The human body relies heavily on enzymes to perform all sorts of functions such as: the breakdown of various foods so that the nutrients can be absorbed, accelerating various chemical reactions which otherwise would be too slow for the requirements of the body, and generating energy quickly and efficiently among others. Then there is a whole series of enzymes whose job is to detoxify chemicals, either foreign (toxins) or ones produced by the body itself including hormones like estrogen. One such large group of enzymes is called the cytochrome P450 (CYP) family which breaks down different chemicals and thus reduces the circulating levels in the blood. In 1989, a researcher by the name of Bailey accidentally discovered that while masking the taste of alcohol with grapefruit juice, the metabolism or breakdown of a drug he was studying was greatly reduced. Later, it was found that components in grapefruit caused interactions with many other types of drugs; in fact 60% of drug actions are affected by grapefruit juice!
What is the mechanism of this interaction? Various components in grapefruit juice like bergamottin interfere with the proper working of one specific member of the CYP P450 family called CYP3A4, which is responsible for metabolizing a large percentage of drugs. Once the CYP3A4 is inhibited, the drug in question stays in the body for a longer period and may thus cause a potentially serious interaction. Generally, a reduction in the dose of the drug is required to prevent toxicity. Pharmacists will often warn patients about grapefruit juice-drug interactions.
Estrogen is one such hormone that is broken down by CYP3A4 especially in premenopausal women when estrogen production is ripe. This becomes less of an issue for women once they approach menopause since estrogen levels go down dramatically. Estrogen is a hormone that causes cells in various tissues like the breast and the uterus to multiply. Now, if the breakdown of estrogen is prevented because the enzyme that breaks it down is inhibited by grapefruit juice, then it is conceivable the levels of estrogen will rise and the hormone will stay longer in the body causing proliferation of tissues and may lead to breast cancer.
Researchers at the University of Hawaii argued that grapefruit juice or fruit would cause an increase in the risk of breast cancer by inhibiting the CYP3A4 enzyme. They investigated the association between grapefruit juice intake and the risk of breast cancer in five different ethnic groups. After adjusting for age, body weight, life style (e.g. smoking), diet (overall caloric intake) and other factors, the researchers noticed that indeed the levels of estrogen were higher in women that regularly ate or drank grapefruit juice. From a consumption of only a quarter of a grapefruit daily, the researchers estimated it may result in a 30% increased risk of breast cancer!
But what about all the fiber and flavonoids that grapefruit is rich in, aren’t these healthy and beneficial against cancer you say? Indeed that would be the case, yet where is the evidence to counteract the findings of the Hawaiian researchers? Researchers at Harvard University lead by William Willett, a giant in the field of nutrition and health took a closer look at the University of Hawaii study. They found in their very large Nurses’ Health Study population that grapefruit juice or fruit intake did NOT result in increased breast cancer risk; rather it had a protective effect.
The contrasting conclusions in the above studies highlight the major drawback of epidemiological or population based studies including: first, that it is difficult to control for the many confusing factors (confounding) even adjusting for such variations is very difficult; second, most of the data regarding intake is derived from self-assessment questionnaires which unfortunately have a serious flaw and finally, perhaps the most important, people are individuals and thus have unique biological responses to diets and supplements that may be different from another person. This last point is what the late great Dr. Roger Williams argued when he proposed his seminal theory of biochemical variation which suggests the urgent need for personalized nutrition.
Monore, KR et-al “Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study” Br J Cancer, 2007; 97:440-445
Kim EH et-al “A prospective study of grapefruit and grapefruit juice intake and breast cancer risk” Br J Cancer, 2008; 98:240-241