December 2010 Issue

When Foods and Drugs Collide — Studies Expose Interactions Between Certain Foods and Medications
By Densie Webb, PhD, RD
Today’s Dietitian
Vol. 12 No. 12 P. 26

Dietitians, physicians, and pharmacists have long known that some drugs are absorbed well on an empty stomach and others with food. They also know that the calcium in dairy products can interfere with the availability of some antibiotics. But thanks to the discovery a little more than a decade ago that grapefruit juice contains powerful natural compounds that interfere with the cytochrome P450 enzyme system, or enzymes in the liver responsible for metabolizing about 50% of drugs currently prescribed1, food-drug interactions have been garnering more attention, and researchers are asking and answering more questions about the roles that foods play in drug metabolism.

Interaction Defined
A food-drug interaction is the alteration of a drug’s pharmacokinetics or pharmacodynamics when certain foods or beverages are consumed at the same time. Older patients are particularly at risk for negative food and drug interactions simply because this population takes more than 30% of all prescription drugs.1 Patients with cancer and/or malnutrition, gastrointestinal tract dysfunction, or acquired immunodeficiency syndrome; patients receiving enteral nutrition; and transplant recipients are also at risk.1

“A food effect can be positive or negative, and it can be quite significant,” said Rebecca Carrier, PhD, an assistant professor in the department of chemical engineering at Northeastern University in Boston, during a symposium on food-drug interactions at the American Chemical Society meeting in Boston earlier this year. Generally, foods can either interfere with the body’s ability to absorb a medication, reducing the dose actually received, or they can increase absorption, which can improve availability of the drug or pose the risk of toxicity.

The same is true for many natural health products. Researchers with Health Canada found that many phytochemical constituents in natural health products have the potential to significantly alter the bioavailability, absorption, distribution, and excretion of prescription drugs in the same way as foods by interfering with drug-metabolizing enzyme systems.2

While grapefruit juice and the compounds it contains are among the most extensively studied foods and beverages for their effects on the metabolism and action of prescription drugs, recent research has found that other foods, including pomegranates, Seville oranges, black pepper, cranberry juice, grape juice, black tea, beer, cruciferous vegetables, kava, licorice root, wine, and olive oil, contain compounds that modulate P450 activity and can affect drug metabolism. But these foods’ effects are far from uniform. Just as each individual has a unique fingerprint and DNA profile, each has a unique P450 profile. So the effect these foods have on drug metabolism varies greatly among people. In fact, Paul Hollenberg, PhD, a professor and chair of the department of pharmacology at the University of Michigan Medical School, who also presented at the Boston meeting, said, “There is a 100-fold variation of P450 systems among individuals, and this impacts how they metabolize drugs.”

Some food compounds that interfere with drug metabolism in the laboratory might not present real-life problems because they are generally consumed in small amounts. For example, an animal study found that piperine, a compound in black pepper, can increase the potency of the antihistamine Allegra (fexofenadine) twofold.3 But pepper (and therefore piperine) is consumed in such small quantities that it’s unlikely to cause any real-life problems. A preliminary human study in Spain suggests that olive oil can increase the levels and the lipid-lowering effects of Zocor (simvastatin), but how much olive oil must be consumed before an effect might be seen is unknown.4

Problematic Pairings
According to Christine Gerbstadt, MD, RD, an American Dietetic Association spokesperson, one of the most medically consequential and well-recognized food-drug interactions is that of vitamin K-rich foods (eg, broccoli, spinach) and Coumadin (warfarin), an anticoagulant prescribed to thin the blood and prevent clots. If someone taking warfarin also consumes a great amount of foods rich in vitamin K, a known blood-clotting factor, the blood-thinning effect can be cancelled out and the results can ultimately be life threatening. New anticoagulants are available that don’t present the same food-drug interaction potential, says Gerbstadt, but they’re also more expensive, making them less-attractive alternatives for patients with limited financial resources or with insurance plans that don’t cover the newer alternatives.

