HMG-CoA Reductase Inhibitors (Statins)

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HMG-CoA reductase inhibitors, also referred to as "statins," are a family of drugs used to reduce high blood levels of cholesterol and LDL ("bad") cholesterol, and to a lesser extent, triglycerides. Statins may also increase blood levels of HDL ("good") cholesterol. These drugs include:

• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)
• Fluvastatin (Lescol)
• Simvastatin (Zocor)
• Lovastatin (Mevacor)
• Pravastatin (Pravacol)

Herbs

Summary of Interactions for statins

Depletion or interference	Coenzyme Q10
Adverse interaction	Grapefruit or grapefruit juice Pomegranate juice* Red yeast rice
Side effect reduction/prevention	None known
Supportive interaction	Fish oil Food (lovastatin) Psyllium (simvastatin) Sitostanol
Reduced drug absorption/bioavailability	St. John's wort (lovastatin, simvastatin)
Other (see text)	Vitamin A* Vitamin B3 (niacin) Vitamin E*

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Supplements

Coenzyme Q10

In patients with high cholesterol, statin therapy results in decreased CoQ10 levels.^{1, 2, 3, 4} Supplementation with 100 mg per day or 10 mg three times per day of CoQ10 has been shown to prevent reductions in blood levels of CoQ10 due to statin therapy.⁵ In one study, people taking CoQ10 along with simvastatin increased their blood CoQ10 concentration by 63%. Many doctors recommend that people taking HMG-CoA reductase inhibitor drugs also supplement with approximately 100 mg of CoQ10 per day, although lower amounts, such as 10 to 30 mg per day, might be effective in preventing the decline in CoQ10 levels.

Fish oil (EPA)

The omega-3 fatty acid EPA in fish oil may improve the cholesterol- and triglyceride-lowering effect of simvastatin. In a preliminary trial, people with high cholesterol who had been taking simvastatin for about three years were able to significantly lower their triglyceride levels and raise their levels of HDL ("good") cholesterol by supplementing with either 900 mg or 1,800 mg of EPA per day for three months in addition to simvastatin.⁶ The authors of the study concluded that the combination of simvastatin and EPA may prevent coronary heart disease better than simvastatin alone.

Sitostanol

A synthetic molecule related to beta-sitosterol, sitostanol, is available in a special margarine and has been shown to lower cholesterol levels. In one study, supplementing with 1.8 grams of sitostanol per day for six weeks enhanced the cholesterol-lowering effect of various statin drugs.⁷

Vitamin B3 (niacin)

Niacin is the form of vitamin B3 used to lower cholesterol and triglyceride levels. Taking large amounts of niacin along with HMG-CoA reductase inhibitors may cause muscle disorders (myopathy) that can become serious (rhabdomyolysis).^{8, 9} Such problems appear to be uncommon.^{10, 11} Moreover, concurrent use of niacin has been reported to enhance the cholesterol-lowering effect of HMG-CoA reductase inhibitors.^{12, 13} People taking statins should consult a doctor before taking niacin.

Vitamin A

A study of 37 people with high cholesterol treated with diet and HMG-CoA reductase inhibitors found blood vitamin A levels increased over two years of therapy.¹⁴ Until more is known, people taking HMG-CoA reductase inhibitors should have blood levels of vitamin A monitored if they intend to supplement with vitamin A.

Vitamin E

In a study of seven patients with high serum cholesterol, eight weeks of simvastatin plus vitamin E 300 IU per day improved markers of blood vessel elasticity more than simvastatin alone.¹⁵ Improved blood vessel elasticity reduces the risk for cardiovascular damage and death. Additional controlled studies are necessary to determine whether supplementation with vitamin E enhances the beneficial effects of other statin drugs.

Interactions with Herbs

Psyllium

In one study, supplementing with 15 grams of psyllium per day for eight weeks enhanced the cholesterol-lowering effect of simvastatin.¹⁶ Further research is needed to determine whether this result applies to other statins.

