Coenzyme Q₁₀ is a safe supplement that may be beneficial in congestive heart failure (CHF) and before cardiac surgery. There is no reliable evidence for its effect as treatment for cancer, Parkinson’s disease, periodontal disease, or aerobic capacity, but it may reduce cardiac toxicity from anthracyclines.

[DFM ] Letter Key

Description

• Coenzyme Q₁₀ (CoQ10, ubiquinone, 2-3-dimethoxy 5-methyl-6-decaphenyl benzoquinone) is a naturally occurring fat-soluble quinone found in high concentrations in mitochondria, particularly in the myocardium.
• Its structure is similar to vitamin K. Although it serves vital functions, coenzyme Q₁₀ is nonessential because the quinone moiety is synthesized from tyrosine and the polyprenyl side chain is synthesized from acetyl-CoA (1).

Food Sources

• Dietary sources, including meat and poultry, may contribute up to a quarter of coenzyme Q₁₀ in the human body (1).

Main Functions/Pharmacokinetics

• Involved in adenosine triphosphate (ATP) production, coenzyme Q₁₀ also transports electrons during cellular respiration and oxidative phosphorylation and regulates the reduced form of nicotinamide adenine dinucleotide (NADH) and succinate dehydrogenase in the respiratory transport chain. Its reduced form, ubiquinol, functions as an antioxidant (2).
• Oral administration of 30 mg causes a peak level of 1 µg/mL within 6 hours; a second peak occurs after 24 hours (this suggests enterohepatic recycling). Administration of 100 mg t.i.d. resulted in steady-state levels of 5.4 µg/mL. The plasma half-life is about 34 hours (2).

[Outline]

