What the forbidden grapefruit has to do with Ontario innovation

An apple a day may keep the doctor away, but a succulent grapefruit mixed with certain medications is forbidden fruit because it could lead to physical distress, a Western University researcher discovered more than 25 years ago.

In the worst case scenario, it could be a deadly cocktail, Dr. David Bailey found. His research changed patient care worldwide.

Bailey is among 50 innovators, identified by Research Matters, a collaborative project involving Ontario’s 21 publicly assisted universities, who have revolutionized the fields of medicine, science, technology, food production and the arts. Also among these game-changers are the Group of Seven artists and Dr. Norman Bethune.

Research Matters’ aim in compiling the list of 50 is to increase public awareness of how the province’s university researchers have helped change the world for the better. Their contributions will be highlighted at the Ontario and Canada Research Chairs Symposium taking place at the Metro Toronto Convention Centre on April 1 and 2.

Homegrown discoveries include the development of the Yukon gold potato, insulin, the anti-gravity flight suit, safe wheelchair transit technology and Technicolor in the movies. The pioneers behind these developments, whose work spans the past 100 years, may not be household names, but their research has had an impact around the globe.

The complete list of discoveries at is available at the yourontarioresearch.ca.

In the case of Bailey, he made the unlikely connection between food, drugs and potentially nasty side effects by chance in 1989.

At the time, food and drugs weren’t on his radar at all — he was investigating the effects of alcohol on felodipine, a commonly prescribed medication that lowers blood pressure. To ensure subjects didn’t know whether they were getting alcohol, Bailey set out to “blind” them by masking the taste of the booze.

He poured orange, lime and grape juice into glasses with 95 per cent pure ethanol from the hospital pharmacy. “None of them worked,” recalls Bailey, now professor emeritus in the department of medicine at Western University and a scientist at London’s Lawson Health Research Institute. It was his wife, Barb, who suggested grapefruit juice.

Findings from the felodipine study were surprising. Subjects had higher than expected drug levels in the blood whether they had taken the medication with or without alcohol.

The cause was not immediately apparent. However, a systematic elimination of the most likely suggested grapefruit juice might have been the culprit.

A clinical pharmacologist, Bailey knew he was on to something and decided to delve further, this time running the grapefruit tests on himself, a la Dr. Jekyll. Unlike the fictional physician, Bailey wasn’t putting his life on the line for science.

“Felodipine is a relatively safe drug,” explains the former track and field athlete — he raced for Canada in the men’s 1500 metres at the 1968 Summer Olympics in Mexico City — who, at 70, maintains a regular fitness regime and is in great physical condition. He was in top form in the late ’80s and an ideal candidate for the pilot.

“In clinical research, you should minimize risks,” says Bailey. “You never design a study you wouldn’t do yourself.” Besides, any experiments of this nature had to be approved by an independent body at arms length from the study.

Bailey first took the drug orally with water, testing his blood levels. Days later he did the same with grapefruit juice. “My levels were five times higher, i.e. the same as taking five tablets compared to just one ” he recalls.

Fact is, no one at the time believed that food could dramatically increase the concentration of drugs in the blood. But he and others noted that in some patients, the levels of certain drugs were 20 times higher, leading to the possibility of serious medical problems.

It was an “aha” moment that changed patient care.

“Like (Alexander) Fleming and penicillin,” says Bailey, referring to the scientist who discovered penicillin by accident, growing in a Petri dish.

“It was one of the biggest food-drug interaction findings ever,” he continues. “The effect of grapefruit juice was just as large as any drug/drug reaction . . . The oddity was more interesting than the reason that we conducted the original investigation.”

Despite the magnitude of the discovery and its potential impact, skeptics hesitated to accept the work because it was so radical.

A formal study that followed on the heels of his pilot was published in the prestigious medical journal The Lancet in 1991.

The team of Canadian researchers from Western University then began generating headlines globally. And since that time there have been hundreds of studies by scientists and clinical researchers assessing the many facets of this interaction and the effects of other foods and natural products. It was found that other citrus fruits such as pomelos, limes and bitter Seville oranges, used in marmalade, also contained the active chemicals furanocoumarins, just like grapefruit.

Furanocoumarins, researchers have learned, interfere with cytochrome P450 3A4, an enzyme in the liver and the lining of the gastrointestinal tract that protects the body against toxins. Grapefruit irreversibly inactivates the enzyme during the absorption process, even if taken hours before or after the medication.

Bailey was thrust back into the international spotlight in 2012 when he was lead author of a study published in the Canadian Medical Association Journal noting that 85 drugs on the market were known or predicted to have a negative impact when taken orally with grapefruit or its juice. Some drugs could cause serious rhythm changes in the heart or produce acute kidney failure.

Patients aged 45 and older — the biggest consumers of both medications and grapefruit — were most vulnerable. “What we are talking about is unintentional overdose and potentially serious adverse consequences,” says Bailey.

The findings reverberated around the globe.

The article also noted that the number of drugs that could interact with grapefruit and in some cases be life-threatening skyrocketed from 17 to 43 in just four years. Among them is the widely prescribed opioid pain reliever oxycodone. “This increase is a result of the introduction of new chemical entities and formulations,” the article noted. These drugs included ones commonly used to treat some cancers, heart disease, high cholesterol, central nervous systems conditions and urinary tract infections.

Starting on April 1, the public is invited to vote on the top five game-changing Ontario discoveries from the Research Matters list, with voting continuing through the summer. People can also go to yourontarioresearch.ca to register for free panel discussions to be held during the Ontario and Canada Research Chairs Symposium or to view the live webcast.