Coenzyme Q10 for Parkinson's disease

Coenzyme Q10 for Parkinson’s disease (Review)

Liu J, Wang L, Zhan SY, Xia Y

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2011, Issue 12

http://www.thecochranelibrary.com

Coenzyme Q10 for Parkinson’s disease (Review)

Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

18DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Co Q10 versus placebo, Outcome 1 Total UPDRS score change. . . . . . . . . 20

Analysis 1.2. Comparison 1 Co Q10 versus placebo, Outcome 2 Motor UPDRS. . . . . . . . . . . . . . 22

Analysis 1.3. Comparison 1 Co Q10 versus placebo, Outcome 3 Mental UPDRS. . . . . . . . . . . . . 23

Analysis 1.4. Comparison 1 Co Q10 versus placebo, Outcome 4 ADL UPDRS. . . . . . . . . . . . . . 24

Analysis 1.5. Comparison 1 Co Q10 versus placebo, Outcome 5 Hoehn & Yahr. . . . . . . . . . . . . . 25

Analysis 1.6. Comparison 1 Co Q10 versus placebo, Outcome 6 Schwab & England (investigator). . . . . . . 26

Analysis 1.7. Comparison 1 Co Q10 versus placebo, Outcome 7 severe viral infection. . . . . . . . . . . . 27

Analysis 1.8. Comparison 1 Co Q10 versus placebo, Outcome 8 Pharyngitis. . . . . . . . . . . . . . . 28

Analysis 1.9. Comparison 1 Co Q10 versus placebo, Outcome 9 Sinusitis. . . . . . . . . . . . . . . . 29

Analysis 1.10. Comparison 1 Co Q10 versus placebo, Outcome 10 Flatulence. . . . . . . . . . . . . . 30

Analysis 1.11. Comparison 1 Co Q10 versus placebo, Outcome 11 Back pain. . . . . . . . . . . . . . . 31

Analysis 1.12. Comparison 1 Co Q10 versus placebo, Outcome 12 Coughing. . . . . . . . . . . . . . 32

Analysis 1.13. Comparison 1 Co Q10 versus placebo, Outcome 13 Diarrhea. . . . . . . . . . . . . . . 33

Analysis 1.14. Comparison 1 Co Q10 versus placebo, Outcome 14 Fall. . . . . . . . . . . . . . . . . 34

Analysis 1.15. Comparison 1 Co Q10 versus placebo, Outcome 15 Fatigue. . . . . . . . . . . . . . . 35

Analysis 1.16. Comparison 1 Co Q10 versus placebo, Outcome 16 Hypercholesterolemia. . . . . . . . . . 36

Analysis 1.17. Comparison 1 Co Q10 versus placebo, Outcome 17 Number of withdrawals due to adverse effects. . 37

Analysis 2.1. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 1 Total UPDRS score change. . 38

Analysis 2.2. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 2 Motor UPDRS. . . . . . 39

Analysis 2.3. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 3 Mental UPDRS. . . . . . 40

Analysis 2.4. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 4 ADL UPDRS. . . . . . 41

Analysis 2.5. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 5 Hoehn & Yahr. . . . . . 42

Analysis 2.6. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 6 Schwab & England (investigator). 43

43HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

44CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

44DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

44SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

44DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .

44INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iCoenzyme Q10 for Parkinson’s disease (Review)


[Intervention Review]

Coenzyme Q10 for Parkinson’s disease

Jia Liu1 , Luning Wang1 , Si-Yan Zhan2, Yinyin Xia3

1Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, China. 2Department of Epidemiology and Biostatistics,

School of Public Health, Peking University Health Science Center, Beijing, China. 3Department of Epidemiology and Biostatistics,

School of Public Health, Peking University Health Science Center, Beijing, China

Contact address: Luning Wang, Department of Geriatric Neurology, Chinese PLA General Hospital, Fuxinglu 28, Beijing, 100853,

China. [email protected].

Editorial group: Cochrane Movement Disorders Group.

Publication status and date: New, published in Issue 12, 2011.

Review content assessed as up-to-date: 16 July 2011.

Citation: Liu J, Wang L, Zhan SY, Xia Y. Coenzyme Q10 for Parkinson’s disease. Cochrane Database of Systematic Reviews 2011, Issue

12. Art. No.: CD008150. DOI: 10.1002/14651858.CD008150.pub2.


A B S T R A C T

Background

A number of preclinical studies in both in vitro and in vivo models of Parkinson’s disease have demonstrated that coenzyme Q10

can protect the nigrostriatal dopaminergic system. Some clinical trials have looked at the neuroprotective effects of coenzyme Q10 in

patients with early and midstage Parkinson’s disease.

Objectives

To assess the evidence from randomized controlled trials on the efficacy and safety of treatment with coenzyme Q10 compared to

placebo in patients with early and midstage Parkinson’s disease.

Search methods

We searched the Cochrane Movment Disorders Group Trials Register, CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE

(January 1966 to March 2011), and EMBASE (January 1985 to March 2011). We handsearched the references quoted in the identified

trials, congress reports from the most important neurological association and movement disorder societies in Europe and America

(March 2011), checked reference lists of relevant studies and contacted other researchers.

Selection criteria

We included randomized controlled trials (RCTs) that compared coenzyme Q10 to placebo for patients who suffered early and midstage

primary Parkinson’s disease. Studies in which the method of randomization or concealment were unknown were included. Cross-over

studies were excluded.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data. All disagreements were resolved by consensus between

authors and were explained. We attempted to contact the authors of studies for further details if any data were missing and to establish

the characteristics of unpublished trials through correspondence with the trial coordinator or principal investigator. Adverse effects

information was collected from the trials.

