Coenzyme Q10 (Ubidecarenone) Injection

Coenzyme Q10 (CoQ10) is found in all cells across all domains of life.^[1][2] It is a redox-active lipid biosynthesized in the mitochondria by the conjugation of a benzoquinone ring with a 10-unit isoprenoid chain.^[2][3][4] It is essential in the production of cellular energy in the form of adenosine triphosphate (ATP).^[5][6] It is a significant antioxidant and therefore prevents free radical generation and modifications of DNA, proteins, and lipids.^[5][6] It can also help in the regeneration of other antioxidants, such as vitamin E.^[7] CoQ10 is also naturally found in some foods, such as meat, nuts, fruits, and vegetables.^[8] However, the average daily dietary intake of CoQ10 is very low, about three to six milligrams, and earlier studies show that dietary intake of CoQ10 does not appear to increase CoQ10 tissue levels above normal.^[8][9]

Subnormal serum levels of Coenzyme Q10 have been observed in patients with advanced heart failure; type 2 diabetes (insulin resistance and high blood glucose levels); neurodegenerative disease, including Parkinson’s disease; metabolic syndrome; hypertension; preeclampsia; certain types of cancer, like breast cancer and melanoma, and more.^{[10][11][12][13][14][15][16][17][18][19]} This data has led researchers to investigate exogenous CoQ10 supplementation as a potential treatment for these conditions. However, research so far is inconclusive or contradictory as to whether exogenous CoQ10 supplementation can help treat or manage symptoms of these conditions.^{[20][21][22][23][24][25][26]}

Coenzyme Q10 is one of the most commonly used dietary supplements.^[27][28] CoQ10 is not FDA-approved for the treatment of any medical condition and there is little data on the safety and efficacy of long-term use of coenzyme Q10.^[29] However, the FDA granted orphan status to an oral coenzymeQ10 drug, called UbiQGel, for its use in clinical trials on patients diagnosed with mitochondrial cytopathies (MC).^[30][31]

CoQ10 deficiency is a known cause of mitochondrial disease. The evidence to date shows promise that CoenzymeQ10 may be a potential treatment of mitochondrial disorders. However, further research is needed to determine the appropriate dosage.^[32]

CoQ10 injections should only be taken under the supervision of a physician.

Coenzyme Q10 is an essential cofactor of intra-complex electron transportation in adenosine triphosphate (ATP) synthesis, also referred to as oxidative phosphorylation.^[33][6] It is vital to the health of all cells, and therefore all tissues and organs, in the body. Cells constantly use ATP as an energy source to conduct biological reactions.

CoQ10 is an antioxidant and therefore prevents free radical generation and modifications of DNA, proteins, and lipids.^[5]

CoQ10 is an endogenous inhibitor of platelets.^[34] Exogenous CoQ10 is an upregulator of the cAMP/PKA pathway, an activator of the A2A adenosine receptor, an inhibitor of phosphodiesterase 3A phosphorylation, and a significant inhibitor of vitronectin-receptor (CD51/CD61) expression.^[34][35][36]

CoQ10 is a ligand and an agonist of the PPARα/γ receptor.^[37] It also functions as an antioxidant in the mitochondria by regenerating alpha-tocopherol from its phenoxyl radical.^[38][39]

CoQ10 is an inotrope.^[40][41][42]

Patients with a known allergy to Coenzyme Q10 should not take this product.

One study found that oral doses of CoQ10 of 100 mg or higher can cause mild insomnia in some individuals.^[26] Some patients may benefit from taking CoQ10 in the morning.

Coenzyme Q10 is eliminated from the body via the biliary tract. It may increase the risk of CoQ10 accumulation in patients with biliary obstruction or hepatic impairment.^[54][29][25]

The literature is contradictory as to whether coenzyme Q10 has antihypertensive properties.^[23] In some clinical trials, coenzyme Q10 lowered both systolic and diastolic blood pressure.^[59][29] Patients with low blood pressure should use precaution when taking CoQ10.

