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Efficient Muscle Distribution Reflects the Positive Influence of Coenzyme Q10 Phytosome in Healthy Aging Athletes after Stressing Exercise

Coenzyme Q10 (CoQ10) is an ubiquitously-distributed molecule with a key role in mitochondrial efficiency, involving protection against peroxidation induced by reactive oxygen species. In athletes during intense training and strenuous exercise, a reactive oxygen species overproduction occurs and can cause muscular stress and damage: a reduction of those undesired effects would be of benefit. CoQ10 antioxidant properties are described in several clinical studies, but efficacy of CoQ10 supplementation in pre-senescent athletes has not yet been clearly demonstrated. A randomized, intervention-controlled, single-center J Food Sci Nutr Res 2020; 3 (4): 262-275 DOI: 10.26502/jfsnr.2642-11000054 Journal of Food Science and Nutrition Research 263 clinical trial was performed in healthy aging (presenescent) runners undergoing exercise training in conditions of high environmental stress. One group used an innovative food-grade CoQ10 phytosome formulation (Ubiqsome) daily for 30 days, while the control group did not take supplementation. Phytosome technique applied to CoQ10 successfully increased CoQ10 bioavailability, as previously demonstrated. CoQ10 levels and oxidative with inflammatory markers were detected in both plasma and muscle. Data obtained highlighted that 500 mg of CoQ10 phytosome (corresponding to 100 mg CoQ10), administered once a day for 30 days significantly improved CoQ10 bioavailability in healthy volunteer aging runners (50-65 years) by increasing both plasmatic and muscular CoQ10 levels, with a reduction of inflammatory cytokines and Malonyl Dialdehyde levels suggesting a protective effect induced by supplementation. The original CoQ10 phytosome formulation results to be of benefit in increasing CoQ10 plasmatic and muscular levels when CoQ10 decrease occurred for oxidative stress conditions, aging or high training.


Introduction
Coenzyme Q10 (CoQ10 or ubiquinone) is a fat-soluble ubiquitous compound that functions as an electron carrier in the mitochondrial respiratory chain, as well as serving as an important intracellular antioxidant [1].
Several studies have demonstrated that CoQ10 is able to protect phospholipids and mitochondrial membrane proteins against peroxidation and DNA against the oxidative damage linked to lipid peroxidation [2,3].
The CoQ10 content in the body changes in different organelles, tissues and among species [4]; even if the endogenous biosynthesis under physiological conditions is sufficient for basic needs, increasing evidence suggests that exogenous administration of CoQ10 can support and improve mitochondrial energy metabolism [5]. The production of CoQ10 is not constant throughout life, as is the functionality of organ and systems with aging. A significant reduction in the rate of CoQ10 biosynthesis is thought to occur during the physiological aging process and aging-associated diseases [6], and subjects of advanced age show a correlation between lower concentrations of coenzyme Q10 and a change in the oxidation-reduction state in favour of the oxidized form that conditions the senescent process. The decrease of CoQ10 content that may occur in mitochondria of some tissues is selective, rather than ubiquitous [4].
The ability to restore oxidative balance may be also compromised during physical activity of a certain intensity when accompanied by oxygen consumption that causes an important increase of reactive oxygen species (ROS) [7]. In the healthy individual, continued practice results in a better ability of increasing the internal antioxidant response and maintaining adequate homeostasis [8]. However, when that response may be compromised, due to an excess of physical work or a deficiency in the mechanisms of adaptation or even as a response to stress, an exogenous supplementation with effective antioxidants acts as good support [9]. There are several studies evaluating the impact on the performance of CoQ10 administration [10] using the oxidized [11] or reduced form [12][13][14]. The efficiency of absorption of orally administered CoQ10 is poor because of its insolubility in water, limited solubility in lipids, and relatively large molecular weight [15].
The objective of the present study is to determine the biological activities of a new food-grade delivery form of CoQ10 (CoQ10 phytosome) in stressing exercise and its effect on the antioxidant capacity in aging athletes compared with controls. The physically stress adaptation response was evaluated before and after daily administration for a one-month period of 500 mg CoQ10 phytosome (containing not less than 100 mg of CoQ10).

Supplement
Subjects were randomized into two groups, one of 12 subjects who were instructed to take Coenzyme Q10 phytosome, 500 mg film-coated tablet (Ubiqsome®, Indena SpA) [18] containing not less than 100 mg of CoQ10 Ubiquinone (in the morning, just before breakfast) for 30 days. The control group, 8 subjects, did not take the supplementation.

Muscle biopsies
Muscle biopsies were performed 5 days before the first and second session tests at the climate chamber, in order to obtain samples for CoQ10 concentration analysis in muscle and muscular characteristics, as previously described [19]. For histological examinations muscle biopsy was orientated and snap-frozen in liquid nitrogen-chilled isopentane and stored at −80ºC until its use. The frozen muscle tissue was evaluated using a

Results
There were no statistically significant baseline differences between subjects in the CoQ10 group (n=11) and control group (n=8), their mean baseline characteristics are presented in Table 1. The CoQ10 plasmatic levels (detected by HPLC) before allocation showed similar values in both groups at baseline in agreement with those reported in other studies [22][23][24].
All the subjects in the intervention group, except two, completed the study. One withdrew for personal reasons after his enrolment and the second subject withdrew before the second session at the chamber due to a muscular injury related to his professional work. There  The values are expressed as mean ± standard deviation, n=11 (CoQ10-supplemented group) and n=8 (control)      with the values displayed in Bhagawan and Chopra [24]. After one month of phytosome supplementation, CoQ10 plasma concentrations were significantly increased, 2.1 times compared to that observed for similar doses administered as oil suspension [27] with a fatty diet, or for a longer time period, i.e. 2 months [28].

Treatment Group Stage Pre intervention Post intervention
Regarding the quality of the study sample, it is important to underline that in other literature studies [28,29] [19], in agreement with the idea that in muscle tissue the CoQ10 mitochondrial concentration seems not to possess saturation kinetics [33]. An increase in CoQ10 muscle concentration after exercise in CoQ10 phytosome-supplemented subjects [11] was previously observed, but no further studies had confirmed the data, up to the present study, that support and extend evidence for the first time in aging athletes.
As we know, athletes may have CoQ10 levels below those desired, due to increased metabolic stress and a higher formation of free radicals and aging process that can induce a significant and general reduction in the CoQ10 biosynthesis. Karlsson [34]  This study exposed a stressing exercise in trained subjects that caused a strong request for the protection of antioxidant and anti-inflammatory systems. This is perhaps the reason for a somewhat different response between the two groups in our study.
It is difficult to separate the oxidative process of aging from that associated with exercise. The complex interplay between age-associated reduction in habitual physical activity and the intrinsic aging processes complicates the interpretation of the aetiology of physical function decline. Assuming aging, and that the different structures of the respiratory chain system started to age from 40-50 years, [39] our study involved pre-senescence subjects; however, from results obtained by tests performed on those subjects, it appeared that those athletes had adequate redox capacity, but also responded to the CoQ10 supplementation.
On the other hand, the release of cytokines resulted highly modified in subjects supplemented with CoQ10; in particular Interleukins (IL-6, IL-8 and IL-10) reduction was observed after exercise after 30 days of CoQ10 phytosome supplementation, indicating a protective effect of the supplement. Those data are in agreement with the decrease of IL-6, IL-8, IL-10 and TNF-α production after CoQ10 administration (for 14 days) in Elite swimmers [40].

Conclusion
The