• DDescription
• FFood Sources
• MMain Functions/Pharmacokinetics

[C ] Letter Key

Clinical Trials

• Myocardial infarction
  • A placebo-controlled study in 144 patients after acute myocardial infarction tested the effect of 120 mg/day of coenzyme Q₁₀ for 4 weeks (3). The incidence of angina was significantly less in the treated group compared with the placebo group (9.5% vs. 28.1%). Total arrhythmias (9.5% vs. 25.3%) and total cardiac events, including nonfatal infarction and cardiac deaths, were also significantly reduced in the treated group (15% vs. 30.9%).
• Angina
  • The effects of coenzyme Q₁₀ in angina are unclear. A double-blind placebo-controlled crossover trial of 12 patients with stable angina found that coenzyme Q₁₀ (50 mg t.i.d. × 4 weeks) increased exercise time (406 ±114 seconds) significantly compared with placebo (345 ± 102 seconds) but did not reduce frequency of angina (4).
  • A crossover study in 20 patients found that 60 mg/day coenzyme Q₁₀ for 4 weeks found that, compared with baseline, coenzyme Q₁₀ treatment significantly decreased angina attacks (by 1.9 episodes/week), decreased nitroglycerine consumption, and increased exercise duration (5).
• CHF
  • A Danish meta-analysis identified 14 controlled trials of patients with CHF receiving adjuvant coenzyme Q₁₀ (60 to 200 mg/day); 8 met criteria for meta-analysis. Seven of eight studies demonstrated significant improvement in measures of heart function, including ejection fraction, stroke volume, cardiac output, cardiac index, and end diastolic volume index (6).
  • Two more recent studies, however, not included in the previously mentioned meta-analysis, found no benefit for coenzyme Q₁₀. A double-blind crossover trial in which 30 patients (27 completed) with ischemic or idiopathic dilated cardiomyopathy and chronic left ventricular dysfunction (ejection fraction 26% ± 6%) were treated with placebo or coenzyme Q₁₀ (33 mg t.i.d.) for 3 months, coenzyme Q₁₀ did not significantly improve resting left ventricular ejection fraction, cardiac volumes, or quality of life indices (7).
  • A randomized, double-blind, placebo-controlled trial of 55 patients (46 completed) with CHF (NYHA III and IV, with ejection fraction less than 40%) receiving standard therapy tested the adjunctive effect of coenzyme Q₁₀ (200 mg/day) against placebo for 6 months (8). There were no significant differences from baseline in either groups in ejection fraction and peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q₁₀ and placebo groups.
• Hypertension
  • A placebo-controlled study in 59 patients tested coenzyme Q₁₀ (60 mg b.i.d.) in 30 patients against a B-complex vitamin (placebo) in 29 hypertensive subjects for 8 weeks and found that, compared with placebo, coenzyme Q₁₀ significantly decreased systolic and diastolic blood pressure (9).
• Tissue reperfusion injury
  • In one study, 30 patients undergoing elective vascular surgery requiring aortic cross-clamping were randomized to coenzyme Q₁₀1 (50 mg/day) or placebo for 7 days preoperatively. Concentrations of malondialdehyde, conjugated dienes, creatine kinase, and lactate dehydrogenase (LDH) were significantly lower in treated group (10). An unblinded trial of coenzyme Q₁₀ (150 mg × 7 days) versus no treatment in 40 patients undergoing elective coronary artery bypass graft (CABG) found that concentrations of malondialdehyde, conjugated dienes, and creatine kinase were lower than in the treated group, which also had a significantly lower incidence of ventricular arrhythmias during recovery period. The number of patients requiring inotropic agents did not differ between groups but dosage of dopamine required to maintain stable hemodynamics was lower in the treated group (11).
  • Acute supplementation, however, does not appear to help postoperative outcomes. A randomized double-blind trial compared placebo to 600 mg coenzyme Q₁₀ (in divided doses 12 hours before surgery) in 20 patients with good left ventricular function undergoing elective coronary revascularization. There was no difference between the two groups in postoperative levels of myoglobin, creatine kinase MB fraction, or cardiac troponin T (12).
• Exercise capacity
  • A double-blind placebo-controlled trial of coenzyme Q₁₀ (120 mg/day × 6 weeks) on aerobic capacity and lipid peroxidation was conducted during exercise in 19 adults (8 of whom were older than 60). Coenzyme Q₁₀ did not affect time to exhaustion, maximal oxygen uptake, or serum malondialdehyde concentration in either younger or older adults (13). Two other controlled studies, each of 18 adults, showed a similar lack of effect of coenzyme Q₁₀ (14,15).
• Parkinson’s disease
  • An uncontrolled pilot study of three doses of coenzyme Q₁₀ (400, 600, or 800 mg daily in divided doses for 1 month) in 15 participants with Parkinson’s disease found no change in the mean score on the motor section of the Unified Parkinson’s Disease Rating Scale (16). Substantial increases in plasma coenzyme Q₁₀ levels were noted, and it was well tolerated. There were no changes in electrocardiogram (EKG), complete blood count (CBC), or blood chemistries; however, two of five patients who took 800 mg/day were noted to have three to five hyaline casts (one also had three to five granular casts) in urinalyses taken at the end of the study.
• Cancer
  • Lower levels of coenzyme Q₁₀ have been noted in cancer patients, and several small uncontrolled studies claim a beneficial effect in women with breast cancer. However, no appropriately controlled clinical trials were identified (17). A small study in 20 children with acute lymphoblastic leukemia and non-Hodgkin’s lymphoma who were being treated with anthracyclines added coenzyme Q₁₀ (100 mg b.i.d.) as an adjunctive treatment in 10 patients (18). Both groups experienced significantly decreased percentage left ventricular fractional shortening. Interventricular septum wall thickening decreased only in the unsupplemented group; two patients in the unsupplemented group had septum wall motion abnormalities compared with none in the supplemented group.
• Diabetes
  • A randomized double-blind placebo-controlled trial in 34 patients with Type 1 diabetes tested coenzyme Q₁₀ (100 mg) versus placebo for 3 months; there were no differences between groups in HbA_1c, mean daily glucose, mean insulin dose, hypoglycemic episodes, cholesterol, or well-being on a visual analog scale.
  • Diabetes mellitus with mitochondrial DNA (ntDNA) 3243 (A-G) is an X-linked mutation that results in progressive insulin secretory effect and neurosensory deafness; it is also called maternally inherited diabetes mellitus and deafness (MIDD) (19). In a study that compared 28 MIDD patients with 16 controls, coenzyme Q₁₀ (150 mg/day × 3 years) prevented progressive hearing loss and improved blood lactate after exercise; it had no effect, however, on the diabetic complications or other clinical symptoms. Coenzyme Q₁₀ had no effect on the insulin secretory capacity in participants with the mutation who had either impaired or normal glucose tolerance and who were studied in parallel (19).
• Periodontal disease
  • A beneficial effect of coenzyme Q₁₀ on periodontal disease has been claimed. According to a review and critique of the dental literature, both controlled studies were methodologically flawed (20). According to this reviewer, a study of 18 patients (21) provided only vague assessments of clinical improvement rather than reproducible measurements. A larger double-blind study of 56 patients compared placebo with coenzyme Q₁₀ (60 mg × 12 weeks); no difference was seen in gingival redness, bleeding, or pus discharge, but a significant difference in tooth mobility was noted at 4 and 12 weeks (22). Although probing depth scores improved in both groups at 12 weeks, apparently there was not a significant difference between the two groups.
• Low density lipoprotein (LDL) oxidation
  • A double-blind placebo-controlled crossover trial in 19 men with CHD and hypercholesterolemia tested lovastatin (60 mg/day) with or with coenzyme Q₁₀ (180 mg per day) for 6 weeks each (23). Although blood LDL ubiquinol concentrations increased, the lag time in copper-mediated oxidation increased only by 5%. This was statistically significant but probably not clinically significant.
• Lipid peroxidation
  • In an uncontrolled study, malonyldialdehyde and 4-hydroxynonenal concentrations decreased significantly in paint and lacquer workers (who are exposed to organic solvents that can cause lipid peroxidation) after 4 weeks of treatment with coenzyme Q₁₀ (24).
• Oxidative DNA damage
  • Coenzyme Q₁₀ in oil (n = 20) or as granulate (n = 20), each in a dose of 30 mg t.i.d., had no effect on oxidative DNA damage (assessed by urinary excretion of 8-oxo-7,8-dihydro-2’-deoxyguanosine, a repair product of oxidative DNA damage) in smokers (25).