As an antioxidant, CoQ10 is contraindicated in patients undergoing chemotherapy and/or radiation therapy. CoQ10, and other antioxidants, may increase the risk of recurrence in cancer patients undergoing treatment.^[26][60][61]

HMG-CoA reductase inhibitors, also known as statins, decrease the amount of Coq10 in the body by inhibiting the production of the CoQ10 precursor mevalonate.^[66][67]

Coenzyme Q10 is similar in chemical structure to vitamin K.^[5] Research is contradictory as to whether vitamin K, and therefore coenzyme Q10, counteract the anticoagulant effects of warfarin.^{[68][69][70][71][72][73][74]} Coenzyme Q10 may increase the rate of metabolism of warfarin by selective interaction with cytochrome p450 enzymes, reducing International Normalized Ratio (INR).^{[10][36][72][75][76]} One study observed an increased risk of bleeding in patients with concomitant administration of CoQ10 and warfarin.^[77]

Early research shows a link between CoQ10 intake and reduced platelet size.^[36] A more recent study also shows that CoQ10 inhibits platelet aggregation.^[34] CoQ10 may increase the risk of bleeding in patients taking platelet agglutination inhibitor drugs, such as acetylsalicylic acid (ASAs), like aspirin; clopidogrel (Plavix); prasugrel (Effient); and ticagrelor (Brilinta).^{[29][36][78][79]}

The evidence is contradictory as to whether CoQ10 improves β-cell function, enhances insulin sensitivity, and decreases blood glucose levels in patients with type 2 diabetes.^[21][80] CoQ10 may augment the effects of other blood glucose-lowering agents, such as biguanides and sulfonylureas, and metformins in people with diabetes, and increase the risk of hypoglycemia.^[81]

One study found that CoQ10 decreases blood glucose in individuals diagnosed with type 2 diabetes.^[82] CoQ10 may augment the effect of insulin and other blood-glucose-lowering agents, such as sulfonylureas and metformin.^[83]

The literature is contradictory as to whether coenzyme Q10 has antihypertensive properties.^[23] In some clinical trials, coenzyme Q10 lowered both systolic and diastolic blood pressure.^[59][29] CoQ10 may augment the effects of antihypertensive medication and is therefore contraindicated in patients taking antihypertensive medication and patients with low blood pressure.

As an antioxidant, CoQ10 is contraindicated in patients undergoing chemotherapy and/or radiation therapy. CoQ10, and other antioxidants, may increase the risk of recurrence in cancer patients undergoing treatment.^[26][60][61]

Limited research on the safety and efficacy of CoQ10 signifies that not all side effects are known. So far, major side effects of oral coenzyme Q10 supplementation have not been reported. There is no data on the side effects of intramuscular or intravenous injection of CoQ10.

Recorded side effects of oral CoQ10 supplementation in adults include rash, epigastric pain, nausea, headache, fatigue, heartburn, increased involuntary movements, anorexia, vomiting, diarrhea, pain in the upper abdomen, dizziness, irritability, sensitivity to light, and elevated liver enzymes.^{[25][29][84][85]}

In children diagnosed with a mitochondrial disorder, oral CoQ10 supplementation has caused mild side effects, including nausea, diarrhea, and heartburn; less commonly reported are headache, dizziness, irritability, and agitation.^[81]

There is no data on the short-term or long-term side effects associated with intravenous and intramuscular injection of CoQ10 in humans. There is little data on the long-term effects of oral CoQ10 supplementation. A review of clinical studies reveals that no serious or frequent side effects were observed in adults with oral administration of CoQ10 when taking 200 mg/day for up to 12 months or 100 mg/day for up to 6 years. However, the review also notes that these studies were not designed to examine side effects and therefore suggests that monitoring side effects was not a priority during these studies.^[86] One study saw impairments in cognitive and sensory function in mice after prolonged administration of high levels of CoQ10.^[87]

The literature is contradictory as to whether coenzyme Q10 lowers blood pressure.^[23][59] In some clinical trials, coenzyme Q10 lowered both systolic and diastolic blood pressure levels.^[29][59] Coenzyme Q10 supplementation is contraindicated for patients who are taking anti‐hypertensive medication. Patients with low blood pressure should use precaution when taking CoQ10.

The safety and efficacy of CoQ-10 injections in pregnancy have not been established. As such, it is difficult to determine a drug-associated risk of adverse developmental outcomes. Women who are pregnant should avoid using this product.

Initial studies show that oral exogenous synthetic CoQ10 may reduce the risk of developing preeclampsia during pregnancy, when administered daily to pregnant women with an increased risk for preeclampsia, starting at 20 weeks gestation.^[65]

The safety and efficacy of CoQ-10 injections in breastfeeding have not been established. As such, it is difficult to determine a drug-associated risk of adverse developmental outcomes. Women who are pregnant or breastfeeding should avoid using this product.

