Life Extension - Warnings

Statins - updated: 22 January 2009

The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications

Biofactors. 2003;18(1-4):101-11

Langsjoen PH, Langsjoen AM.

The depletion of the essential nutrient CoQ10 by the increasingly popular cholesterol lowering drugs, HMG CoA reductase inhibitors (statins), has grown from a level of concern to one of alarm. With ever higher statin potencies and dosages, and with a steadily shrinking target LDL cholesterol, the prevalence and severity of CoQ10 deficiency is increasing noticeably. An estimated 36 million Americans are now candidates for statin drug therapy. Statin-induced CoQ10 depletion is well documented in animal and human studies with detrimental cardiac consequences in both animal models and human trials. This drug-induced nutrient deficiency is dose related and more notable in settings of pre-existing CoQ10 deficiency such as in the elderly and in heart failure. Statin-induced CoQ10 deficiency is completely preventable with supplemental CoQ10 with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function.

Publication Types:

• Review

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

Rundek T, Naini A, Sacco R, Coates K, DiMauro S.

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10). OBJECTIVE: To measure CoQ(10) levels in blood from hypercholesterolemic subjects before and after exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days. DESIGN: Prospective blinded study of the effects of short-term exposure to atorvastatin on blood levels of CoQ(10). SETTING: Stroke center at an academic tertiary care hospital.Patients We examined a cohort of 34 subjects eligible for statin treatment according to National Cholesterol Education Program: Adult Treatment Panel III criteria. RESULTS: The mean +/- SD blood concentration of CoQ(10) was 1.26 +/- 0.47 micro g/mL at baseline, and decreased to 0.62 +/- 0.39 micro g/mL after 30 days of atorvastatin therapy (P<.001). A significant decrease was already detectable after 14 days of treatment (P<.001). CONCLUSIONS: Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.

Publication Types:

• Prospective blinded study

Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients

J Atheroscler Thromb. 2005;12(2):111-9

Mabuchi H, Higashikata T, Kawashiri M, Katsuda S, Mizuno M, Nohara A, Inazu A, Koizumi J, Kobayashi J.

Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 +/- 0.21 to 0.46 +/- 0.10 microg/ml (p < 0.0001), and from 0.10 +/- 0.06 to 0.06 +/- 0.02 microg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion.

Publication Types:

• Trial

Statin drugs decrease the plasma level of coenzyme Q10 (ubiquinone) in the organism

Ideggyogy Sz. 2007 Jul 30;60(7-8):295-300

Rákóczi K, Párdutz A, Vécsei L.

In this paper the authors review the relationship and the possible interaction between the HMG-CoA reductase inhibitors (statins) and the CoQ10 (ubiquinone) based on the current literature. The statins are widely used in the clinical practice. Inhibiting the synthesis of mevalonic acid they decrease the plasma cholesterol level. Since mevalonic acid is also required for ubiquinone synthesis statins could influence ubiquinone metabolism. Many studies confirmed the relationship between statin therapy and lower plasma ubiquinone level. Much less data are available about the tissue concentration changes of ubiquinone during statin therapy. The authors try to summarise the consequences of the interaction between statin therapy and ubiquinone metabolism.

Publication Types:

• Review

Coenzyme Q10 and statins: biochemical and clinical implications

Mitochondrion. 2007 Jun;7 Suppl:S168-74. Epub 2007 Mar 27

Littarru GP, Langsjoen P.

Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.

Publication Types:

• Review

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

Strey CH, Young JM, Molyneux SL, George PM, Florkowski CM, Scott RS, Frampton CM.

Although not currently indicated for chronic heart failure (CHF), statins have been associated with improved outcome in retrospective analysis. However, statin therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have adverse effects on heart failure states. We hypothesized that atorvastatin treatment improves endothelial function in patients with chronic heart failure independent of LDL-cholesterol alterations. Furthermore, we assessed how reductions in coenzyme Q(10) levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40% were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm resistance vessel function was assessed by venous occlusion plethysmography during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Atorvastatin treatment lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p<0.001) and improved endothelium-dependent vasodilatation during acetylcholine infusion (p=0.015). Endothelium-dependent forearm blood flow improvements correlated with reductions in coenzyme Q(10) levels (p=0.011), but not with LDL-cholesterol levels (p=0.084). Coenzyme Q(10) remained the significant variable predicting improvement in NO dependent endothelial function after adjusting for LDL-cholesterol levels (p=0.041). In conclusion, short-term atorvastatin therapy improved endothelial function in chronic heart failure patients. Further studies are required to determine whether coenzyme Q(10) reductions are limiting the maximum favourable effects of statin therapy on the microcirculation.

Publication Types:

• Randomized Controlled Trial

Coenzyme Q10: an independent predictor of mortality in chronic heart failure

J Am Coll Cardiol. 2008 Oct 28;52(18):1435-41

Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AM.

OBJECTIVES: The aim of this study was to investigate the relationship between plasma coenzyme Q(10) (CoQ(10)) and survival in patients with chronic heart failure (CHF). BACKGROUND: Patients with CHF have low plasma concentrations of CoQ(10), an essential cofactor for mitochondrial electron transport and myocardial energy supply. Additionally, low plasma total cholesterol (TC) concentrations have been associated with higher mortality in heart failure. Plasma CoQ(10) is closely associated with low-density lipoprotein cholesterol (LDL-C), which might contribute to this association. Therefore we tested the hypothesis that plasma CoQ(10) is a predictor of total mortality in CHF and could explain this association. METHODS: Plasma samples from 236 patients admitted to the hospital with CHF, with a median (range) duration of follow-up of 2.69 (0.12 to 5.75) years, were assayed for LDL-C, TC, and total CoQ(10). RESULTS: Median age at admission was 77 years. Median (range) CoQ(10) concentration was 0.68 (0.18 to 1.75) micromol/l. The optimal CoQ(10) concentration for prediction of mortality (established with receiver-operator characteristic [ROC] curves) was 0.73 micromol/l. Multivariable analysis allowing for effects of standard predictors of survival--including age at admission, gender, previous myocardial infarction, N-terminal peptide of B-type natriuretic peptide, and estimated glomerular filtration rate (modification of diet in renal disease)--indicated CoQ(10) was an independent predictor of survival, whether dichotomized at the ROC curve cut-point (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.2 to 3.3) or the median (HR: 1.6; 95% CI: 1.0 to 2.6). CONCLUSIONS: Plasma CoQ(10) concentration was an independent predictor of mortality in this cohort. The CoQ(10) deficiency might be detrimental to the long-term prognosis of CHF, and there is a rationale for controlled intervention studies with CoQ(10).

Publication Types:

• Clinical Trial

Publication Types:

• Review