1Coenzyme Q10 for Parkinson’s disease (Review)


Main results

Four randomized, double-blind, placebo-controlled trials with a total of 452 patients met the inclusion criteria and were included in

the review. In overall, there were improvements in activities of daily living (ADL) UPDRS (WMD -3.12, 95% CI -5.88 to -0.36) and

Schwab and England (WMD 4.43, 95% CI 0.05 to 8.81) for coenzyme Q10 at 1200 mg/d for 16 months versus placebo.

In safety outcomes, only the risk ratios (RR) of pharyngitis (RR 1.04, 95% CI 0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to

3.16) are mild elevated between coenzyme Q10 therapy and placebo and there were no differences in the number of withdrawals due

to adverse effects (RR 0.61, 95% CI 0.23 to 1.62).

Authors’ conclusions

Coenzyme Q10 therapy with 1200 mg/d for 16 months was well tolerated by patients with Parkinson’s disease. The improvements

in ADL UPDRS and Schwab and England were positive, but it need to be further confirmed by larger sample. For total and other

subscores of UPDRS, the effects of coenzyme Q10 seemed to be less clear.

P L A I N L A N G U A G E S U M M A R Y

[Coenzyme Q10 for Parkinson’s Disease.]

[Mitochondrial dysfunction has been well established to occur in Parkinson’s disease and appears to play a role in the pathogenesis of

the disorder. A deficit in brain coenzyme Q10 status may be involved in the pathophysiology of Parkinson’s disease. Mitochondria play

a central role in apoptotic cell death through a number of mechanisms. Coenzyme Q10 as an antioxidant, can affect certain of these

processes. Theoretically, coenzyme Q10 can interfere with Parkinson’s disease progression. There are four randomized, double-blind,

placebo-controlled trials that tested coenzyme Q10 for Parkinson’s disease. The results show coenzyme Q10 at dose of 1200mg/d for

16 months is well-tolerated and might disability as measured improve ADL UPDRS and Schwab and England. However this data is

uncertain and precludes that this treatment be recommended for clinical use without further confirmatory trials are done.]

B A C K G R O U N D

Description of the condition

Parkinson’s disease (PD) is the second most common progressive

neurodegenerative disorder and is characterized by several cardi-

nal symptoms including resting tremor, rigidity, bradykinesia, and

postural instability (Calne 1992). PD is believed to result from

a progressive loss of dopaminergic neurons in the substantia ni-

gra (Lang 1998). Once 80% or so of the dopamine producing

cells have been damaged the symptoms of PD begin to be no-

ticed (Neutel 2007). The prevalence rates range from 57 to 371

per 100,000, worldwide (Lang 1998; Strickland 2004). The in-

cidence increases with age and peaks between the ages of 70 and

79 years (Twelves 2003). Since populations are aging slowly, and

recognition of parkinsonism is improving, it is anticipated that

the incidence and prevalence will rise in the next decades (Neutel

2007).

Description of the intervention

Coenzyme Q10 (Co Q10) is composed of a quinine ring and a

10 isoprene unit tail; it is distributed in all membranes through-

out a cell (Crane 2001). Co Q10 is an essential cofactor in the

mitochondrial electron transport pathway and is also a lipid-solu-

ble antioxidant. It is endogenously synthesised via the mevalonate

pathway, and some is obtained from the diet (Molyneux 2008).

However, supplementary oral administration of Co Q10 has been

found to increase Co Q10 levels in plasma, platelets, and white

blood cells (Niklowitz 2007). Coenzyme Q10 as a vitamin-like

substance has been used in a variety of disorders primarily related

to suboptimal cellular energy metabolism and oxidative injury, e.g.

primary hypertension and heart failure (Ho 2009; Kumar 2009).

Studies also supported the efficacy of Coenzyme Q10 as a neu-

roprotectant for neurodegenerative disorders such as Parkinson’s

disease and certain encephalomyopathies (Bonakdar 2005).



How the intervention might work

It has been well established that mitochondrial dysfunction occurs

in PD and appears to play a role in the pathogenesis of the disorder.

Mitochondrial function has been evaluated in PD patients with

early untreated disease. A significantly reduced mitochondrial level

of Co Q10 was found from the PD subjects compared with age

and gender matched control subjects (Shults 1997). A deficit in

brain Co Q10 status may be involved in the pathophysiology of

PD (Hargreaves 2008). A key component of the mitochondrial

electron transport chain (ETC) is Co Q10, which not only serves as

the electron acceptor for complexes I and II of the ETC but is also

an antioxidant. In addition to being crucial to the bioenergetics

of the cell, mitochondria play a central role in apoptotic cell death

through a number of mechanisms and Co Q10 can affect certain

of these processes (Shults 2005). Co Q10 may possibly slow the

progression of PD.

Why it is important to do this review

A number of preclinical studies in in vitro and in vivo models

of PD have demonstrated that Co Q10 can protect the nigros-

triatal dopaminergic system. Oral supplementation with Co Q10

can reduce the loss of dopamine and dopaminergic axons in the

striatum in one-year old mice treated with 1-methyl-4-phenyl-

1,2,3,6-tetrahydropyridine (MPTP) (Beal 1998). Experiments on

monkeys also reported that 10 days of oral supplementation with

Co Q10 (15 to 22 mg/kg, a dose range similar to that used in the

phase II trial in patients with PD) prior to treatment with MPTP

significantly attenuated the loss of nigral dopaminergic neurons

(Horvath 2003). At the same time, several clinical trials looked at

the neuroprotective effects of Co Q10 in early and midstage PD

patients.

