Results

Three different formulations containing the equivalent of 100 mg of CoQ10 were used:

• Q10Vital® water-soluble CoQ10 syrup
• Ubiquinol capsules
• Ubiquinone capsules

A single dosage of one capsule and 5 mL of syrup was used. The study was divided into three 48-h treatment periods separated by a 1-week washout period.

The bioavailability of the tested formulations was compared using the area under the baseline-corrected concentration curve (∆AUC₄₈).

Based on the analysis of ∆AUC₄₈ for total CoQ10 and a comparison to ubiquinone:

• The bioavailability of the Q10Vital water-soluble CoQ10 syrup was 2.4 fold higher (95% CI 1.3 to 4.5, p= 0.002).
• The bioavailability of ubiquinol was not significantly increased (1.7 fold, 95% CI 0.9 to 3.1, p= 0.129).
• The proportion of ubiquinol in plasma was around 90% when participants consumed a formulation with ubiquinol or ubiquinone. No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, which indicated that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone (p= 0.424 for Q10Vital versus ubiquinone and p= 0.841 for Q10Vital versus ubiquinol).

Four different CoQ10 formulations were examined in this study:  

• Colloidal-Q10*: 30 mg CoQ10 per capsule
• Solubilizate 1: 60 mg CoQ10 per capsule
• Oil-based formulation: 30 mg CoQ10 per capsule
• Solubilizate 2: 30 mg CoQ10 per capsule

*Colloidal-Q10 is a CoQ10 formulation based on a VESIsorb delivery system that mimics the natural absorption process of the mixed micellar transport system of the human body to improve the bioavailability of poorly water-soluble drugs. 

Subjects were randomized to consume a single oral dose of 120 mg CoQ10. To compare bioavailability, maximum concentration (C_max) and area under the curve from 0 to 10 hours (AUC_{0-10 h}) were assessed. 

• The highest C_max values were observed after colloidal-Q10 administration, where it had the highest plasma concentration levels after 1 hour and continued to increase before reaching a C_max value of 6.89 mcg/mL at about 4 hours.
• The plasma concentration of colloidal-Q10 remained well above the levels of the 3 other products throughout the 24-hour period. 
• The relative bioavailability, calculated using the AUC0-10h values, was also noted to be highest for colloidal-Q10, and values were reported to be 30.6, 6.1, 4.9, and 10.7 mcg/mL*h for colloidal-Q10, solubilizate 1, the oil-based formulation, and solubilizate 2, respectively. 
• The relative bioavailability of colloidal-Q10 was 622% compared to the oil-based formulation, 499% compared to solubilizate 1, and 286% compared to solubilizate 2. 
• The findings of this study suggested that colloidal Q10 improved the enteral absorption and the bioavailability of CoQ10 in humans. 

Two different CoQ10 formulations, each containing 100 mg of CoQ10 were examined in this study:

• Reduced Coenzyme Q10 (CoQH-CF)
• Coenzyme Q10

CoQH-CF is a specially formulated liquid soft gel CoQ10 preparation with reduced CoQ10 106.25 mg, capric acid 9.37 mg, D-limonene oil 336.25 mg, a-lipoic acid 6.25 mg, and caprylic acid 21.88 mg. 

Subjects were randomized to a single dose of one of the two treatments. The bioavailability was compared using plasma concentrations (C_max) and area under the curve from 0 to 72 hours (AUC_0-72). 

• Significantly higher plasma concentrations were demonstrated for the CoQH-CF formulation at 5, 6, 8, 12, 24, 48 and 72 h post-dose compared to the CoQ10 formulation
• The AUC of reduced and total Coenzyme Q10 was significantly higher (p< 0.001) in subjects administered CoQH-CF resulting in 4.3-fold higher plasma AUC_0–72 h (430% increase) in subjects receiving CoQH-CF compared to subjects receiving Coenzyme Q10.
• Oxidized Coenzyme Q10 in plasma was higher (p< 0.001) in subjects receiving CoQH-CF compared to subjects receiving Coenzyme Q10 resulting in a 3.3-fold higher plasma AUC_0–72 h (329% increase). Total CoQ10 reached maximum plasma concentrations 15.5 ± 19.6 h after supplementation with CoQH-CF and 26.5 ± 25.8 h after supplementation with Coenzyme Q10, respectively.
• Overall, reduced CoQH-CF liquid soft gel formulation was found to provide superior bioavailability

Four different CoQ10 formulations were examined in this study: 

• Plain chewable wafers containing 300 mg CoQ10, referred to as a plain chewable wafer
• Chewable wafers containing 600 mg CoQ10 and 300 IU of vitamin E, referred to as chewable wafer with vitamin E
• Hard gelatin capsules containing 600 mg CoQ10, referred to as hard capsules
• Mega Q-Gel “100” soft gel capsules containing 100 mg CoQ10 solubilized in an oil-based vehicle, together with 150 IU d-alpha tocopherol, referred to as soft gel capsules

Subjects were randomized to receive a 600 mg dose of CoQ10. The primary outcome variable was the area under the CoQ10 concentration-time curve from 0 to 48 hours (AUC_0-48). Secondary outcome variables included maximum plasma concentration (C_max) and time to maximum plasma concentration (t_max).

