2.1. Udział w prawidłowym pozyskiwaniu energii w procesach metabolicznych (ID 1508, 1512, 1720, 1912, 4668)

The claimed effects are “energy metabolism”, “ubiquinione takes part in electron-transferring in the respiratory chain”, “for physiological energy”, “energy production, muscle function” and “energising by stimulating the obtainance of adenosine triphosphate from the cellular energetic processes”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effects relate to energy-yielding metabolism.
The Panel considers that contribution to normal energy-yielding metabolism is a beneficial physiological effect.

2.2. Utrzymanie prawidłowego ciśnienia tętniczego (ID 1509, 1721, 1911)

The claimed effects are “blood pressure”, “heart health” and “maintenance and promotion of heart health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel notes that the claimed effect relates to the maintenance of normal blood pressure.
Blood pressure is the pressure (force per unit area) exerted by circulating blood on the walls of blood
vessels. Elevated blood pressure, by convention 140 mmHg (systolic) and/or 90 mmHg (diastolic), may compromise the normal function of the arteries.
The Panel considers that maintenance of normal blood pressure is a beneficial physiological effect.

2.3. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 1510)

The claimed effects are “antioxidant activity” and “normal antioxidant properties”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effects relate to the protection of cells and molecules from oxidative damage caused by free radicals.
Reactive oxygen species (ROS) including several kinds of radicals are generated in biochemical processes (e.g. respiratory chain) and as a consequence of exposure to exogenous factors (e.g. radiation, pollutants). These reactive intermediates damage biologically relevant molecules such as DNA, proteins and lipids if they are not intercepted by the antioxidant network, which includes free radical scavengers such as antioxidant nutrients.
The Panel considers that protection of DNA, proteins and lipids from oxidative damage may be a beneficial physiological effect.

2.4. Udział w prawidłowym przebiegu procesów poznawczych (ID 1511)

The claimed effect is “protection of healthy neurological system”. The Panel assumes that the target population is the general population.
In the context of the clarifications provided, the Panel assumes that the claimed effect refers to normal cognitive function. Cognitive function includes memory, attention (concentration), learning, intelligence and problem solving, which are well defined constructs and can be measured by validated psychometric cognitive tests.
The Panel considers that contribution to normal cognitive function is a beneficial physiological effect.

2.5. Utrzymanie prawidłowego stężenia cholesterolu we krwi (ID 1721)

The claimed effect is “maintenance and promotion of heart health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effect relates to the maintenance of normal blood cholesterol concentrations.
Low-density lipoproteins (LDL) carry cholesterol from the liver to peripheral tissues, including the arteries. Elevated LDL-cholesterol, by convention >160 mg/dL (>4.14 mmol/L), may compromise the normal structure and function of the arteries. High-density lipoproteins (HDL) act as cholesterol
scavengers and are involved in the reverse transport of cholesterol in the body (from peripheral tissues back to the liver).
The Panel considers that maintenance of normal blood cholesterol concentrations is a beneficial physiological effect.

2.6. Wzrost wytrzymałości i/lub wydolności (ID 1913)

The claimed effect is “physical activity”. The Panel assumes that the target population is active individuals in the general population.
In the context of the proposed wordings, it is unclear whether the claim refers to endurance capacity or to endurance performance. It should be noted that in the literature these terms are often used as synonyms. Endurance capacity refers to the exercise time to volitional fatigue when exercising at a constant workload or speed. Endurance performance relates to completing a certain task (running a certain distance) as fast as possible. This claim will be evaluated in relation to both of these definitions.
The Panel considers that an increase in endurance capacity and/or endurance performance is a beneficial physiological effect.

