Atorvastatin Decreases the Coenzyme Q10 Level in the Blood of Patients at Risk for Cardiovascular Disease and Stroke
 
   

Atorvastatin Decreases the Coenzyme Q10 Level
in the Blood of Patients at Risk for
Cardiovascular Disease and Stroke

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:
   Frankp@chiro.org
 
   

FROM: Archives of Neurology 2004 (Jun);   61 (6):   889–892 ~ FULL TEXT

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


Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.


In this group of patients beginning treatment with atorvastatin (a statin drug to reduce cholesterol levels), the average concentration of coenzyme Q10 in blood plasma decreased within 14 days, and had fallen by approximately 50% after 30 days of treatment. Depressed Co-Q levels appear to be a major contributor to the muscle pain that forces so many to discontinue the drug. For those who choose to use Statins, rather than the safe and effective combination of sterols and stanols, they should begin immediate supplementation with Co-Q 10 to offset the usual side-effects.


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.


From the FULL TEXT Article

COMMENT

Few drugs are as widely used as the statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, that effectively decrease blood levels of cholesterol and protect against various cardiovascular diseases related to atherogenesis. Similarly, few drugs have generated as much controversy as the statins: [2] adverse effects, predominantly affecting skeletal muscle, [3 ,15] have been widespread and severe enough to force one pharmaceutical company to withdraw cerivastatin from the market. However, statins are still widely used and their safety is still debated. The common mechanism of action of these drugs, inhibition of cholesterol metabolism at the level of mevalonic acid, has the unintended consequence of impairing the synthesis of other compounds that share mevalonate as a precursor, such as dolichols and CoQ10 (ubiquinone). In our well-controlled longitudinal study, atorvastatin caused a rapid and substantial decrease of plasma CoQ10 concentrations, which was evident 14 days after the initiation of therapy and was even more marked after 30 days of therapy.

Impaired synthesis of CoQ10 could well explain the variety of adverse effects reported because of the central role of this compound in energy generation through the mitochondrial respiratory chain and because of its antioxidant properties. [4] Indirect support for a pathogenic role of CoQ10 deficiency comes from data from patients with idiopathic—presumably primary—CoQ10 deficiency. These patients have a mitochondrial encephalomyopathy, most commonly presenting as an autosomal recessive spinocerebellar atrophy syndrome. [16-17] A rarer myopathic variant combines central nervous system signs (ataxia, epilepsy, and mental retardation) with a mitochondrial myopathy dominated by recurrent rhabdomyolysis and myoglobinuria (which is, perhaps not coincidentally, one of the most severe adverse effects of statin treatment). [5-7]

It is, therefore, not surprising that, starting with Folkers et al, [18] several groups have studied the effects of statins on the blood concentration of CoQ10 in humans, in patients with hypercholesterolemia and in healthy subjects. It is somewhat difficult to compare results because different studies used different statins, different dosages, and long- or short-term exposures. In addition, some studies were conducted on few or even single individuals, and others on larger series. A double-blind placebo-controlled study [10] of healthy volunteers treated for 1 month with either pravastatin, 20 mg/d (n = 10), or simvastatin, 20 mg/d (n = 10), for 4 weeks showed similar decreases (50% and 54%, respectively) of blood CoQ10 levels, whereas 10 individuals receiving placebo showed no change. In another large study, [9] 45 hypercholesterolemic patients were randomized in a double-blind trial: one group received increasing doses of pravastatin sodium (20, 40, and 80 mg/d) and a second group received increasing doses of lovastatin (10, 20, and 40 mg/d) for a total of 18 weeks. In both groups, there was a gradual decrease of blood CoQ10 level: after 18 weeks, the CoQ10 level was 80% of baseline with pravastatin and 71% of baseline with lovastatin.

The only study [12] with negative results involved 12 healthy subjects: 6 received pravastatin sodium, 20 mg/d, for 4 weeks and 6 received atorvastatin calcium, 10 mg/d, for 4 weeks. After a washout period, each group received the alternate drug for another 4 weeks. No change in blood CoQ10 level was found at the end of each treatment. This study is noteworthy because—like ours—it used atorvastatin, although the dose was much lower than that used by us and the number of subjects was much smaller. We took advantage of the availability of blood samples from a large cohort of hypercholesterolemic patients in whom we studied the short-term (2- and 4-week) effects of atorvastatin calcium, 40 mg/d, on carotid artery elasticity by B-mode ultrasonography. The results on carotid artery elasticity will be reported elsewhere. This was a large and uniform population of patients from whom samples of plasma were obtained at baseline and after 2 and 4 weeks of therapy. All samples were kept frozen until the CoQ10 assay to minimize methodological variations. Baseline CoQ10 concentrations corresponded to accepted normative values, from our own experience and from the literature, and were relatively uniform (Figure 1). There was a highly significant and marked (about 50%) decrease of the CoQ10 concentration after 2 weeks of atorvastatin administration, which was essentially unchanged after 4 weeks of treatment. To our knowledge, this is the first unequivocal demonstration that atorvastatin — like pravastatin and simvastatin [10] — also reduces blood levels of CoQ10, and to about the same extent.

Our patients did not report severe adverse effects during 30 days of exposure to atorvastatin. In particular, there were no complaints of myalgia or weakness. Only one subject experienced weakness and tingling in the legs, which disappeared 2 days after reducing the dose of atorvastatin calcium to 40 mg/d (the plasma CoQ10 level was 0.84 µg/mL at baseline, 0.38 µg/mL on day 14, and 0.34 µg/mL on day 30). The most common adverse effects were flatulence and constipation, which usually resolved within days.

Our study does not address the question of whether tissue levels of CoQ10 were also decreased by atorvastatin. One previous study [11] of healthy volunteers treated with simvastatin, 20 mg/d, for 4 weeks had shown a 30% decrease of blood CoQ10 level, contrasting with a paradoxical increase of muscle CoQ10 level. Despite this limitation, our findings raise the possibility of a widespread inhibition of CoQ10 synthesis in patients treated with atorvastatin. Given the many patients exposed to relatively high doses of this drug and the persistent occurrence of adverse effects related to statins, it may be reasonable to add CoQ10 in patients receiving long-term treatment with statins in general, and atorvastatin in particular. This recommendation is strengthened by the general experience that oral CoQ10—even in high doses—is well tolerated by patients. [16-17 ,19-23]



Return to the Co-Q10 Page

Since 8-05-2004

             © 1995—2014    The Chiropractic Resource Organization    All Rights Reserved