The Unexpected Ways Food Interferes With Drug Effectiveness

Occasionally, the food we eat can interfere with how drugs are supposed to work. Scientists are now trying to harness these effects to boost the efficacy of treatments.

It was an embarrassing – and after five hours, a painful – problem. A 46-year-old man arrived at a hospital emergency room in Tamil Nadu, India, suffering from a prolonged erection. He had taken sildenafil – better known as Viagra – to treat erectile dysfunction before having sex with his wife. Even though he had taken the medication within the prescribed dose, nothing he tried could resolve the situation.

Doctors were initially baffled, until they learned that the man had also consumed a large amount of pomegranate juice beforehand. They treated him with an injection to counteract the drug’s effects and advised him to avoid the juice in the future. Their conclusion: the juice had inadvertently amplified the potency of the drug.

This case is one of many examples of how foods can interact with medications in unexpected ways. A growing body of medical literature documents such interactions, which can sometimes be bizarre or dangerous. While many reports are anecdotal – isolated cases or small clusters – researchers are now systematically investigating how foods, drinks, and herbs can alter the way pharmaceuticals behave in the human body. Grapefruit, for example, is well known for enhancing the power of certain drugs, raising the risk of side effects or even making normal doses toxic. By contrast, fiber-rich foods can reduce the effectiveness of some medications.

Although drugs typically undergo years of testing to ensure safety and efficacy, there are thousands of pharmaceuticals on the market and countless possible food combinations. Reviews suggest that food–drug interactions pose a significant challenge to safe oral pharmacotherapy. Some scientists now hope to exploit these interactions, using foods to improve drug performance.

“Most drugs are unaffected by food,” says Patrick Chan, professor of pharmacy practice and administration at Western University of Health Sciences in California. “But in cases where food does affect a drug, those are the ones we need to watch carefully.”

Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require drug developers to test for food effects, typically by comparing how drugs behave in fasting individuals versus those consuming a standardized high-fat, high-calorie meal – often consisting of toast with butter, bacon, fried eggs, hash browns, and whole milk.

Yet, as Jelena Milešević, a research associate at the Center of Research Excellence in Nutrition and Metabolism in Belgrade, Serbia, points out, it is nearly impossible to test for every possible interaction. “Human metabolism is like a little factory, with many inputs and outputs,” she explains. Once the body’s chemical reactions intertwine with those of food and drugs, “it’s huge, and very difficult to separate.”

Food can affect drugs in two main ways: by interacting directly with the drug’s active ingredients or by altering how the body processes the medication.

Some food–drug interactions have been recognized since the 1980s. Grapefruit and grapefruit juice, for instance, can interfere with a wide range of medications, including cholesterol-lowering statins, blood pressure drugs such as nifedipine and felodipine, and immunosuppressants like cyclosporine. Grapefruit can also boost the potency of anti-malarials (such as artemether and praziquantel) and antivirals (such as saquinavir) by inhibiting the enzyme cytochrome P450 3A4, which is responsible for breaking down many drugs. Without this enzyme, drugs remain in the body longer and at higher concentrations, which can become toxic – as with sildenafil (Viagra).

“Without this enzyme, the drugs stay longer in the body and the concentrations can become very toxic,” explains Maria da Graça Campos, who directs the Observatory of Drug–Herb Interactions at the University of Coimbra in Portugal. Fruit juices are especially potent because they are condensed and contain higher levels of active compounds than whole fruit.

Cranberries, too, were once thought to interact with the anticoagulant warfarin. Case reports suggested that cranberry juice – or even cranberry sauce consumed daily, as in one unusual Thanksgiving case – might intensify warfarin’s blood-thinning effect. However, systematic reviews and controlled studies found no consistent interaction at normal consumption levels. One widely cited trial, which reported no interaction, was funded by a cranberry juice manufacturer – highlighting the challenges of bias in the literature.

“Most of the evidence comes from poor-quality case reports that ignore obvious confounders,” notes Anne Holbrook, director of clinical pharmacology and toxicology at McMaster University in Canada. To answer such questions, she says, large randomized trials are needed. The type of cranberry product (fresh juice, concentrate, or extract), the dose, and the timing relative to drug intake can all influence potential interactions, adds Andrew McLachlan, dean of pharmacy at the University of Sydney.

Reflecting these uncertainties, in 2011 the FDA removed its warning against cranberry use with warfarin, but the UK’s National Health Service still advises patients to avoid cranberry juice while taking the drug.

Importantly, not all food–drug interactions make drugs more toxic. Some can diminish their effectiveness – potentially rendering vital treatments less reliable.

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