Another well-known food-drug interaction is that of foods containing the substance tyramine, including chocolate, beer, wine, avocados, some aged cheeses, and some processed meats, and monoamine oxidase (MAO) inhibitors, a type of antidepressant. Tyramine slows the metabolism of these drugs and can result in a dangerous rise in blood pressure.

The most well-publicized food-drug interaction of late has certainly been that of grapefruit juice and a virtual pharmacopeia of drugs. But some experts say its effects are still occasionally underestimated. According to Hollenberg, drinking just a glassful of grapefruit juice per day can lead to dangerous increases in the blood levels of some drugs, such as the cholesterol-lowering drugs Lipitor (atorvastatin) and Zocor. Researchers have discovered that the molecule bergamottin found in grapefruit juice inactivates drug-metabolizing enzymes in the liver, allowing drug levels to build up in the bloodstream. It can take up to four days for the body to metabolize the offending chemical and for the effects of a single glass of grapefruit juice to wear off. The juice can also interact to cause higher blood levels of the antianxiety medicine Buspar (buspirone), the antimalaria drugs Quinerva or Quinite (quinine), and Halcion (triazolam), a medication used to treat insomnia. Other drugs that grapefruit juice may also affect include calcium channel blockers, immunosuppressants, sedatives, antidepressants, and drugs for erectile dysfunction.

Natural licorice, which contains the compound glycyrrhizin, can reduce the effectiveness of blood pressure medications and diuretics such as Aldactone (spironolactone). It can also increase the risk of Lanoxin (digoxin) toxicity. (Lanoxin is used to treat congestive heart failure and abnormal heart rhythms.) While most licorice snacks sold in the United States are made with artificial licorice flavoring and contain no glycyrrhizin, imported licorice snacks and herbal supplements and tinctures are likely to contain the compound and have the potential to interfere with prescription medications and trigger the dangerous side effects.

Plenty of research suggests that drinking tea is healthful, but research also shows that black tea can have powerful inhibitory effects on the P450 drug-metabolizing system. In a laboratory study performed by Canadian researchers, black tea was found to be a more powerful inhibitor of the enzymes than single-ingredient herbal teas such as St. John’s wort, goldenseal, feverfew, or cat’s claw.5 Herbal tea blends were second only to black tea in their inhibitory effects. While the researchers said it is difficult to extrapolate the findings and precisely apply them to humans, they do believe the study accurately identified products for low or high levels of drug interactions.

Laboratory studies have found that resveratrol, an antioxidant compound found in red wine and peanuts, inhibits platelet aggregation, and high intakes could increase the risk of bleeding when consumed with anticoagulant drugs such as Coumadin.6 The compound also inhibits the P450 enzyme system and could theoretically increase the toxicity of several drugs, including statins, calcium channel antagonists, HIV protease inhibitors, immunosuppressants, antihistamines, benzodiazepines, and drugs used to treat erectile dysfunction. However, it would likely take supplemental doses of resveratrol rather than a couple of glasses of wine to cause problems.

Uncovering the Mechanisms
At the Boston symposium, several experts presented results of their ongoing work to uncover the exact mechanisms behind these food and drug interactions. By better understanding these mechanisms, researchers hope they can ultimately provide ways to improve the therapeutic benefit of medications. For example, the uptake of some drugs into cells is facilitated by binding to lipoproteins. Changing the level of lipids in a person’s blood, whether short term (from a high-fat meal) or long term (from an overall change in dietary fat), can alter the amount of a drug that ultimately reaches the target site and increase the chances of a successful outcome. Researchers are attempting to identify a wide variety of dietary factors that both improve and impede the absorbability of specific drugs. But the possible combinations of foods and drugs are infinite. According to Carrier, computer models that factor in dietary changes are being used to try to predict what will happen when foods interact with certain drugs and in certain forms and how that might affect drug absorption.

