Bill Turner never knew that drinking a popular soda could adversely affect his recovery from a double-lung transplant. What ensued was a true medical mystery, leading to the identification of a new food and drug interaction.
It took a team of medical sleuths at Vanderbilt University Medical Center to get to the bottom of what was causing the 35-year-old to have abnormal blood chemistries during a post-transplant check up.
Aaron Milstone, M.D., assistant professor of Medicine in the division of Allergy/Pulmonary & Critical Care Medicine and medical director of Vanderbilt’s Lung Transplant Program, was seeing Turner, a new double-lung transplant recipient, in clinic for a post-transplant appointment.
Prior to this clinic visit, the patient’s transplant and post-operative recovery was without incident. Turner’s blood chemistries for organ rejection and anti-rejection medication levels were all completely normal.
However, on this particular clinic visit, blood was drawn to monitor among other things the level of anti-rejection drug cyclosporine in Turner’s body. Lab tests revealed cyclosporine serum levels were elevated to more than double the suggested concentration, creating the potential for drug toxicity and serious side effects, such as kidney damage or central nervous system damage for the patient. The question was why.
Milstone and transplant coordinator Haley Hoy questioned Turner extensively about the possibility of altered cyclosporine doses, a change in the time of day the patient was taking medications, change in the time of blood draws for testing, food or beverages consumed with medications, or possible illness. Turner indicated he felt fatigued and was experiencing nervous tremors, but had done nothing different.
Turner was tested again two days later and his cyclosporine serum levels were well within therapeutic limits. This pattern repeated itself again at the next month’s clinic visit. His cyclosporine levels were highly elevated, over twice the accepted level on the day of the clinic visit, but then normal again upon retesting two days later.
“Bill would feel awful with that high cyclosporine level. His kidney function had deteriorated, and he was experiencing tremor. He just didn’t feel well,” Milstone said. “After this process of high and normal levels repeated itself, we began a dietary inquiry. Is there something in Bill’s diet that was doing this? We could not figure out why someone with a stable cyclosporine level would suddenly have a level more than two times therapeutic.”
Milstone says all transplant patients are counseled not to consume grapefruits or Mediterranean oranges because those citrus products contain a compound, called bergamottin (pronounced bur-GA-mot-tin), that blocks metabolism of certain medications in the liver, particularly cyclosporine.
Over a period of several weeks, Turner and Hoy carefully went over everything Turner was eating or drinking hoping for a clue. “We really struggled with this,” Hoy said.
“I started thinking about strange things in my diet,” Turner said. “That’s when I thought about Sun Drop. Since it’s a citrus soda I wondered if it had grapefruit juice in it.”
Sun Drop is a popular citrus soft drink, introduced in 1951, that according to the corporate website of Texas-based Dr Pepper/Seven Up, Inc. (Sun Drop’s parent corporation), is the nation’s seven-time sales leader in the citrus soda category. Sun Drop is sold throughout the South Atlantic region of the United States.
“I emailed the company asking for information about the specific contents of Sun Drop, but of course never heard back,” Turner said.
Suspecting Turner’s hunch was correct about his frequent caffeine fix, Milstone contacted Philip Johnston, Pharm.D., assistant director of Vanderbilt Pharmaceutical Services, for help solving the mystery.
Johnston, well aware of the effect of citrus products on the metabolism of certain drugs, began a circuitous pursuit of the beverage’s basic ingredient information from Sun Drop’s corporate parent.