Anti-Aging Nutrient Review and Update, Part 2
Ward Dean, MD
Coenzyme Q10, also known as CoQ10, is a normal and essential component of the membranes of mitochondrial the intracellular organelles that manufacture ATP, the basic energy molecule of the cell. CoQ10 plays a critical role in the production of energy in nearly every cell of the body, and is found in most living systems.
For this reason, it was named ubiquinone (for ubiquitous quinone) by its discoverer, R.A. Morton. CoQ10 has been shown to improve many conditions associated with aging, and to extend the lifespan of several organisms.
Mechanisms of Action
CoQ10 is a vitamin-like fat-soluble nutrient (quinone) and functions as an important component of the mitochondrial energy electron transduction chain (oxidative phosphorylation) and in the production of adenosine triphosphate (ATP).
CoQ10 is a powerful antioxidant, capable of inhibiting lipid peroxidation in mitochondrial membranes (its chemical structure is similar to that of Vitamin E). It has cardioprotective, cytoprotective, and neuroprotective properties, is a calcium channel blocker and membrane stabilizer, modulates prostaglandins, inhibits intracellular phospholipases and preserves myocardial NaK-ATPase.1
Clinical Uses of CoQ10
Congestive Heart Failure
A number of studies have confirmed CoQ10s effectiveness in improving cardiac function in cases of cardiomyopathy and congestive heart failure. In one six-year study of 122 patients with New York Heart Association classes II, III and IV chronic dilated cardiomyopathy, subjects were treated with 100 mg CoQ10 each day. At the beginning of the study, the mean ejection fraction a measure of ventricular blood flow was 41 percent. Ejection fraction increased to 59 percent after only six months on CoQ10. Eighty-seven percent of the participants experienced significant improvement in their ejection fraction during this time, and improved by one or two New York Heart Association classes. Those in class II achieved the greatest benefit. All of these subjects became asymptomatic after CoQ10 administration. Despite these positive results, the authors suggested that the 100 mg dose of CoQ10 was too low, and the subjects might have done even better on higher doses.2
Angina pectoris is chest pain caused by decreased blood flow (and decreased oxygenation) of the heart. In an early Japanese study, 12 patients (average age 56 years) with stable angina were given 150 mg of CoQ10 per day for four weeks. CoQ10 reduced anginal frequency and nitroglycerin use and increased exercise time and time to ST-segment depression.3 (ST-segment is an abnormality on an electrocardiogram indicating the heart is not getting enough oxygen, presenting an increased risk of heart attack.) These results were confirmed in more recent studies, using doses ranging from 30 to 600 mg per day.4
CoQ10 is also helpful in hypertension. In mild or borderline cases, it may be all that is needed. For example, in one study conducted at the Department of Veterans Affairs Medical Center in Boise, Idaho, physicians administered 120 mg of CoQ10 to 46 male and 37 female hypertensive patients (mean age was nearly 70 in both cases). Systolic blood pressure was reduced by an average of 17.8 mmHg.5 Australian researchers obtained similar blood-pressure-lowering results with a dose of 200 mg CoQ10 in 74 hypertensive diabetics.6
Protection Against Statin Toxicity
Statins, or 3-hydroxy-3-methylglutaryl Co A (HMG-CoA) reductase inhibitors, are effective drugs for lowering cholesterol. However, published data confirm that statins can cause myopathies (muscle disease), rhabdomyolysis (muscle damage), and renal failure. In May 2000, the FDA warned about liver failure with regard to statin drugs. Statins have been associated with an increased incidence of cataracts, cancer, peripheral neuropathies and some psychiatric disturbances.
Statins lower CoQ10 levels in the heart, skeletal and liver tissues. In mice, statins lower ATP levels, and impair energy metabolism. Although package inserts and marketing material do not mention the statins-CoQ10 link, two U.S. patents filed in January and February of 1989 and granted in 1990 describe a method for counteracting statin-associated myopathy and potential liver damage by concurrent administration of the statins with CoQ10. Both of these patents were assigned to Merck & Co.
