By Dr. Duane Graveline, M.D., M.P.H.
Statins lower cholesterol through inhibition of the mevalonate pathway of cholesterol biosynthesis. An unfortunate and inevitable side effect of mevalonate blocking is interference of ubiquinone metabolism. Ubiquinone is more commonly known by the names Coenzyme Q10 or Co Q10.
The implications of this were well known to the pharmaceutical industry from the very beginning of statin development. CoQ10 is arguably our most important essential nutrient. Its role in energy production is to make possible the transfer of electrons from one protein complex to another (within the inner membrane of the mitochondria) to its ultimate recipient, ATP ( adenosine triphosphate.)
The adult human body pool of CoQ10 has been reported to be 2 grams, and requires replacement of about 0.5 gram per day. This must be supplied by endogenous synthesis or dietary intake. Synthesis decreases progressively in humans above age 21, and the average ubiquinone content of the western diet is less than 5 mg/day. Thus, Co-enzyme Q10 supplementation appears to be the only way for older people to obtain their daily need of this important nutrient.
Nearly 60 million people will be taking statin drugs this year in the United States alone. Most of these people will be over 50 years of age and few of them will be on supplemental CoQ10. Simple logic dictates that the statin drug impact on CoQ10 availability and mitochondrial energy production will be profound.
The heart is usually the first to feel statin associated CoQ10 depletion because of its extremely high energy demands. Physicians are seeing this as cardiomyopathy and congestive heart failure but chronic fatigue is also being reported and we must remember that every cell in the body is dependent upon adequate energy reserves.
In addition to its critically important role in energy production, CoQ10 has a possibly even greater role within the mitochondria as an anti-oxidant, with a free-radical quenching ability perhaps 50 times greater than that of vitamin E.
Without adequate stores of CoQ10 and lacking the repair mechanisms common to nuclear DNA, irreversible oxidative damage to mitochondrial DNA results from buildup of superoxide and hydroxyl radicals. We must remember that our mitochondria are in immediate contact with oxygen - front line warriors, so to speak, in our struggle to obtain life-giving oxygen without sustaining excessive oxidative damage.
The inevitable result of excessive free radical accumulation is an increase in the rate of mitochondrial mutations. Only in the early eighties did researchers learn that our mitochondrial DNA codes for a number of molecules vital to energy supply. It specifies the structure of thirteen proteins and twenty-four RNA molecules involved in the energy production sequence.
Since that time investigators have learned that the result of mutations in mitochondrial DNA cause or contribute to a wide range of disorders. Evidence indicates that this process, known as somatic mitochondrial mutation, may be involved in diabetes and may well contribute to heart failure.
A growing body of evidence indicates that genetic injury in mitochondria may also play a role in the aging process and in the chronic degenerative diseases which we encounter in later life. Ongoing research fully documents the reality that our energy production declines and somatic mitochondrial DNA mutations increase as we grow older. The activity of certain of our respiratory protein complexes has been found to fall with age within the brain, skeletal muscles, heart and liver.
Additionally, various rearrangement mutations in mitochondrial DNA are noted more commonly in aging brain tissue (especially memory areas and motor sites), as well as skeletal & heart muscle. Few of these mutations reach detectable levels before age 40, but they increase exponentially after that. In the absence of sufficient CoQ10 this entire process is accelerated. The obvious inference is that an inevitable consequence of widespread statin use will be aggravation of these very factors those in preventive medicine are trying to modulate.
Ubiquinone in a slightly altered form known as ubiquinol is found in all cellular membranes where it has a vital function in maintaining membrane integrity. Compromise of this important role is thought to be involved in the increasing number of statin associated neuropathies as well as the many myopathy reports and the frequently fatal form of muscle damage known as rhabdomyolysis.
Although Baycol was removed from the market because of its association with excessive deaths from rhabdomyolysis, deaths from this extreme form of muscle cell breakdown still are being reported since all statins share this tendency. It should be added that muscle damage with its at times disabling aches and pains remains the most commonly reported side effect of statin drugs use. It is nothing but collateral damage in the misguided war on cholesterol.
I have written before of the value of CoQ10 in congestive heart failure. Belardinelli and others gave additional documentation in a paper (1) published in the European heart Journal. Recognizing the natural decline in plasma coenzyme Q10 with age and failing hearts, the authors set up a study to determine whether this could be improved by oral CoQ10 to improve both cardiocirculatory efficiency and endothelial function.
They studied 23 patients (20 men, three women, mean age 59±9 years) with stable congestive heart failure secondary to coronary artery disease. A double-blind, placebo-controlled cross-over design was used. Patients were assigned to each of the following treatments: oral CoQ10 (100 mg three times daily), CoQ10 plus supervised exercise training (ET) five times a week), placebo, and placebo plus ET. Each phase lasted 4 weeks. Both peak O2 take-up and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ10 and after ET as compared with placebo. CoQ10 supplementation resulted in a four-fold increase in plasma CoQ10 level, whereas the combination with ET further increased it. No side effects were reported with CoQ10.
The authors concluded that supplemental CoQ10 improves functional capacity, endothelial function, and left ventricular contractility in congestive heart failure without any side effects. The combination of CoQ10 and ET resulted in higher plasma CoQ10 levels and more pronounced effects on all the above-mentioned parameters.
I cite this study to support my thoughts concerning CoQ10 supplementation by those currently taking or proposing to take statin drugs of any kind. Crestor use can be associated with an up to 50% reduction in cholesterol synthesis and other brands such as Lipitor, Vytorin and Zocor often give cholesterol reductions of over 40%. In my own case using Lipitor, 10mg daily, my cholesterol plunged from 275 to 150 in a matter of a few short weeks.
Statin drugs work by inhibition of the reductase step of the mevalonate path, which unfortunately is at the very beginning of this branching tree of biochemical reactions. In effect, it girds the tree to achieve cholesterol reduction. I want to emphasize that with this dramatic effect on the mevalonate pathway to achieve decreased cholesterol synthesis, comparable reductions in CoQ10 are inevitable for it is just another branch of the tree. Dr. Peter Langsjoen, a cardiologist in Tyler, Texas has been researching for years the effects of CoQ10 supplementation in his statin associated congestive heart failure patients and has published widely on this subject (2).
If by some miracle the anti-inflammatory effect of statin drugs could be achieved by a different biochemical mechanism than mevalonate pathway manipulation, I might never have had reason to write my Lipitor, Thief of Memory and Statin Drugs Side Effect books. Nearly all of the serious side effects of statin drugs are caused by this collateral damage to vital biochemical components of the mevalonate pathway.
(1) Belardinelli R and others. Coenzyme Q10 and exercise training in chronic heart failure. European Heart Journal, July 2006
(2) Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in Heart Disease. Cardiovascular Disease Biofactors 9:273-85, 1999
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated July 2011