Coenzyme Q10 (CoQ10) for Metabolic Syndrome (MS)

 [ Abstract ] Metabolic syndrome (MS) is a clinical syndrome characterized by the convergence of obesity, hyperglycemia, dyslipidemia, hyperinsulinemia, and hypertension, each of which is interrelated and contributes to the development of the disease. Weight gain is the main risk factor for MS, and insulin resistance is the main pathophysiological mechanism and central component of MS. The prevalence of cardiovascular disease (CVD) is significantly increased in MS patients, and the pathophysiological mechanism of CVD caused by each component of MS is not clear. Coenzyme Q10 (CoQ10) is a potent antioxidant that scavenges free radicals and protects cells from oxidation, and plays an important role in MS and CVD. CoQ10 supplementation can improve MS, increase ventricular ejection fraction and reduce the incidence of myocardial infarction in patients with myocardial infarction. In recent years, CoQ10 has gradually become a hot research topic. This article discusses the relationship between CoQ10, MS and CVD and the progress of research.

 

Metabolic syndrome (MS) is a pro-inflammatory state characterized by increased activity of inflammatory cytokines and contains a series of risk factors associated with the development of cardiovascular disease (CVD).1 The incidence of MS is increasing year by year, and its components are metabolically interrelated and independently associated with atherosclerosis. The incidence of MS is increasing year by year, and its components are metabolically interrelated and independently associated with atherosclerosis, which contributes to the development of atherosclerotic CVD and seriously affects human health. Coenzyme Q10 (CoQ10) is a potent antioxidant that plays an important role in metabolism. Studies have shown that CoQ10 supplementation can improve inflammation and insulin resistance (IR), improve cardiomyocyte metabolism, and possibly reduce the incidence of myocardial infarction. This article summarizes the research progress of CoQ10 and MS components and CVD.

 

1 Overview of MS, CVD, CoQ10

1.1 MS

In 1988, Gerald [1] described a group of metabolic abnormalities with pathophysiological features centered on IR and used the term X-syndrome to describe the potential relationship between IR, hypertension, type 2 diabetes mellitus (T2DM) and CVD. 1998, the World Health Organization (WHO) was the first to propose a definition and diagnostic criteria, in which IR was considered to be a major contributing factor to MS [2]. In 1998, the World Health Organization (WHO) was the first to propose a definition and diagnostic criteria, in which IR was considered to be the main causative factor of MS [2]. In 2005, the International Diabetes Federation (IDF) proposed a unified definition, emphasizing the importance of central obesity as a necessary condition for the diagnosis of MS [3]. In 2005, the International Diabetes Federation (IDF) proposed a harmonized definition emphasizing the importance of central obesity as a necessary condition for the diagnosis of MS [3].

 

China's diagnostic criteria for MS are three or more of the following: (1) abdominal obesity (i.e., central obesity): waist circumference ≥ 90 cm in men and ≥ 85 cm in women; (2) hyperglycemia: fasting blood glucose ≥ 6.1 mmol/L or blood glucose ≥ 7.8 mmol/L 2 h after glucose loading and/or those who have already been diagnosed with diabetes mellitus and are under treatment; (3) hypertension: blood pressure ≥ 130/85 mmHg (1 mmHg=0.133 kPa) and/or those who have already been diagnosed with hypertension and are under treatment; (4) fasting triglyceride (TG) ≥ 0.133 kPa (1 mmHg=0.133 kPa); and (5) diabetes insipidus. (iii) Hypertension: blood pressure ≥ 130/85 mmHg (1 mmHg=0.133 kPa) and/or those who have been diagnosed and treated for hypertension; (iv) fasting triglyceride (TG) ≥ 1.70 mmol/L; (v) fasting high density lipoprotein (HDL-C) < 1.04 mmol/L. 1.04 mmol/L [4].

