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© 2003 Memorial Sloar-Kettering Cancer Center
(Monograph)
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Full Text |
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Barrie Cassileth
and K. Simon Yeung
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Coenzyme
Q10
(2,3 dimethoxy-5 methyl-6-decaprenyl benzoquinone)
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| Clinical Summary |
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Synthesized
endogenously by mammals. Patients use this supplement to treat cancer,
congestive heart failure, arrhythmias, Parkinson disease and hypertension,
and to prevent anthracycline cardiomyopathy. Coenzyme Q10 (CoQ10) is
essential for the production of adenosine triphosphate. It also has
antioxidant membrane stabilizing properties, prevents mitochondrial
deformity, and maintains myocardial calcium ion channels during ischemic
insults. CoQ10 has low bioavailability following oral administration and
distributes widely throughout the body. Metabolites are excreted via the
biliary tree. Data on effects on congestive heart failure do not concur.
Case reports describing efficacy for breast cancer exist in the
literature, but there are no controlled clinical trials. Use of CoQ10 to
prevent anthracycline-induced cardiomyopathy requires additional research.
A recent study also shows that CoQ10 may be effective in early Parkinson
Disease. No significant adverse effects are reported. CoQ10 is
structurally similar to vitamin K and therefore may antagonize the effects
of warfarin. It may antagonize the effects of chemotherapy via antioxidant
activity. Ubiquinone may reduce the effect of radiation therapy. UbiQgel™,
a CoQ10 formulation, is an FDA approved orphan drug under study in
mitochondrial diseases (e.g. MELAS syndrome, Kearns-Sayre syndrome).
Additional research is required to establish the role of CoQ10
supplementation.
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| Scientific Name |
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2,3
dimethoxy-5 methyl-6-decaprenyl benzoquinone
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| Also Known As |
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Ubiquinone,
ubidecarenone, ubiquinol, CoQ, CoQ10
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| Brand Name |
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UbiQgel™
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| Food Sources
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Food
contains clinically insignificant amounts.
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| Purported Uses |
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• Angina
• Cancer
prevention
• Cardiovascular
disease
• Chemotherapy
side effects
• Congestive
heart failure
• HIV
and AIDS
• Hypertension
• Infertility
• Migraine
prophylaxis
• Parkinson’s
disease
• Periodontal
disease
• Strength
and stamina
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Mechanism Of Action
[1], [2] |
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Coenzyme
Q10 (CoQ10), known to have antioxidant and membrane stabilizing
properties, is the only endogenously produced lipid with a redox function
in mammals. All cells are capable of synthesizing CoQ10 and no
redistribution between organs occurs through the blood. CoQ10 is necessary
for adenosine triphosphate (ATP) production. Its role as a mobile electron
carrier in the mitochondrial electron-transfer process of respiration and
coupled phosphorylation is well established. It has a direct regulatory
role on succinyl and NADH dehydrogenases. Like vitamin E, CoQ10 is a
lipid-soluble antioxidant. Like vitamin C, reduced CoQ10 effectively
regenerates alpha-tocopherol from the alpha tocopheroxyl radical. CoQ10
has been demonstrated to scavenge free radicals produced by lipid
peroxidation and prevent mitochondrial deformity during episodes of
ischemia, and it may have some ability to maintain the integrity of
myocardial calcium ion channels during ischemic insults. Its major
mechanism of action is protection of ischemic tissue from reperfusion
damage. CoQ10 appears capable of stabilizing cellular membranes and
preventing depletion of metabolites required for ATP resynthesis.
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Pharmacokinetics
[1], [2] |
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Absorption:
Uptake of dietary CoQ in the liver does not affect the synthesis of
endogenous CoQ, which supports the notion that CoQ does not exert any
feedback inhibition on its own biosynthesis. Animal studies demonstrate a
bioavailability of 2-3%. With high doses of dietary CoQ, the blood
concentration in both rats and humans can be increased about 2- to 4-fold.
Following ingestion of 100 mg of CoQ, peak plasma levels occur between 5
and 10 hours. Tmax is approximately 6.5 hours, which indicates slow
absorption from the GI tract possibly due to the high molecular weight and
low water solubility of CoQ.
Distribution:
The mean plasma levels after a single 100 mg oral dose of CoQ in human
subjects is 1.004+/- .37 mg/mL. In humans, CoQ is found in relatively high
concentrations in the heart, liver, kidney, and pancreas. The plasma
half-life of CoQ in different tissues varies between 49-125 hours.
Following absorption from the GI tract, CoQ is taken up by chylomicrons.
The major portion of an exogenous dose of CoQ is deposited in the liver
and packaged into VLDL lipoprotein.
Metabolism/Excretion:
It is assumed that metabolism and excretion of exogenous CoQ is analogous
to endogenously produced CoQ. The excretion of CoQ is predominantly via
the biliary tract.
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Contraindications
[8] |
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Ubiquinone
intake may reduce effect of radiation therapy.
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Adverse Reactions
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Infrequent:
Nausea, diarrhea, and appetite suppression
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Drug Interactions
[3], [4] |
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HMG-CoA
reductase inhibitors: Endogenous levels of CoQ may be
reduced by lovastatin, atorvastatin and simvastatin. The HMG-CoA reductase
enzyme is responsible for catalyzing the conversion of acetyl CoA to
cholesterol and synthesis of CoQ10.
Warfarin: CoQ may antagonize the effects of warfarin. CoQ is
structurally similar to vitamin K.
Chemotherapy: Theoretically, CoQ may decrease the efficacy
of chemotherapy due to antioxidant activity.
