Citrus soda interacts with cyclosporine, maybe statins

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Citrus soda interacts with cyclosporine, maybe statins

16 Apr 2004

Bill 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.

Milstone, M.D., assistant professor of Medicine in the division of

Allergy/Pulmonary & Critical Care Medicine and medical director of

Vanderbilt¹s Lung Transplant Program, was seeing , a new double-lung

transplant recipient, in clinic for a post-transplant appointment.

Prior to this clinic visit, the patient¹s transplant and post-operative

recovery was without incident. ¹s 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 ¹s 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 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. indicated he felt fatigued and was experiencing nervous

tremors, but had done nothing different.

was tested again two days later and his cyclosporine serum levels

were well within therapeutic limits. This pattern repeated itself again at

the next month¹s 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.

³Bill would feel awful with that high cyclosporine level. His kidney

function had deteriorated, and he was experiencing tremor. He just didn¹t

feel well,² Milstone said. ³After this process of high and normal levels

repeated itself, we began a dietary inquiry. Is there something in Bill¹s

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.²

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, and Hoy carefully went over

everything was eating or drinking hoping for a clue. ³We really

struggled with this,² Hoy said.

³I started thinking about strange things in my diet,² said. ³That¹s

when I thought about Sun Drop. Since it¹s a citrus soda I wondered if it had

grapefruit juice in it.²

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 Drop¹s

parent corporation), is the nation¹s seven-time sales leader in the citrus

soda category. Sun Drop is sold throughout the South Atlantic region of the

United States.

³I emailed the company asking for information about the specific contents of

Sun Drop, but of course never heard back,² said.

Suspecting ¹s hunch was correct about his frequent caffeine fix,

Milstone contacted Philip ston, Pharm.D., assistant director of

Vanderbilt Pharmaceutical Services, for help solving the mystery.

ston, well aware of the effect of citrus products on the metabolism of

certain drugs, began a circuitous pursuit of the beverage¹s basic ingredient

information from Sun Drop¹s corporate parent.

³We thought there was something significant about this, and we needed to

check with the bottler,² ston said. ³We found the bottler in Tullahoma,

from Tullahoma we were referred to the corporate headquarters in Dallas, and

from there we were referred to a customer service division in St. Louis. We

sent a formal letter to a customer service representative, who in turn

delivered the letter to someone in their formulation division.

³We didn¹t expect them to give us their formula. That¹s a trade secret. But

we were very interested in whether the beverage had a bergamottin component.

After several days, and another phone call, the company responded by email

saying that Sun Drop contains the type of ingredient you refer to in your

letter.²

ston says the admission was enough to convince him and Milstone of the

cause of ¹s high cyclosporine levels.

Both say a formal study is needed to examine the extent of the effects of

Sun Drop, and a growing number of other drinks containing citrus products,

on the disruption of excretion and absorption of cyclosporine and certain

other prescription drugs.

Although there isn¹t a body of published evidence yet, there is strong

evidence to suggest beverages containing bergamottin also alter the

absorption and excretion of statins (HMG-CoA reductase inhibitors), or as

they are more commonly known, cholesterol-lowering drugs, affecting a high

percentage of the U.S. population on this class of drugs.

ston and Milstone have submitted an article for publication in the

journal Transplantation regarding the effect of Sun Drop on cyclosporine

levels, suggesting that such citrus-containing products be labeled to

include this information.

, who has recovered completely from the ordeal and is doing well, is a

bit humble about his discovery, its potential benefit to transplant

patients, and to all those taking cholesterol-lowering drugs.

³I guess it¹s good for transplant patients to know about Sun Drop,² he said.

³I would hope this might make food and beverage manufacturers think about

the way products are labeled, and hopefully provide better labeling with

appropriate cautions for people.²

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