Why Grapefruit and Statin Drugs Do Not Mix

If you have been prescribed a statin drug to treat high cholesterol, your doctor or pharmacist may have advised you to avoid grapefruit or grapefruit juice while on treatment. While that may sound oddly specific, there is a good reason why you want to steer clear of this particular fruit. Not only can grapefruit alter the level of medication in your blood, but it can also increase the risk of side effects, some of which may be serious. There are other types of drugs that may be affected by grapefruit, too.

Statin drugs, also known as HMG-CoA reductase inhibitors, work by blocking the enzyme that your body needs to produce cholesterol. In addition to lowering "bad" LDL cholesterol and raising "good" HDL cholesterol, statin drugs can also decrease the level of triglycerides circulating in your blood.

The interaction is caused by an organic compound in grapefruit known as furanocoumarin. Furanocoumarins are found in other fruits and vegetables (such as celery, parsnips, and pomegranates), but are especially high in grapefruit and grapefruit juice.

The problem with furanocoumarins is that they deactivate a kidney enzyme known as cytochrome P4503A4 (CYP3A4), which the body uses to break down certain drugs so that they can be excreted from the body. When this happens, the drug concentration can increase dramatically and, with it, the risk of side effects.

The abnormal accumulation of atorvastatin, lovastatin, or simvastatin in the blood can lead to potentially serious side effects, including:

• Hyperglycemia, which increases the risk of type 2 diabetes
• Liver damage
• Neurological symptoms, including confusion and memory loss
• Rhabdomyolysis, a breakdown of muscle tissue that can lead to kidney failure and death

The risk can vary dramatically from one person to the next. While women and people over 65 appear to be at greatest risk, studies remain conflicted as to the actual risk. A number of studies have suggested that side effects like these are uncommon and are mostly associated with a pre-existing kidney, liver, or neurologic condition.

Other statin drugs remain largely unaffected by the consumption of grapefruit. These include:

• Crestor (rosuvastatin)
• Lesco (fluvastatin)
• Pravachol (pravastatin)

This is because the two drugs are broken down by an entirely different enzyme known as CYP2C9. Pravastatin is metabolized by yet a different mechanism.

There is a popular assumption that grapefruit may be safe if eaten before or after a dose of Lipitor, Mevacor, or Zocor. At present, no one really knows where the "safe" line is.

What is known is that statin drug levels can increase by anywhere from 80 percent to 260 percent if the medication is taken at the same time as grapefruit. If taken 12 hours apart, that drops to between 44 percent and 66 percent. The effect remains the same whether you cook the grapefruit or drink frozen or homogenized juice.

How this translates to the "safe" consumption of grapefruit remains unclear. Most doctors will tell you that an occasional serving of juice or fruit will do you no harm. Most evidence suggests that serious problems are more likely to occur if you consume large quantities over an extended period of time.

Other drugs are equally affected by grapefruit and grapefruit juice. In some cases, the fruit can block enzymatic action and increase the concentration of the drug. In others, it can interfere with protein transporters in the blood, reducing the concentration and effect of the drug.

These include:

• Certain anti-arrhythmia drugs, like amiodarone
• Certain anti-anxiety drugs, like buspirone
• Some antihistamines, like Allegra (fexofenadine)
• Certain corticosteroids, like budesonide
• Some hypertension medications, like nifedipine
• Some organ transplant rejection drugs, like cyclosporine

Speak with your doctor or pharmacist if you regularly consume grapefruit to ensure that it doesn't interfere with your medications.

If you truly love grapefruit and can't do without it, ask your doctor about switching to another statin or lowering your dose. If you consume grapefruit every now or then, it is unlikely to do any real harm. What is most important is that you avoid the regular consumption or overconsumption of furanocoumarin in any form. Switch to oranges or other safe fruits and save grapefruit for special occasions.