However, for more than 14 years, the producers of statins have not acted upon this information and failed to reveal the statin-CoQ10 relation to millions of statin users and to the medical community.
The concern by physicians and scientists regarding the depletion of CoQ10 by the statins is growing from a level of concern to one of alarm. With ever higher statin potencies and dosages, and with a steadily shrinking target LDL cholesterol, the prevalence and severity of CoQ10 deficiency is increasing noticeably.
An estimated 36 million Americans are now using statin drug therapy. Statin-induced CoQ10 depletion is well documented in animal and human studies with detrimental cardiac consequences in both animal models and human trials. This drug-induced nutrient deficiency is dose-related and more notable in settings of pre-existing CoQ10 deficiency such as in the elderly and in heart failure.
We are currently in the midst of a congestive heart failure epidemic in the United States, and this epidemic may be due, in large part, to the excessive use of statin drugs and inadequate use of CoQ10.7
Neurologic and Neurodegenerative Disorders
CoQ10 has the potential to be a beneficial agent in any neurodegenerative disease which is characterized by impaired mitochondrial function and/or excessive oxidative damage. CoQ10 has been found to be protective against neuronal toxins in animal models of Parkinsons disease, amyotrophic lateral sclerosis and Huntingtons disease.8
Recent clinical trials in these disorders demonstrate that supplemental CoQ10 can slow functional decline particularly of Parkinsons disease.9 Parkinsons is a degenerative neurological disorder for which no treatment has been shown to slow its progression. Nevertheless, in a large, multicenter study, 80 subjects with early Parkinsons were administered CoQ10 at dosages of 300, 600 or 1,200 mg per day. They were followed for 16 months. Those who received CoQ10 experienced less disability than those who received the placebo, and the benefit was greatest in those who received the highest dosage.10
A short confirmatory study was conducted by scientists in Germany, giving CoQ10 in daily doses of 360 mg for four weeks to 28 Parkinsons patients. CoQ10 supplementation provided a mild but significant symptomatic benefit on Parkinsons symptoms and a significantly better improvement in performance compared with placebo.11
Australian researchers recently reported a reduction of glycosylated hemoglobin (HbA1c an indicator of blood sugar control) in a large group of hypertensive diabetics who received a daily CoQ10 dosage of 200 mg per day.6
In 1994, a dramatic report of two cancer patients treated with CoQ10 was published.12 The first was of a 59-year-old woman who had intraductal carcinoma (cancer) of the left breast, which resolved completely on a daily dose of 390 mg CoQ10. A second patient, after breast surgery, was found to have residual intraductal carcinoma in the tumor bed. She refused additional surgery, and was placed on 300 mg CoQ10 per day.
Over a year later, there was no evidence of residual tumor or metastases. Despite practicing oncology for 35 years, over which he had treated about 200 cases of breast cancer per year, one of the authors commented that he had never [before] seen a spontaneous complete regression of a 1.5-2.0 cm breast tumor and ha[d] never seen a comparable regression on any conventional anti-tumor therapy.
