Coenzyme Q10 Faces a Backlash
Coenzyme Q10 Faces a BacklashBy Jay K. Udani, MD, and Joshua J. Ofman, MD, MSHSCongestive 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.1
Pharmacokinetics
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.
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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.6,7
We 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.
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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.