CoQ-10 is a natural component found in human breast milk.^[62][63] Currently, there is no data available regarding the effects of exogenous synthetic CoQ-10 on CoQ-10 concentrations in breast milk.^[64] Additionally, there is no data on how exogenous synthetic CoQ-10 affects milk production or its effects on the breastfed infant.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

1. Marappan G. (April 22nd 2020). Coenzyme Q10: Regulators of Mitochondria and beyond. Apolipoproteins, Triglycerides and Cholesterol, Viduranga Y. Waisundara and Miljana Z. Jovandaric. IntechOpen. Accessed online at: https://www.intechopen.com/chapters/71878
2. Stefely JA, Pagliarini DJ. Biochemistry of Mitochondrial Coenzyme Q Biosynthesis. Trends Biochem Sci. 2017; 42(10):824–843.
3. Shukla S and Dubey KK. CoQ10 a super-vitamin: review on application and biosynthesis. 3 Biotech. 2018 May; 8(5): 249.
4. Acosta MJ, Fonseca LV, Desbats MA, Cerqua C, Zordan R, Trevisson E, Salviati L. Coenzyme Q biosynthesis in health and disease. Biochim Biophys Acta. 2016;1857(8):1079-1085.
5. Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011; 3(3):466-467.
6. Freye ECK, Strobel HP. Coenzyme Q10 Supplements which Increase ATP Synthesis within Mitochondria and Protect Against Toxic Sodium Azide. Acta Scientific Nutritional Health. 2018;2(7):2-9.
7. Genova ML and Lenaz G. New developments on the functions of coenzyme Q in mitochondria. Biofactors. 2011;37(5):330-54.
8. Pravst I, Zmitek K, Zmitek J. Coenzyme Q10 contents in foods and fortification strategies. Crit Rev Food Sci Nutr. 2010;50(4):269-80.
9. Weber C, Bysted A, Hølmer G. Intestinal absorption of coenzyme Q10 administered in a meal or as capsules to healthy subjects. Nutrition Research. 1997;17(6):941-945.
10. Sharma A, Fonarow GC, Butler J, Ezekowitz JA, Felker GM. Coenzyme Q10 and Heart Failure: A State-of-the-Art Review. Circulation: Heart Failure. 2016;9.
11. Garrido-Maraver J, Cordero MD, Oropesa-Ávila M, et al. Coenzyme Q10 Therapy. Mol Syndromol. 2014;(3-4):187-197.
12. Miyake Y, Shouzu A, Nishikawa M, Yonemoto T, Shimizu H, Omoto S, Hayakawa T, Inada M. Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung. 1999;49(4):324-329.
13. Mischley LK, Allen J, Bradley R. Coenzyme Q10 Deficiency in Patients with Parkinson’s Disease. J Neurol Sci. 2012;318(1-2):72–75.
14. Casagrande D, Waib PH, Jordão Júniora AA. Mechanisms of action and effects of the administration of Coenzyme Q10 on metabolic syndrome. 2018;13:26-32.
15. Yamagami T, Shibata N. Bioenergetics in clinical medicine: studies on coenzyme Q10 and essential hypertension. Res Comm Chem Path Pharmacol 1975;11(2):273–288.
16. Teran E, Racines-Orbe M, Vivero S, Escudero CA. Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels. Free Radical Biology and Medicine. 2003;35(11):1453-1456.
17. Cooney RV, Dai Q, Gao YT, et al. Low plasma coenzyme Q10 levels and breast cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev. 2011; 20(6):1124-1130.
18. Lesser GJ and Vitolins MZ. Coenzyme Q10. Cancer Network. 2011;25(10). Accessed online at: https://www.cancernetwork.com/view/coenzyme-q10.
19. Folkers K, Ostemborg A, Nylander M, Morita M, Mellstedt H. Activities of vitamin Q10 in animal models and serious deficiency in patients with cancer. Biochem Biophys Res Commun. 1997; 234:296299.
20. Lorenzo AD, Iannuzzo G, Parlato A. Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement. J Clin Med. 2020;9(5):1266.
21. Shen Q and Pierce JD. Supplementation of Coenzyme Q10 among Patients with Type 2 Diabetes Mellitus. Healthcare (Basel). 2015;3(2):296-309.
22. Golbidi S, Ebadi SA, Laher I. Antioxidants in the treatment of diabetes. Curr Diabetes Rev. 2011;7(2):106-25.
23. Ho MJ, Li ECK, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst Rev. 2016;2016(3):CD007435.
