Effects of Ubiquinol and Ubiquinone on Vascular Function in Healthy Adults With Borderline High LDL-Cholesterol

This randomized, double-blind, placebo-controlled, parallel-group clinical trial is designed to evaluate and compare the effects of reduced CoQ10 (Ubiquinol) and oxidized CoQ10 (Ubiquinone) on vascular endothelial function in generally healthy adults with borderline high LDL-cholesterol.

Coenzyme Q10 (CoQ10) exists in two interconvertible forms, reduced CoQ10 (Ubiquinol) and oxidized CoQ10 (Ubiquinone). The study is designed to determine whether Ubiquinol provides a superior effect on vascular endothelial function compared with Ubiquinone and placebo. Vascular endothelial function will be assessed using brachial artery flow-mediated dilation (FMD), a non-invasive measure of endothelial function.

A total of 120 eligible participants will be enrolled and randomized in a 1:1:1 ratio to one of three treatment groups: Ubiquinol 200 mg/day, Ubiquinone 200 mg/day, or identical placebo. Participants will take two soft capsules once daily for 8 weeks, preferably after breakfast or lunch containing fat, with water or warm water.

The study population will consist of generally healthy males aged 35-65 years and post-menopausal females up to 65 years of age, with a BMI of 18.5-29.9 kg/m² and borderline high LDL-cholesterol between 100 and 159 mg/dL. Eligible participants will also have a screening FMD value between 2.5% and 6.0% and no current acute or uncontrolled chronic illness.

Study assessments will be performed at baseline, Week 4, and Week 8. The primary endpoint is the change in FMD from baseline through Week 4 and Week 8. Secondary assessments will include changes in plasma CoQ10 levels, including total, reduced (Ubiquinol), and oxidized (Ubiquinone) CoQ10 concentrations and the reduced-to-total CoQ10 ratio. Additional secondary assessments will include plasma nitric oxide measured through nitrite/nitrate quantification, LDL oxidation susceptibility, and oxidative stress markers including malondialdehyde (MDA), oxidized LDL (oxLDL), and total antioxidant capacity (TAC).

Safety will be evaluated throughout the 8-week study by assessing treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs).

The primary objective is to evaluate the superiority of reduced CoQ10 (Ubiquinol) over oxidized CoQ10 (Ubiquinone) in improving vascular endothelial function as measured by FMD. The study will also generate scientific evidence regarding the effects of the two forms of CoQ10 and collect mechanistic and biomarker data that may support future structure/function claims and related scientific and commercial applications.

• Ubiquinol (Dietary supplement): Ubiquinol 200 mg/day, administered orally as two soft capsules once daily for 8 weeks. Participants will be instructed to take the capsules with water or warm water after breakfast or lunch containing fat.
• Ubiquinone (Dietary supplement): Ubiquinone 200 mg/day, administered orally as two soft capsules once daily for 8 weeks. Participants will be instructed to take the capsules with water or warm water after breakfast or lunch containing fat.
• Placebo (Other): Identical placebo soft capsules administered orally as two capsules once daily for 8 weeks according to the study randomization schedule.

Primary outcomes

• Change in Flow-Mediated Dilation (FMD) [Baseline, Week 4, Week 8]: Change in Flow-Mediated Dilation (FMD), a measure of vascular endothelial function.

