Coenzyme Q10 to Enhance Aerobic Exercise
Coenzyme Q10 to Enhance Aerobic Exercise
By Dónal P. O’Mathúna, PhD
Coenzyme q10 (also called coq10, ubiquinone, or ubidecarenone) is a lipid that is readily available in meat and seafood. It has some similarities to vitamins, especially vitamins E and K, but is not classified as such because it is produced in the human body. Dietary supplementation most commonly is recommended for adjuvant treatment of congestive heart failure, not as first-line therapy.1 Studies have found that cardiac patients taking CoQ10 have improved ejection fraction, exercise tolerance, cardiac output, and stroke volume. Evidence that CoQ10 benefits patients with angina or hypertension is less conclusive to date.1 The exercise-related results quickly caught the attention of athletes. Although the research does not support its ergogenic effectiveness, athletes continue to use CoQ10 in the hope that it will improve their aerobic performances.
Biochemistry
CoQ10 is a member of the coenzyme Q group of compounds with similar structures and functions. All contain a ring, called the "head," and a long chain, the "tail," which is made up of repeating five-carbon units called isoprenoid units (see Figure, below).2 The parentheses enclose one isoprenoid unit, with the subscript indicating the number of units in the particular compound. Human coenzyme Q contains 10 isoprenoid units, hence the name CoQ10. The bacterial form is CoQ5 and the rodent form is CoQ9.
CoQ10 is highly lipophilic and lodges within the lipid layers of cell membranes. It is found in the inner membranes of mitochondria, the organelles regarded as the "power houses" of all cells. CoQ10 also is found in other membranes where it functions as a membrane stabilizer and an antioxidant.
Pharmacology
CoQ10 plays a vital role in the electron transport chain (ETC) found in mitochondria. The primary source of energy in living organisms is adenosine triphosphate (ATP). During exercise lasting longer than 30 seconds, ATP must be continuously regenerated via metabolism of carbohydrates, lipids, or proteins. All of these produce high-energy electrons that are funneled through CoQ10 shortly before ATP itself is produced. Rare cases of CoQ10 deficiency have been reported, in which symptoms included progressive muscle weakness, seizures, and encephalopathy.3 Treatment with CoQ10 reversed the muscle weakness, but not the encephalopathy.
Mechanism of Action
The antioxidant properties of CoQ10 are believed to underlie the beneficial effects found in cardiac patients. Exercise can produce free radicals, which are oxidants that may play a role in exercise-induced muscle soreness and damage.4 Therefore, the antioxidant properties of CoQ10 may benefit athletes, although this mechanism of action has not been well established.
The primary use of CoQ10 by some athletes is based upon its essential role in ATP production. Normal CoQ10 levels do not saturate the ETC, and supplementation increases plasma CoQ10 levels, leading to speculation that supplementation could increase ATP production and aerobic exercise performance.5 However, CoQ10 is only one of several compounds involved in the ETC; increased serum CoQ10 levels might not necessarily lead to increased mitochondrial levels or performance enhancement.
Clinical Studies
Several books were published on CoQ10 between the 1970s and early 1990s. A review of these found seven studies, mostly supportive of an ergogenic effect for CoQ10.5 However, these studies have been critiqued because they were not published in peer-reviewed journals,6 and all had at least one serious methodological failing, including no statistical validation, no control group, no placebo, or no randomization.7
A search of PubMed and International Pharmaceutical Abstracts (using "coenzyme Q," "CoQ10," and "ubiquinone") produced 12 controlled trials of the ergogenic effects of CoQ10 in humans. Nine of these studies used CoQ10 alone (summarized in Table 1,below); three used CoQ10 in combination with other supplements (summarized in Table 2, below).