• The mean AUC_0-48 values (mcg/mL × hours) were as follows: 57.9 ± 19.3 (plain chewable wafers), 54.4 ± 17.2 (chewable wafers with vitamin E), 56.9 ± 19.6 (soft gel capsules), and 53.3 ± 21.9 (hard capsules).
• The mean C_max values (mcg/mL) were reported as 1.51 ± 0.46 (plain chewable wafers), 1.34 ± 0.41 (chewable wafers with vitamin E), 1.42 ± 0.47 (soft gel capsules), and 1.38 ± 0.57 (hard capsules). Higher values were noted for the plain chewable wafer formulation compared to the chewable wafer with vitamin E (98.3% CI 0.75 to 2.02) and hard capsule formulations 98.3% CI 0.44 to 1.17), but the geometric mean ratios were not statistically significant. 
• The mean t_max values (hours) were as follows: 17.4 ± 11.2 (plain chewable wafers), 20.9 ± 12.7 (chewable wafers with vitamin E), 13.3 ± 8.8 (soft gel capsules), and 14.3 ± 11.7 (hard capsules). The chewable wafer with vitamin E formulation had a higher geometric mean than the hard capsule (p= 0.008) and soft gel capsule (p= 0.007) formulations.
• No serious or severe adverse events occurred during the conduct of the trial.
• While the plain chewable wafer and soft gel capsule formulations appeared to have slightly better bioavailability overall, it was suggested that the formulation (chewable wafer, hard capsule, soft capsule) does not have a major impact on bioavailability. 

Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease

Design

Randomized, double-blind, placebo-controlled, parallel-group pilot trial

Objective

To evaluate the safety and clinical effects of ubiquinol-10 treatment by assessing changes in total Unified Parkinson's Disease Rating Scale (UPDRS) scores over 96 weeks of treatment

Study Groups

Group A (experience wearing off)

Placebo (n= 15)

Ubiquinol-10 (n= 16)

Group B (without levodopa)

Placebo (n= 13)

Ubiquinol (n= 20)

Inclusion Criteria

Diagnosis of PD conforming to the United Kingdom Brain Bank criteria, patients on levodopa with an "on" phase rating between 1 and 3 on the modified Hoehn and Yahr (H&Y) scale, received the same anti-parkinsonian drug regimen for at least 8 weeks prior to baseline assessment, no exposure to ubiquinol-10 or oxidized coenzyme Q10 (CoQ10)

Exclusion Criteria

Signs of parkinsonism unrelated to PD, dementia or other serious disease, malignant tumor, a history of brain surgery, and adverse events caused by medications

Methods

Eligible patients were divided into two groups: Group A experiencing wearing off and Group B not receiving levodopa with or without dopamine agonists. Patients were then randomized to receive either ubiquinol-10 300 mg/day (3 capsules BID) or placebo for 48 weeks in Group A or 96 weeks for Group B. 

Duration

Outcome Measures

Primary: change in total UPDRS score (Part I + II + III + IV) measured in "on" phase

Other: individual subscale of UPDRS scores, plasma levels of CoQ10

Baseline Characteristics

Group A

Placebo (n= 15)

Age, years

Female

Total UPDRS 

On 

Off

12.3 ± 5.5

28.3 ± 12.1

17.2 ± 11.1

31.8 ± 14.0

7.3 ± 5.2

-

7.4 ± 4.7

-

On-phase, h

Off-phase, h

11.3

5.5

10.3

6.5

-

-

-

-

Levodopa daily dose, mg

Results

Endpoint

Group B

Ubiquinol-10

Total UPDRS 48th week for Group A and 96th week for Group B

p-value vs. placebo

2.9 ± 8.9 (n= 12)

-

-4.2 ± 7.5 (n= 14)

0.018

5.1 ± 10.3 (n= 8)

-

3.9 ± 8.0 (n= 14)

0.785

No significant differences were noted in any subscales of UPDRS scores during any time points in both treatment groups compared to the placebo. 

Supplementation with ubiquinol-10 increased plasma levels of total CoQ10 as much as ten times compared to baseline, while placebo treatment did not. There were no relationships between baseline UPDRS, or change in total UPDRS, and plasma levels of the ratio of oxidized/total CoQ10 (%CoQ10) or ubiquinol-10. 

