Serendipitous discoveries are legendary in science. Fleming’s discovery of penicillin, Perkin’s of mauve, Silver’s of post-it notes, Roentgen’s of x-rays, Fahlberg’s of saccharin, Plunkett’s of Teflon, Spencer’s of microwave cooking, Becquerel’s of radioactivity, Goodyear’s of vulcanized rubber, de Mestral’s of Velcro, Benedictus’ of safety glass, and Pfizer’s discovery of Viagra all were accidental findings in the sense that they were not the result of a search for a particular goal. To their credit, all these scientists were able to capitalize on their chance observation. Dr. David Bailey’s 1991 discovery of the grapefruit juice effect on medications can be added to this list.
Dr. Bailey and colleagues at the University of Western Ontario had been studying felodipine, a blood pressure–lowering drug, and wondered if it interacted with alcohol. They decided on a double-blind trial in which some subjects were to take the drug with alcohol and some without. This meant that the taste of alcohol had to be masked, and after some experimentation Dr. Bailey concluded that grapefruit juice was up to the task. One group took the medication with pure grapefruit juice, the other with grapefruit juice laced with alcohol. To the researchers’ surprise, the alcohol had no effect, but in both groups the blood levels of felodipine were three times higher than expected.
It turns out that furanocoumarins, naturally occurring compounds in grapefruit, interfere with the activity of cytochrome P450, an enzyme found in the intestinal wall that degrades foreign organic molecules. Since the body regards medications as foreign substances, the enzyme goes into action to degrade them. If the enzyme’s action is blocked, a medication can reach higher than desired concentrations in the blood potentially increasing side effects. Subsequent research revealed that a number of medications, including some statins, blood pressure drugs, anti-anxiety agents and antihistamines, were found to be susceptible to the grapefruit juice effect. Since not all drugs have been studied, the general recommendation is to abstain from grapefruit juice when taking meds since the effect can last for 24 hours.
Now for another chance finding. Dr. Bailey extended his research to many other drugs and was surprised when the antihistamine fexofenadine, the active ingredient in the allergy medication Allegra, resulted not in higher, but lower blood levels when taken with grapefruit, orange or apple juice! In this case, some component in these juices blocks the action of “organic anion transporting polypeptides (OATPs), molecules that ferry the medication from the gut into the bloodstream. Further research revealed that some other drugs can also have a reduced effect if taken with fruit juices including the antibiotic ciprofloxacin, some beta-blockers and the asthma medication montelukast. The number of drugs that have been studied in this context is limited, so there may be others whose absorption is blocked by the intake of fruit juice. Since the blocking of the transport proteins lasts only about four hours, there is no interference if medications are taken at least four hours distant from fruit juice intake.
Fruit juices are not the only concern when it comes to interactions with medications. Calcium containing foods, such as dairy products, can reduce the absorption of iron supplements as well as of antibiotics such as tetracycline, doxycycline and ciprofloxacin if consumed within two hours of taking the medication. Bisphosphonates used to prevent or treat bone loss should be taken on an empty stomach with an hour wait before eating. The same goes for thyroid medications, but the wait time should be extended to four hours if dairy products are consumed.
Alcohol is a no-no with antidepressants of the “serotonin re-uptake inhibitor class (SSRIs)” due to a risk of gastrointestinal bleeding. It should also be avoided when taking stimulants such as Adderall, prescribed for attention deficit disorder (ADD), since amphetamine, the active ingredient in Adderall can mask the sedative effect of alcohol and cause people to drink more. The effect of the anticoagulant warfarin is can be reduced by vitamin K which is found in broccoli, Brussels sprouts, spinach and kale. These nutritious vegetables do not have to be eliminated, just kept at a constant level of consumption with no sudden increase or decrease of intake.
Monoamine oxidase inhibitors (MAOIs) such as phenelzine, used to treat depression, can increase blood levels of tyramine, a compound that occurs naturally in foods such as cheese, cured meats, sauerkraut and soy sauce. Since tyramine is normally metabolized by the enzyme monoamine oxidase (MAO), blocking the activity of this enzyme increases blood levels of tyramine, possibly boosting blood pressure to dangerous levels.
British author John Mortimer, creator of Rumpole, the cantankerous but likeable barrister who matches wits with London's criminal element, made use of the tyramine reaction in "Rumpole and the Expert Witness". The story centers around a physician's clever plot to precipitate the early demise of his wife. The motive is an age old one; another woman has entered the picture. But the method by which the unfortunate victim is dispatched is novel: the murder weapon is a cheese soufflé! This is not murder by cholesterol, the foul deed is accomplished with the nefarious use of a monoamine oxidase inhibitor.
The physician had arranged for his wife to be prescribed a monoamine oxidase inhibitor for her depression. Then, as a treat, he made her a cheese soufflé and served it up with some wine. The tyramine in the cheese and wine conspired with the antidepressant to achieve the desired end; the unfortunate wife succumbed to a stroke. Mortimer knew his chemistry!
