The global prevalence of MASLD is on the rise, and its association with cardiovascular events is substantiated by baseline endothelial, vascular, and myocardial dysfunction. Notably, there is a dearth of efficacious pharmaceutical interventions for the treatment of MASLD.
In this randomized, prospective trial involving patients with MASLD, daily coenzyme Q10 at a dose of 240 mg led to larger reductions in liver steatosis compared to the placebo group at the 6 months follow-up. In addition, coQ10 resulted in remarkable improvement of endothelial, vascular and myocardial function compared to the placebo group. Meaningful improvement in the lipid profile were more common in the coQ10 group than the placebo group. Moreover, treatment with coQ10 led to similar adverse events with placebo and no drug discontinuation due to serious adverse events.
In a recent meta-analysis with NAFLD patients, the effect of CoQ10 supplementation on lipid profile revealed non-significant decrease in TC, LDL, HDL, and TG[24]. In the present study individuals who received CoQ10 exhibited significant changes in the plasma levels of LDL signifying substantial improvement in their lipid profile. It is crucial to note that the duration of the intervention may be a key factor in determining the effectiveness of CoQ10 supplementation, since in the studies included in the meta-analysis, treatment spanned from 4 to 12 weeks, whereas in the present study, treatment extended to 24 weeks. Furthermore, it should be noted that patients with NAFLD might exhibit diverse responses to distinct CoQ10 dosages. In above studies CoQ10 dosage varied from 20 to 100 mg daily, while in the present study patients received 240 mg per day. Comparative studies with different CoQ10 dosages are of utmost importance to determine their varying effects on lipid profile and liver steatosis. Similar to the present study, combination therapy involving antioxidants, vitamins, and herbs has demonstrated potential efficacy in other studies[25].
In our study, all participants received comprehensive dietary guidance that adhered to the fundamental principles of the Mediterranean diet. Additionally, they were motivated and encouraged to actively engage in a minimum of 150 minutes of moderate exercise on a weekly basis. The dietary instructions aimed to align with the holistic approach of the Mediterranean diet, emphasizing the consumption of nutrient-rich foods, while the encouragement for regular physical activity underscored the importance of maintaining a healthy and active lifestyle. The diminished CAP score observed in both groups encompasses all the mentioned factors above; however, individuals who received CoQ10 exhibited significant improvement in liver steatosis, despite the BMI remaining constant. This indicates significant improvement in hepatic fat accumulation. This study is the second one to report liver steatosis changes with coQ10 supplementation. Farsi et al.[26] found significant improvement in NAFLD grades after treatment with coQ10.
CoQ10 has been shown to lower blood pressure at doses between 100 and 200 mg per day in a number of studies involving human participants[27, 28]. In the course of the present study, the administration of CoQ10 led to a noteworthy decrease in systolic blood pressure, registering a reduction of 7 mmHg, while its impact on diastolic blood pressure was observed to be minimal. These findings indicate a potential role for CoQ10 in managing hypertension, whether used independently or in combination with other conventional anti-hypertensive medications. However, it is imperative to conduct more meticulously monitored clinical trials.
Endothelial dysfunction is a condition that contributes to the pathophysiology of vascular disease in MASLD patients. It manifests prior to the development of atherosclerotic lesions or the occurrence of clinical events and is considered as a trustworthy marker of subclinical atherosclerosis. Endothelial function improvements with coQ10 supplementation have been shown mainly in patients with DM with 2 clinical trials using 200 mg/day of coQ10 for 12 weeks showing significant improvements in brachial artery flow-mediated dilatation[29, 30]. Larijiani et al.[31] supplemented 65 intermediate risk individuals with 30 mg/day coQ10 for 1 year and showed significant improvements in PWV. In our study, we assessed endothelial function using PBR, a technologically advanced and sophisticated method. We demonstrated, six months post-treatment with CoQ10, a substantial reduction in the PBR of sublingual artery microvessels and a decrease in AIX. Additionally, patients receiving CoQ10 exhibited significant alterations in arterial elasticity, as evidenced by changes in PWV and FMD of the brachial artery. It is crucial to highlight that these impactful changes were absent in the placebo group across all the aforementioned vascular metrics. This comprehensive analysis underscores the multifaceted positive effects of CoQ10 on vascular health. The observed reductions in PBR and AIX indicate improved microvascular perfusion and reduced arterial stiffness, respectively. The notable changes in PWV and FMD further signify enhanced arterial flexibility and endothelial function in patients undergoing CoQ10 treatment. These findings not only contribute to the growing body of evidence supporting the cardiovascular benefits of CoQ10 but also emphasize its potential role in ameliorating various aspects of vascular function.
Administering CoQ10 may also be beneficial as adjunctive treatment in heart failure. CoQ10 has been demonstrated to ameliorate symptoms, lower adverse cardiovascular events, and lower cardiovascular mortality in individuals with heart failure [32, 33]. Considering the heightened cardiovascular risk associated with MASLD patients, this study demonstrated a noteworthy correlation between CoQ10 supplementation and left ventricular function. In particular, we observed a significant improvement in coronary microcirculation, as assessed by CFR, and an improvement in left ventricular performance as assessed by GLS
A major finding in our study was the notable association between the percentage reduction in CAP score and improvements in PBR and PWV. This suggests that as the CAP score decreased, indicative of reduced liver steatosis, there were concurrent positive changes in PBR and PWV. Additionally, the study revealed a reverse relationship between the percentage reduction in CAP score and the percentage increase in CFR and FMD of the brachial artery, further highlighting the potential cardiovascular benefits associated with the reduction in liver steatosis in the presence of CoQ10 supplementation. These findings underscore the complex interplay between liver health and cardiovascular function, shedding light on the potential role of CoQ10 in ameliorating liver steatosis and its correlated improvements in endothelial, vascular, and myocardial aspects.
This study has some limitations. It is a single center study with a relatively small number of participants. Nevertheless, it thoroughly evaluates the effect of coQ10 in a well selected population with MASLD, matched for baseline characteristics, by studying endothelial, vascular and myocardial function. In order to better understanding the effects ofcoQ10 administration, prospective large-scale studies with longer follow-up are needed.