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A Grapefruit a Day? When foods and meds interact.

Grapefruit. Kale. St. John's wort. Some foods and supplements just don't mix with some drugs. The wrong combo could dampen a drug's effect ... or deliver a heftier dose. Here are some of the more common ones.

Q: How can a food interfere with a drug?

A: Sometimes, it's because of similarities in the way that the body handles foods and drugs. Or it's because of the chemistry of the food or the drug. For example, taking a drug with a meal can increase or decrease the absorption of the drug.

Q: So the drug might not work?

A: Right. Certain antibiotics, for example, do a great job of binding to minerals like calcium. When the antibiotic does that, it's not going to be completely absorbed. And neither is the calcium.

That's a big deal if somebody is taking an antibiotic for an infection. I remember a patient who had a urinary tract infection and was taking one of those antibiotics--ciprofloxacin--and nobody had told her how to take it.

She was taking it with yogurt every day. The infection didn't get better, and then became resistant to the antibiotic. Eating yogurt a few hours later would have been fine.

Q: How can foods interfere with how the body handles drugs?

A: The body tends to think of most drugs as foreign or toxic compounds, and is always trying to figure out how to get rid of them.

Enzymes make slight changes to the structure of the drug--usually to make it more water soluble--so you can get rid of it through bile or urine. That's what we mean when we say that the enzymes metabolize the drug.

Q: And some foods can affect one of those enzymes?

A: Yes. Grapefruit juice is a good example. It contains a number of compounds that can destroy one of the main enzymes, cytochrome P450 3A4.

If that happens, any drug that would normally be metabolized by that enzyme--which is about 50 percent of all the drugs we have--wouldn't be fully metabolized. That would increase the amount of drug in the body. [See "A Bitter Surprise," p. 8.]

Q: So drinking grapefruit juice means you get a bigger dose of a drug?

A: Not always. Here's the kicker: Compounds in grapefruit juice can also inhibit some transporters that help some drugs get into and out of cells.

The transporters are there for our normal physiologic substances like glucose and vitamins. But it turns out that a lot of drugs use one or more of those same transporters.

So for some drugs--like the allergy drug fexofenadine, or Allegra--grapefruit and some other fruit juices can actually reduce the amount that gets absorbed when taken together.

Q: Which other juices?

A: Some of the same or similar compounds are in orange and apple juice and in green tea. But they tend to be in higher concentrations in grapefruit juice.

And the way that grapefruit juice can totally take out an enzyme might mean that its interactions are more likely to cause side effects than the other juices.

Q: Why do labels on many drugs say to avoid alcohol?

A: It depends on the medicine. Alcohol can affect the central nervous system, the liver, and the kidneys. So, for example, if somebody is taking an antidepressant that also affects the central nervous system, alcohol may amplify the drug's side effects like drowsiness and dizziness.

Or, if somebody has several drinks every day, that can eventually increase the enzymes that metabolize a lot of medications.

Q: Because the enzymes are revved up to metabolize the alcohol?

A: Yes. In that case, the medicine might not have a chance to do its work before the enzymes break it down.

On the other hand, a binge drinking episode has the potential to curb blood flow to the liver, which can reduce metabolizing enzymes. So you're not clearing the drug and have a greater risk for side effects. It's a complicated story.

Q: How do vitamin K-rich foods like leafy greens affect warfarin, or Coumadin?

A: Many people on warfarin were told to never eat leafy greens. But that has changed.

Warfarin works to thin the blood in part by blocking vitamin K, which the body needs to make blood clot. So if you consume a lot of vitamin K, you're countering what the warfarin is doing. But it would take a lot of vitamin K to do that.

Q: Is the most important thing to be consistent from day to day?

A: Yes. The dietitians I work with don't recommend any decrease in patients' leafy greens. For example, if they like to have collard greens on a regular basis, then go ahead.

Some anticoagulation clinics actually give patients a vitamin K supplement. They found that if somebody's intake is very consistent, it makes it easier to manage warfarin.

Q: Do people on some blood pressure drugs have to avoid potassiumrich foods?

A: Most people don't have to worry.

One group of medications causes your body to hold on to potassium. Those are drugs like ACE inhibitors, angiotensin II receptor blockers, and potassium-sparing diuretics.

But it's really hard to get too much potassium from your diet. Your body is going to clear whatever you get from food unless you have poor kidney function.

It's rare to tell people to avoid consuming too much, because foods that contain potassium, like fruits and veggies, are really good for you.

Q: So you don't need to stop eating bananas or yogurt?

A: Right. However, people who take those drugs should avoid potassium supplements and salt substitutes made of potassium chloride, unless there is a medical reason to take them.

Multivitamins typically have too little potassium to matter.

Q: Do some diuretics cause you to lose potassium in your urine?

A: Yes, but in most cases, people are given a potassium supplement along with the drugs. Otherwise, they might have to eat several bananas every day to get an adequate amount. And bananas wouldn't supply much of the chloride that the diuretics deplete.

Q: Are older adults more likely to have food-drug interactions?

A: The short answer is yes. It's hard to generalize, but they're more likely to be taking more medications, taking more medications for chronic, ongoing conditions, and have several diseases going on.

Unfortunately, as we age our body's ability to compensate for things like food-drug interactions tends to be less efficient.

Q: How can you avoid an interaction?

A: It's important to follow instructions for taking any drug. But if you're starting a new medication, take the time to ask the pharmacist about it.

Pharmacists want to spend time talking to people about their medicines and how to use them appropriately. For a lot of busy primary care physicians, it's just not in their wheelhouse.