 

1.2 CVD

The pathophysiology of CVD is complex, with atherosclerosis as the underlying pathogenetic mechanism, leading to the development of coronary, cerebrovascular, and peripheral vascular disease, and ultimately to myocardial infarction, arrhythmia, or stroke. Emerging evidence suggests that inflammatory mechanisms play a key role in the development of atherosclerosis, and that activation of pro-inflammatory signaling pathways, expression of cytokines/chemokines, and increased oxidative stress are among the mechanisms contributing to atherosclerosis [5].

 

1.3 CoQ10

CoQ10 is synthesized in the inner mitochondrial membrane and is an essential compound. CoQ10 is synthesized in the inner mitochondrial membrane and is an essential compound for the human body. Its structural basis is a quinone-like chemical group with high lipophilicity, and it is part of the electron transport chain necessary for the production of adenosine triphosphate (ATP) in mitochondria.CoQ10 is important in metabolism as an intercellular antioxidant that protects the plasma membrane from peroxidation.

 

2 MS and CVD

2.1 Obesity and CVD

Changing lifestyles and rapid urbanization have led to an obesity epidemic. Obesity is one of the main components of MS and increases the risk of IR, T2DM and CVD. There is growing evidence that heterogeneity in adipose composition and distribution of adipose tissue is critical for the development of IR and cardiometabolic disorders. Studies have shown that approximately one-third of obese patients do not exhibit significant cardiometabolic abnormalities, and that these metabolically healthy obese patients have low visceral adiposity, low levels of inflammatory markers, and high insulin sensitivity [6].

 

Adipose tissue is an important organ for the secretion of adipokines, and common adipokines include adiponeetin (ADP) and leptin. Adipose tissue is an important organ for the secretion of adipokines, including adiponeetin (ADP) and leptin, etc. The accumulation of adipose tissue can increase the secretion of pro-inflammatory mediators, such as interleukin 6 (IL-6), tumour necrosis factor-α (TNF-α), and C-reactive protein (CRP), which can promote inflammatory reactions.

 

Lipocalins slow down the formation of atherosclerotic plaques and play a crucial role in the prevention of IR, diabetes and atherosclerosis, providing potential therapeutic targets for the treatment of obesity, IR, T2DM and atherosclerosis [7].

Leptin is an adipocyte-secreted hormone regulated by obesity-related genes that is pro-inflammatory and stimulates the release of pro-inflammatory cytokines [8] . It has pleiotropic effects on nutritional and metabolic status, immune response regulation, inflammation and cardiovascular function.

 

IL-6 is a potent inflammatory cytokine, and elevated levels of IL-6 have been monitored in adipose tissue of patients with MS; epidemiologic studies have reported an association between increased IL-6 concentrations and hypertension, atherosclerosis, and cardiovascular events [9].

 

2.2 IR and CVD

IR is a compensatory increase in insulin secretion by pancreatic β-cells due to decreased insulin sensitivity of target tissues, resulting in hyperinsulinemia. In animal models, compensated hyperinsulinemia can play a key role in atherosclerotic plaque formation by altering the expression pattern of estrogen receptor-related genes [10] . A meta-analysis of 65 studies showed that IR is a good predictor of CVD.11 Monti et al.12 found that hepatic insulin resistance was positively correlated with the leptin/lipocalin ratio, lipoprotein(a), and TNF-α, which are new markers of cardiovascular risk.

 

2.3 Hyperglycemia and CVD

T2DM is a major risk factor for CVD. The progression of atherosclerosis in patients with diabetes mellitus involves multiple metabolic abnormalities. The main biochemical pathways involved in the development of hyperglycemia-induced cardiovascular disease are as follows: oxidative stress, increased formation of advanced glycation end products (AGEs), activation of AGEs receptors, increased production of polyols and hexosamines, activation of protein kinase C, and chronic vascular inflammation [13].

