Hyperlipidemia is a condition that causes blood to contain elevated levels of cholesterol and lipids. As a result, hyperlipidemia has been shown to increase the risk of stroke, heart disease and pancreatitis. Many patients take cholesterol-lowering medications in the drug class known as statins to regulate the amount of lipids in the bloodstream. Many drugs belonging to the statin class are metabolized in the liver by a specific enzyme (CYP3A4). Unfortunately, grapefruit and grapefruit juice contain bioflavonoids and other compounds that are a potent inhibitor of the CYP3A4 enzyme. This effect does not appear to be as significant in the Crestor brand (rosuvastatin), which is metabolized by a different enzyme, CYP2C9.
Crestor (Rosuvastatin)
Approved in 2003 by the FDA, rosuvastatin is used to treat patients with hyperlipidemia and hypercholesterolemia. Rosuvastatin works by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting enzyme in the synthesis of cholesterol. In contrast to other popular statin drugs including simvastatin, atorvastatin and lovastatin that are metabolized by CYP3A4, rosuvastatin is primarily metabolized by the enzyme CYP2C9.
Statin-Induced Myopathy and Rhabdomyolysis
Muscle pain and weakness are symptoms of myopathy that cause the greatest concern in patients who are taking statin medications. As a result of enzyme inhibition by compounds found in grapefruit juice, the levels of statin medication in the bloodstream may increase. In severe cases, muscle breakdown and cell death leads to a condition termed rhabdomyolysis. According to the Zocor brand (simvastatin) product package insert, the risk of rhabdomyolysis increases as higher doses are used. In theory, this suggests that increased simvastatin levels are associated with increased risk of muscle deterioration. Although the mechanism by which simvastatin causes muscle breakdown is not definitively known, it has been suggested that the drug inhibits the synthesis of important enzymes and proteins that are used by muscle cells.
Other Adverse Effects of Grapefruit and Statins
The breakdown of muscle leads to the release of myoglobin which is normally eliminated by the kidneys. In addition to the increased burden on the kidneys, myoglobin is toxic to kidney cells and could potentially lead to renal failure. Increased levels of statin medications can also place additional strain on the liver which is primarily responsible for their metabolism. Statin therapy has been known to cause significant elevation in liver enzymes which may be an indicator of injury to the liver. Many other drugs are also metabolized by CYP3A4 enzymes. Following grapefruit inhibition, increased statin levels can compete with other drugs for the remaining enzymes. As a result, toxicity and adverse effects can occur with other medications that are metabolized by the same enzymes as statins.
Grapefruit and Rosuvastatin
According to the Crestor brand (rosuvastatin) package insert, the use of grapefruit is not a restriction when taking rosuvastatin. It has been hypothesized that grapefruit does not inhibit CYP2C9 as potently as it does CYP3A4. Although there is no definitive evidence to show that grapefruit significantly affects rosuvastatin, patients should still eat grapefruit only in moderation.
Significance
Grapefruit is often restricted in patients using statin therapy for high cholesterol. If grapefruit is a significant part of the diet, patients should consider speaking to their physician about alternative statins that have not been found to have a significant interaction with either grapefruit or grapefruit juice.
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