Secondary outcomes

• Change in Total Plasma CoQ10 Concentration [Baseline, Week 4, Week 8]: Change from baseline in the absolute concentration of total coenzyme Q10 (CoQ10) in plasma, measured in μg/mL.
• Change in Plasma Ubiquinol Concentration [Baseline, Week 4, Week 8]: Change from baseline in the absolute concentration of reduced coenzyme Q10 (ubiquinol) in plasma, measured in μg/mL.
• Change in Plasma Ubiquinone Concentration [Baseline, Week 4, Week 8]: Change from baseline in the absolute concentration of oxidized coenzyme Q10 (ubiquinone) in plasma, measured in μg/mL.
• Change in Ratio of Reduced to Total CoQ10 [Baseline, Week 4, Week 8]: Change from baseline in the ratio of reduced CoQ10 (ubiquinol) to total CoQ10 in plasma.
• Change in Plasma Nitric Oxide (NO) [Baseline, Week 4, Week 8]: Change from baseline in plasma nitric oxide (NO), assessed by nitrite/nitrate quantification.
• Change in LDL Oxidation Susceptibility [Baseline, Week 4, Week 8]: Change from baseline in LDL oxidation susceptibility, measured as lag time using a copper-induced assay.
• Change in Malondialdehyde (MDA) Levels [Baseline, Week 4, Week 8]: Change from baseline in serum levels of malondialdehyde (MDA), an oxidative stress marker.
• Change in Oxidized LDL (oxLDL) Levels [Baseline, Week 4, Week 8]: Change from baseline in serum levels of oxidized low-density lipoprotein (oxLDL), an oxidative stress marker.
• Change in Total Antioxidant Capacity (TAC) [Baseline, Week 4, Week 8]: Change from baseline in serum total antioxidant capacity (TAC).

Other outcomes

• Treatment-Emergent Adverse Events [Baseline, Week 4, Week 8]: Number and proportion of Treatment-Emergent Adverse Events (TEAEs).
• Treatment-Emergent Serious Adverse Events [Baseline, Week 4, Week 8]: Number and proportion of Treatment-Emergent Serious Adverse Events (TESAEs).

Sex: All, ages: 35 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Males aged 35-65 with BMI 18.5-29.9 kg/m².
* Post-menopausal females up to age 65 with BMI 18.5-29.9 kg/m².
* Generally healthy individuals with mild cardiovascular risk factors, specifically -borderline high LDL-C between 100 and 159 mg/dL.
* No current acute or uncontrolled chronic illness.
* Screening FMD: 2.5-6.0%.

Exclusion Criteria:

* Having been diagnosed with known allergies to any ingredients in the product.
* Relevant history or presence of any medical disorder potentially interfering with this study, including but not limited to malabsorption, significant gastrointestinal diseases (e.g., severe constipation, diarrhea, inflammatory bowel disease such as Crohn's disease or ulcerative colitis), severe psychiatric illness which in the opinion of the investigator would interfere with optimal participation in the study, and known cardiovascular disease or stroke, except for conditions deemed clinically insignificant by the investigator (e.g., clinically insignificant atherosclerotic lesions observed by imaging studies).
* Smokers >10 cigarettes per day.
* Subjects consuming >2 alcoholic units per day.
* Subjects reporting a change >5% in body weight within 1 month prior to Screening Visit.
* Subjects playing competitive or high-intensity physical activity.
* Subjects using lipid-altering drug therapy or supplements, nitric oxide donors, phosphodiesterase inhibitors, high-dose antioxidant supplements (including vitamin C), flavonoid-enriched products, or Ubiquinol/Ubiquinone supplements within 4 weeks prior to Screening Visit.
* Having a history of cancer within the past 5 years.
* Having a history of immunosuppression/immune deficiency disorders, including HIV infection, AIDS, multiple sclerosis, Crohn's disease, rheumatoid arthritis, organ transplant, or currently using oral or systemic immunosuppressive medications and biologics and/or undergoing radiation or chemotherapy.
* Currently using or having regularly used corticosteroids (systemic or topical, not nasal or ocular) within the past 4 weeks.
* Having diseases such as asthma, diabetes, epilepsy, hypertension, hyperthyroidism, or hypothyroidism that are not controlled by diet or medication.
* Individuals having multiple health conditions may be excluded from participation even if the conditions are controlled by diet, medication, etc.
* Having started a long-term medication within the last 2 months.
* Having planned surgeries or invasive medical procedures during the study.
* Noninvasive medical procedures or surgeries will be reviewed for their impact on the study outcome and acceptability by the Investigator or designee.
* Currently participating in any other clinical trial at SFRI or another research facility or doctor's office.