Life Extension Magazine February 2010
Reverse Mitochondrial Damage
By Julius Goepp, MD
Progressive loss of function in the mitochondria—the cellular generators responsible for nearly all the body’s energy output—speeds aging and death.
Mitochondrial dysfunction has been linked to an array of degenerative illnesses, ranging from diabetes and neurological disorders to heart failure.1,2
In 2007, a group of researchers reported a major (but little-known) breakthrough in our understanding of how mitochondrial dysfunction unfolds—and what can be done to protect yourself against its lethal impact.3
They discovered that potentially deadly defects in human mitochondria, including molecular decay and membrane injury, begin to appear and can be detected nearly a decade before the onset of permanent damage to the DNA.3
More importantly, their analysis revealed that in its initial stages, mitochondrial dysfunction is reversible, enabling the life and health of cells to be prolonged at the molecular level. The key lies in early interventions to ensure optimal mitochondrial function before irreversible DNA damage occurs.
In this article, we review the latest research on a set of compounds that specifically target and enhance mitochondrial function through multiple modes of action.
The Cellular Death Spiral
Mitochondria are responsible for converting energy from the food you ingest into usable “currency.” Carbohydrates, fats, and proteins are broken down inside your cells into components that enter the cellular powerhouses known as mitochondria. Throughout this cellular journey, these “macronutrients” undergo a complex series of biochemical transformations that generate adenosine triphosphate (ATP), the molecular energy currency behind all biological functions. To give you an idea of ATP’s life-sustaining importance, your body converts a volume of ATP equal to your entire weight every day.
At the core of this energy conversion matrix lies the electron transport chain, a series of molecules embedded in the inner mitochondrial membrane. It serves as the “power line” through which needed chemical energy is released and transferred into vital ATP.
This energy-intensive process throws off an immense number of electrons within the mitochondria, resulting in constant exposure to free radicals—and rendering the mitochondria especially vulnerable to oxidative damage.4-6
The result is a cellular death spiral: the mitochondria gradually deteriorate, leading to a decrease in vital ATP production and a deadly increase in free radical generation. Over time, this continuous free-radical onslaught destroys the mitochondria through progressive membrane damage and molecular decay.
As levels of oxidative damage from mitochondrial dysfunction steadily rise with age,7,8 the body’s antioxidant defenses gradually weaken at the same time, accelerating cellular senescence and death.4,9,10
Left unchecked, this fatal cycle speeds the general decline in overall function that accompanies aging4,11 and contributes to the onset of degenerative disease.12-15
CoQ10’s Rejuvenating Power
Coenzyme Q10 (CoQ10) powerfully safeguards mitochondria from age-related decay and death through two principal pathways.
It plays an essential role in the electron transport chain, facilitating the efficient transfer of electrons into ATP for use in cellular function.16 CoQ10 resides primarily on the inner membranes of the mitochondria; 95% of all cellular energy production depends on it.
CoQ10 also acts as a powerful free radical scavenger, neutralizing their lethal action and dramatically reducing oxidative damage. The more available CoQ10 in the mitochondria, the less free radical damage.16 This is one of the reasons why the highest CoQ10 concentrations are found in the most energy-intensive organs: the brain, heart, liver, and kidneys.17
CoQ10 levels in our vital organs, like the heart, steadily rise after birth and peak at about 20 years of age. After that, they undergo a continuous decline.18 Fortunately, three decades of cutting-edge research have shown us how to restore CoQ10 levels in the mitochondria to slow and even reverse the effects of aging.19-22
In pre-clinical models, CoQ10 supplementation protects tissue from lethal DNA damage and increases lifespan.23 It boosts mitochondrial function and total energy output in heart muscle in aging animals.24 And in animal models, lifelong CoQ10 supplementation has been shown to decrease oxidative damage in skeletal muscle, increase native antioxidant enzymes, and favorably modify age-related changes in muscular energy metabolism.25
Until 2007, the only form of CoQ10 available was ubiquinone. Unfortunately, the ubiquinone form ofCoQ10 has limited absorption.26 Another form of CoQ10, known as ubiquinol, remains up to eight times longer in the blood.27,28
The Heart Health Warrior
Dense with mitochondria, the heart requires more energy than any other organ—and the greatest concentration of CoQ10.29 This is especially true for aging individuals, even those with advanced chronic heart disease. Scores of studies show that chronic heart conditions, including congestive heart failure (CHF), are characterized by diminished levels of CoQ10 in heart tissue. Its therapeutic benefit has proven just as profound for these individuals.
In a 2008 study, standard CoQ10 supplements failed to improve either CoQ10 levels or cardiac performance in individuals suffering from CHF, while ubiquinol succeeded on both fronts.30
The study involved individuals with advanced CHF. Their hearts pumped less than half as well as normal, with low CoQ10 levels despite taking an average of 450 mg/day of standard CoQ10. When the same people took ubiquinol (580 mg/day on average), their CoQ10 blood levels vaulted into the therapeutic range—and their hearts’ pumping action improved by 77%.
At the outset of this study, every participant suffered from category IV CHF (the most severe form), presenting continuous symptoms—even at rest—with severely limited activity. By the end of the study, the average CHF score had fallen to category II, indicated by mild symptoms (such as slight shortness of breath and/or angina) and minimal limitations during ordinary activity.31
CoQ10 supplementation also increases heart muscle contractility—the strength of the heart’s squeezing action—enabling the heart to pump more blood more efficiently, even in patients with advanced CHF.32
Chronic CoQ10 deficiency has been linked to poor surgical outcomes in elderly patients compared to younger ones.21,33 By energizing cardiac mitochondria, CoQ10 exerts a powerful effect on cardiac performance in individuals with CHF. Supplementation with CoQ10 and other antioxidants and heart-energizing nutrients such as L-carnitine and taurine reduces distended heart volume in patients—a vital factor in reducing the risk of bypass surgery.34
Following a heart attack, cardiac tissue is at great risk for further injury, including a second attack. In patients recovering from recent heart attacks, just 120 mg of CoQ10 per day produced remarkable benefits.35 After one year, only 25% of supplemented patients suffered a cardiac event, compared with 45% in the placebo group, and cardiac deaths were significantly fewer compared with placebo. Supplemented patients also had increased high-density lipoprotein (HDL) and dramatically lower measures of oxidative stress.
CoQ10 also benefits people undergoing cardiac surgery, particularly older adults whose outcomes tend to be worse than younger people’s, owing to declining mitochondrial function and density in heart tissue.21
Treating heart tissue with CoQ10 improves its metabolic stress response and speeds recovery after ischemia (loss of blood flow)—two major concerns after cardiac surgery.21 Oral CoQ10 therapy for one week before surgery improves mitochondrial energy efficiency and post-operative heart function, while reducing heart muscle damage and shortening hospital stays.21 A 2008 study also showed significantly fewer arrhythmias (abnormal heart beats), less need for medications to boost cardiac strength, and less need for blood transfusion in patients who received CoQ10 supplementation prior to cardiac surgery, compared to patients who did not receive CoQ10.36