One of the most frequent causes of hospital admissions in older adults is the devastating condition known as congestive heart failure. Characterized by disabling symptoms of difficulty breathing, fatigue, and swelling of the extremities, congestive heart failure also increases the risk of early demise.
Fortunately, scientists have discovered that the mitochondrial energizer coenzyme Q10 (CoQ10) can offer powerful assistance to those challenged with congestive heart failure, improving the heart’s pumping ability and even reducing the need for medications.
Since CoQ10 levels are depleted by aging and statin medications and tend to be low in those with congestive heart failure, achieving optimal blood levels of CoQ10 may be an important strategy for safeguarding cardiac health.
What is CoQ10?
It has been 50 years since Fred Crane discovered CoQ10 in 1957.1 Since that time, scientists have discovered what this extraordinary molecule is and what it does in settings of both health and disease. It is important to clarify that a coenzyme should not be confused with an enzyme (a protein that accelerates a biochemical reaction). A coenzyme is a simple molecule (many vitamins are coenzymes) that is essential for the normal function of specific enzyme systems in our cells. Coenzyme Q10 is the cofactor or coenzyme for three large enzyme systems that are essential for 90% of cellular energy production. Because the heart muscle uses more energy than any other tissue and normally has the highest concentration of CoQ10, it is very sensitive to CoQ10 deficiency.
Coenzyme Q10 is well established to be a clinically relevant first-line antioxidant in our defense system against excess oxidative stress. It is the only fat-soluble antioxidant that is synthesized by our body and is capable of regeneration back to its reduced or antioxidant form through normal cellular enzyme systems. Its location in the lipid mitochondrial membranes is particularly important, as mitochondria are the major site of free-radical production, and CoQ10 is an excellent free-radical scavenger.
Coenzyme Q10 and Congestive Heart Failure
In the late 1960s and early 1970s, it became clear that patients suffering from congestive heart failure had measurable deficiency of CoQ10 in both blood and heart muscle, and that the degree of deficiency correlated with the severity of heart failure. Much of this work was performed as a collaborative effort between Professor Karl Folkers, PhD, Gian Paolo Littarru, MD, and Denton Cooley, MD.2 In 1980, my father, cardio-logist Per H. Langsjoen, MD, met with Karl Folkers, and together they performed the first human trial of CoQ10 in the treatment of congestive heart failure in the United States.3 I joined my father as a cardiology fellow in 1983 and after this favorable controlled study was published in 1985, we went on to evaluate the long-term efficacy of CoQ10 therapy in 126 patients with congestive heart failure.4
Figure 1. Statin Therapy, Plasma CoQ10, and Congestive Heart Failure
This demonstrates the simultaneous drop in
plasma CoQ10 level and ejection fraction in a
70-year-old female patient started on statin therapy.
Note that ejection fraction and CoQ10 level increased
after statin therapy was discontinued
Congestive heart failure is a condition in which there is weakening of heart muscle function so that fluid or congestion backs up and causes swelling or edema in the liver, lungs, the lining of the intestine, and the lower legs and feet. It was our initial concern that CoQ10 may have been acting as a stimulant that could bring about short-term improvement in heart muscle function but actually increase mortality over time. This is similar to flogging an exhausted horse, making him run faster for a few hundred yards only to promptly drop dead. By following these 126 heart failure patients for six years, it became clear that the improvement in heart function was sustained and that overall mortality was one third of expected.4 It was at this time that we realized CoQ10 represented a major advance in the treatment of a disease that previously could be only palliated and never cured.
In the course of this six-year study, the 126 patients were followed very closely with measurement of blood CoQ10 levels and heart function every three months.4 We unexpectedly came across the detrimental effect of the cholesterol-lowering drugs known as HMG-CoA reductase inhibitors, or more simply as statins. The first statin drug, lovastatin (Mevacor®) came on the market in 1987, and five of our heart failure patients were started on this drug by their primary care physicians. All five of these stabilized patients had a significant decline in their blood CoQ10 levels and a decline in their heart function and clinical status. Their heart failure worsened to such a degree that two patients became critically ill and one went on to require a heart transplant. This clinical deterioration in our patients was particularly frightening at the time because we had no idea of the dramatic CoQ10-depleting effects of the newly released statin drugs. One patient in particular showed a simultaneous drop in plasma CoQ10 level and ejection fraction when started on statin therapy, with improvement after the statin was discontinued (see figure 1). My father first presented these data in Rome, Italy, in January of 1990.5 Shortly after my father left the podium, a member of the audience shouted into one of the aisle microphones, “This is pharmaceutical terrorism!” To which my father calmly responded, “Yes, but who is the terrorist?” Later that year in May and in June of 1990, Merck went on to secure two patents that would combine CoQ10 with statin drugs in the same capsule to prevent muscle and liver damage.6 The first of these patents was with co-inventor Michael Brown of Nobel Laureate fame for his work with low-density lipoprotein (LDL) receptors. Unfortunately, these patents have never been acted on and to this day, the vast majority of physicians and patients are completely unaware of statin-induced CoQ10 depletion.
The Trouble with Statins
All statin drugs block the biosynthesis of both cholesterol and CoQ10, which explains statins’ common side effects of fatigue, muscle pain and muscle weakness, and a worsening of heart failure (see figure 2).