No systematic review with meta-analysis currently exists in the

peer-reviewed literature that focuses on Co Q10 for patients with

PD. This review is designed to comprehensively examine the cur-

rent literature in order to evaluate the efficacy and safety of treat-

ment with Co Q10 in patients with early and midstage PD in

order to guide and normalize its use in clinical treatment.

O B J E C T I V E S

To assess the evidence from randomized controlled trials for the

efficacy and safety of treatment with Co Q10 compared to placebo

in patients with early and midstage PD.

M E T H O D S

Criteria for considering studies for this review

Types of studies

We included randomized controlled trials (RCTs) that compared

Co Q10 to placebo. Studies in which the methods of random-

ization or concealment were unknown were included. Cross-over

studies were excluded.

Types of participants

We included studies with participants, aged 30 years or older, of

either sex and with early and midstage PD according to the Hoehn

and Yahr stage. Participants were evaluated according to the Uni-

fied Parkinson’s Disease Rating Scale (UPDRS) (Fahn 1987) from

the time of study entry to its termination. Patients were excluded

if they had fluctuations or any secondary causes of parkinsonism,

such as drug-induced parkinsonism and structural lesions. Partic-

ipants were either stable on antiparkinsonism medications for the

treatment of their symptoms or not at the time of entry to the

study.

Types of interventions

Oral Co Q10, including nanoparticular and standard formula-

tions, from 300 mg/d to 2400 mg/d versus placebo. Vitamin E

could be added to the formulation as a lipophilic carrier and the

placebo contained the same dosage of vitamin E. Use of an an-

tiparkinsonism drug remained stable throughout the whole trial if

it had been used before study enrollment. The minimum duration

of treatment was four weeks.

Types of outcome measures

Primary outcomes

Efficacy

The rate of progression of PD as measured by the change in the

total UPDRS score

Safety

The number of patients with adverse effects



Secondary outcomes

Efficacy

The change in the respective UPDRS subscores

The outcome of quality of life scales

Plasma level of Co Q10

Mitochondrial assays

Safety

The number of withdrawals due to adverse effects

Search methods for identification of studies

Electronic searches

(1)The Cochrane Central Register of Controlled Trials (CEN-

TRAL) (The Cochrane Library 2009, Issue 4):

#1. PARKINSONIAN DISORDERS explode tree 1 (MeSH)

#2. parkinson*

#3. (#1 or #2)

#4. ubiquinone single term (MeSH)

#5. ubiquinone

#6. coenzyme Q10

#7. (#4 or #5 or #6)

#8. (#3 and #7)

(2)Example for Medline(1966 to present) search through OVID

Gateway:

1.Parkinson$.tw.

2.exp Parkinsonian Disorders/

3.1 or 2

4.coenzyme Q10/

5.coenzyme Q10.tw

6.ubiquinone.tw

7.or/4-6

8.randomized controlled trial.pt.

9.controlled clinical trial.pt.

10.randomized controlled trials/

11.random allocation/

12.double?blind method/

13.single?blind method/

14.clinical trial.pt.

15.exp clinical trials/

16.clin$ with trial$.tw.

17.random$.tw.

18.exp research design/

19.or/8-20

20.limit 19 to animal

21.limit 19 to human

22.20 and 21

23.20 not 22

24.19not 23

25. 3 and 7 and 24

(3)Example for EMBASE(1980 to present) through OVID Gate-

way:

1. Parkinson Disease/

2. Parkinsonism/

3. Parkinson$.tw.

4. 1 or 2 or 3

4. coenzyme Q10/

5. coenzyme Q10.tw

6. ubiquinone.tw

7.or/4-6

8.clinical trial/

9.multicenter study/

10.phase 2 clinical trial/



13.randomized controlled trial/

14.controlled study/

15.meta analysis/

16.double blind procedure/

17.single blind procedure/

18.randomization/

19.major clinical study/

20.placebo/

21.drug comparison/

22.clinical study/

23.(clin$ adj25 trial$).tw.

24.((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or

mask$)).tw.

25.placebo$.tw.

26.random$.tw.

27.control$.tw.

28.or/8-27

29.human/

30.nonhuman/

31.8 and 30

32.30 not 31

33.28 not 32

34.4 and7 and 33

(4) Online searching of conference proceeding through the ISI

proceedings database (1990 to present):

#1 TS=( coenzyme Q10 OR ubiquinone)

#2 TS=(TRIAL OR RANDOM* OR PLACEBO* OR CON-

TROL*)

#3 #1 AND #2

Searching other resources



(5) Handsearching of conference proceedings including:

Movement Disorders - Maryse Lapeyre-Mestre; Completed:

1994,1996; Still searching: 1986-93, 1995, 1997-98;

European Journal of Disorders of Communication - Julie Speller;

Dysphagia - Julie Speller;

Physiotherapy - Julie Speller;

European Neuropsychopharmacology - Pascale Jolliet;

Italian Journal of neurological Sciences - Carlo Colosimo;

International Congresses of Movement Disorders;

International Congresses on Parkinson’s Disease;

World Congresses of Neurology;

Annual meetings of the American Academy of Neurology;

Meetings of the American Neurological Society;

Meetings of the European Federation of Neurological Sciences;

Meetings of the European Neurological Society;

Meetings of the Scandinavian Congress of Neurology.

(6) Checking reference lists of relevant trials to identify any addi-

tional

trials.

(7) Previous reviews.

(8) Personal communication: we will contact other researchers in

the field.