Putting It in Perspective
According to Hollenberg, grapefruit growers have seen a 50% drop in sales since news of grapefruit’s interference with drug metabolism first surfaced. Instead of the grapefruit finding being disseminated as “While you’re taking this drug, avoid grapefruit juice,” it was translated as “Grapefruit juice is bad for you.” However, research is under way to develop methods for extracting the offending chemical, bergamottin, from grapefruit juice, much as caffeine is extracted from coffee. Researchers are also investigating other methods, such as selective breeding, UV light, and heat treatment, in an effort to make grapefruit juice safe to drink with any medication.

The estimated 20 million Americans taking statins for high cholesterol who want to drink grapefruit juice may have the option of switching to Pravachol (pravastatin), which doesn’t involve the P450 enzyme system in its metabolism and so is unaffected by the juice. But that is an option patients must discuss with their physicians.

Who’s Minding the Drugs?
A physician prescribes a drug, a pharmacist dispenses it, and a dietitian provides dietary guidance to a person taking the drug. But who is responsible for putting it all together and ensuring no potentially harmful food and drug pairings occur? Pharmacists are currently on the front lines, placing stickers on pill bottles and providing printouts of interactions and caveats. But as electronic medical records become more commonplace, something that is expected to become an integral part of the healthcare system as a result of healthcare reform, automatic electronic alerts of potential food-drug interactions are likely to become the norm, leaving less room for human error.

“Dietitians are the stop-gap measure to prevent injury to patients” until that happens, says Gerbstadt. She says by the time patients or clients reach the RD, they’ve already been to their physician, who was likely pressed for time; they’ve already had their prescriptions filled by the pharmacist, with a line of impatient people waiting behind them. During one-on-one counseling, dietitians can ask the probing questions: “Do you drink grapefruit juice?” “Do you drink tea?” “Do you eat licorice? If so, what kind?” “Do you take any herbal supplements?” “Do you drink milk?” “Do you consume calcium-fortified foods or beverages?”

In an ideal world, all three health professionals would see a full medication list and review that with a patient. But, Gerbstadt says, the reality is that the patient is lucky if one of those three people sees that list and has the time to go over it. “Real healthcare,” she says, “comes from the ear that has the time to listen and is the most approachable.” In the case of food-drug interactions, that individual may be the dietitian.

— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Tex.

 

References
1. Genser D. Food and drug interaction: Consequences for the nutrition/health status. Ann Nutr Metab. 2008;52(suppl 1):29-32.

2. Scott IM, Leduc RI, Burt AJ, et al. The inhibition of human cytochrome P450 by ethanol extracts of North American botanicals. Pharmaceutical Biology. 2006;44(5):315-327.

3. Jin M, Han H. Effect of piperine, a major component of black pepper, on the intestinal absorption of fexofenadine and its implication on food-drug interaction. J Food Sci. 2010;75(3):H93-96.

4. Vaquero MP, Sanchez MFJ, Jimenez RS, et al. Major diet-drug interactions affecting the kinetic characteristics and hypolipidaemic properties of statins. Nutr Hosp. 2010;25(2):193-206.

5. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine. 2003;10(4):334-342.

6. Bertelli AA, Giovannini L, Giannessi D, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React. 1995;17(1):1-3.

 

Several Food-Drug Interactions*

Drug

Food

Increase Drug Effect

Decrease Drug Effect

Some statins
(eg, Lipitor, Zocor, Mevacor, Advicor)

Grapefruit, pomegranate, and cranberry juices

 

 

Antidepressants
(MAO inhibitors)

Chocolate and other foods containing tyramine

 

 

Allergy medications (eg, Allegra)

Black pepper

 

 

Potentially all drugs metabolized by P450 liver enzymes

Black tea

 

 

Cancer drugs
(eg, tamoxifen)

Beer

 

 

Anticlotting agents
(eg, Plavix)

Fatty fish

 

 

Beta-blockers
(hypertension medications)

Meat

 

 

Blood thinners
(eg, Coumadin)

Leafy greens

 

 

Beta-blockers
(hypertension medications)

Natural licorice

 

 

Antibiotics
(eg, Cipro, tetracycline)

Milk and calcium-fortified juices

 

 

— Author compiled table using multiple sources

*This listing of interactions is not exhaustive.

ADVERTORIAL