Figure 2. Biosynthetic Pathway Leading
to Cholesterol, Coenzyme Q10, and Dolichol
All statin drugs (HMG-CoA reductase inhibitors)
block the biosynthesis of both cholesterol and CoQ10,
which explains their common side effects of fatigue,
muscle pain, and a worsening of heart failure.
When CoQ10 levels are lowered by statin drug therapy, one of the first changes to occur is a weakening of heart muscle function, known as diastolic dysfunction. This has nothing to do with diastolic blood pressure, but rather represents impairment in the relaxing or filling phase of the cardiac cycle. After heart muscle contracts, it takes a great deal of cellular energy, or ATP, to re-establish the calcium gradients such that muscle fibers may relax. Thus, if diastolic dysfunction is severe, it can result in congestive heart failure.
In 2004, a study published in the American Journal of Cardiology showed that diastolic dysfunction (heart muscle weakness) occurred in 70% of previously normal patients treated with 20 mg a day of Lipitor® for six months. This heart muscle dysfunction was reversible with supplemental CoQ10.7 Heart failure that develops after years of statin drug therapy can be termed statin cardiomyopathy and may well be playing a role in the epidemic of congestive heart failure in the United States.
It is important for the reader to be aware that for every adverse side effect caused by statin drug therapy, one can find a drug company-sponsored trial concluding that statins actually benefit the condition they may induce. Good examples are studies that suggest statins are useful in the treatment of cancer,8 when in fact some studies suggest that they could be carcinogenic;9,10 another study suggests that statin therapy may be helpful in dementia,11 when other evidence indicates that statins impair mental function;12,13 finally, studies that conclude statin therapy improves heart failure,14 when in fact it appears to weaken both skeletal muscle and heart muscle.7,15
In an effort to determine the prevalence of adverse effects from using statins, we studied 50 consecutive new patients, all of whom were taking a statin drug at the time of their initial visit.16
All 50 patients were found to have one or more side effects from statin therapy, so we discontinued their statin drugs and began supplemental CoQ10. Patients were followed for an average of 28 months with the following observations in the prevalence of adverse effects:
A high prevalence of skeletal muscle pain and weakness at 64% on initial visit was reduced to 6% in follow-up.
Fatigue decreased from 84% to 16%.
Shortness of breath went from 58% down to 12%.
Memory loss was reduced from 8% to 4%.
Peripheral neuropathy decreased from 10% to 2%.
There were no adverse effects from stopping statin drug therapy with no cases of heart attack or stroke during follow-up. Overall, there was an improvement in heart muscle function on discontinuation of statin therapy and addition of supplemental CoQ10. However, due to powerful propaganda surrounding both cholesterol and statin drug therapy, many patients and physicians are afraid to stop statin therapy.
Cholesterol and Heart Disease
Atherosclerosis remains a disease of unknown cause. Many factors more important than cholesterol—such as stress, smoking, hypertension, insulin resistance, high triglycerides, diabetes, and low testosterone (in men)—contribute to atherosclerosis and cardiovascular disease.17-19 Despite this, the theory that cholesterol is the dominant villain responsible for atherosclerosis has been promulgated for over 60 years, making the pharmaceutical industry’s anti-cholesterol campaign the most profitable medical myth of all time.
Statin drugs do show some benefit in reducing mortality in individuals with pre-existing coronary artery disease.20 This benefit occurs irrespective of cholesterol lowering and is likely secondary to their subtle anti-inflammatory or plaque-stabilizing effects.21 The vilification of cholesterol and the associated aggressive lowering of cholesterol blood levels has brought about increasingly severe CoQ10 deficiency in a large number of patients, making it absolutely critical to restore CoQ10 levels in these individuals.
Optimal CoQ10 Levels Improve Heart Failure
In the early years of our experience with CoQ10 therapy, no one knew the therapeutic or ideal plasma level of CoQ10 for the treatment of heart failure. Over the course of 25 years, it has become clear that maximum improvement in heart function will not occur unless plasma levels are greater than 3.5 micrograms per milliliter (mcg/mL). By 2006, there were a total of 22 randomized, controlled trials involving a total of 1,605 patients evaluating the therapeutic benefit of supplemental CoQ10 in congestive heart failure.22-24 The majority of studies were favorable, showing significant improvement in heart muscle function. Furthermore, there have been 34 open-label trials involving 4,221 patients evaluating the clinical utility of CoQ10 in heart failure, and again clear benefits were observed without any adverse effect or drug interaction. Despite these studies, CoQ10 remains obscure to most physicians and is not routinely used in the treatment of congestive heart failure. This is in part due to the pervasive anti-nutrient bias in conventional medical practice, medical literature, and medical education.
Out of a total of 22 controlled trials of supplemental CoQ10 in congestive heart failure, only three have failed to show significant benefit. The first study by Permanetter et al. failed to measure plasma CoQ10 levels, such that there is no way to know if therapeutic CoQ10 levels were attained.25 The second trial by Watson et al. demonstrated a mean treatment plasma CoQ10 level of only 1.7 mcg/mL, with only two of the 30 patients having a plasma level greater than 2.0 mcg/mL.26 Finally, the third study by Khatta et al. demonstrated a mean treatment plasma CoQ10 level of 2.2 ± 1.2 mcg/mL, indicating that some patients on treatment had levels as low as 1.0 mcg/mL.27 Unfortunately, these last two trials with sub-therapeutic CoQ10 levels are the most frequently quoted as evidence for a lack of benefit for CoQ10 in heart failure