Table 1
Summary of results of trials using CoQ10 alone
Study Subjects Blinding Dose Duration Significant Results Non-Significant Results Zuliani et al8 12 untrained adults N/A 100 mg/d 1 month Reduced free fatty acids (P < 0.05) Five metabolic tests Roberts9 24 healthy college students Double-blind 100 mg/d 28 days N/A VO2max and two other tests within daily variation Braun et al10 10 elite cyclists N/A 100 mg/d 8 weeks N/A Time to exhaustion and three metabolic tests Porter et al11 15 middle- aged men Double-blind 150 mg/d 2 months Subjective measure of vigor VO2max, lactate threshold Laaksonen et al12 19 trained adults Double-blind, crossover 120 mg/d 6 weeks Time to exhaustion increased with placebo (P = 0.0003) VO2max Malm et al13 18 well-trained adults Double-blind 120 mg/d 22 days Aerobic cycling test and total work improved with placebo (P < 0.001) VO2max and five other tests Ylikoski et al14 25 elite cross- country skiers Double-blind, crossover 90 mg/d 6 weeks VO2max (P = 0.02), anaerobic threshold (P = 0.0003), aerobic, threshold (P = 0.0001) Lactic acid clearance Weston et al15 18 cyclists, triathletes Double-blind 1 mg/kg/d 28 days N/A VO2max and eight other tests Bonetti et al7 28 cyclists Single-blind 100 mg/d 8 weeks N/AVO2max, seven other respiratory tests, and five metabolic tests
| Table 2 | ||||||
|
Summary of results of trials with CoQ10 combined with other compounds |
||||||
| Study | Subjects | Blinding | CoQ10 Dose | Other Compounds | Duration | Non-Significant Results |
| Snider et al18 | 11 triathletes | Double-blind, crossover | 100 mg/d | 500 mg cyto- chrome C, 100 mg inosine, 200 IU vitamin E | 4 weeks | Time to exhaustion and three metabolic tests |
| Kaikkonen et al16 | 37 marathoners | Double-blind | 90 mg/d | 13.5 mg vitamin E | 3 weeks | Lipid peroxidation and muscle damage |
| Nielsen et al17 | 7 triathletes | Double-blind, crossover | 100 mg/d | 600 mg vitamin C and 270 mg vitamin E | 6 weeks | VO2max, fatigue test, and three metabolic tests |
The nine studies supplementing with CoQ10 alone involved triathletes, cyclists, cross-country skiers, and untrained adults.7-15 Doses ranged from 90 to 150 mg/d. All of the studies used small numbers of subjects, lasted 1-2 months, and measured a wide range of outcomes.
Of the studies published in peer-reviewed journals, seven measured VO2max (the amount of oxygen consumed while exercising, which is a proxy for the energy-generating capability of mitochondria). Of these, six found no significant differences between those taking CoQ10 and the subjects taking placebo. The one study in which the VO2max improved significantly (P = 0.02) also found significant improvements in anaerobic threshold (P = 0.0003) and aerobic threshold (P = 0.0001).14
In contrast, two studies found that those receiving placebo had significant improvements compared to those receiving CoQ10. In one, trained adults in the placebo group had significantly increased time to exhaustion (P = 0.0003), although the VO2max did not differ between the groups.12 In the second, untrained adults did significantly better on an aerobic cycling test and in total work output in the placebo group compared to those taking CoQ10 (P < 0.001).13
Three studies used CoQ10 in combination with other vitamins and supplements (see Table 2, above). Vitamins C and E were used for their antioxidant properties.16,17 The CoQ10, vitamin E, inosine, and cytochrome c combination was called coenzyme athletic performance system, but it was not stated if this was a proprietary product.18 These studies found no statistically significant benefits from the CoQ10 combination supplements.
All clinical trials with CoQ10 found significantly increased plasma levels of CoQ10 after supplementation. However, any ergogenic effect would require increased CoQ10 levels in muscle cells and their mitochondria. To investigate whether oral CoQ10 supplements increase these levels, 17 well-trained men volunteered for a double-blind, randomized trial.19 Each took either CoQ10 (120 mg/d) or placebo. After 20 days, plasma CoQ10 levels were significantly higher in those taking CoQ10 (P < 0.05) and were unchanged in the placebo group. Muscle biopsies revealed no significant changes in the CoQ10 levels in skeletal muscle or the mitochondrial fraction of the muscle. No correlation was found between the plasma and muscle CoQ10 levels. The rate of ATP synthe-sis in isolated mitochondria was measured in four subjects, and also was found to be unchanged with supplementation.
Adverse Effects
Adverse effects have not been reported in clinical trials, although mild GI disturbances have been reported in less than 1% of patients.20 Although CoQ10 is an antioxidant, there are concerns it may act as a pro-oxidant under acidic conditions. To evaluate this, plasma creatine kinase (CK) activity was measured in 15 trained men after exercising.21 The men were randomly assigned to receive CoQ10 120 mg/d or placebo for 15 days. On days 11 and 15, CK levels were significantly higher in those taking CoQ10, but unchanged in the placebo group. CK levels returned to normal five days after CoQ10 supplementation ceased. The authors concluded "that under conditions with high proton concentration (e.g., high-intensity exercise) and Q10 supplementation, there is increased cell damage."
Drug Interactions
There are reports that CoQ10 can decrease the effectiveness of warfarin.2 CoQ10 is chemically similar to vitamin K and may have similar pro-coagulant activity.20
The HMG CoA reductase inhibitors ("statins") inhibit cholesterol and CoQ10 synthesis, leading to lower CoQ10 levels. Whether this is clinically significant is unknown. There is concern that CoQ10 supplements may interfere with medications for hypertension or diabetes, but these effects are not believed to be widespread.20
Formulation
CoQ10 supplements are formulated as oil-based capsules, powder-filled capsules, tablets, and soft-gel capsules containing microemulsions.2 The latter are claimed to have better bioavailability than other formulations. The most common doses are 70-150 mg/d CoQ10 for several weeks.