A more recent study indicated that breast cancer is associated with a decrease of plasma CoQ10 levels, and the worse the cancer, the greater the decrease in CoQ10.13
CoQ10 is dramatically effective in treating periodontal disease, a common malady of aging. In an early study, eight patients received CoQ10 at 25 mg, twice a day, versus a placebo group. The results showed a reduction in pocket depth with photographic evidence of improved gingival health.14 In a more recent study, CoQ10 was used topically, with significant improvement.15
Dr. Ram B. Singh of the Heart Research Laboratory and Center for Nutrition in Moradabad, India, reported on a new indication for CoQ10 therapy, in a patient with acute glomerulonephritis, renal failure and high levels of lipid peroxides. He administered 180 mg per day of CoQ10, with a resultant lowering of lipid peroxides and significant improvement in renal function.16
In a follow-up study of 11 patients with chronic renal failure (serum creatinine levels were 5 mg/dL or above) who were on intermittent dialysis, Dr. Singh again administered CoQ10 at a dosage of 180 mg per day. After four weeks of treatment, the patients experienced significant reductions in serum creatinine and blood urea and significant increases in creatinine clearance and urine output, and fewer subjects required dialysis.17
Life Extension Research with CoQ10
Dr. Bliznakovs Mouse Experiment
One of the earliest anti-aging experiments with CoQ10 was conducted in 1980 by Dr. Emile G. Bliznakov, a pioneering CoQ10 researcher. Bliznakov divided middle-aged (16 to 18 months) white mice into two groups: one group received regular injections of CoQ10 while the other received a placebo injection (salt water). Bliznakov found that all of the mice in the saline (control group) died within eight months after the start of the experiment, whereas the CoQ10 animals survived to significantly greater maximum lifespan (up to 12 more months). The mean survival time was extended by 56 percent (Fig. 1).18
Dr. Fahys Mouse Experiment
Similar results were also reported in an unpublished study by Dr. Gregory M. Fahy, then Director of the Organ Cryopreservation Laboratory at the American Red Cross Jerome Holland Laboratory in Rockville, Md.19 I recently discussed Dr. Fahys findings with him at the 33rd Annual Meeting of the American Aging Association in St. Petersberg, Fla. Dr. Fahy confirmed his observations, in female mice of a different strain, although no effect on the mean lifespan of male mice was seen (probably because only five male mice were examined).
Drs. Harris and Coles Mouse Experiments at UCLA
Another longevity study with CoQ10 was completed in 1994 by Dr. Steven Harris, at Dr. Roy Walfords Laboratory at the UCLA Medical Center in Los Angeles. Walfords lab was especially suited for longevity experiments because of his pioneering work in the study of the anti-aging effects of caloric restriction. Dr. Walford (see box at right) was one of the first scientists to document the delay in the decline of the immune system in calorie-restricted mice.
Two groups of female mice were used. The first group was placed on a mildly restricted diet to ensure against obesity (which happens in this strain with ad lib feeding), and to mimic the average nonobese health-conscious consumer. The second group was given this diet with 0.1 percent CoQ10 added by weight of food. This dosage was equivalent to a human dosage of approximately 750 mg of CoQ10 per day.
At 39 months of age (which is close to the 42-month maximum lifespan for these mice), 50 percent of the CoQ10 treated mice were still alive, compared with only 25 percent of the control animals. The average lifespan for the controls was 30.8 months, whereas the average lifespan of the CoQ10 group was 37.0 months (a 20 percent increase).
A few days after the 43-month mark, however, all animals in both groups were dead, demonstrating that although CoQ10 achieved a significant rectangularization of the survival curve, a true right shift or extension of the entire curve to the right was not achieved (Fig. 2). The last CoQ10 treated animal only outlived the last control by four days.
The scientists reported that animals that received CoQ10 appeared to be much healthier than the control animals. The most spectacular difference between the two groups, however, was the far greater level of activity in the CoQ10 animals at about the 50 percent survival point than in the control animals (which appeared to be close to death in many cases).
Coles and Harris suggest that CoQ10 may be able to slow some deteriorative processes that are associated with aging in laboratory mice, although there was no retardation of the increase in the mortality rate.
Most significantly, although the maximum lifespan of the animals was not increased, the average lifespan of the animals was increased by 20 percent. To fully appreciate the
significance of a 20 percent increase, consider that scientists have estimated that a total cure of all cancers would result in an increase in the average human lifespan of only 4 percent.20
Finnish Rat and Mouse Experiment
A subsequent study in 1998 by scientists in Finland produced disappointing results, however.21 The scientists administered CoQ10 to rats and mice, at a dose of 10 mg/kg/day. This dose is roughly comparable to the dosage used by Drs.Coles and Harris in the UCLA study previously described. The results indicated that CoQ10 had no significant effect, positive or negative, on the lifespan of either the rats or mice.
Spanish Rat Experiment
Scientists in Spain recently published another report of the lifespan-extending properties of CoQ10 in rats. In their study, they used two groups of rats fed a diet that contained 8 percent fat (containing 61 percent polyunsaturated fatty acids).
