Q10

The co-enzyme Q10 (Q10, synonyms trans-2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzochinon, CoQ10 and ubichinon-10) was discovered by isolating Q10 from the mitochondria of a beef heart in 1957. It is a lipophilic, vitamin-look-alike substance, structurally linked to vitamin K and tocopherol. While having some potentially beneficial effects on a cellular level, clinically relevant effects in humans so far have not been demonstrated. In this section we will discuss the properties of the antioxidant Q10 and both the rationale and evidence for clinical use in the management of diabetes and its complications.

Background

Q10 is an endogenous enzyme cofactor present in the mitochondria of each cell of all aerobic organisms. It is an important component of the mitochondrial respiratory chain Figure 1. Ubiquinone to Ubiquinol conversion
Figure 1. Ubiquinone to Ubiquinol conversion
and exists in a reduced form (ubiquinol) and an oxidized form (ubiquinone)( see figure 1). It acts like a cofactor in the production of adenosinetrifosfaat (ATP), the most important energy source of our body, by oxidative phosphorylation. Q10 also plays a role in the antioxidant defense system by recycling and regenerating other antioxidants such as tocopherol and ascorbate. Measurements of plasma Q10 have been regarded as a useful measurement of the overall Q10 status[1].

Sources, requirements and biological availability

The intracellular production of Q10 requires the aminoacid tyrosine and its production is dependent on the presence of a few crucial vitamins e.g. vitamin B6, B12 and folic acid. Another source of Q10 is the daily food which contains about 3-5 milligrams Q10; especially organ meat, fish and poultry are exogenous sources enriched in Q10. Normally, there is no need for supplementary intake, because endogenous synthesis and diet are likely to provide sufficient Q10 levels[2]. Increased requirements, because of cellular deficiencies, may occur in disease states that uncouple oxidative phosphorylation or increase cellular energy demand, such as patients with diabetes mellitus and heart failure[2][3].
Q10 supplementation can increase the Q10 level 10 to 30 times. There is no recommended daily dose and it is well tolerated and safe[4]. The lipophilic character of Q10 influences the biological availability. The oil-based Q10 supplements have a higher biological availability compared to the powder-based preparations.

Rationale for Q10’s effectiveness in the treatment of diabetes

The hyperglycemic state in patients with diabetes mellitus is associated with higher levels of oxidative stress. This is supposed to play a central role in the pathogenesis of endothelial dysfunction by decreasing the availability of nitric oxide as well as by activating pro-inflammatory pathways. The potent antioxidant Q10 may decrease oxidative stress by quenching reactive oxygen species (ROS) and by “recoupling” mitochondrial oxidative phosphorylation. In this way Q10 reduces the production of the superoxide anion radicals[5]. Exogenous supplementation of Q10 may also act synergistically with anti-atherogenic agents, such as fibrates and statins, to improve endotheliopathy in diabetes[6][7][8].

Animal and clinical studies

It has been shown from animal diabetes models as well as from human diabetes studies that oral Q10 supplementation can increase mitochondrial and tissue Q10 concentrations, but it does not improve glycemic control or diminish insulin requirements [4][9][10][11][12]. An experimental animal model of type 2 diabetes mellitus (T2DM) showed reduced levels of oxidative stress, an ameliorated left ventricular diastolic dysfunction and remodelling of the diabetic heart when treated with Q10[13]. In a type 1 animal model exogenous Q10 increased myocardial Q10 and improved myocardial relaxation[14]. In other experimental animal models of T2DM there were significant beneficial effects of chronic exogenous Q10 therapy on albuminuria, mitochondrial function, glomerular hyperfiltration, renal ATP production, and tubulointerstitial fibrosis[15][16]. However, in one of these models, the ‘diabetic’ mice had no changes in total or mitochondrial concentrations of renal Q10, despite evidence of ROS production and reduced antioxidant activity. This suggests that boosting antioxidant defenses via Q10 was probably not the mechanism of action responsible for the renal benefits of Q10 seen in these mice[15]. Recently, Q10 was investigated in a type 2 diabetes mouse model, which demonstrated favourable effects of Q10 on preventing the development of peripheral neuropathy and the protection against neuronal loss[17]. A beneficial effect of Q10 supplementation on endothelial function has been found in dyslipidaemic patients with T2DM[18]. However, other human type 2 diabetes studies, showing increased plasma Q10 concentrations, demonstrated no significant positive impact on vascular reactivity and microcirculatory endothelial activation[6][10].