Data collection and analysis

Selection of studies

Two review authors (LJ, WL) independently assessed titles and

abstracts identified from the literature search and obtained the full

text of potentially relevant studies. Two review authors (LJ, WL)

independently evaluated the eligibility (on the basis of information

accessible in the published data) and assessed the methodological

quality of these studies. Any discordance was resolved by discussion

or by an independent party if agreement still could not be obtained.

Data extraction and management

Two review authors independently extracted eligible data from the

published reports onto standardised forms and cross-checked them

for accuracy. Disagreements regarding inclusion were resolved by

consensus between authors and were recorded. We attempted to

contact the authors of the studies for further details if any data were

missing and to establish the characteristics of unpublished trials

through correspondence with the trial coordinator or principal

investigator. We used checklists to independently record details of

the:

• methods of generating randomization schedule;

• method of concealment of allocation;

• blinding of assessors;

• use of an intention-to-treat analysis (all participants initially

randomized included in the analyses as allocated to groups);

• adverse events and drop outs for all reasons;

• important imbalance in prognostic factors;

• participants (country, number of participants, age, gender,

inclusion and exclusion criteria);

• comparison (details of the intervention in treatment and

control groups; details of co-intervention(s) in both groups;

duration of treatment);

• outcomes and time points of measures (number of

participants in each group and outcome, regardless of

compliance).

Assessment of risk of bias in included studies

Methodological quality was assessed independently by two review

authors (LJ, WL) according to method of randomization, blind-

ing of treatment and outcome assessment, completeness of fol-

low up, and whether intention-to-treat analysis was carried out or

was possible from the published data. The quality of the included

studies was evaluated according to the Cochrane Collaboration

Handbook criteria (based on the allocation concealment). We as-

sessed whether the treatment groups were comparable with regard

to demographics, clinical characteristics, and the number of pa-

tients excluded or lost to follow up within each trial; and whether

the definition of outcomes and entry and exclusion criteria were

comparable across the different trials. Sources of bias were con-

sidered on a study-by-study basis and studies were to be excluded

if the authors agreed that they were significantly biased. In such

cases, reasons for exclusion were recorded.

Measures of treatment effect

We expected the RCTs to measure both event (dichotomous)

data and continuous data. Continuous data were expressed as

weighted mean differences (WMD) or standardised mean differ-

ences (SMD), and dichotomised data were expressed as risk ra-

tios (RR). We calculated the WMD with 95% confidence interval

(CI). If studies did not use the same outcome, we used the SMD

with 95% CI. For all binary outcomes we calculated RR with 95%

CI. As it was possible that some trials (or groups within a trial) had

no adverse events or no drop outs, we calculated risk differences

(RD) instead of RRs in these specific situations, again with 95%

CI.

Unit of analysis issues

We described variability in participants, interventions, and the

outcomes studied (clinical diversity) in an additional table. This

did not influence the selection of trials.

Dealing with missing data

We attempted to contact the authors of the studies for further

details if any data were missing and to establish the characteristics



of unpublished trials through correspondence with the trial coor-

dinator or principal investigator.

Assessment of heterogeneity

To test for heterogeneity we used the I2 (Higgins 2003) statistic

(alpha level 50%) for all comparisons. If we found statistically

significant heterogeneity, we calculated the overall effects using a

random-effects model instead of a fixed-effect model.

Assessment of reporting biases

The effect of publication bias was to be analysed with a funnel

plot if a significant result was found (Egger 1997).

Data synthesis

Formal meta-analysis using the RevMan software was performed,

where possible, although substantial heterogeneity between the

studies can prevent this. Otherwise we will give a descriptive sum-

mary of the results.

Subgroup analysis and investigation of heterogeneity

We planned that if there is significant heterogeneity we will at-

tempt to identify possible causes by carrying out a number of sub-

group analyses. Where relevant, and where data were available,

subgroup analysis was to include age, gender, severity of disease

(such as total UPDRS score, UPDRS motor score, Hoehn and

Yahr scale score at baseline), using antiparkinsonism medication

or not, the dosage of Co Q10, and the duration of treatment. As

a formal method of comparing subgroups, we used the Chi2 test

(to test for significant differences between both subgroups of par-

ticipants). For all statistical analyses we used the latest version of

the Cochrane Collaboration’s Review Manager software (RevMan

2008).

Sensitivity analysis

If heterogeneity of the selected trial estimates was present, we

planned to investigate the source by doing a sensitivity analysis.

For positive results, we also planned to assess the effect of missing

outcomes from patients excluded after randomization by perform-

ing a best and worse case sensitivity analysis.

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies; Characteristics of ongoing studies.

Using our search methods, 648 references were considered further.

After screening of titles and abstracts, full papers of seven studies

were obtained and assessed for eligibility. Two were excluded due

to an invalid control. Agreement between the review authors on

exclusion was 100%. At the same time, two trial reports were

identified as the same trial. To sum up, a total of four trials were

included. There is also an ongoing Phase III randomized controlled

trials on this intervention.

Results of the search

Four randomized, double-blind, placebo-controlled trials, with a

total of 452 patients, met the inclusion criteria and were included

in the review. Summary details of these trials are given in the

Characteristics of included studies table.

Included studies

Five studies were selected according to the criteria (Mueller 2003;

Shults 2002; Sotirios 2009; Storch 2007; The NINDS NET-PD

2007). However, two trial reports were identified as the same trial

(Sotirios 2009; The NINDS NET-PD 2007). Therefore, a total

of four studies were included in this review (Mueller 2003; Shults

2002; Storch 2007; The NINDS NET-PD 2007).

Excluded studies

Two studies were excluded based on the reason that they were

open-label trials without matched controls (Shults 2004; Strijks

1997).