Because CoQ10 is a lipid, its absorption is poor, highly variable, and strongly dependent on the contents of the stomach. When taken on an empty stomach, very little is absorbed. More than 60% of an oral dose of CoQ10 is excreted unchanged in the feces.19 All formulations are best taken with food, especially fat-rich foods. Once absorbed into the blood, CoQ10 enters lipid membranes throughout the body, requiring about three weeks of supplementation before serum concentrations maximize.2
Conclusion
A general picture of lack of efficacy of CoQ10 as an exercise-enhancing agent is becoming apparent. This contrasts with the exercise benefits found in some cardiac patients. Nonetheless, the bulk of the research shows no ergogenic benefit for healthy individuals and athletes. Two studies found that CoQ10 interfered with performance. One study supports a theoretical concern about tissue damage resulting from a pro-oxidant effect when CoQ10 is found in an acidic environment, such as occurs in tissues after exercise.
Recommendation
Given the lack of evidence that CoQ10 supplements are effective ergogenic aids, use by athletes should be discouraged. Although serious adverse effects have not been reported, the finding that CoQ10 may have a pro-oxidant effect raises concern about its use. Since exercise itself can be a source of oxidative stress, the long-term use of any supplement that might further increase oxidative damage should be discouraged.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing, Columbus, OH.
References
1. Tran MT, et al. Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy 2001;21:797-806.
2. Coenzyme Q10 (CoQ10). In: PDR for Nutritional Supplements. Montvale, NJ: Medical Economics; 2001:103-106.
3. Baynes J, Dominiczak MH. Medical Biochemistry. New York: Mosby; 1999:87-91.
4. Goldfarb AH. Nutritional antioxidants as therapeutic and preventive modalities in exercise-induced muscle damage. Can J Appl Physiol 1999;24:249-266.
5. Bucci L. Nutrients as Ergogenic Aids for Sports and Exercise. Boca Raton, FL: CRC; 1993:53-57.
6. Williams MH, Leutholtz BC. Nutritional ergogenic aids. In: Maughan RJ, ed. Nutrition in Sport. Oxford, UK: Blackwell Science; 2000:356-366.
7. Bonetti A, et al. Effect of ubidecarenone oral treatment on aerobic power in middle-aged trained subjects. J Sports Med Phys Fitness 2000;40:51-57.
8. Zuliani U, et al. The influence of ubiquinone (CoQ10) on the metabolic response to work. J Sports Med Phys Fitness 1989;29:57-62.
9. Roberts J. The effects of coenzyme Q10 on exercise performance [abstract]. Med Sci Sports Exerc 1990;22 (suppl):S87.
10. Braun B, et al. Effects of coenzyme Q10 supplementation on exercise performance, VO2max, and lipid peroxidation in trained cyclists. Int J Sport Nutr 1991;1: 353-365.
11. Porter DA, et al. The effect of oral coenzyme Q10 on the exercise tolerance of middle-aged, untrained men. Int J Sport Med 1995;16:421-427.
12. Laaksonen R, et al. Ubiquinone supplementation and exercise capacity in trained young and older men. Eur J Appl Physiol Occup Physiol 1995;72:95-100.
13. Malm C, et al. Effects of ubiquinone-10 supplementation and high intensity training on physical performance in humans. Acta Physiol Scand 1997;161: 379-384.
14. Ylikoski T, et al. The effect of coenzyme Q10 on the exercise performance of cross-country skiers. Mol Aspects Med 1997;18(suppl):S283-S290.
15. Weston SB, et al. Does exogenous coenzyme Q10 affect aerobic capacity in endurance athletes? Int J Sport Nutr 1997;7:197-206.
16. Kaikkonen J, et al. Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: A placebo-controlled double-blind study in marathon runners. Free Radic Res 1998;29:85-92.
17. Nielsen AN, et al. No effect of antioxidant supplementation in triathletes on maximal oxygen uptake, 31P-NMRS detected muscle energy metabolism and muscle fatigue. Int J Sport Med 1999;20:154-158.
18. Snider IP, et al. Effects of coenzyme athletic performance system as an ergogenic aid on endurance performance to exhaustion. Int J Sport Nutr 1992;2: 272-286.
19. Svensson M, et al. Effect of Q10 supplementation on tissue Q10 levels and adenine nucleotide catabolism during high-intensity exercise. Int J Sport Nutr 1999; 9:166-180.
20. Coenzyme Q-10. Accessed at www.naturaldatabase.com on Sept. 24, 2001.
21. Malm C, et al. Supplementation with ubiquinone-10 causes cellular damage during intense exercise. Acta Physiol Scand 1996;157:511-512.
O'Mathuna DP. Coenzyme Q10 to Enhance Aerobic Exercise. Altern Med Alert 2002;5:5-8.Subscribe Now for Access
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