24. Xu X, Pan JR, Zhang YZ, CoQ10 alleviate preeclampsia symptoms by enhancing the function of mitochondria in the placenta of pregnant rats with preeclampsia. Hypertens Pregnancy. 2019;38(4):21-222.
25. Coenzyme Q10 (PDQ®) Patient Version. PDQ Cancer Information Summaries [Internet]. National Cancer Institute. September 16, 2020.
26. Coenzyme Q10 (PDQ®) Health Professional Version. PDQ Cancer Information Summaries [Internet]. National Cancer Institute. June 04, 2020.
27. Raizner AE. Coenzyme Q10. Methodist Debakey Cardiovasc J. 2019;15(3):185-191.
28. Barnes PM and Bloom B. Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. National Health Statistics Reports Number 12. Centers for Disease Control and Prevention. December 10, 2008. Accessed online at: https://www.cdc.gov/nchs/data/nhsr/nhsr012.pdf.
29. Wyman M, Leonard M, Morledge T. Coenzyme Q10: A therapy for hypertension and statin-induced myalgia? Cleveland Clinic Journal of Medicine. 2010;77(7):435-442.
30. FDA grants Orphan Drug designation to nutritional supplement. Pharmaceutical Online. Published. July 25, 2000. Accessed November 08, 2020 at: https://www.pharmaceuticalonline.com/doc/fda-grants-orphan-drug-designation-to-nutriti-0001.
31. Hargreaves IP. Coenzyme Q10 as a therapy for mitochondrial disease. The International Journal of Biochemistry & Cell Biology. 2014;49:105-111.
32. Neergheen V, Chalasani A, Wainwright L, et al. Coenzyme Q10 in the Treatment of Mitochondrial Disease. J Inborn Errors Metab Screen. 2017;5.
33. Lenaz G, Fato R. The role of Coenzyme Q in mitochondrial electron transport. Mitochondrion. 2007;7Suppl:S8-33.
34. Yang Y, Ya F, Shi Y, Zuo X, et al. Coenzyme Q10 attenuates platelet function through targeting cAMP/PKA pathway. Conference: the XXVII Congress of the International Society on Thrombosis and haemostasis at Melbourne, Australia. 2019.
35. Ya F, Xu Xr, Shi Y, Gallant RC, et al. Coenzyme Q10 Upregulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth. Mol Nutr Food Res. 2019;63(23):e1900662.
36. Serebruany VL, Ordonez JV, Herzog WR, Rohde M, Mortensen SA, Folkers K, Gurbel PA. Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression. J Cardiovasc Pharmacol. 1997;29(1):16-22.
37. Tiefenbach J, Magomedova L, Liu J, Reunov AA, et al. Idebenone and coenzyme Q10 are novel PPARα/γ ligands, with potential for treatment of fatty liver diseases. Dis Model Mech. 2018;11(9).
38. Evolution of Metabolic Pathways. Ubiquinone CMT. Ragai K. Ibrahim, Ingrid Muzac, in Recent Advances in Phytochemistry, 2000.
39. Lass A, Forster MJ, Sohal RS. Effects of coenzyme Q10 and alpha-tocopherol administration on their tissue levels in the mouse: elevation of mitochondrial alpha-tocopherol by coenzyme Q10. Free Radic Biol Med. 1999;26(11-12):1375-82.
40. Zozina VI, Covantev S, Goroshko OA, Krasnykh LM, Kukes VG. Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem. Curr Cardiol Rev. 2018;14(3):164-174.
41. Vargiu R, Littarru GP, Faa G, Mancinelli R. Positive inotropic effect of coenzyme Q10, omega-3 fatty acids and propionyl-L-carnitine on papillary muscle force-frequency responses of BIO TO-2 cardiomyopathic Syrian hamsters. Biofactors. 2008;32(1-4):135-144.
42. de Frutos F, Gea A, Hernandez-Estefania R, Rabago G. Prophylactic treatment with coenzyme Q10 in patients undergoing cardiac surgery: could an antioxidant reduce complications? A systematic review and meta-analysis. Interactive CardioVascular and Thoracic Surgery. 2015;20(2):254–259.
43. Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol 1990;30:596–608.
44. Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong JY , Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal of Human Hypertension. 2007;21:297–306.
45. D’Andrea GM. Use of Antioxidants During Chemotherapy and Radiotherapy Should Be Avoided. CA Cancer J Clin. 2005;55(5).