The experimental groups diet was supplemented with 0.7 mg/kg/day of CoQ10. The supplemented animals reached a significantly higher mean lifespan (2.5 months, or 11.7 percent higher than the controls) and a significantly higher maximum lifespan (six months, or 24 percent higher) (Fig. 3).22
Japanese Nematode Experiment
Finally, another positive study has just been published indicating that CoQ10 extends the lifespan of nematodes (Fig. 4).23 The scientists used CoQ10 concentrations of 50 and 150 mcg/ml of distilled water. Admittedly, extending the lifespan of a nematode is less exciting than extending the lifespan of a mammal, but it is a further indication that something positive is going on at a fundamental level.
CoQ10 appears to qualify as a highly beneficial anti-aging nutrient, based on its multiple mechanisms of action, its broad range of effects on a number of life-threatening or debilitating clinical conditions, its lifespan-extending properties in more than one species, and complete absence of adverse effects. Beneficial effects have been demonstrated in some conditions with as little as 30 to 60 mg per day.
Of the known lifespan studies with CoQ10 (four mouse, two rat, and one nematode), two of the mouse studies (Bliznakovs and Fahys) resulted in increased maximum lifespan, one resulted in increased mean lifespan (Coles and Harris), and one showed no change; one rat study showed no change; and one rat and nematode study each resulted in increased mean and maximum lifespan.
The more serious the condition, the greater the dose that should be taken. As research continues to accumulate, it appears that the higher the dosage the greater the benefit (as evidenced by the 390 mg dose in breast cancer, and 1,200 mg dose in Parkinsons disease), and that the only limiting factor on CoQ10 dosage is the cost.
Criteria for Selecting Anti-Aging Nutrients for This Series
For this series of articles reviewing top anti-aging nutrients, Ward Dean, MD, has selected substances based on several criteria:
1. The mechanism by which the substance is believed to act. Most substances discussed are involved in one or more theories of aging (i.e., antioxidants/free radical theory; cross linkage inhibitors/cross linkage theory; hormone receptor sensitizers/neuroendocrine theory, etc).
2. The health-enhancing effect of the substance.
3. Whether the substance has shown the capability to reverse or restore a biomarker to a more youthful state.
4. Has the substance demonstrated the ability to extend the maximum lifespan of one or more experimental organisms?
5. Practical considerations: An individuals pill capacity how many capsules/ tablets is a person willing to take? Cost and availability for example, some substances are beyond the reach of many people due to high cost or other impediments (i.e., legal issues, availability, requirement for a prescription, etc.).
Based on these criteria, the series of articles presents what Dr. Dean considers to be the most effective anti-aging/life extending substances readily available today. The substances featured are presented in no particular order. The first article in the series focused on DHEA, appearing in the June 2004 issue.
Remembering Dr. Roy Walford
Dr. Roy Walford, one of the great pioneers of life- extension and antiaging medicine, died April 27, 2004, from complications of amyotrophic lateral sclerosis (commonly known as ALS, or Lou Gehrigs Disease). He was 79 (he would have been 80 June 29).
Dr. Walford observed that caloric restriction was the most effective means of extending the lives of experimental animals; he wrote four books on the subject. He practiced what he preached and applied his calorically restricted diet to himself. His colleagues joked, Roy may not live any longer, but it will sure seem like it.
We invited Dr. Walford to speak at the Monaco Anti-Aging Conferences, but unfortunately his failing health prevented him from making the trip. Nevertheless, he believed his
restricted diet enabled him to survive with his disease much longer than had he followed a more traditional diet.
Well miss you, Roy. Rest in peace. (For information about Dr. Walford go to www.walford.com.)
Ward Dean, M.D.
1. Greenberg, Steven, M.D. and Frishman, William H., M.D. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol 1990;30:596-608.
2. Langsjoen, P.H., Langsjoen, P.H., and Folkers K. Long-term efficacy and safety of CoQ10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol Feb. 15, 1990;65:521-523.