Summary

In conclusion, despite an increase in tissue levels of Q10, there is no positive effect of supplementation of the antioxidant Q10 on glycemic control and there is not any established benefit in the management of diabetic complications. Therefore, routine Q10 supplementation is not generally recommended in human diabetes.

References

  1. ^ Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40:445 – 453.

  2. ^ Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S. Coenzyme Q10 in health and disease. Eur J Clin Nutr. 1999;53:764 – 770.

  3. ^ Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990;30:596 – 608.

  4. ^ Erikson JG, Forsén TJ, Mortensen SA, Rohde M. The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors, 1999;9:315 – 318.

  5. ^ Chew GT, Watts GF. Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the “recoupling hypothesis”. QJM 2004;97: 537 – 548]

  6. ^ Playford DA, Watts GF, Croft KD, Burke V. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis 2003;168:169 - 79

  7. ^ Chew GT, Watts GF, Davis TM, Stuckey BG, Beilin LJ, Thompson PL, Burke V, Currie PJ. Hemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction. Diabetes Care. 2008;31:1502 – 1509

  8. ^ Hamilton SJ, Chew GT, Watts GF. Coenzyme Q10 improves endothelial dysfunction in statine-treated type 2 diabetic patients. Diabetes Care. 2009;32:810 – 812.

  9. ^ Sohal RS, Kamzalov S, Sumien N, Ferguson M, Rebrin I, Heinrich KR, Forster MJ. Effect of coenzyme Q10 intake on endogenous coenzye Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice. Free Radic Biol Med 2006;40:480 – 7.

  10. ^ Lim SC, Lekshiminarayanan R, Goh SK, Ong YY, Subramaniam T, Sum CF, Ong CN, Lee BL. The effect of coenzyme Q10 on microcirculatory endothelial function of subjects with type 2 diabetes mellitus. Atherosclerosis. 2008;196:966 – 969.

  11. ^ Henriksen JE, Andersen CB, Hother-Nielsen O, Vaag A, Mortensen SA, Beck-Nielsen H. Impact of ubiquinone (coenzyme Q10) treatment on glycaemic control, insulin requirement and well-being in patients with type 1 diabetes mellitus. Diabet Med. 1999;16:312 – 318.

  12. ^ Andersen CB, Henriksen JE, Hother-Nielsen O, Vaag, Mortensen SA, Beck-Nielsen H. The effects of coenzyme Q10 on blood glucose and insulin requirement in patients with insulin dependent diabetes mellitus. Mol Aspects Med. 1997;18 Suppl:S307 – 309.

  13. ^ Huynh K, Kiriazis H, Du XJ, Love JE, Jandeleit-Dahm KA, Forbes JM, McMullen JR, Ritchie RH. Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes. Diabetologia. 2012;55(5):1544 – 53.

  14. ^ Serizawa T, Oku J, Iizuka M, Ohya T, Ohtani Y, Sugiura S, Murakami T, Sugimoto T. Beneficial effects of coenzyme Q10 on impaired left ventricular performance in streptozotocin diabetic rats. Jpn Heart J. 1988;29:233 – 242.

  15. ^ Sourris KC, Harcourt BE, Tang PH, Morley AL, Huynh K, Penfold SA, Coughlan MT, Cooper ME, Nguyen TV, Ritchie RH, Forbes JM. Ubiquinone (coenzyme Q10) prevents renal mitochondrial dysfunction in an experimental model of type 2 diabetes. Free Radic Biol Med. 2012;52(3):716 – 723)

  16. ^ Persson MF, Franzén S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F. Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes. Diabetologia. 2012;55:1535 – 1543.

  17. ^ Shi TJ, Zhang MD, Zeberg H, Nilsson J, Grünler J, Liu SX, Xiang Q, Persson J, Fried KJ, Catrina SB, Watanabe M, Arhem P, Brismar K, Hökfelt TG. Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db-/db- mouse, a type 2 diabetes model. Proc Natl Acad Sci U.S.A. 2013;110:690 – 695.

  18. ^ Watts GF, Playford Da, Croft KD, Ward NC, Mori TA, Burke V. Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in type II diabetes mellitus. Diabetologia 2002;45:420 – 426.

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