46. Ambrosone CB, Zirpoli GR, Hutson AD, McCann WE, McCann SE, Barlow WE. Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol. 2020:38(8);804-814.
47. Teran E, Hernandez I, Nieto B, Tavara R, Ocampo JE, Calle A. Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Int J Gynaecol Obstet. 2009;105(1):43-45.
48. Tang PH, Miles MV, Steele P et al. Determination of coenzyme Q(10) in human breast milk by high-performance liquid chromatography. Biomed Chromatogr. 2006;20:1336-43.
49. Niklowitz P, Menke T, Giffei J, Andler W. Coenzyme Q10 in maternal plasma and milk throughout early lactation. Biofactors. 2005;25(1-4):67-72.
50. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Coenzyme Q10. [Updated 2018 Dec 3].
51. Sood B and Keenaghan M. Coenzyme Q10. StatPearls [Internet]. April 16, 2020.
52. Nawarskas, JJ. HMG-CoA reductase inhibitors and coenzyme Q10. Cardiol Rev. 2005;13(2):76-79.
53. Lurie Y, Loebstein R, Kurnik D, Almog S, Hillel Halkin H. Warfarin and vitamin K intake in the era of pharmacogenetics. Br J Clin Pharmacol. 2010;70(2):164–170.
54. Oren B and Shvartzman P. Unsuspected source of vitamin K in patients treated with anticoagulants: a case report. Fam Pract. 1989;6(2):151-152.
55. Kurnik D, Lubetsky A, Loebstein R, Almog S, Halkin H. Multivitamin supplements may affect warfarin anticoagulation in susceptible patients. Ann Pharmacother. 2003;37(11):1603-16066.
56. Violi F, Lip GYH, Pignatelli P, Pastori, D. Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True? Medicine (Baltimore). 2016;95(10):e2895.
57. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7; quiz 1228-1230.
58. Crader MF, Johns T, Arnold JK. Warfarin Drug Interactions. StatPearls [Internet]. May 05, 2020.
59. Combs AB, Porter TH, Folkers K. Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10- enzyme systems. Res Commun Chem Pathol Pharmacol. 1976;13(1):109-14.
60. Zhou Q, Zhou S, Chan E. Effect of coenzyme Q10 on warfarin hydroxylation in rat and human liver microsomes. Curr Drug Metab. 2005 Apr;6(2):67-81.
61. Landbo C and Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger. 1998. 25;160(22):3226-7.
62. Shalansky S, Lynd L, Richardson K, Ingaszewski A, Kerr C. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27(9):1237-47.
63. Khayata M, Gabra JN, Nasser MF, Litman GI, Bhakta S, Rainaa R. Comparison of Clopidogrel With Prasugrel and Ticagrelor in Patients With Acute Coronary Syndrome: Clinical Outcomes From the National Cardiovascular Database ACTION Registry. Cardiol Res. 2017;8(3):105–110.
64. Michelson A. Antiplatelet therapies for the treatment of cardiovascular disease. Nature Reviews Drug Discovery. 2010;9(2):154-69.
65. McCarty MF. Can correction of sub-optimal coenzyme Q status improve b-cell function in type II diabetics? Medical Hypotheses. 1999;52(5):397-400.
66. Mitochondrial disorders in children: Co-enzyme Q10 (ES11). National Institute for Health and Care Excellence. March 28, 2017.
67. Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism: clinical and experimental. 2010:59; 285-292.
68. Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR. Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia (A nested case-control analysis). Diabetes Care. 2008;31(11):2086-2091.
69. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 15 (Suppl): s287-94, 1994.
70. Feigin A, Kieburtz K, Como P, Hickey C, Claude K, Abwender D, Zimmerman C, Steinberg K, Shoulson I. Assessment of coenzyme Q10 tolerability in Huntington’s disease. Mov Disord. 1996;11(3):321-323.
71. Overvad K, Diamant B, Holm L, Hùlmer G, Mortensen SA, and Stender S. Coenzyme Q10 in health and disease. Eur J Clinical Nutr. 199;53:764-770.
72. Sumien N, Heinrich KR, Shetty RA, Sohal RS. Prolonged Intake of Coenzyme Q(10) Impairs Cognitive Functions in Mice. J Nutrition. 139(10):1926-32.