Risk of bias in included studies

Allocation

All the studies had well concealed methods of allocation. How-

ever, they made use of different kinds of randomization such as

numbered containers, computer generated, and a randomization

list generated by the investigator. All were considered reasonable.

Blinding

The four studies were all double-blind trials. In one trial (Storch

2007), the randomization list was generated by one investigator

(RK). And it should be clarified that if RK went on to participate

this trial after randomization, although the title called double-

blind trial.



Incomplete outcome data

Nearly all the studies have individuals who did not complete the

trials; the trial by Mueller 2003 recorded that “All participants were

reevaluated under identical conditions 4 weeks later”. However,

in every study the percentage of participants lost to follow up was

less than 5% and reasons for losses were specified. All withdrawals

after randomization were included in the data analysis.

Selective reporting

None known

Other potential sources of bias

Some data were presented in a line or column graph, which meant

we could not obtain the accurate figures for the mean value and

standard deviation. We made inquiries to the primary investigator

but unfortunately responses were rare. Therefore we had to discard

some uncertain data in our analysis, which may cause potential

bias. In future updates, once we have acquired the required infor-

mation, we can improve this process.

Effects of interventions

Total UPDRS score change (comparisons 1.1)

Three included trials (Mueller 2003; Shults 2002; The NINDS

NET-PD 2007) measured the changes in total UPDRS score, with

Co Q10 from 300 mg/d to 2400 mg/d. However, there were no

differences between coenzyme Q10 at any dose and placebo. All

the 95% CI spanned zero, which meant no statistical significance.

Number of patients with all expected adverse effects (compar-

isons 1.7 to 1.16)

There was no difference in common adverse effects, even in a dose

of 1200 or 2400 mg/d, compared with placebo. No severe adverse

effects were reported which were believed to be related to Co Q10

therapy.

• 1200 mg/d Co Q10 versus placebo: severe viral infection,

pharyngitis, sinusitis, diarrhea, back pain (RR 1.04, 95% CI

0.14 to 7.70).

• 2400 mg/d Co Q10 versus placebo: sinusitis (RR 0.63, 95%

CI 0.21 to1.82); back pain (RR 1.50, 95% CI 0.44 to 5.09).

The risk ratios of other common adverse effects were all less than

one (please see Data and analyses).

Change in the respective UPDRS subscore and quality of life

scales

For motor UPDRS (comparisons 1.2), mental UPDRS (compar-

isons 1.3) and Hoehn and Yahr (comparisons 1.5), there were also

no differences between coenzyme Q10 at any dose and placebo.

All the 95% CI spanned zero, which meant no statistical signifi-

cance.

Only the dose of 1200 mg/d for 16 months appeared to be effec-

tive (comparisons 1.4 and 1.6), in activities of daily living (ADL)

UPDRS (WMD -3.12, 95% CI -5.88 to -0.36) and Schwab and

England (WMD 4.43, 95% CI 0.05 to 8.81).

Plasma level of Co Q10

Two studies (Shults 2002; Storch 2007) mentioned this outcome.

The group receiving Co Q10 always had a significant increase in

the mean Co Q10 plasma level, comparing with the placebo group.

The mean plasma levels of Co Q10 were significantly related to

the dosage of receiving Co Q10.

Mitochondrial assays

Only one study (Shults 2002) referred to the mitochondrial assays.

Results of the assay of the activity of complex I normalized to the

activity of citrate synthetase did not indicate a significant effect of

Co Q10. In this assay, the activity of complex I did not depend

on endogenous Co Q10, as an excess of exogenous Co Q10 was

added. There was also a significant increase in the activity of the

electron transport chain with treatment with Co Q10.

Number of withdrawals due to adverse effects (comparison

1.17)

There were two studies which reported the withdrawals due to

adverse effects (Storch 2007; The NINDS NET-PD 2007). No

difference existed between Co Q10 therapy and placebo (RR 0.61,

95% CI 0.23 to 1.62).

Sensitive analysis

A sensitivity analysis was undertaken to split the short-term versus

long-term (at least 12 months) efficacy of Co Q10 for PD patients.

The results were robust to changes in the way the analysis was

done. In long-term use of Co Q10, there were improvements at

dosage of 1200mg/d in ADL UPDRS (WMD -3.12, 95% CI -

5.88 to -0.36) and Schwab and England (WMD 4.43, 95% CI

0.05 to 8.81), but not in other items or dosages (please see Data

and analyses).

D I S C U S S I O N

Summary of main results

Four randomized, double-blind, placebo-controlled trials with a

total of 452 patients met the inclusion criteria and were included

in the review. In overall, there were improvements in ADL UPDRS

(WMD -3.12, 95% CI -5.88 to -0.36) and Schwab and England

(WMD 4.43, 95% CI 0.05 to 8.81) for coenzyme Q10 at 1200

mg/d for 16 months versus placebo.

In safety outcomes, only the RR of pharyngitis (RR 1.04, 95% CI

0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to 3.16) are

mild elevated between coenzyme Q10 therapy and placebo and

there were no differences in the number of withdrawals due to

adverse effects (RR 0.61, 95% CI 0.23 to 1.62).



Overall completeness and applicability ofevidence

Three of the four studies had individual participants who did not

complete the study. Nevertheless, the percentage of loss to follow

up for all the 452 patients was less than 5%, which is regarded

as acceptable. In addition, nearly all the reasons for losses were

specified. At the same time, all withdrawals after randomization

were included in the data analysis (please see Characteristics of

included studies). Therefore, the evidence from this review is valid

and applicable for clinical guidance.

