Coenzyme Q10 for the Treatment of Congestive Heart Failure
March 1998; Volume 1: 25-27
By Jay K. Udani, MD, and Joshua J. Ofman, MD, MSHS
Congestive heart failure (chf) is the most common cause of hospitalizations in elderly Americans.1 Any therapy shown to reduce hospital admissions, length of stay, or improve the quality of life in patients with CHF would be a welcome addition to the myriad of drugs currently used. These include diuretics, ACE-inhibitors, digoxin, beta blockers, and vasodilators. One therapy that has gained popularity in the lay press is Coenzyme Q10, which has been promoted for the treatment of a variety of cardiac disorders including CHF, angina, and generalized cardiovascular fitness.History/Culture
Coenzyme Q10 (also known as ubiquinone, or Co-Q10) is an antioxidant produced by the body and also found in small amounts in most foods, especially meat and seafood.1 It was isolated in the pure form in 1957 by Dr. Fred Crane at the University of Wisconsin. However, all of the world’s patents for Co-Q10 are held by Japanese companies who are the only source for the supplements. It is among the top six pharmaceuticals sold in Japan today.1Pharmacokinetics
Co-Q10 is a fat-soluble antioxidant and a member of the quinone family with a structure similar to Vitamins E and K, but it is not classified as a vitamin. Its bioavailabilty is based on fat digestion. Newer, soft-gel capsules have been found to have higher bioavailability than older dry tablets or powdered forms.Mechanism of Action
Co-Q10 is an essential component of the mitochondria and plays a role in ATP production.2 Co-Q10 is a carrier for two-electron transfer within the lipid phase of the mitochondrial membrane, and it is vital for proper energy production.3 Co-Q10 has also shown antioxidant properties in membranes, the ability to stabilize membranes, 3,4 and a role in oxidative phosphorylation.5 There are no data demonstrating that Co-Q10 promotes or improves oxygen utilization by cardiac myocytes.Clinical Trials
The role of Co-Q10 in cardiovascular disease is based upon the hypothesis that patients with significant heart disease have a Co-Q10 deficiency compared to their healthy counterparts. Clinical studies have shown that patients with New York Heart Association (NYHA) Class III-IV CHF have significantly lower blood and tissue levels of Co-Q10 than NYHA Class I-II patients or healthy controls.6,7We performed a systematic review of the available world literature on Co-Q10. A search was done of computerized medical databases including MEDLINE, CATLINE, and HSRPROJ, in addition to textbooks and the Internet, using search terms Co-Q10, ubiquinone, and congestive heart failure.’
Most studies evaluating the cardiac effects of Co-Q10 analyzed echocardiographic and hemodynamic parameters, showing significant increases in LV wall thickness, mitral valve inflow slope, fractional shortening8 and ejection fraction.9 The most rigorous trial that reported clinical outcomes was a placebo-controlled study with Co-Q10 in 651 patients with NYHA Class III or IV CHF over one year. This study found a significant decrease in the number of hospitalizations (23% vs. 37%; P < 0.001; relative risk reduction [RRR] 38%; absolute risk reduction [ARR] 14%; NNT = 7), episodes of pulmonary edema (6% vs. 30%; P < 0.001; RRR 61%, ARR 24%, NNT = 4), and episodes of cardiac asthma (30% vs. 61%; P < 0.001; RRR 51%, ARR 31%, NNT = 3).10 The relative risk reductions range from 38-61%, and the absolute risk reductions range from 14-31%. In other words, three to seven patients with CHF must be treated with Co-Q10 rather than placebo in order to avoid one poor outcome.
While head-to-head comparisons are not available, these numbers compare favorably to the decreased hospitalization rates found with ACE inhibitors and digoxin, the current standards of therapy. Two other non-randomized clinical studies showed improvement in NYHA Class, cyanosis, and edema,11,12 but since they are not randomized controlled trials, it is difficult to draw firm conclusions.