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| Literature Summary And Critique |
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Shults
CW, et al. Effects
of coenzyme Q10 in early Parkinson disease. Arch
Neurol
2002;59:1541-50.
A multicenter, randomized, placebo-controlled, double-blind, dose-ranging
trial in 80 otherwise healthy patients with early Parkinson disease.
Patients received placebo or coenzyme Q10 at dosages of 300, 600, or 1200
mg daily, split into 4 doses. Recent or concurrent use of antioxidants was
not permitted. Patients were followed for up to 16 months or until
treatment with levodopa was required. Primary outcome measured was Unified
Parkinson Disease Rating Scale (UPDRS); the study was projected to have
73% power to detect a difference of 6 points in total UPDRS score. Mean
total change was +11.99 in the placebo group and +6.69 in the 1200-mg/d
group (p=0.4). Time until treatment with levodopa was not effected by
treatment. Side effect profile for all doses of coenzyme Q10 was mild and
similar to that for placebo. These results must be confirmed with larger
studies, but this study does suggest that dosages of <200 mg/d in
previous trials may have been inadequate.
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Khatta
M. The effect of coenzyme Q10 in patients with congestive heart failure. Ann
Intern Med
2000;132:636-40.
A
prospective, randomized, double-blind, placebo-controlled trial evaluating
coenzyme Q10 (CoQ) supplementation in patients with NYHA Class III or IV
heart failure. Patients were randomized to receive 200 mg/day CoQ (n=23)
or placebo (n=23) for 6 months. The study was designed to detect a 2.8 mL/kg/min
difference in peak oxygen consumption. Other outcomes measured were
changes in left ventricular ejection fraction and exercise duration. No
adverse events were reported. No significant improvement was noted in
patients supplemented with 200 mg/day CoQ. However, as Shults et al.
(2002) suggest, doses <200 mg/d may be inadequate.
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Watson
PS, et al. Lack
of effect of coenzyme Q on left ventricular function in patients with
congestive heart failure. J
Am Coll Cardiol
1999;33:1549-52.
A prospective, randomized, double-blind, crossover design study evaluating
99 mg/day CoQ on 30 patients with chronic heart failure and left
ventricular dysfunction. Patients received either placebo or 33 mg CoQ
thrice daily for three weeks followed by 1-week washout period. Treatment
groups crossed over to alternate treatment for 12 weeks. Transthoracic
echocardiogram, Swan-Ganz catheterization, and quality of life assessments
were conducted prior to and following each treatment period. No adverse
events were reported during the study. No significant improvements were
documented following 12 weeks of supplementation with CoQ. However, as
Shults et al. (2002) suggest, doses <200 mg/d may be inadequate. |
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Lockwood
K, et al. Partial and complete regression of breast cancer in patients in
relation to dosage of coenzyme Q10. Biochem Biophys Res Comm 1994;199:1504-8.
A case report series, originally presented at the Eighth International
Symposium on the Biomedical and Clinical Aspects of Coenzyme Q, November
1993, in Stockholm. Dr. Lockwood supplemented 32 breast cancer patients
with 90 mg coenzyme Q10, linolenic acid, fatty acids, beta-carotene,
vitamin C, vitamin E, and selenium. A trial is reported in which 32 breast
cancer patients were supplemented with 90 mg/day CoQ, resulting in 6
complete remissions. However, the results were not statistically
significant because CoQ levels were similar to a comparison group. The
physician presents two case reports of patients with intraductal
carcinoma, both status post surgical resection, with recurrent local
disease who went into remission with CoQ doses up to 390 mg/day. No
additional data from the trial are provided. The physician suggests CoQ as
a viable treatment alternative for breast cancer, although clinical trials
are lacking.
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Lockwood
K, et al. Progress on therapy of breast cancer with vitamin Q10 and the
regression of metastasis. Biochem
Biophys Res Comm
1995;212:172-7.
Additional case report series describing complete remission of three
patients with metastatic intraductal carcinoma treated with 390 mg/day CoQ.
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| References |
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[1] Greenberg
S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J
Clin Pharmacol 1990;30:596-608.
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[2] Dallner
G, Sindelar PJ. Regulation of ubiquinone metabolism. Free Radic Biol
Med 2000;29:285-94.
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[3] Folkers
K, et al. Lovastatin
decreases coenzyme Q levels in humans. Proc Natl Acad Sci
1990;87:8931-4.
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[4] Pronsky
ZM. Power's and Moore's Food-Medication Interactions, 11th ed.
Pottstown (PA): Food Medication Interactions; 2000.
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[5]
Fuke
C, Krikorian SA, Couris RR. Coenzyme
Q10: a review of essential functions and clinical trials. US
Pharmacist
2000;25:28-41.
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[6]
Rozen
TD, et al. Open
label trial of coenzyme Q10 as a migraine preventive. Cephalgia
2002;22:137-41.
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[7]
Lister,
RE. An open, pilot study to evaulate the potential benefits of coenzyme
Q10 combined with Gingko biloba extract in fibromyalgia syndrome. J
Int Med Res 2002;30:195-9.
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[8]
Lund
E, el al.Effect of radiation therapy on small-cell lung cancer is reduced
by ubiquinone intake. Folia Microbiol. 1998;4:505-6. |
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[9]
Shults,
C., et al.Effects of Coenzyme Q10 in Early Parkinson Disease. Arch
Neurol. 1998;4:505-6.
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| Written |
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01/01/2002 |
| Updated |
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12/13/2002
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Disclaimer: http://www.mskcc.org/mskcc/print/11790.cfm |
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Source: http://www.mskcc.org/mskcc/print/11571.cfm?RecordID=475 |