Quality of the evidence

We believe the quality of the evidence is credible. The search

method was rigorous and well performed. Moreover, all the in-

cluded trials were high quality through our evaluation (please see

Characteristics of included studies). The reasons for excluding

trials were also specified (please see Characteristics of excluded

studies). The eligible data were analysed with official updated soft-

ware.

Potential biases in the review process

Some data in the included trials were presented in a line or column

graph. This led to our inability to obtain the accurate figures,

for example the mean value and standard deviation. We made

inquiries to the primary investigator for the detailed information

and are awaiting responses. Therefore, we had to discard some

uncertain data in our analysis, which may cause potential bias.

Agreements and disagreements with otherstudies or reviews

This is the first systematic review on this topic, as far as we are

aware and so we have no other review to compare with.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

The Co Q10 dose of 1200 mg/d is well-tolerated by patients with

PD. The improvements of coenzyme Q10 at 1200 mg/d for 16

months in ADL UPDRS and Schwab and England were positive,

but it need to be further confirmed by larger sample. However, for

total and motor UPDRS, the effect seems to be less clear. More

well-designed studies are required to establish an effect.

Implications for research

More research is required in the future, particularly well-designed,

double-blind randomized controlled trials. The focal point should

be as follows.

(1) The efficacy and safety of high doses, such as 1200 mg/d, 2400

mg/d and 3000 mg/d.

(2) The difference in efficacy and safety between different forms,

such as nanoparticular Co Q10 and standard formulation.

(3) All the data, including the scale scores and biochemistry out-

comes, should be published in detail and as complete as possible;

at least the mean value and standard deviation should be provided

as well as a line or column graph.

Actually, there is an ongoing study in this field (please see

Characteristics of ongoing studies), which is also a randomized,

double blind treatment trial. The paticipants are the patients with

idiopathic PD, and the prospective sample size is 600. The inter-

vention is Co Q10 1200mg/d with vitamin E 1200 IU/day versus

placobo with vitamin E 1200 IU/day. The primary outcomes are

changes in UPDRS total score and subsores. Therefore, we will

consider this trial in the next update, if the data is available.

A C K N O W L E D G E M E N T S

The authors would like to acknowledge the help provided by the

Cochrane Movement Disorders Group.

R E F E R E N C E S

References to studies included in this review

Mueller 2003 {published data only}

Müller T, Büttner T, Gholipour AF, Kuhn W. Coenzyme

Q10 supplementation provides mild symptomatic benefit

in patients with Parkinson’s disease. Neuroscience Letters

2003;341(3):201–4. [MEDLINE: 12697283]

Shults 2002 {published data only}

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb

S, et al.Parkinson Study Group. Effects of coenzyme Q10

in early Parkinson disease: evidence of slowing of the

functional decline. Archives of Neurology 2002;59(10):

1541–50. [MEDLINE: 12374491]

Sotirios 2009 {published data only}

Parashos SA, Swearingen CJ, Biglan KM, Bodis-Wollner

I, Liang GS, Ross GW, et al.NET-PD Investigators.

Determinants of the timing of symptomatic treatment

in early Parkinson disease: The National Institutes of

Health Exploratory Trials in Parkinson Disease (NET-PD)



Experience. Archives of Neurology 2009;66(9):1099–104.

[MEDLINE: 19597081]

Storch 2007 {published data only}

Storch A, Jost WH, Vieregge P, Spiegel J, Greulich W,

Durner J, et al.German Coenzyme Q(10) Study Group.

Randomized, double-blind, placebo-controlled trial on

symptomatic effects of coenzyme Q(10) in Parkinson

disease. Archives of Neurology 2007;64(7):938–44.

[MEDLINE: 17502459]

The NINDS NET-PD 2007 {published data only}

NINDS NET-PD Investigators. A randomized clinical trial

of coenzyme Q10 and GPI-1485 in early Parkinson disease.

Neurology 2007;68(1):20–8. [MEDLINE: 17200487]

References to studies excluded from this review

Shults 2004 {published data only}

Shults CW, Flint Beal M, Song D, Fontaine D. Pilot trial of

high dosages of coenzyme Q10 in patients with Parkinson’s

disease. Experimental Neurology 2004;188(2):491–4.

[MEDLINE: 15246848]

Strijks 1997 {published data only}

Strijks E, Kremer HP, Horstink MW. Q10 therapy in

patients with idiopathic Parkinson’s disease. Molecular

Aspects of Medicine 1997;18 Suppl:237–40. [MEDLINE:

9266528]

References to ongoing studies

Phase III {unpublished data only}

Parkinson Study Group. Effects of Coenzyme Q10 in

Parkinson Disease - Phase III.

Additional references

Beal 1998

Beal MF, Matthews RT, Tieleman A, Shults CW.

Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,

3,6-tetrahydropyridine (MPTP) induced loss of striatal

dopamine and dopaminergic axons in aged mice. Brain

Research 1998;783:109–14.

Bonakdar 2005

Bonakdar RA, Guarneri E. Coenzyme Q10. Review.

American Family Physician 2005;72(6):1065–70.

Calne 1992

Calne DB, Snow BJ, Lee C. Criteria for diagnosing

Parkinson’s disease. Annals of Neurology 1992;32 Suppl:

125–7.

Crane 2001

Crane FL. Biochemical functions of coenzyme Q10. Journal

of the American College of Nutrition 2001;20(6):591–8.

Egger 1997

Egger M, Davey Smith G, Schneider M, Minder C. Bias

in meta analysis detected by a simple, graphical test. BMJ

1997;315(7190):629–34.

Fahn 1987

Fahn S, Elton RL, UPDRS Development Committee.

