Zymes llc. CoQ10 and Statin Therapy

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CoQ10 and Statin Therapy

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Statins and Their Effect on Coenzyme Q10

Statins (e.g. ZOCOR, LIPITOR, and PRAVACHOL) are drugs used to treat people with elevated cholesterol, a major risk factor for heart disease. Statins reduce cholesterol by blocking a key enzyme (HMG CoA reductase) in the pathway that produces cholesterol.

The body uses the same pathway that produces cholesterol to produce coenzyme Q10 (CoQ10), as illustrated in the simplified diagram below. When statins block this pathway to reduce cholesterol, coenzyme Q10 production may be reduced as well. 1 Many clinical studies have shown that when blood levels of LDL-cholesterol are reduced by statins, blood levels of coenzyme Q10 are also reduced. 2-12 Other studies, however, have shown that statins may not affect blood levels of coenzyme Q10. 13 Two recent reviews of this topic suggest that more research is needed to clarify our understanding of the effect of statin therapy on coenzyme Q10. 14, 15

Cholesterol Transport in Blood

Cholesterol is a lipid and therefore cannot be dissolved in water or blood. Every cell in the body needs cholesterol to make cell membranes. Additionally, specialized cells use cholesterol to make bile for digestion of fats, or to make steroid hormones like cortisol, estrogen, and testosterone. In order for cholesterol to be transported in blood to different organs in the body, it is packaged into water soluble droplets called LDL (low density lipoprotein). LDL is often referred to as “bad cholesterol” because of the link between high LDL levels and cardiovascular disease.

When cholesterol levels are inappropriately high, LDL can transport cholesterol to the arteries where it has been associated with atherosclerosis leading to heart attacks and strokes. Cholesterol can also be carried away from cells, including those in the arteries, back to the liver for elimination from the body by HDL (high density lipoprotein). HDL is often referred to as “good cholesterol” because it has been associated with reduction in atherosclerosis, heart attacks and strokes.

Just as LDL acts as a carrier for cholesterol, LDL carries coenzyme Q10 and other water insoluble molecules throughout the blood stream. An important function of coenzyme Q10, when carried as part of LDL, is to act as an antioxidant, along with vitamin E, to help prevent oxidation of LDL. Oxidation of LDL is associated with the production of toxic free radicals and is believed to contribute to atherosclerosis and heart disease by stimulating the body’s inflammatory and immune responses. Antioxidants, such as coenzyme Q10 and vitamin E, can protect LDL from such oxidative damage.

These antioxidants exist in two forms, oxidized and reduced. The reduced form of vitamin E is converted to the oxidized form when it inactivates free radicals. Coenzyme Q10 then regenerates vitamin E from its oxidized form, back to its reduced form so that it may continue to protect against oxidative damage to LDL. Dietary supplementation with coenzyme Q10 may increase the coenzyme Q10 content of LDL, enhancing its antioxidant capacity. 16 Animal studies have shown that supplementation with Coenzyme Q10 alone, or together with vitamin E, can reduce atherosclerosis. 17, 18

In addition, some of the side effects associated with statins are fatigue and muscle weakness (also known as myopathy, or myalgia). Reduced levels of coenzyme Q10 may contribute to these side effects. Some physicians believe that dietary supplementation with coenzymeQ10 can ameliorate these effects. 19 More research is needed to prove definitively that supplementation effectively prevents these effects.

References:

  1. Folkers K, Langsjoen P, Willis R., Richardson P, Xia LJ, Ye CQ, Tamagawa H. Lovastatin decreases coenzyme Q levels in humans. PNAS. 1990;87:8931-8934.
  2. Bleske BE, Willis RA, Anthony M, Casselberry N, Datwani M, Uhley VE, Secontine SG, Shea MJ. The effect of pravastatin and atorvastatin on coenzyme Q10. Am Heart J. 2001 Aug;142(2):E2.
  3. 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(3):226-229.
  4. Human JA, Ubbink JB, Jerling JJ, Delport R, Vermaak WJ, Vorster HH, Lagendijk J, Potgieter HC. The effect of Simvastatin on the plasma antioxidant concentrations in patients with hypercholesterolaemia. Clin Chim Acta. 1997 Jul 4;263(1):67-77.
  5. Mabuchi H, Higashikata T, Kawashiri M, Katsuda S, Mizuno M, Nohara A, Inazu, A, Koizumi J, Kobayashi J. Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. J Atheroscler Thromb. 2005;12(2):111-9.
  6. Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Ronnemaa T. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. JAMA. 2002 Feb 6;287(5):598-605.
  7. Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18 Suppl:S137-44.
  8. Palomaki A, Malminiemi K, Solakivi T, Malminiemi O. Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo. J Lipid Res. 1998 Jul;39(7):1430-7.
  9. Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru GP.Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 2003;18(1-4):113-24.
  10. Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004 Jun;61(6):889-92.
  11. Strey CH, Young JM, Molyneux SL, George PM, Florkowski CM, Scott RS, Frampton CM. Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. Atherosclerosis 2005 Mar;179(1):201-6. Epub 2004 Dec 29.
  12. Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. J Clin Pathol. 1993 Nov;46(11):1055-7.
  13. Colquhoun DM, Jackson R, Walters M, Hicks BJ, Goldsmith J, Young P, Strakosch C, Kostner KM. Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. Eur J Clin Invest. 2005 Apr;35(4):251-8.
  14. Hargreaves IP, Duncan AJ, Heales SJ, Land JM.The effect of HMG-CoA reductase inhibitors on coenzyme Q10: possible biochemical/clinical implications. Drug Saf. 2005;28(8):659-76.
  15. Levy HB, Kohlhaas HK. Considerations for supplementing with coenzyme Q10 during statin therapy. Ann Pharmacother. 2006 Feb;40(2):290-4. Epub 2006 Jan 31.
  16. Mohr D, Bowry VW, Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta. 1992;1126(3):247-254.
  17. Witting PK, Pettersson K, Letters J, Stocker R. Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice. Free Radic Biol Med. 2000;29(3-4):295-305.
  18. Thomas SR, Leichtweis SB, Pettersson K, et al. Dietary co-supplementation with vitamin E and coenzyme Q(10) inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol. 2001;21(4):585-593.
  19. Sinatra ST. The Sinatra Solution, Basic Health Publications, 2005.
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