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A Bitter Surprise

In the late 1980s, researchers wanted to test whether drinking alcohol interfered with a new blood-pressure-lowering medicine called felodipine.

"To make this study more scientifically valid, we tried to find a beverage that would mask the taste of the alcohol," says David Bailey, professor emeritus of clinical pharmacology at the Schulich School of Medicine at Western University and a scientist at the Lawson Health Research Institute in Ontario, Canada.

"One Saturday evening my wife and I went through everything we could find in the refrigerator." The best masker: grapefruit juice.

But when the researchers checked the concentrations of the drug in the study participants' blood, they were puzzled. It was as though everyone--those who drank alcohol plus grapefruit juice and those who drank just grapefruit juice--had gotten at least three times the dose of felodipine. (1)

"This was a huge effect that no one had ever seen before with food," says Bailey. "It took a while to convince people that it was real."

Could grapefruit mess with other medications? Bailey and his colleagues went on to uncover the two ways it can:

* Increased absorption. Felodipine was the first example. Grapefruit inhibits cytochrome P450 3A4 (CYP3A4), a key enzyme that breaks down many drugs in the small intestine and the liver. With the enzyme hobbled, a higher dose of the drug ends up in your blood. (2)

Bailey says that upwards of 100 medications may be affected (though not all lead to serious side effects).

Some of the best known are the cholesterol-lowering statins atorvastatin, simvastatin, and lovastatin. Consuming even a normal amount of grapefruit juice or grapefruit increases the risk that the statins will cause muscle pain or damage that in rare instances can lead to kidney failure. (2)

It's safest to avoid grapefruit juice--and eating grapefruit--altogether if you're taking any of those statins, says Bailey. (Grapefruit is unlikely to boost the effects of fluvastatin, pravastatin, pitavastatin, or rosuvastatin, which are not metabolized by CYP3A4.)

The culprit: furanocoumarins, a group of naturally occurring chemicals in grapefruit that can also show up in pomelos and Seville (bitter) oranges, which are used to make marmalade. Other (sweet) oranges are okay.

The impact differs from person to person. "Everybody has CYP3A4 in their gut, but the amount varies," explains Bailey. "And unfortunately, the interaction is not readily predictable."

It's not enough to drink only a small glass of juice, or to drink it a few hours before or after your medication.

"Furanocoumarins are very potent," Bailey says. "There is enough in 7 oz. of grapefruit juice to inactivate the enzyme."

And the effect can last for days ... until your body makes new enzyme.

* Decreased absorption. In a second group of medications, grapefruit and some other juices have the opposite effect: They make it harder for the drugs to be absorbed. (3)

That's why the label of the allergy drug fexofenadine (Allegra), for example, says "Do not take with fruit juices." (So far, only grapefruit, orange, and apple juices have been tested.) Compounds in the juices interfere with some uptake transporters on our intestinal cells that absorb drugs.

"The worry here is that you're losing the benefit of the drug," explains Bailey.

The good news: the effect is short-lived. You just need to take the drug about four hours before or after a glass of juice. (3)

(1) Clin. Invest. Med. 12: 357, 1989.

(2) CMAJ 185: 309, 2013.

(3) Br. J. Clin. Pharmacol. 70: 645, 2010.

Caption: It's not just grapefruit. Fruit juices like orange and apple can also affect the absorption of some drugs.

St. John's Worst

It's not only certain foods (or other medications) that can spell trouble. Some supplements do, too.

One of the worst offenders: St. John's wort. A phytochemical in the herb ramps up the cytochrome P450 3A4 (CYP3A4) enzyme. (That's the opposite of what grapefruit does to the enzyme.) That spurs the breakdown of many drugs.

"St. John's wort is pretty potent," says Gary Asher, director of integrative medicine services at the University of North Carolina Lineberger Comprehensive Cancer Center.

"And it's a double whammy," he adds. That's because the herb also steps up the activity of a drug transporter called P-glycoprotein, or P-gp. (1)

"Think of P-gp as a sump pump," says Asher. "It actually clears stuff out of the cell." With both CYP3A4 and P-gp working overtime, "you get lower drug levels."

One of the best-known interactions: oral contraceptives. Taking birth control pills with St. John's wort makes them less effective. (2) And that raises the risk of an unintended pregnancy. St. John's wort also dampens the effect of some drugs for cancer, depression, organ transplant, HIV, and heart failure, among others. (1)

"So the safest advice is to avoid taking St. John's wort if you also take other medications," says Asher.

(St. John's wort may be okay with some drugs, he acknowledges, but it requires expertise to find out.)

Other supplements, including goldenseal, kava kava, and concentrated garlic or green tea, may also affect some meds. (1)

So tell your doctor or pharmacist if you take a supplement in addition to prescription or over-the-counter medications.

Otherwise, says Asher, "a provider can't even begin to evaluate your risk."

(1) Am. Fam. Physician 96: 101, 2017.

(2) Contraception 94: 668, 2016.

Caption: Play it safe. Avoid St. John's wort if you take any medications.

Joseph Boullata is a professor of clinical nutrition at Drexel University and a pharmacy specialist at the Hospital of the University of Pennsylvania. An expert in nutritional pharmacotherapy, Boullata has edited a handbook of drug-nutrient interactions for clinicians. He spoke with Nutrition Action's Lindsay Moyer.
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Author:Boullata, Joseph
Publication:Nutrition Action Healthletter
Date:Apr 1, 2018
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