Grapefruit, hormones, and postmenopausal breast cancer risk
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Grapefruit juice is known to interact with many prescription drugs. The inhibitory effect of grapefruit on the intestinal cytochrome P450 3A4 (CYP3A4) system was discovered accidentally in 1989 during a study designed to test the effect of ethanol on a calcium-channel blocker. Grapefruit juice was given to study subjects to mask the taste of the alcohol. Subsequent investigations found that grapefruit juice interacts with more than 60% of orally administered drugs leading to elevation of their serum concentrations. Consumption of a single glass can produce the maximal acute effect with enhanced drug bioavailability occurring up to 24 hours after juice consumption. Importantly, the magnitude of interaction between drugs and grapefruit juice is markedly variable among individuals. 
 
 
 
 
 
 
 
 Since 1989, the list of drug interactions with grapefruit juice has expanded to include estrogen and progesterone. In fact, U.S. FDA mandated labeling for hormone products for postmenopausal women now contains a warning that grapefruit juice may increase blood concentrations of estrogen. In addition to its effect on administered hormones, scientists have shown that levels of estrogen produced naturally by the body are also elevated in postmenopausal women who consume very modest amounts of grapefruit. Recently, we reported a 30% increased risk of breast cancer among postmenopausal women who consume the equivalent of ½ grapefruit or more every other day. 
 
 
 
 
 
 
 
 Researchers have identified furanocoumarins as the active ingredient in grapefruit responsible for enhancing the systemic exposure of CYP3A4 substrates. Furanocoumarins are a class of organic chemical compounds produced by a variety of plants and occur at higher concentrations than aflatoxins. Many furanocoumarins are toxic and are produced by plants as a defense mechanism against various types of predators ranging from insects to mammals.
 
 
 
 
 
 
 
 We will characterize the acute and chronic effects of consumption of different grapefruit products on hormone levels using a dietary intervention study. Under strictly controlled conditions, we will measure serum hormones in healthy, postmenopausal female volunteers, both before and after administration of grapefruit (whole fruit and juice).
 
 
 
 
 
 
 
 We will recruit approximately 60 postmenopausal women, all of whom will meet specific recruitment criteria. From each volunteer we will collect two baseline blood samples before grapefruit administration. Participants will then be randomly assigned to one of the following groups: (1) ½ of whole grapefruit; (2) one glass of fresh processed juice “not from concentrate” (refrigerated section of grocery store); or (3) one glass of juice from concentrate. From blood samples taken over several weeks we will measure estrone (E1), estradiol (E2), the conjugate E1 sulphate, and sex-hormone-binding globulin (SHBG).
 
 
 
 
 
 
 
 If the dietary intervention study proposed by this grant application produces results supporting the grapefruit-estrogen hypothesis, it has the potential of having a significant clinical impact of reducing breast cancer incidence.