Adverse Events

Not assessed 

Study Author Conclusions

This is the first report showing that ubiquinol-10 may significantly improve PD with wearing off, as judged by total UPDRS scores, and that ubiquinol-10 is safe and well tolerated.

InpharmD Researcher Critique

The study is limited by its small sample size, and results among the Japanese population may not readily apply to the US population. Additionally, as the study utilized the reduced formulation of CoQ10, use of different formulations could have changed the findings. 

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit

Design

Phase III, randomized, placebo-controlled, double-blind clinical trial

N= 600

Objective

Study Groups

Placebo (n= 203)

CoQ10 1200 mg (n= 201)

CoQ10 2400 mg (n= 196)

Inclusion Criteria

Age ≥ 30 years, presence of all 3 cardinal signs of PD (rest tremor, bradykinesia, rigidity), modified Hoehn and Yahr stage ≤ 2.5, no current or anticipated disability requiring dopaminergic therapy in the next 3 months

Exclusion Criteria

Use of any PD medication within 60 days of baseline visit, use of any symptomatic PD medication for > 90 days, atypical or drug-induced parkinsonism, diagnosis of PD of 5 years or more duration, Unified Parkinson’s Disease Rating Scale (UPDRS) rest tremor score ≥ 3 for any limb, Mini-Mental State Examination score ≤ 25, history of stroke or other serious illness, taking supplements judged to influence outcomes, neuroleptic patients, receiving doses of vitamin E exceeding 800 IU or of vitamin C exceeding 300 mg, substantial exposure to CoQ10 within 120 days

Methods

Patients were randomized to receive 1200 mg/day or 2400 mg/day of CoQ10, or matching placebo, each with 1200 IU/day of vitamin E, which is thought to have synergistic antioxidant effects and enhance CoQ10 absorption. Patients were reevaluated at 1, 4, 8, 12, and 16 months for PD disability sufficient to require dopaminergic therapy and for UPDRS score. 

Duration

Enrollment: January 2009 to October 2010

Intervention: 16 months

Outcome Measures

Primary: change in total UPDRS score from baseline to 16 months, or to the last visit prior to development of sufficient symptoms requiring dopaminergic therapy (“end point”) if this occurred earlier

Secondary: time to reach end point; changes in mental, motor, and activities of daily living UPDRS subscales; changes in Modified Schwab and England activities of daily living scale (SE-ADL); changes in modified Rankin and Symbol digit scores

Baseline Characteristics

Placebo (n= 203)

CoQ10 1200 mg (n= 201)

CoQ10 2400 mg (n= 196)

Age, years

Male

White

Duration of PD, years

UPDRS score

Total

Mental

ADL

Motor

22.7

0.7

5.5

16.5

22.7

0.8

5.8

16.2

22.8

0.7

5.6

16.4

Hoehn and Yahr stage

1.6

1.7

1.6

Modified SE-ADL scale

Modified Rankin Score

Symbol digit score

No significant difference reported between groups for any baseline characteristics.

Results

Endpoint

Placebo (n= 203)

CoQ10 1200 mg (n= 201)

CoQ10 2400 mg (n= 196)

Change in UPDRS score from baseline

Total

Mental

ADL

Motor

6.92 ± 0.63

0.41 ± 0.09

2.23 ± 0.23

4.23 ± 0.45

7.50 ± 0.62

0.45 ± 0.09

2.76 ± 0.23

4.24 ± 0.45 

8.01 ± 0.63

0.60 ± 0.09

2.50 ± 0.23

4.88 ± 0.45

Modified SE-ADL scale

Modified Rankin score

Symbol digit score

No statistically significant differences were reported between treatment groups for any outcome. 

Adverse Events

No group differences in number of adverse events (including moderate to severe events, or events potentially related to study drug) were reported. Overall, 73.5% of participants reported an adverse event, mostly mild and considered unrelated to the study drug. The most commonly reported adverse events included back pain, constipation, insomnia, anxiety, and tremor. Significant differences for individual adverse events were only noted for insomnia (3.0% placebo, 6.5% CoQ10 1200 mg, 3.1% CoQ10 2400 mg; p= 0.04) and hypertension (0%, 3.5%, 2.6%; p= 0.03). 

Study Author Conclusions

In summary, although this phase II (QE3) study shows that CoQ10 can be safely administered to patients with early PD at dosages of 1200 and 2400 mg/d, no therapeutic efficacy was demonstrated. In view of these results, the authors cannot recommend CoQ10 for the treatment of early PD.

InpharmD Researcher Critique

This study was terminated on April 29, 2011 due to both active treatment groups reaching prespecified termination criterion for futility. Results of this study conflicted with a previous phase II study (QE2); however, the previous study incorporated a limited sample size (N= 80).