3.1. Udział w prawidłowym pozyskiwaniu energii w procesach metabolicznych (ID 1508, 1512, 1720, 1912, 4668)

A total of 86 references were provided in the consolidated list in relation to this claim. Most of the references were narrative reviews from textbooks and scientific journals in relation to the biochemical function, metabolism, kinetics and antioxidant capacity of coenzyme Q10, and to the potential therapeutic applications of high supplemental doses (>100 mg/day) in patients with heart failure, diabetes and/or hypertension. Some of the references provided reported on outcomes in relation to physical performance, blood pressure, oxidative damage and antioxidant function, whereas others reported on in vitro/ex vivo studies on the saturation kinetics of coenzyme Q10 in relation to different enzymes in animal muscle biopsies, such as in beef heart mitochondria (Lenaz et al., 1994; 1997). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
One uncontrolled intervention study was provided on the effect of coenzyme Q10 supplementation (100 mg/day) for six months in middle aged post-polio subjects (n=3) and healthy volunteers (n=4). Muscle energy metabolism during exercise and recovery was measured using 31P-NMR spectroscopy (Mizuno et al., 1997). The Panel considers that no conclusions can be drawn from this small and uncontrolled study for the scientific substantiation of the claimed effect.
In another randomised, double-blind, placebo controlled intervention study the effect of coenzyme Q10 supplementation (300 mg/day), for four weeks in elderly subjects prior to hip replacement, on muscle fibre type composition and induced changes in gene and protein expression, was measured in muscle biopsies (Linnane et al., 2002). Results on gene expression were presented for five subjects (treatment/placebo: 3/2), and on fibre type composition in 14 subjects (treatment/placebo: 7/7). A
significant effect was observed on both gene expression and induced protein synthesis, as well as on fibre type (higher proportion of type IIb „fast twitch‟ fibre) in the intervention compared to the control group. The Panel notes the small number of subjects included in the study and that, although the changes observed in relation to coenzyme Q10 supplementation might affect muscle energy metabolism, the relevance of these results to the claimed effect are unclear.
The Panel notes that no data have been provided supporting an effect of coenzyme Q10 consumption on energy-yielding metabolism under the proposed conditions of use in the target population.
The Panel concludes that a cause and effect relationship has not been established between the consumption of coenzyme Q10 (ubiquinone) and contribution to normal energy-yielding metabolism.

3.2. Utrzymanie prawidłowego ciśnienia tętniczego (ID 1509, 1721, 1911)

A total of 54 references were presented in the consolidated list in relation to this claim. One meta- analysis focused on coenzyme Q10 supplementation as a therapy in patients with heart failure. In three non-controlled intervention studies and seven randomised controlled trials in humans, oral coenzyme Q10 intake was studied in patients with clinical heart disease, mainly heart failure. Subjects in these studies cannot be considered representative of the general population in relation to the claimed effect. There were 21 review papers and eight textbook chapters that discussed the role of coenzyme Q10 in heart disease, coenzyme Q10 status in relation to statin treatment, and/or the role of coenzyme Q10 in human health from a mechanistic or physiological viewpoint. These papers and textbook chapters did not contain original data on the health effects of oral coenzyme Q10 intake in non-clinical populations. Furthermore, there was one conference abstract on the effect of coenzyme Q10 in heart failure patients, one animal study (in mice) on the relation between age and mitochondrial coenzyme Q10 concentrations and one biopsy study assessing coenzyme Q10 concentrations in the heart tissue of patients with cardiomyopathy. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The US Institute of Medicine (IoM, 2005) report on dietary reference intakes for vitamins and minerals was cited in the consolidated list, but no information on coenzyme Q10 in relation to blood pressure could be retrieved.
Two systematic reviews and one meta-analysis on the health effects of coenzyme Q10, including blood pressure, were presented. Tran et al. (2001) performed a systematic review on the safety and efficacy of oral coenzyme Q10 as co-adjuvant in the pharmacological treatment of different clinical conditions, including hypertension. The Panel considers that no scientific conclusions can be drawn from this systematic review for the scientific substantiation of the claim. A systematic review (Rosenfeldt et al., 2003) on the effects of coenzyme Q10 in the treatment of hypertension and a meta-analysis (Rosenfeldt, 2007) of clinical trials on coenzyme Q10 consumption in the treatment of hypertension were provided. The meta-analysis included a number of human intervention studies on the effects of coenzyme Q10 on blood pressure, of which four had a randomised controlled design (Yamamagi et al., 1986; Burke et al., 2001; Digiesi et al., 1990; Singh et al., 1999) and are described below. Three of these have also been cited individually in the consolidated list (Yamamagi et al., 1986; Burke et al., 2001; Digiesi et al., 1990).
Six intervention studies in humans were provided on the effects of coenzyme Q10 intake on blood pressure. One was a one arm, uncontrolled human study on the effects of coenzyme Q10 supplementation (100 mg/day) for 10 weeks on blood pressure in 26 subjects with essential hypertension (Diegisi et al., 1994), from which no conclusions could be drawn for the scientific substantiation of the claimed effect owing to the uncontrolled nature of the study.
Two randomised controlled trials (Singh et al., 1999; Yamagami et al., 1986) on the effect of coenzyme Q10 consumption on blood pressure included subjects who were on conventional (pharmacological) antihypertensive treatment before and during the studies. The Panel considers that no conclusions can be drawn from these studies for the substantiation of the claim as the evidence provided does not establish that interactions between coenzyme Q10 and antihypertensive treatment can be excluded.
A placebo-controlled cross-over study was conducted by Digiesi et al. (1990) including 18 Italian patients (four women, mean age 56 years) with baseline blood pressure of 167/103 mmHg on antihypertensive pharmacological treatment, which was suspended two weeks prior to enrolment. Patients were not selected for low coenzyme Q10 status. Coenzyme Q10 (100 mg/day) and placebo were administered for 10 weeks with a 2-week washout period in between. Blood pressure values were recorded weekly. The Panel notes the small size of the study, that differences in blood pressure changes between interventions were not reported, that intermediate blood pressure measurements were not reported nor considered in the statistical analysis, and that carry-over effects were not assessed. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
In a placebo-controlled, parallel intervention, 76 older patients (35 women, mean age 68 years) with isolated systolic hypertension (ISH), who were asked to discontinue antihypertensive medications 10 days before enrolment, were randomised to consume 120 mg/day coenzyme Q10 or placebo for 12 weeks (Burke, 2001). Nine normotensive subjects were also recruited and all received coenzyme Q10 (120 mg/day) for 12 weeks. The Panel notes that differences in blood pressure changes between treatment and placebo ISH groups were not reported. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.
In a 12-week placebo-controlled intervention, 80 subjects (mean age 53 years) with type 2 diabetes, dyslipidaemia and blood pressure <160/90 mmHg who were not on antihypertensive medication were randomised to consume coenzyme Q10 (200 mg/day) and fenofibrate (200 mg/day), coenzyme Q10 and fenofibrate placebo, coenzyme Q10 placebo and fenofibrate, or double placebo (Hodgson et al., 2002). The primary outcome of the study was endothelial dysfunction. Secondary outcomes were blood lipids, blood pressure, glycaemic control and markers of oxidative stress. A total of 74 subjects completed the study and entered data analysis. A significant reduction in systolic (-6.1±2.6 mmHg, p=0.021) and diastolic (-2.9±1.4 mmHg, p=0.048) blood pressure was observed in subjects consuming 200 mg/day coenzyme Q10 with or without fenofibrate (n = 36) compared to subjects not consuming coenzyme Q10 (n = 38). No interaction between coenzyme Q10 and fenofibrate was observed for any of the variables studied. The Panel notes that change in blood pressure was not the primary outcome of the study, that no statistical adjustment for multiple outcomes was considered, that data analysis was only provided for completers, that a direct comparison between the double placebo group and the CoQ10 and fenofibrate placebo groups was not reported, and that in a more recent publication the same research group found an interaction between CoQ10 and fenofibrate for blood pressure (Chew et al., 2008). The Panel considers that these weaknesses greatly limit the conclusions that can be drawn from this study with respect to an independent effect of CoQ10 on blood pressure.
No evidence for a mechanism by which CoQ10 could exert the claimed effect has been provided.
In weighing the evidence, the Panel took into account that most of the studies presented have been conducted in hypertensive patients on pharmacological treatment for hypertension, that the evidence provided does not establish that interactions between coenzyme Q10 and antihypertensive treatment can be excluded, and that only one intervention study with considerable weaknesses reported a significant effect of coenzyme Q10 supplementation on blood pressure.
The Panel concludes that a cause and effect relationship has not been established between the consumption of coenzyme Q10 (ubiquinone) and the maintenance of normal blood pressure.

