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Statin Update
CoQ10 deficiency in muscle cell mitochondria results in poor cellular respiration. Oxidative mechanisms and endothelial cell inflammation are recognized as important factors in coronary heart disease and atherosclerosis. Evidence shows CoQ10 supplementation can improve the circulatory process and prevent such irreversible and often fatal conditions as cardiomyopathy, congestive heart failure, and rhabdolmyolysis (muscle wasting induced by statin drug toxicity).5

Since their introduction, HMG-CoA reductase drugs (statins) have helped millions of people to lower their cholesterol levels. At the same time, however, studies have shown that statin stalwarts such as Lipitor® (atorvastatin),6,7 Zocor® (simvastatin),7 Pravacol® (pravastatin),7,8 and Mevacor® (lovastatin)8,9 can deplete natural levels of CoQ10 throughout the body.

Statins have surpassed hypertension medications in generating revenues for pharmaceutical manufacturers, accounting for an estimated $16 billion in revenues in 2003. These are powerful drugs, but they also carry the risk of a dose-dependent decrease in the body’s production of CoQ10. The FDA does not require statin manufacturers to alert patients and physicians to this potential consequence, even though many recent studies have demonstrated that CoQ10 deficits in statin users can cause cognitive, muscular, cardiovascular, and other problems. Conversely, CoQ10 supplementation can alleviate these issues in many patients, researchers have found.

Statins sold in Canada are required to carry on their labels a precautionary warning expressly stating that such CoQ10 depletion can lead to impaired cardiac functioning in patients with congestive heart failure. The US government requires no such warning, despite an emerging generation of “super-statins” (rosuvastatin, pitavastatin) that may further increase the risk and rate of CoQ10 depletion in patients taking the drugs. Schering-Plough recently introduced Zetia®, a product that quadruples the dose of first-generation statins. The FDA approved another powerful drug, Astra-Zeneca’s Crestor®, in August 2003.

Writing in the November 2003 issue of Smart Money magazine, journalist Eleanor Laise took Pfizer to task for failing to address patients who have suffered memory loss, severe muscle pain, and other symptoms of CoQ10 depletion after taking the company’s best-selling statin Lipitor“. She noted that Pfizer has thus far balked at acknowledging any association between statins, CoQ10 depletion, and serious side effects.10

While drug manufacturers and the FDA have yet to weigh in on the issue, Merck, maker of the popular Zocor“, applied for patents in 1989 and 1990 for CoQ10-simvastatin combination products. The company’s 1989 patent application states that a combined statin-CoQ10 product might be effective against not only cardiomyopathy, but also elevated levels of the enzyme transaminase, which reflects liver damage. The company has thus far declined to exercise these patents, and the FDA and other major drug manufacturers have yet to acknowledge the risk of CoQ10 depletion from statins.

According to a Pfizer official quoted in the Smart Money article, the drug company has been unable to document “any specific effect” on the heart muscle during clinical trials, a surprising statement considering that several studies by respected medical researchers at the time Lipitor“ was being tested warned of the cardiovascular dangers of CoQ10 depletion.

“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,” notes Dr. Peter Langsjoen of East Texas University, in a comprehensive review of animal and human studies of statins and CoQ10 depletion published last year in the journal Biofactors.6 “With ever higher statin potencies and doses, and with a steadily shrinking target LDL cholesterol, the prevalence and severity of CoQ10 deficiency are increasing noticeably.”

Under revised target cholesterol guidelines issued by the National Institutes of Health in 2001, as many as 36 million Americans are now candidates for therapeutic statin intervention, up from 13 million under the old guidelines. Yet the issue of CoQ10 depletion remains unresolved within the regulatory milieu that addresses side effects and warning-label requirements.

“We are currently in the midst of a congestive heart failure epidemic in the United States . . . As physicians it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a widespread deficiency of a nutrient critically important to heart function,” writes Dr. Langsjoen.

Dr. Langsjoen joined Dr. Mark Silver of the Heart Failure Institute at Advocate Christ Medical Center in Oak Lawn, IL, in presenting a study design for determining whether CoQ10 levels might be used to measure myocardial diastolic function as an early marker of ventricular dysfunction.11

They reasoned that statins in-hibit HMG-CoA reductase, the rate-limiting step that inhibits cholesterol and CoQ10 synthesis in the liver. Because CoQ10 plays an important role during oxidative phosphorylation in the myocardial cell, evaluating CoQ10 action on ATP might be used as an early-warning indicator of potential heart problems. After a number of baseline cardiovascular and metabolic measurements are established for each subject, the researchers suggest, they would receive oral atorvastatin (Lipitor®) of 20 mg per day for three to six months, with baseline levels repeated after three and six months of treatment. Patients demonstrating reduced measurement of diastolic left ventricular function that worsened during the three to six months of statin therapy would then receive 300 mg per day for three months, with follow-up echocardiogram and blood CoQ10 level measurements. The objective would be to see if CoQ10 supplementation could reverse statin-induced heart failure.

