Why Grapefruit Juice and Certain Medications Don’t Mix?

Ever notice a warning label on certain prescription medications advising the patient to avoid eating grapefruits or drinking grapefruit juice, and wondered how such a healthful treat could be ill-advised? In February 2012 the FDA issued a consumer report explaining the connection.

Although generally healthy, grapefruits contain certain chemicals that can inhibit key proteins involved in drug metabolism. Depending on which protein is inhibited, the result will either be an increase in blood concentrations of the drug to potentially toxic levels, or a decrease in the amount of medication reaching target tissues.

How can one fruit have such seemingly opposite affects? The first scenario – toxic levels of the drug accumulating in the bloodstream – occurs when metabolism of a particular drug depends on enzymes known as CYP3A4. These enzymes are found in both the small intestine and the liver. Normally, this means that drug metabolism starts even as it is being absorbed through the intestine and into the bloodstream. Grapefruit inhibits the activity of CYP3A4 – resulting in a too-high concentration of the drug entering the patient’s bloodstream. These higher concentrations may result in direct toxicity, or, over time, may result on liver damage, as it forces the liver to work harder to metabolize the drug. Not all drugs rely on these CYP3A4 enzymes for metabolism, which is why not all medications are affected. Scientists have known for some time that the cholesterol-lowering statin drugs such as Zocor and Lipitor are affected by CYP3A4 inhibition; more recent studies indicate grapefruit consumption can affect a longer list of medicines, including those prescribed to treat high blood pressure (Nifediac and Afeditab), depression or anxiey (Zoloft and BuSpar) and erectile dysfunction (Viagara and Cialis).

The second scenario – needed medication not reaching the target cells – results from grapefruit’s inhibition of a type of protein known as a transporter protein – a protein on cellular surfaces which helps molecules to enter cells. Allergy medicine such as Benadryl and Allegra rely in part on these transporter proteins to enter cells; their inhibition results in lower intercellular drug concentrations with a corresponding loss of effectiveness.

So continue to enjoy what remains a healthy treat – but just be sure to read your medication labels first.