Impact of Ubiquinol Supplementation on Endothelial Function in Subjects at Risk of Cardiovascular Disease Development

INTERVENTION: The study aims to evaluate the impact of a supplementation with ubiquinol (reduced form of ubiquinone or reduced CoQ10) on endothelial function and oxidative stress in patients with mild to moderate dyslipidemia. During Screening Visit the eligibility criteria will be verified and, if fulfilled, each subject will be randomized to one of the 3 study groups after signing the Informed Consent Form. At Screening Visit and at Week 4, subjects will receive the assigned test product, according to randomization, for consumption at home during the coming 4 weeks and leave the facility. The study products include test treatment (ubiquinol, two dosages, 100 and 200 mg daily) and placebo; details on these study products are given in the study products dossiers. Each product (ubiquinol or placebo), have to be taken daily at breakfast and dinner (total two pills: 1 before breakfast and 1 before dinner). The active study products, Ubiquinol‐QH 100 mg, will be provided in the form of softgel capsules. Each active softgel capsule contains ubiquinol (Kaneka QHâ„¢ active antioxidant form of coenzyme Q10) 100 mg. The product contains also soy and other ingredients: medium chain triglycerides, gelatin, glycerin, ascorbyl palmitate, purified water, beeswax, soy lecithin, annatto extract. Placebo will consist of softgel capsules too, matching the active study products but without any active principle. The subjects will consume 2 softgel capsules per day according to the following scheme: ‐ Group A ‐ Ubiquinol 200mg/day: 2 Ubiquinol‐QH 100 mg soft capsules/day ‐ Group B ‐ Ubiquinol 100mg/day: 1 Ubiquinol‐QH 100 mg soft capsule and 1 Placebo capsule /day ‐ Group C – Matched placebo: 2 Placebo capsules/day The study products, provided as softgel capsules, will be consumed at home by the subjects, one capsule in the morning and one capsule in the evening, with a meal. Subjects will be instructed to complete a daily diary, in order to evaluate the complianc CONDITION: Cardiovascular ‐ Diseases of the vasculature and circulation including the lymphatic system Dyslipidemia;Endothelial Dysfunction; ; Dyslipidemia ; Endothelial Dysfunction Metabolic and Endocrine ‐ Metabolic disorders PRIMARY OUTCOME: Change in endothelium‐dependent vasodilation at week 8, assessed through non‐invasive ultrasound measurement of the flow‐mediated dilation (FMD) of the brachial artery. Measures will be conducted by a trained sonographer using a dedicated ultrasound machine and analysed through an edge‐detection and wall‐tracking software developed by Quipu (Pisa, Italy).[Visit 2 (8 weeks)] INCLUSION CRITERIA: This study will include male and post‐menopausal female subjects. ‐ Male aged 35 ‐ 65 years (35 and 65 included). ‐ Post‐menopausal female (without a period for more than 1 year), until 65 years (65 included). ‐ Subjects enrolled for primary prevention but never treated (only life style modification suggested, according guidelines). ‐ FMD level measured between 2,5% and 6% (at Screening Visit). ‐ Body mass index (BMI) between 18.5 and 29.9 kg/m2. ‐ LDL Cholesterol levels between 130 and 200 mg/dl (based on previous evaluation, performed within 1 month from the Screening Visit). SECONDARY OUTCOME: Change in endothelium‐dependent vasodilation at week 4, assessed through non‐invasive ultrasound measurement of the flow‐mediated dilation (FMD) of the brachial artery. Measures will be conducted by a trained sonographer using a dedicated ultrasound machine and analysed through an edge‐detection and wall‐tracking software developed by Quipu (Pisa, Italy).[Visit 1 (4 weeks)] Change in the ratio between oxidized and total Coenzyme Q10 (CoQ10) plasma levels (composite outcome). Oxidized and total CoQ10 levels will be measured by high‐pressure liquid chromatography (HPLC) using a direct extraction method.[Visit 1 (4 weeks), Visit 2 (8 weeks)] Evaluation of plasma levels of nitric oxide quantified in terms of its stable reaction product (nitrites and nitrates) through the Griess reaction.[Visit 1 (4 weeks), Visit 2 (8 weeks)] Evaluation of plasma levels of peroxinitrite (evaluation of oxidative inactivation of NO to peroxinitrite using fluorescent probes).[Visit 1 (4 weeks), Visit 2 (8 weeks)] Evaluation of susceptibility to oxidation of plasma lipoprotein quantified as kinetic of conjugate dienes formation following copper exposure.[Visit 1 (4 weeks), Visit 2 (8 weeks)]