3.3. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 1510)

Most of the references provided were narrative reviews on the (biochemical) functions of coenzyme Q10 and its potential role in disease prevention and treatment, especially cardiovascular disease. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect. Also, a number of human studies on the effects of coenzyme Q10 supplementation on the antioxidant capacity of plasma (e.g. assessed by the TRAP method) were cited. The Panel notes that this measure is a marker of antioxidant status and does not assess oxidative damage to molecules.
Six human intervention studies on effects of coenzyme Q10 supplementation on lipid peroxidation were cited (Alleva, 1995; Stocker et al., 1991, revised by Kaikkonen et al., 2002; Mohr et al., 1992; Singh et al., 2005; Weber et al., 1994; Kontush et al., 1994).
Three human intervention studies were presented on the effects of coenzyme Q10 supplementation (from 30 to 100 mg/day) on LDL resistance to oxidation ex vivo (lag time) assessed by different methods (Alleva, 1995; Stocker et al., 1991, revised by Kaikkonen et al., 2002; Mohr et al., 1992). Also, a cross-sectional study on the association between the rate of (induced) oxidative modification of LDL and its ubiquinol-10 content in healthy blood donors (Kontush et al., 1994) was provided. The Panel notes that LDL resistance to oxidation ex vivo is not a reliable marker of lipid peroxidation (Griffiths et al., 2002).
Three human intervention studies were presented on the effects of coenzyme Q10 supplementation (from 90 to 200 mg/day) on plasma concentrations of malondialdehyde (MDA) and/or thiobarbituric acid reactive substances (TBARS) and/or lipid hydroperoxides (Stocker et al., 1991, revised by Kaikkonen et al., 2002; Singh et al., 2005; Weber et al., 1994). The Panel notes that measuring TBARS is not an accepted method to assess lipid peroxidation (non specific) and that MDA and lipid hydroperoxides measured by HPLC are not reliable markers of lipid peroxidation when used alone (Griffiths et al., 2002; Lykkesfeldt, 2007; Knasmüller et al., 2008).
Two rat studies on the effect of supplementation with coenzyme Q10 on DNA strand breaks were presented (Quiles et al., 2004; 2005), as well as one in vitro study with human lymphocytes (Tomasetti et al., 1999). The Panel considers that the evidence provided in animal and in vitro studies does not predict an effect of coenzyme Q10 consumption on the protection of DNA from oxidative damage in humans, and that no scientific conclusions can be drawn from these studies for the substantiation of the claimed effect.
In weighing the evidence, the Panel took into account that LDL resistance to oxidation ex vivo is not a reliable marker of lipid peroxidation, that measuring TBARS is not an accepted method to assess lipid peroxidation, that MDA and lipid hydroperoxides measured by HPLC are not reliable markers of lipid peroxidation when used alone, and that evidence provided in animal and in vitro studies does not predict an effect on the protection of DNA from oxidative damage in humans.
The Panel concludes that a cause and effect relationship has not been established between the intake of coenzyme Q10 (ubiquinone) and protection of DNA, proteins or lipids from oxidative damage.