3. Kamikawa, T. et al. Effects of CoQ10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol Aug. 1, 1985;56:247-251.
4. Overvad, K., Diamant, B., Holm L. et al. CoQ10 in health and disease. Eur J Clin Nutr 1999;53:764-770.
5. Burke B.E., Neuenschwander, R., and Olson, R.D. Randomized, double-blind, placebo-controlled trial of CoQ10 in isolated systolic hypertension. S Med J Nov. 2001;94(11):1112-1117.
6. Hodgson, J.M., Watts, G.F., Playford, D.A., Burke, V. and Croft, K.D. CoQ10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002 Nov.;56(11):1137-42.
7. Langsjoen, P.H. and Langsjoen, A.M. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of CoQ10. A review of animal and human publications. Biofactors 2003;18(1-4):101-11.
8. Beal, M.F. CoQ10 as a possible treatment for neurodegenerative diseases. Free Radic Res 2002;36(4):455-460.
9. Shults, C.W. CoQ10 in neurodegenerative diseases. Curr Med Chem 2003 Oct.;10(19):1917-21.
10. Shults, C.W., Oakes, D., Kieburtz, K., Beal, M.F., Haas, R., Plumb, S., Juncos, J.L., Nutt, J., Shoulson, I., Carter, J., Kompoliti, K., Perlmutter, J.S., Reich, S., Stern, M., Watts, R.L., Kurlan, R., Molho, E., Harrison, M., Lew, M. Parkinson Study Group. Effects of CoQ10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 2002 Oct.;59(10):1541-50.
11. Muller, T., Buttner, T., Gholipour, A.F., and Kuhn, W. CoQ10 supplementation provides mild symptomatic benefit in patients with Parkinsons disease. Neurosci Lett
2003 May 8;341(3):201-4.
12. Lockwood, K., Moesgaard, S., and Folkers, K. Partial and complete regression of breast cancer in patients in relation to dosage of CoQ10. Biochem Biophys Res Comm 1994, 199: 3, 1504-1508.
13. Jolliet, P. et al. Plasma CoQ10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 1998;36(9):506-509.
14. Wilkinson, E.G. et al, Bioenergetics in clinical medicine VI. Adjunctive treatment of periodontal disease with CoQ10. Res Comm Chem Pathol Pharmacol Aug. 1976; 14(4): 715-719.
15. Hanioka, T. et al. Effect of topical application of CoQ10 on adult periodontitis. Mol Aspects Med 1994;15(Suppl):s241-s248.
16. Singh, R.B. and Singh, M.M. Effects of CoQ10 in new indications with antioxidant vitamin deficiency. J Nutr Environ Med 1999; 9:223-228.
17. Singh, R.B., Khanna, H.K., and Niaz M.A. Randomized, double-blind placebo-controlled trial of CoQ10 in chronic renal failure: Discovery of a new role. J Nutr Environ Med 2000; 10:281-288.
18. Bliznakov, E.G. Coenzyme Q10, the immune system, and aging, in: Biomedical and Clinical Aspects of Coenzyme Q, Vol 3, by K. Folkers, and Y. Yamamura, (eds), Elsevier-North Holland, Amsterdam, 1981.
19. Fahy, G.M. Life extension benefits of CoQ10. Anti-Aging News 1983, 3: 7, 73-78.
20. Coles, L.S., and Harris, S.B. Co Q-10 and lifespan extension, in: Advances in Anti-Aging Medicine, Vol 1, by R. Klatz, Mary Ann Liebert, Inc., Larchmont, New York, 1996.
21. Lonnrot, K., Holm, P., Lagerstedt, A., Huhtala, H., and Alho, H. The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue concentration
and life span of male rats and mice. Biochem Mol Biol Int 1998, 44: 4, 727-737.
22. Quiles, J.L., Ochoa J.J., Hertas, J.R., and Mataix, J. CoQ supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. Experimental Gerontology 2004, 39: 189-194.
23. Ishii, N., Senoo-Matsuda, N., Miyake, K., et al. CoQ10 can prolong C. elegans lifespan by lowering oxidative stress. Mech Ageing and Dev 2004, 125: 1, 41-46.
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