Abstract 639: The effect of grapefruit intake on endogenous serum estrogen levels in postmenopausal women

Abstract

Abstract The inhibitory effect of grapefruit juice on the intestinal cytochrome P450 3A4 system interacts with more than 60% of orally administered drugs leading to elevation of their serum concentrations. While grapefruit has been shown to lead to elevated serum levels of estrogens when hormones are administered orally, there are no published data on the effect of grapefruit intake on endogenous levels. To begin to address that data gap, we conducted a dietary intervention study among healthy postmenopausal volunteers to determine whether endogenous estrogen levels are significantly affected by grapefruit consumption. We tested 4 grapefruit products: whole fresh grapefruit, fresh squeezed juice “not from concentrate,” shelf-stable juice from concentrate, and grapefruit soda. The majority of volunteers were recruited through the Love/Avon Army of Women. The six-week study consisted of a run-in period of three weeks, a two-week period of grapefruit consumption, and a one-week wash-out period. Eight fasting blood samples were collected during the study. An additional 5 samples drawn at 1, 2, 4, 8 and 10 hours after initial grapefruit intake were collected during an acute-phase study. Serum assays for estrone (E1), estradiol (E2), estrone-3- sulfate (E1S), and sex hormone-binding globulin (SHBG) were conducted. Sixty-two women participated in the study, 10 of whom also participated in the acute phase. Only the whole grapefruit had statistically significant effects on endogeneous estrogen levels. The largest increases were seen in the women with the highest BMI. The changes were evident at 24 hours and remained relatively constant over the 2 week period. With whole grapefruit at the average BMI of 26.6 kg/m2, E1S increased overall by 10.6% (p=0.031), and at a BMI of 30 kg/m2 this increased to 16.4% (p=0.003). Approximately double the effects were seen around 10 hours after whole grapefruit consumption. The effects of fresh juice consumption were around 25% of these increases but were not statistically significant. Small increases in E1 were seen with whole grapefruit, but no increase was seen in E2. The findings of the present study suggest an important interaction between grapefruit consumption and serum levels of endogenous E1S. The increase in E1S is difficult to interpret in term of risk of breast cancer as we found only a small increase in E1 and failed to find any increase in E2. More detailed studies are needed to gain an understanding how the increased levels of E1S are not reflected in similar increases in E1 and E2, and whether the increased E1S levels are reflected in an increase in E1 and E2 levels in the breast itself. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 639. doi:1538-7445.AM2012-639