3.4. Udział w prawidłowym przebiegu procesów poznawczych (ID 1511)

Four references were provided to substantiate the claimed effect, including one narrative review, two human studies and one animal study.
One human study evaluated the efficacy of idebenone versus tacrine in patients suffering from dementia of the Alzheimer type (Gutzmann et al., 2002). The Panel considers that no conclusions can be drawn for the scientific substantiation of the claimed effect from a study using a synthetic analogue
of coenzyme Q10, and furthermore that the study did not evaluate endpoints of relevance for the claimed effect in those patients who were suffering from dementia.
The narrative review was related to the treatment of neurodegenerative diseases with coenzyme Q10 (Young et al., 2007), and one human study investigated the effect of coenzyme Q10 in subjects with Parkinson‟s disease (Shults et al., 2002). The evidence provided does not establish that results obtained in patients with neurodegenerative diseases can be extrapolated to the general population with regard to normal cognitive function.
The animal study examined whether supplemental intake of coenzyme Q10 (ubiquinone-10) or alpha- tocopherol, either alone or in combination, could improve cognitive and psychomotor performance of aged mice (McDonald et al., 2005). The Panel considers that evidence provided in animal studies is not sufficient to predict the occurrence of an effect of coenzyme Q10 consumption on cognitive function in humans.
The Panel notes that no references were provided from which conclusions could be drawn for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of coenzyme Q10 (ubiquinone) and contribution to normal cognitive function.

3.5. Utrzymanie prawidłowego stężenia cholesterolu we krwi (ID 1721)

Only one reference was provided in relation to this claim on the use of coenzyme Q10 as a therapeutic adjuvant in patients with congestive heart failure. The Panel considers that no conclusions can be drawn from this reference for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of coenzyme Q10 (ubiquinone) and the maintenance of normal blood cholesterol concentrations.

3.6. Wzrost wytrzymałości i/lub wydolności (ID 1913)

Three references were provided in the consolidated list for the scientific substantiation of the claimed effect (Cerioli et al., 1991; Yamabe and Fukuzaki., 1991; Zeppilli et al., 1991). These references were published in a book and details given in the description of the studies are limited.
In the first one arm, uncontrolled intervention (Cerioli et al., 1991) 12 healthy untrained male subjects were studied before and after 30 days of supplementation with 100 mg/day of coenzyme Q10. In a second one arm, uncontrolled intervention (Yamabi and Fukuzaki, 1991), nine female patients complaining of “easy fatigability and decreased work ability” were given 90 mg/day of coenzyme Q10 for six months. The study by Zeppilli et al. (1991) described the effects of coenzyme Q10 supplementation (100 mg/day for 30 days) on work capacity in both athletes (n=9) and sedentary subjects (n=10), as well as in a group of patients with “mitochondrial disease” (n=8). Athletes and sedentary volunteers received coenzyme Q10 for 30 days and placebo for an additional 30 days with a 21-day washout period in between. However, it is unclear from the paper whether treatment and placebo were administered in a random order or in the sample order to all subjects. Statistical methods used for data analysis were not reported and direct comparisons between coenzyme Q10 and placebo were not made for any of the groups. The Panel considers that no conclusions can be drawn from these small, uncontrolled studies for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of coenzyme Q10 (ubiquinone) and an increase in endurance capacity and/or endurance performance.