Adverse Effects
No adverse effects were documented in the studies reviewed above. Other studies have shown mild transient nausea.1,8 No drug-to-drug interactions have been documented.Formulation and Dosage
The usual formulation is a tablet or capsule, formed from dry powder. As mentioned previously, there is a soft gel capsule form with higher bioavailability. The dose used in the largest clinical trial was 2 mg/kg/d10, but reported doses vary from 50-150 mg/d. The clinical trials did not specify whether Co-Q10 was given as capsule, tablet, or powder, and no specific brand of Co-Q10 was mentioned. Another study looked specifically at the bioavailability of various formulations of Co-Q10.13 The formulations tested were Co-Q10 alone, Co-Q10 with soy bean oil, and Co-Q10 and soybean oil with polysorbate 80 and lecithin phosphatidylcholine as additives. The soybean oil suspension of Co-Q10 (trade name Bioquninon) had the highest bioavailability.13 The cost of Co-Q10 varies, but a 70 kg person taking 2 mg/kg/d would spend approximately $60 per month.Conclusion
Co-Q10 appears to be a promising agent in the symptomatic treatment of CHF. A mortality benefit has not, however, been established as it has with ACE inhibitors. Comparative studies with conventional therapies regarding clinical outcomes are needed. Although the mechanism of action is based upon a relative deficiency of Co-Q10 in the body, there have been no studies showing that specifically reversing the level of documented deficiency improves the clinical course of CHF. Until Co-Q10 is shown to reduce mortality in CHF, conventional therapy with ACE inhibitors, diuretics, digoxin, and beta blockers remain the cornerstones of therapy. Since Co-Q10 is safe and can improve some clinical outcomes and hemodynamic parameters in patients with CHF, we recommend its use as an adjunct to the traditionally prescribed therapies using a soybean oil suspension capsule at a dose of 2 mg/kg/d.References
1. Carper J. Miracle Cures. New York: Harper Collins; 1997.2. Hendler S. The Doctor’s Vitamin and Mineral Encyclopedia. New York: Simon & Schuster; 1990.
3. Crane FL, et al. The essential functions of Coenzyme Q10. Clin Investig 1993;71(8 Suppl):S55-59.
4. Spigset O. Coenzyme Q10 in the treatment of heart failure. Are any positive effects documented? Tidsskr Nor Laegeforen 1994:114(8):939-942.
5. Greenberg S. Coenzyme Q10: A new drug for cardiovascular disease. J Clin Pharmacol 1990;30(7):596-608.
6. Folkers K, et al, eds. Biomedical and Clinical Aspects of Coenzyme Q10. Volumes 1-4. Amsterdam: Elsevier Science Publishers; Vol.1, 1977; Vol.2, 1980; Vol.3, 1982; Vol.4, 1984.
7. Mortensen SA. Coenzyme Q10: Clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure. Int J Tissue React 1990;12(3):155-162.
8. Langsjoen H, et al. Usefulness of coenzyme Q10 in clinical cardiology: A long-term study. Mol Aspects Med 1994;15:S165-175.
9. Morisco C, et al. Non-invasive evaluation of cardiac hemodynamics during exercise in patients with chronic heart failure: Effects of short-term coenzyme Q10 treatment. Mol Aspects Med 1994;15:S155-163.
10. Morisco C, et al. Effect of coenzyme Q10 therapy in patients with congestive heart failure: A long-term multicenter randomized study. Clin Investig 1993;71(8 Suppl):S134-136.
11. Baggio, E, et al. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. Co-Q10 Drug Surveillance Investigators. Mol Aspects Med 1994;15:S287-294.
12. Folkers K, et al. Therapy with coenzyme Q10 of patients in heart failure who are eligible or ineligible for a transplant. Biochem Biophys Res Commun 1992;182(1):247-53.
13. Weis M, et al. Bioavailability of four oral Coenzyme Q10 formulations in healthy volunteers. Mol Aspects Med 1994;15Suppl:S273-280.
Dr. Udani is Chief Resident, Internal Medicine, Cedar-Sinai Medical Center in Los Angeles.
Coenzyme Q10 Faces a Backlash
When it comes to the popular dietary supplement Coenzyme Q10, your patients may have received mixed messages from the popular press. While not so long ago the supplement was hailed as a near cure-all (some sources allege it can slow the aging process, halt the spread of cancer, and prevent heart disease, among other things), recent articles have questioned its usefulness and noted that it is also an expensive supplement.
The June 1997 issue of Men’s Health advised its readers to "leave Coenzyme Q on the shelf", pointing out that the nutrient is naturally manufactured by the body, is found in many foods, and, priced at about $40 for 100 tablets— relatively expensive for a nutritional supplement.
Its reputation is causing many people to dismiss CoQ10 supplements, notes an article in the November 1997 issue of Environmental Nutrition. n
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