THE HEALTH BENEFITS OF COENZYME Q10

THE HEALTH BENEFITS OF COENZYME Q10

Coenzyme Q10 (CoQ10) is an essential compound of the human body which is synthesized in the mitochondrial inner membrane. The molecule of CoQ10 has a highly lipophilic character and the base of its structure belongs to quinone chemical group. Because it has a “tail” of 10 isoprenoid units attached to its benzoquinone “head,” which determines its low polarity and allows its fast diffusion through mitochondrial membrane. It should be taken into consideration that CoQ10 exists in 2 forms: oxidized (ubiquinone) and reduced (ubiquinol). The most abundant form in humans and most mammals is ubiquinone. It has been found in plants and microorganisms too ^{[1, 2]}.

Ubiquinones can be produced by all animals, including humans. As a result, CoQ10 is not considered a vitamin can be found in human blood and all organ systems. Ubiquinone is found in the highest concentrations in the heart, kidneys, liver, and muscles. Additionally, it has been reported on the distribution and content of ubiquinones in a variety of foods, including meat, poultry, eggs, dietary fats, cereals, dairy products, fruits, and vegetables. The largest concentrations are seen in meats and dietary fats ^{[1, 2]}.

1. FUNCTIONS OF CoQ10 IN CARDIOVASCULAR DISEASES

Cardiovascular diseases are one of the leading causes of death worldwide. Oxidative stress is considered to be an essential player in the development of this group of diseases. In such a way, it’s possible that antioxidants can reduce the risk of cardiovascular disease. There are several theories about the role of CoQ10’s mechanism of action in cardiovascular disease ^[2].

Firstly, ubiquinone should be reduced to ubiquinol to completely show its antioxidative function. It is known, that Reactive Oxygen Species (ROS) can cause serious cellular damage by means of reacting with cell membranes, DNA and protein centers. Furthermore, the products of oxidative stress and cytokines can promote hypertrophy by stimulating the development of myocytes. Ubiquinol, a reduced form of CoQ10, inhibits the production of lipid peroxyl radicals at the initial of the process. That is the reason why CoQ10 is considered to be a very potent antioxidant against ROS and free radicals in biological membranes. Second, CoQ10 is essential for the heart’s energy requirements. For example, the process of cardiac contraction, which involves the release of Ca²⁺ from the sarcoplasmic reticulum and the following activation of the contractile proteins requires energy. There is a theory that myocardial failure may be induced by a reduction in energy synthesis in mitochondria. However, as previously stated, CoQ10 is the most important component in the transport of electrons required for ATP generation ^[2].

1.1 Heart Failure

Apart from its antioxidant and electron carrier functions, CoQ10 displays a wide range of interesting properties for the treatment of cardiovascular diseases, including a positive effect on myocardial Na⁺-K⁺ ATPase activity, its protective effect on endothelial cells, endothelial cell protection, prostaglandin metabolism influence, and anti-viscosity effect. Concretely, chronic heart failure patients enormously benefit from CoQ10 supplementation for the improvement of their condition. This is due to the fact that CoQ10 levels in blood and endomyocardial biopsies of heart failure patients were found to be significantly decreased. Furthermore, a reduction in CoQ10 levels was correlated with the severity of symptoms, with those with lower levels being more affected ^[3].

1.2 Hypertension

Blood pressure appears to be lowered by CoQ10. The specific process is unknown, although one theory suggests that it works by maintaining nitric oxide, which reduces peripheral resistance. Nitric oxide lowers blood pressure by relaxing peripheral arteries. In some forms of hypertension, superoxide radicals that inactivate nitric oxide are overproduced; CoQ10, with its antioxidant effects, may prevent these free radicals from inactivating nitric oxide. Alternatively, CoQ10 may boost the production of the prostaglandin prostacyclin (PGI2) a potent vasodilator and inhibitor of platelet aggregation, or it may enhance the sensitivity of arterial smooth muscle to PGI2, or both ^[4]. In a randomized, double-blind, placebo-controlled study, it was observed that after 12 -week of CoQ10 administration, the systolic blood pressure was lowered to normal limits ^[2].

1.3 CoQ10 and statin-associated muscle symptoms

HMG-coenzyme A reductase inhibitors are the most effective atherosclerotic disease preventive therapies for lowering LDL and minimizing cardiac events in patients with coronary artery disease and in previously healthy patients. Consequently, statins are one of the most prescribed drugs in the United States. While generally well tolerated in most adults, statins are commonly associated with muscle complaints, termed statin-associated muscle symptoms (SAMS). Symptoms range from minor muscle aches to more severe muscle pains, severe cramps, muscle weakness, and, in rare instances, rhabdomyolysis ^[5].

Statins reduce cholesterol production by inhibiting the mevalonate pathway, which also produces compounds needed for normal mitochondrial function, including ubiquinone or CoQ10. Statin-induced reductions of CoQ10 in blood and organs such as the heart and liver have been shown in animal and human studies. Since CoQ10 is fundamentally important to mitochondrial function and cellular energy production (ATP), the depletion of CoQ10 and resultant mitochondrial dysfunction is hypothesized as the primary pathophysiologic cause of SAMS. That is the rationale for adopting exogenous CoQ10 supplementation to treat SAMS ^[5].

Multiple trials have investigated the use of CoQ10 in patients with SAMS. The published evidence is conflicting, with some trials indicating a benefit and others indicating none. Although individual clinical trials have arrived at conflicting conclusions, the largest and most recent meta-analysis by Qu et al. suggests a benefit of CoQ10 in preventing or treating statin myopathy ^[5].