Red yeast rice

A supplement containing red yeast rice (Monascus purpureas) has been shown to effectively lower cholesterol and triglycerides in people with moderately elevated levels of these blood lipids.¹⁷ However, red yeast rice contains small amounts of naturally occurring HMG-CoA reductase inhibitors and the use of red yeast rice in combination with a statin drug might increase the adverse effects of the drug. For that reason, red yeast rice should not be used if you are currently taking a statin medication.

St. John's wort

Taking St. John's wort (Hypericum perforatum) along with lovastatin or simvastatin may lower blood levels of the drug, resulting in decreased effectiveness.¹⁸ People taking either of these statin drugs should not take St. John's wort without the supervision of a doctor.

Other Interactions

Grapefruit or grapefruit juice

Grapefruit contains substances that may inhibit the body's ability to break down statins; consuming grapefruit or grapefruit juice might therefore increase the potential toxicity of these drugs. In a study of healthy volunteers, ingesting 200 ml of grapefruit juice along with simvastatin increased blood levels of the drug, compared with taking simvastatin with water.¹⁹ There is one case report of a woman developing severe muscle damage from simvastatin after she began eating one grapefruit per day.²⁰ People taking HMG-CoA reductase inhibitors should not eat grapefruit or drink grapefruit juice.

Pomegranate juice

Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice.^{21, 22} The degree of inhibition is about the same for each of these juices. Therefore, it would be reasonable to expect that pomegranate juice might interact with statin drugs in the same way that grapefruit juice does.

Food

Though the absorption of most statins is not affected by taking the drug with food, blood levels of lovastatin are increased.²³ Consequently, lovastatin should be taken with a meal.

References

1. Laaksonen R, Ojala JP, Tikkanen MJ, et al. Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1994;46:313-7.
2. Ghirlanda G, Oradei A, Manto A, et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993;33:226-9.
3. Watts GF, Cummings MH, Umpleby M, et al. Simvastatin decreases the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in heterozygous familial hypercholesterolaemia: pathophysiological and therapeutic implications. Eur J Clin Invest 1995;25:559-67.
4. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA 1990;87:8931-4.
5. Miyake Y, Shouzu A, Nishikawa M, et al. Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung 1999;49:324-9.
6. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22-5.
7. Goldberg AC, Ostlund RE Jr, Bateman JH, et al. Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs. Am J Cardiol 2006;97:376-9.
8. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm 1995;52:1639-45.
9. Yee HS, Fong NT. Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Ann Pharmacother 1998;32:1030-43.
10. Jacobson TA, Amorosa LF. Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol 1994;73:25D-9D.
11. Jokubaitis LA. Fluvastatin in combination with other lipid-lowering agents. Br J Pract Suppl 1996;77A:28-32.
12. Davignon J, Roederer G, Montigny M, et al. Comparative efficacy and safety of pravastatin, Nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994;73:339-45.
13. Jacobson TA, Jokubaitis LA, Amorosa LF. Fluvastatin and niacin in hypercholesterolemia: a preliminary report on gender differences in efficacy. Am J Med 1994;96(suppl 6A):64S-8S.
14. Muggeo M, Zenti MG, Travia D, et al. Serum retinol levels throughout 2 years of cholesterol-lowering therapy. Metabolism 1995;44:398-403.
15. Neunteufl T, Kostner K, Katzenschlager R, et al. Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 1998;32:711-6.
16. Moreyra AE, Wilson AC, Koraym A. Effect of combining psyllium fiber with simvastatin in lowering cholesterol. Arch Intern Med 2005;165:1161-6.
17. Heber D, Yip I, Ashley JM, et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231-6.
18. Wolters Kluwer Health, Inc. Facts and Comparisons [online] 2007 [cited 2007 Feb]. Available from www.factsandcomparisons.com.
19. Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004;58:56-60.
20. Dreier JP, Endres M. Statin-associated rhabdomyolysis triggered by grapefruit consumption. Neurology 2004;62:670 [Letter].
21. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705-6.
22. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother 2006;40:1472-3.
23. Wolters Kluwer Health, Inc. Facts and Comparisons [online] 2007 [cited 2007 Feb]. Available from www.factsandcomparisons.com.

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Last Review: 01-21-2009

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires February 2010.

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