 

2.4 Hypertension and CVD

Hypertension is a major single risk factor for CVD, and a review published in 2019 describes 18 genotypes/phenotypes that are associated with nearly 50% of the population with essential hypertension, suggesting that precise treatment and prevention strategies for specific subtypes of essential hypertension are feasible [14]. The risk of cardiovascular events is approximately 40% higher in adults with hypertension or treated with antihypertensive medications at the age of 30 years than in their normotensive peers, and cardiovascular events tend to occur approximately 5 years earlier in hypertensive individuals than in individuals with lower blood pressure levels [15].

 

2.5 Lipids and CVD

In patients with MS, dyslipidemia is characterized by elevated triacylglycerols, lowered HDL cholesterol, and either normal or elevated LDL. Lipids are deposited in the subendothelium of the arteries, causing damage to endothelial cells and the development of atherosclerosis.LDL particles in patients with MS are smaller and denser, less resistant to oxidative stress, and have a prolonged plasma half-life, which makes it easier for them to penetrate into the arterial wall [16].

 

3 CoQ10 with MS

CoQ10 is a potent antioxidant that scavenges free radicals and protects cells from oxidation. Recent studies have found that CoQ10 levels in T2DM patients are significantly lower than those in the healthy population [17] . The rationale for CoQ10 supplementation is based on its key role in cellular energy metabolism and as an antioxidant, as well as its potential role in regulating oxidative stress and inflammation.

 

Results from randomized trials in patients with MS have shown beneficial effects of CoQ10 supplementation on serum insulin levels, IR, β-cell function, and total plasma antioxidant capacity [18]. In one analysis, CoQ10 supplementation significantly reduced levels of inflammatory markers IL-6, TNF-α, and CRP [19]. Randomized controlled clinical trials have shown that CoQ10 supplementation significantly improves glycemic control and vascular dysfunction in patients [20], and Hosseinzadeh et al. [21] reported significant improvements in HbA1c levels after daily CoQ10 supplementation. a meta-analysis by Zhang et al. [22] demonstrated significant improvements in glycemic control and lipid levels in patients with CoQ10 supplementation. A meta-analysis by Zhang et al [22] confirmed that CoQ10 supplementation significantly improved glycemic control and lipid levels in patients.

 

In terms of lipids, a meta-analysis conducted by Sharifi et al [23] showed that CoQ10 significantly lowered triacylglycerol concentrations in patients with CVD, and Jorat et al [24] found that supplementation with CoQ10 significantly lowered total cholesterol and increased HDL cholesterol levels in patients with cardiovascular disease.

 

The effects of CoQ10 supplementation on blood pressure have also been extensively studied in recent years, and Mohseni et al [25] found that CoQ10 supplementation significantly lowered systolic blood pressure in the absence of lifestyle interventions, but did not improve other cardiovascular risk factors.

 

4 CoQ10 and CVD

Oxidative stress is an important factor in the development of CVD, and CoQ10 inhibits the initial process of lipid peroxyl radical formation, counteracting ROS and free radicals in biofilms.ROS have been shown to promote atherosclerotic plaque formation [26].

Ivanov et al [27] found that intravenous CoQ10 administered 10 min after coronary artery occlusion resulted in smaller myocardial infarct size, less post-infarction left ventricular hypertrophy, and higher ejection fraction in a rat model.Huang et al [28] found that 1 month after percutaneous coronary angioplasty, patients with myocardial infarction who had a higher plasma CoQ10 concentration had a better LV function at 6-month follow-up.Shah et al [29] found that CoQ10 reduced the incidence of fatal and nonfatal myocardial infarction. Shah et al [29] found that CoQ10 reduced the incidence of fatal and nonfatal myocardial infarction.

 

5 Summary

MS is a complex pathophysiologic state with a well-documented relationship to CVD, and CoQ10 plays an important role in metabolism as a potent antioxidant. Continued exploration of the exact pathophysiologic mechanisms between the three is needed to provide further targeted therapies to reduce the risk of CVD.

 

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