1.4 Atherosclerosis

CoQ10 in its reduced form, ubiquinol, inhibits protein and DNA oxidation but it is the effect on lipid peroxidation that has been most deeply studied. The peroxidation of cell membrane lipids and lipoprotein lipids in the circulation is inhibited by ubiquinol. Dietary supplementation with CoQ10 results in increased resistance of LDL to the initiation of lipid peroxidation ^[4].

CoQ10 has been shown in several trials to reduce macrophage accumulation, foam cell formation and lipid accumulation. Furthermore, through reverse cholesterol transport (RCT), one strategy that has been intensively explored related with the macrophage’s role in atherosclerosis has identified new ways to increase the clearance of an excess of cholesterol from peripheral cells and lesions. This pathway is mediated by a number of lipid and cholesterol transporters, including the widely-studied cholesterol efflux proteins, ATP-binding cassette transports A1 and G1 (ABCA1 and ABCG1). CoQ10 appears to increase macrophage RCT via a microRNA-ABCG1 interaction, hence assisting in the prevention of atherosclerosis development ^[6].

2. CoQ10 AND SKIN

CoQ10 is an endogenous lipid-soluble antioxidant present in all membranes that serves as a cofactor for three mitochondrial enzymes (complexes I, II, and III) and has been shown to reduce mitochondrial oxidative damage. The mechanism of action of CoQ10 as an antioxidant has been shown to: (a) reduce free radicals’ production, (b) be involved in vitamin E regeneration, (c) reduce keratinocyte DNA damage, (d) reduce UVA-induced MMP production in fibroblasts, (e) enhance collagen and elastin expression, inhibit IL-1α, IL-6 production, and melanin synthesis, and (f) inhibit MMPs and regulate the sulfide oxidation pathway ^[1].

In a double-blind, placebo-controlled trial with 33 healthy volunteers, one clinical study in 2017 examined the effect of dietary CoQ10 supplementation (with either 50 or 150 mg/day for 12 weeks). Both doses of CoQ10 significantly reduced wrinkles and micro-relief lines and improved skin smoothness. Notably, the high dose of CoQ10 showed additional improvement of wrinkles in the nasolabial folds, corner of the mouth lines, and upper radial lip lines. However, the CoQ10 supplementation had no significantly effect on skin hydration or dermal thickness. Therefore, the human skin benefits of CoQ10 are well established due to its antioxidant mechanisms of action and involvement in cellular energy levels to maintain homeostasis and enhance dermal health ^[1].

3. CoQ10 AND AGING

Human aging is a normal multifactorial process resulting from the interaction of genetic and environmental factors. It is characterized by multi-organ system functional decline in association with the risk of age-related diseases (dementia, neurodegenerative disorders, osteoporosis, arthritis, diabetes, cardiovascular disease, age-related hearing loss, and cancer). An oxidative imbalance between the formation of reactive oxygen species and antioxidant mechanisms, resulting to oxidative stress, is a common hypothesis to explain some of the pathophysiology of age and degenerative diseases ^[7].

The decline of CoQ10 levels during aging could be one of the major causes in the development of chronic diseases in the elderly. Furthermore, since CoQ10 is involved in a variety of cellular functions in addition to being an antioxidant, proper absorption of CoQ10 into cells is critical for improving cell activity during aging. Maintenance of CoQ10 functional levels at cell membranes either through dietary supplementation or improved endogenous production, can be an important strategy for enhancing health during aging ^[4].

SIDE EFFECTS AND INTERACTIONS OF CoQ10

Although CoQ10 is present naturally in the human body and should therefore be well tolerated, a variety of adverse reactions have been observed, though infrequent and generally mild. These include decreased appetite, diarrhea, dizziness, dyspepsia, and nausea/vomiting. Despite one report suggesting that supplementing with CoQ10 reduced the effects of warfarin, a later controlled study found no such interaction ^[5].

REFERENCES

1. Vollmer D, West V, Lephart E. Enhancing Skin Health: By Oral Administration of Natural Compounds and Minerals with Implications to the Dermal Microbiome. International Journal of Molecular Sciences. [Internet]. 2018 [cited 2022 Feb 1]; 19: 1-35. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213755/
2. Zozina V, Covantev S, Goroshko O, Krasnykh L, Kukes V. Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem. Current Cardiology Reviews. [Internet]. 2018 [cited 2022 Mar 24]; 14: 164-74. Available form:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131403/
3. Pastor-Maldonado C, Suárez-Rivero J, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Munuera-Cabeza M, et al. Coenzyme Q10: Novel Formulations and Medical Trends. International Journal of Molecular Sciences. [Internet]. 2020; 21: 1-23. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697799/
4. Garrido-Maraver J, Cordero M, Oropesa-Avila M, Vega A, de la Mata M, Pavon A, et al. Clinical applications of coenzyme Q10. Frontiers in Bioscience (Landmark). [Internet]. 2014 [cited 2022 Mar 24]; 19: 619-33. Available form: http://www.imrpress.com/journal/FBL/19/4/10.2741/4231
5. Raizner A. Coenzyme Q10. Methodist Debakey Cardiovascular Journal. [Internet]. 2019 [cited 2022 Mar 24]; 15: 185-91. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822644/
6. Suárez-Rivero J, Pastor-Maldonado C, de la Mata M, Villanueva-Paz M, Povea-Cabello S, Álvarez-Córdoba M, et al. Atherosclerosis and Coenzyme Q10. International Journal of Molecular Sciences. [Internet]. 2019 [cited 2022 April 18]; 20: 1-17. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834161/
7. Barcelos I, Haas R. CoQ10 and Aging. Biology (Basel). [Internet]. 2019 [cited 2022 April 18]; 8: 1-22. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627360/