[Outline]

• CClinical Trials
  • Myocardial infarction
  • Angina
  • CHF
  • Hypertension
  • Tissue reperfusion injury
  • Exercise capacity
  • Parkinson’s disease
  • Cancer
  • Diabetes
  • Periodontal disease
  • Low density lipoprotein (LDL) oxidation
  • Lipid peroxidation
  • Oxidative DNA damage

[AD ] Letter Key

Adverse Reactions

• Coenzyme Q₁₀ is very safe. Adverse events have been limited to occasional reports of gastrointestinal upset.
• A 35-year-old woman with mitochondrial encephalopathy developed urticaria after treatment with coenzyme Q₁₀ and bromazepam; skin tests for both were negative, but an oral provocation test with ubiquinone (not bromazepam) was positive (29). As coenzyme Q₁₀ was considered a necessary treatment for this patient, rush desensitization was done and effectively desensitized the patient.

Drug Interactions

• Warfarin
  • A 72-year-old woman on warfarin developed less responsiveness to the drug after starting to take coenzyme Q₁₀ regularly. After discontinuing coenzyme Q₁₀, warfarin responsiveness returned (30).

[Outline]

• AAdverse Reactions
• DDrug Interactions
  • Warfarin

[FL ] Letter Key

Factors Decreasing Availability/Absorption

• Statins: In 17 men treated with simvastatin (20 to 40 mg/day for a mean of 4.7 years), discontinuing simvastatin for 4 weeks increased coenzyme Q₁₀ levels 32%; resumption of treatment caused coenzyme Q₁₀ levels to decrease 25% (26).
• Advanced cardiac failure is associated with lower levels of tissue coenzyme Q₁₀ (27). Plasma coenzyme Q₁₀ levels are decreased in subjects with hyperlipidemia and in smokers (28). Cancer, mitochondrial disease, and mevalonate kinase deficiency are also associated with low coenzyme Q₁₀ levels.
• Phenylketonuria (PKU) is associated with reduced serum coenzyme Q₁₀, most likely because dietary restrictions reduce intake; also, tyrosine availability may be diminished in PKU (1).

Laboratory Tests

• Coenzyme Q₁₀ serum levels can be measured by high-pressure liquid chromatography (HPLC); however, appropriate reference levels are not well established.
• Studies in normal participants have found normal values to range from 0.3 to 3.84 µg/mL, with most readings clustering between 0.6 to 1.0 µg/mL.

[Outline]

• FFactors Decreasing Availability/Absorption
• LLaboratory Tests

Usual doses are 90 to 390 mg/day.

