhibits the proliferation of MCF-7 cells via insulin-stimulated uptake.  Naringenin may serve as an anti-proliferative agent, the authors suggested.

Br J Cancer. 2007 Aug 6;97(3):440-5. Epub 2007 Jul 10.
Comment in: Br J Cancer. 2008 Jan 15;98(1):240-1.
Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study.
Monroe KR, Murphy SP, Kolonel LN, Pike MC.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9175, USA. kmonroe@usc.edu

This study established a link between intake of grapefruit and risk of breast cancer.  Previous in vitro and in vivo studies showed cotochrome p450 3A4 or CYP3A4 involved in the metabolism of estrogen and there is evidence that grapefruit inhibits CYP3A4 and increases plasma estrogen concentrations, which have been known to be a risk factor for breast cancer.

The researchers followed 50,000 postmenopausal women from five racial/ethic groups who participated in the Hawaii-Los Angeles Multiethnic Cohort Study.  During the follow-up, 1657 incident breast cancer cases were recorded.  They found grapefruit intake was associated with a 30 percent increased risk of breast cancer in those who consumed one-quarter grapefruit or more per day compared to those who did not consume any.  According to the authors, the magnitude of increase in the risk was comparable to the increased risk of breast cancer in those who received estrogen therapy or estrogen-progestin therapy.  The researchers concluded that grapefruit intake may increase risk of breast cancer in postmenopausal women.

Nutr Cancer. 2007; 58(2):127-35.
Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal Mexican American women: the Multiethnic Cohort Study.
Monroe KR, Murphy SP, Henderson BE, Kolonel LN, Stanczyk FZ, Adlercreutz H, Pike MC.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. kmonroe@usc.edu

This study also found intake of grapefruit and avocado was linked with an increased risk of estrone levels, meaning that use of grapefruit may increase risk of breast cancer.  The researchers investigated dietary fiber intake and its relationship with serum estrogen levels in 242 naturally postmenopausal Latina women.  Dietary habits were surveyed and estrone (E1), estradiol and sex-hormon-binding globulin were measured.  They found dietary fiber decreased the levels of estrone and estradiol by 22 and 17 percent respectively in those who had highest intake of fiber compared to those who consumed the least amounts.

The decrease in estrone and estradiol was particularly significant when fiber was considered in the analysis along with soluble and insoluble nonstarch polysaccharides, 47 and 41 percent respectively.  But high intake of soluble nonstarch polysaccharides was linked to increase in both hormones by 64 and 69 percent respectively.

British Journal of Cancer (2008) 98, 240-241.
doi:10.1038/sj.bjc.6604105 www.bjcancer.com Published online 20 November 2007
A prospective study of grapefruit and grapefruit juice intake and breast cancer risk
E H Kim1, S E Hankinson1,2, A H Eliassen2 and W C Willett1,2
1Harvard School of Public Health, Boston, MA 02115, USA
2Channing Laboratory, Department of Medicine, Harvard Medical School & Brigham and Women's Hospital, Boston, MA 02115, USA

This is a letter to respond to the study linking grapefruit intake and increased risk of breast cancer published in the British Journal of Cancer.

The authors said that the Monroe et al's study could not examine grapefruit juice intake and therefore they examined it in participants of the Nurses' Health Study, which was a prospective cohort consisting of women aged 30 to 55 years in 1976.

But the researchers said they did not find an overall association between intake of grapefruit or grapefruit juice intake and breast cancer risk in the studied women.  No association was observed either when alcohol, saturated fat, dietary fiber and soluble fiber, which were included in the analysis by Monroe et al.

No association was observed either when groups were classified based on their body mass index.  However, stratification by hormone therapy showed a significant decrease in risk of breast cancer in women who had greater intake of grapefruit in the group who never used hormone therapy, a 22% reduction.  This is contradictory to what was found by Monroe et al.

This study further found increased grapefruit intake excluding grapefruit juice intake was not associated with decreased breast cancer risk in those with estrogen and progesterone receptor positive cancers, but was indeed associated with the decreased risk in those with hormone receptor-negative cancers, a possible 40 percent reduction when those consuming 1/4 grapefruit or more per day were compared to those who consumed none.

The researchers also examined the association between grapefruit intake and estrogen levels among 701 postmenopausal women who did not use hormone replacement.  They did not find a significant correlation between the two.

The researchers said "our findings do not support an adverse effect of consumption of grapefruit or grapefruit juice on risk of breast cancer or endogenous hormone levels."