The Unified Parkinson’s Disease Rating Scale. In: Fahn S,

Marsden CD, Calne DB, editors. Recent Developments in

Parkinson’s Disease. Vol 2. Florham Park, NJ: Macmillan

Healthcare Information; 1987:153-163,293-304.

Hargreaves 2008

Hargreaves IP, Lane A, Sleiman PM. The coenzyme Q10

status of the brain regions of Parkinson’s disease patients.

Neuroscience Letters 2008;447(1):17–9.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG.

Measuring inconsistency in meta-analyses. BMJ 2003, 327

(7414):557-60.

Ho 2009

Ho MJ, Bellusci A, Wright JM. Blood pressure lowering

efficacy of coenzyme Q10 for primary hypertension.

Cochrane Database Syst Rev 2009 Oct 7, (4):CD007435.

Horvath 2003

Horvath TL, Diano S, Leranth C, Garcia-Segura LM,

Cowley MA, Shanabrough M. Coenzyme Q induces nigral

mitochondrial uncoupling and prevents dopamine cell loss

in a primate model of Parkinson’s disease. Endocrinology

2003;144(7):2757–60.

Kumar 2009

Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme

Q10 in cardiac disease, hypertension and Meniere-like

syndrome. Pharmacol Ther 2009;124:259–268.

Lang 1998

Lang AE, Lozano AM. Parkinson’s disease. First of two

parts. New England Journal of Medicine 1998;339:1044–53.

Molyneux 2008

Molyneux SL, Young JM, Florkowski CM, Lever M, George

PM. Coenzyme Q10: Is There a Clinical Role and a Case

for Measurement?. Clinical Biochemistry Reviews 2008;29

(2):71–82.

Neutel 2007

Neutel D, Ferreira J, CoelhoMM, RosaMM, Rascol O,

Sampaio C. Piribedil versus levodopa in earlyParkinson’s

disease. CochraneDatabase of Systematic Reviews

2007, Issue 3. Art.No.: CD006710. DOI:

10.1002/14651858.CD006710.

Niklowitz 2007

Niklowitz P, Sonnenschein A, Janetzky B, Andler W, Menke

T. Enrichment of coenzymeQ10 in plasma and blood cells:

defense against oxidative damage. International Journal of

Biological Sciences 2007;3(4):257–62.

RevMan 2008

TheNordic Cochrane Centre, The Cochrane Collaboration.

Review Manager (RevMan). 5.0 for Windows.

Copenhagen: The Nordic Cochrane Centre, The Cochrane

Collaboration, 2008.

Shults 1997

Shults CW, Haas RH, Passov D, Beal MF. Coenzyme Q10

levels correlate with the activities of complexes I and II/III

in mitochondria from parkinsonian and nonparkinsonian

subjects. Annals of Neurology 1997;42(2):261–4.



Shults 2005

Shults CW. Therapeutic role of coenzyme Q10 in

Parkinson’s disease. Pharmacology & Therapeutics 2005;107

(1):120–30.

Strickland 2004

Strickland D, Bertoni JM. Parkinson’s prevalence estimated

by a state registry. Movement Disorders 2004;19(3):318–23.

Twelves 2003

Twelves D, Perkins K, Counsell C. Systematic Review

of Incidence Studies of Parkinson’s Disease. Movement

Disorders 2003;18(1):19–31.∗ Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Mueller 2003

Methods Single center, parallel-group, placebo-controlled, double-blind trial

Participants Germany

28 randomized: 7 males and 7 females to Co Q10 group ; 7 males and 7 females to

placebo group

Incl: Those who was treated and stable PD patients with statin free, CT or MRI scans

showed no evidence of any parenchymal lesion or atrophy

Excl: dementia, electrophysiological or neuroradiological evidence of additional CNS

pathology exceeding PD, previous exposure to neuroleptics or any drugs affecting the

dopaminergic system, treatment with digitalis, retinopathy or color blindness, i.e. red/

green

In placebo group, Mean age 64.36yrs, 50% male,Mean Total UPDRS score 17.36; FMT

118.79

In Co Q10 group, Mean age 66.21yrs, 50% male, Mean Total UPDRS score 23.29;

FMT 159.29

Interventions Daily oral application of 360 mg Co Q10 lasting 4 weeks or placebo. The optimum

titrated antiparkinson’s drug regime, consisting of levodopa/benserazide, one dopamine

agonist and/or selegiline, remained stable throughout the whole trial

Outcomes Total UPDRS score

UPDRS motor score

Farnsworth-Munsell 100 Hue test total error score

Notes Mean FU: 4 weeks

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment (selection bias) Low risk Quote: “We randomly (numbered con-

tainers) assigned participating, statin free,

non-fluctuating out-patients to one of the

groups.”

Comment: Adequate

Blinding (performance bias and detection

bias)

All outcomes

Low risk Quote: “followed them under double-blind

conditions.” “We blinded UPDRS raters to

the results of the FMT at both timepoints.

”

Comment: Adequate



Mueller 2003 (Continued)

Incomplete outcome data (attrition bias)

All outcomes

Low risk Quote: “All participants were reevaluated

under identical conditions 4 weeks later.”

Comment: All randomized patients were

included.