1. Artuch R, Vilaseca M-A, Moreno J et al. Decreased serum ubiquinone-10 concentrations in phenylketonuria. Am J Clin Nutr 1999;70:892–895.
2. Tran MT, Mitchell TM, Kennedy DT et al. Role of coenzyme A10 in chronic heart failure, angina, and hypertension. Pharmacotherapy 2001;21:797–806.
3. Singh RB, Wander GS, Rastogi A et al. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther 1998;12:347–353.
4. Kamikawa T, Kobayashi A, Yamashita T et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol 1985;56:247–251.
5. Mazzola C, Giffanti EE, Vaccarella A et al. Non-invasive assessment of coenzyme Q10 in patients with chronic stable effort angina and moderate heart failure. Curr Ther Res 1987;41:923–932.
6. Soja AM, Mortensen SA. Behandling af kronisk hjerteinsufficiens med coenzyme Q10 belyst ved metaanalyser af klinisk kontrollerede undersogelser. Ugeskr Laeger 1997;159:7302–7308.
7. Watson PS, Scalia GM, Galbraith A et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol 1999;33:1549–1552.
8. Khatta M, Alexander BS, Krichten CM et al. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med 2000;132:636–640.
9. Singh RB, Niaz M, Rastogi SS et al. Effect of hydrosoluble coenzyme Q10 on blood pressure and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203–208.
10. Chello M, Mastroroberto P, Romano R et al. Protection by coenzyme Q10 of tissue reperfusion injury during abdominal aortic cross-clamping. J Cardiovasc Surg 1996;37:229–235.
11. Chello M, Mastroroberto P, Romano R et al. Protection by coenzyme Q10 from myocardial reperfusion injury during coronary artery bypass grafting. Ann Thorac Surg 1994;58:1427–1432.
12. Taggart DP, Jenkins M, Hooper J et al. Effects of short-term supplementation with coenzyme Q10 on myocardial protection during cardiac operations. Ann Thorac Surg 1996;61:829–833.
13. Laaksonen R, Fogelholm M, Himberg J-J et al. Ubiquinone supplementation and exercise capacity in trained young and older men. Eur J Appl Physiol 1995;72:95–100.
14. Malm C, Svensson M, Ekblom B et al. Effects of ubiquinone-10 supplementation and high intensity training on physical performance in humans. Acta Physiol Scand 1997;161:379–384.
15. Weston SB, Zhou S, Weatherby RP et al. Does exogenous coenzyme Q10 affect aerobic capacity in endurance athletes? Int J Sport Nutr 1997;7:197–206.
16. Shults CW, Beal MF, Fontaine D et al. Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in Parkinson patients. Neurology 1998;50:793–795.
17. Physician Data Query (PDQ)-National Cancer Institute’s comprehensive cancer database. Information summary on coenzyme Q10. http:nci.nih.gov/cancer_information.
18. Iarussi D, Auricchio U, Agretto A et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. Mol Aspects Med 1994;15(Suppl):207–212.
19. Suzuki S, Hinokio Y, Ohtomo M et al. The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A-G) mutation. Diabetologia 1998;41:584–588.
20. Watts TLP. Coenzyme Q-10 and periodontal treatment: is there any beneficial effect? Br Dent J 1995;178:209–213.
21. Wilkinson EG, Arnold RM, Folkers K. Bioenergetics in clinical medicine. VI. Adjunctive treatment of periodontal disease with coenzyme Q10. Res Commun Chem Pathol Pharmacol 1976;14:715–719.
22. Iwamoto Y, Watanabe T, Okamoto H et al. Clinical effect of coenzyme Q10 on periodontal disease. In: Folkers K, Yamamura Y, eds. Biomedical and clinical aspects of coenzyme Q, Vol 3. New York: Elsevier Science, 1981:109–119.
23. Palomaki A, Malminiemi K, Solakivi T et al. Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo. J Lipid Res 1998;39:1430–1437.
24. Dlugosz A, Sawicka E. The chemoprotective effect of coenzyme Q on lipids on the paint and lacquer industry workers. Int J Occup Med Environ Health 1998;11:153–163.
25. Prieme H, Loft S, Nyyssonen K et al. No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7, 8-dihydro-2’-deoxyguanosine excretion in smokers. Am J Clin Nutr 1997;65:503–507.
26. Laaksonen R, Ojala J-P, Tikkanen MJ et al. Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharm 1994;46:313–317.
27. Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci U S A 1985;82:901–904.
28. Kontush A, Reich A, Baum K et al. Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia. Atherosclerosis 1997;129:119–126.
29. Schiavino D, Nucero E, Zoppi A et al. Rush desensitization with ubiquinone. Allergy 1997;52:783–784.
30. Landbo C, Almdal TP. Interaction between warfarin and coenzyme Q10. (In Danish). Ugeskrift for Laeger 1998;160:3226–3227.