At the University of Texas at Austin’s Biochemical Institute, researcher Dr. Flora Pettit discovered that CoQ10 may be helpful in assessing susceptibility to statin toxicity and determining which patients might benefit from CoQ10 supplementation.

She reported in the journal Drug Metabolism and Drug Interactions that even low levels of statins are toxic to human lymphocytes in cell cultures, adding that the patient’s own plasma reversed this toxicity in some instances.12 Adding CoQ10 to plasma, however, was more effective than plasma alone in reversing cell toxicity in some of these patients, Pettit and colleagues found.

Coumadin® and CoQ10
While some doctors have suggested that CoQ10 might interfere with the effects of the popular blood-thinner warfarin (Coumadin“), a trial by Danish researcher Jyette Engelsen and colleagues, published in the Danish medical journal Ugeskrift for Laeger, found no association between CoQ10 supplementation (100 mg per day) and the clinical anti-coagulant effect observed in a group of 24 patients on long-term warfarin

treatment.13

Moreover, the study’s randomized, double-blind, placebo-controlled, cross-over methodology presents a far more convincing argument that the risk is minimal. Nevertheless, warfarin patients are advised to consult their doctors and frequently monitor their blood test results to assess clotting time (prothrombin time/INR), especially in the first two weeks (something that is already done in most cases, the scientists noted).

Muscular Dystrophy
Muscular dystrophy patients receiving CoQ10 therapy showed significantly less cytogeneic and DNA damage than their untreated counterparts, according to a study by Dr. Lucia Migliore and colleagues at Pisa University in Italy. They compared basal levels of nuclear DNA (nDNA) damage as measured by chromosomal and DNA alterations in leukocytes in 13 patients.14

The subjects, ranging in age from 29 to 74 and presenting with several forms of muscular dystrophy, were compared with a subgroup of 10 patients who received a two-week course of ubidecarenone, a CoQ10 analogue. Untreated muscular dystrophy patients showed an increased level of chromosomal damage (frequency of micronucleated lymphocytes) compared with equally matched individuals receiving CoQ10.

“Patients receiving ubidecare-none showed a statistically significant reduction in the frequency of micronucleated cells after therapy, while only a slight decrease was observed in the levels of both primary DNA damage and oxidized bases,” the scientists reported in the January 2004 issue of Mutagenesis.

Cancer
Several interesting studies were reported on CoQ10’s effects against certain cancers. Studying differences between malignant and non-malignant prostate cancer cells, Dr. Jose L. Quiles and colleagues at the University of Granada, Spain, found that malignant cells respond very differently to coenzyme Q10.15

CoQ10 supplementation significantly lowered cell growth of the PC3 cancer line without affecting non-malignant cells. The authors noted that if the findings are confirmed, they might present a “novel and interesting” approach using coenzyme Q10 in cancer therapy.

Reproduction
CoQ10 may play a role in the health of sperm cells in fighting male infertility, according to Dr. Antonio Mancini and colleagues at the Institute of Endocrinology at Catholic University of the Sacred Heart in Rome, Italy.16

In an earlier study, they found CoQ10 was present in seminal fluid and directly correlated to sperm motility in infertile men, with the exception of those with varicocele, a dilation of the pampiniform venous plexus associated with infertility.

A follow-up published in the journal Metabolism evaluated distribution of CoQ10 in seminal fluid and plasma in 32 varicocele patients and healthy male controls in an effort to determine whether any metabolic abnormalities played a role in various seminal parameters in varicocele patients.

The researchers reported a significantly higher proportion of CoQ10 in the seminal fluid of varicocele subjects, with high cellular CoQ10 levels correlated with low sperm concentration and motility, suggesting that such patients may be more sensitive to peroxidative damage and therefore reduced energy utilization that might then translate into defective motility. Further, the findings might indicate a possible molecular defect involved in the condition.

Females also demonstrate a reproductive protective benefit. During preeclampsia, a life-threatening disorder affecting about 7% of late-stage pregnancies, women suffer edema, hypertension, and proteinuria. Serum levels of CoQ10 are severely decreased in preeclampsia patients, reported Dr. Enrique Teran, a scientist at the University of Ecuador in Quito.17

In a study published in the journal Free Radical and Biological Medicine, Dr. Teran and his colleagues measured concentrations of CoQ10 in a group of 18 healthy pregnant women, 12 subjects with preeclampsia, and 22 women who were not pregnant or hypertensive. In the normal pregnant women, CoQ10 levels were significantly higher than in nonpregnant women or those with preeclampsia. The mean level of CoQ10 was 1.08 in healthy pregnant women, 0.86 in non-pregnant women, and 0.70 in women with preeclampsia.