Based upon extensive pharmacological research, scientists have established that through the inhibition of the CYP3A4 enzyme system, grapefruit interacts with more than 60% of orally administered drugs leading to elevation of serum concentrations. An effect is seen with the whole fruit as well as the juice and chronic consumption may enhance the magnitude of the effect. Considerable research has been done to elucidate the mechanism of the interaction and investigators have recently identified furanocoumarins as the active ingredient in grapefruit responsible for enhancing the systemic exposure of CYP3A4 substrates.
In vitro and in vivo studies have shown that CYP3A4 is involved in the metabolism of hormones. Grapefruit, an inhibitor of CYP3A4, has been shown to lead to elevated serum levels of estrogens when hormones are administered orally. U.S. Food and Drug Administration (FDA) mandated labeling for hormone products for postmenopausal women now contains a warning that grapefruit juice may increase plasma concentrations of estrogen. We have recently shown that endogenous serum levels of estrogen are also elevated in postmenopausal women who consume very modest amounts of grapefruit and, moreover, have now shown that their risk of breast cancer is significantly increased - generally, a 30% increase among subjects who consume the equivalent of ½ grapefruit or more every other day. Since it is well established that estrogen is associated with breast cancer risk, it is biologically plausible that regular intake of grapefruit would increase a woman’s risk of breast cancer mediated through the effect on estrogen levels. However, to date, there is very limited published data on the effect of grapefruit intake on sex hormone levels. The importance of understanding, in detail, the interactions between dietary intake of grapefruit and serum hormone levels has become more evident, not only acute interactions but the effects of chronic consumption on hormone absorption and metabolism. Scientists need to definitively establish the link between grapefruit consumption and circulating estrogen levels.
This study at the University of Southern California is investigating whether eating grapefruit affects the hormones of postmenopausal women. The researchers were looking to enroll at least 65 volunteers. The Call to Action for this study was sent to Army of Women members on May 5, 2009. The researchers were able to close enrollment on May 7, 2009, after the Army of Women provided them with 203 women who were interested in enrolling in the study.