Shults 2002

Methods Multicenter, randomized, double-blind, placebo-controlled, with 4 parallel groups

Participants The United States (10 Parkinson Study Group sites)

80 randomized: 16 to placebo, 21 to 300 mg/d, 20 to 600 mg/d, 23 to 1200 mg/d

Incl: The diagnosis of PD have been made within the previous 5 years in men or in

women 30 years or older, and did not require treatment for their disability

Excl: Any medication for PD within 60 days before the baseline visit. secondary parkin-

sonism, MMSE< 24, other nervous system disease and serious illness

In placebo group, Mean age 63.1yrs, 75% male, Mean Total UPDRS score 24.1

In Co Q10 300 mg/d group, Mean age 60.9yrs, 57% male, Mean Total UPDRS score

23.9


23.0


22.7

Interventions Placebo, or Co Q10 300 mg/d, 600 mg/d and 1200 mg/d respectively


UPDRS mental score

UPDRS motor score

UPDRS ADL score

Percentage of patients who was considered to required levodopa

Plasma Co Q10 levels

NADH to cytochrome-c reductase

Adverse events

Notes Median FU: 16 months for all the outcomes

Risk of bias


Allocation concealment (selection bias) Low risk Quote: “allocation using a computer-gen-

erated randomization plan that included

stratification by the investigator and block-

ing (with a block size of 8) to ensure that

each investigator had approximately the

same number of subjects assigned to each

treatment group.”

Comment: Adequate



Shults 2002 (Continued)


bias)

All outcomes

Low risk Quote: “ Subjects, enrolling investigators,

enrolling coordinators, and other person-

nel involved in the care of the patients and

the acquisition and analysis of data were

masked to treatment assignment until com-

pletion of the study.”

Comment: Adequate


All outcomes

Low risk Quote: “ Three subjects prematurely ter-

minated or were lost to follow-up from the

study before the investigator determined

that they had reached the point that their

disability warranted use of levodopa. In-

creased tremor, lower-back pain, and in-

creased nocturia developed in 1 subject

who was receiving 1200 mg/d of Co Q10

and who prematurely terminated. This

subject was noncompliant, and the inves-

tigator did not believe that the symptoms

were related to the study drug. This subject

was lost to follow-up.”

Comment: Withdrawals after randomiza-

tion were included in data analysis, and the

reasons were specified

Sotirios 2009

Methods Please see The NINDS NET-PD 2007

Participants Please see The NINDS NET-PD 2007

Interventions Please see The NINDS NET-PD 2007

Outcomes Please see The NINDS NET-PD 2007

Notes Please see The NINDS NET-PD 2007

Risk of bias


Allocation concealment (selection bias) Low risk Please see The NINDS NET-PD 2007


bias)

All outcomes

Low risk Please see The NINDS NET-PD 2007



Sotirios 2009 (Continued)


All outcomes

Low risk Please see The NINDS NET-PD 2007

Storch 2007

Methods Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group,

single-dose trial

Participants Germany, at 13 movement disorder clinics, from September 2003 to January 2005

131 randomized: 67 to placebo, including 46 with levodopa; 64 to Co Q10, including

43 with levodopa

Incl: Subjects were between 40 and 75 years of age, had received the diagnosis of PD

according to the UK Brain Bank criteria had a rating on the modified Hoehn-Yahr scale

between II and III and 16 points or more on the UPDRS motor score and were on stable

antiparkinsonian medication with or without levodopa for at least 4 weeks prior to study

enrollment

Excl: They had been exposed to Co Q10 during the last 3 months prior to study inclu-

sion; were taking more than 149 IU of vitamin E or calcium, magnesium, and/or other

vitamins for more than 3 months prior to study inclusion; were receiving cholesterol-

lowering drugs, thyroid hormones, antiarrhythmic compounds, warfarin, metformin, or

clozapine; had an identifiable cause of parkinsonism or signs for atypical parkinsonian

disorders; had hypothyroidism or current evidence of epilepsy or psychosis; or had lev-

odopa-induced motor fluctuations or dyskinesias

In placebo group, Mean age 62.3yrs, 70.1% male, 68.7% with levodopa therapy, Mean

Co Q10 plasma level 0.94ug/mL3 ; Mean total UPDRS score 38.6

In Co Q10 group, Mean age 60.7yrs, 68.7% male, 67.2% with levodopa therapy, Mean

Co Q10 plasma level 0.99ug/mL3 ; Mean total UPDRS score 35.5

Interventions Nanoparticular Co Q10 suspension 100 mg 3 times a day or matching placebo for a

treatment period of 3 months. After that, the subjects underwent a withdrawal from

study drug for 2 months and a final assessment of the severity of the symptoms of PD was

made. Doses of levodopa and all other antiparkinsonian medications were kept constant

throughout the study

Outcomes UPDRS ADL score

UPDRS motor score

Total UPDRS score

Hoehn and Yahr scale

Plasma Co Q10 levels

Adverse events and withdrawals due to adverse event

Notes Mean FU: 2 months after 3 months treatment period

Risk of bias




Storch 2007 (Continued)

Allocation concealment (selection bias) Low risk Quote: “Subjects were randomly assigned

to nanoparticular Co Q10 suspension (100

mg 3 times a day; Nanoquinon from MSE

Pharmazeutika) or matching placebo for a

treatment period of 3 months centrally by

the contract research organization accord-

ing to a randomization list generated by 1

of us (R.K.). Randomization was stratified

by comedication of levodopa.”

Comment: Adequate


bias)

All outcomes

Low risk Quote: “We therefore undertook a ran-

domized, double-blind, placebo-controlled

trial on symptomatic effects of nanopartic-

ular CoQ10 in stable patients with mid-

stage PD, a randomization list generated by

1 of us (R.K.).”

Comment: The author should point out if

R.K. go on to participate the next step after

randomization


All outcomes

Low risk Quote: “changes of antiparkinsonian med-

ication led to exclusion from the perpro-

tocol population in 4 and 3 subjects, re-

spectively. All randomized patients were in-

cluded in the primary efficacy and safety

analysis (intent-to-treat population), but

13 patients were excluded from the Co Q10

group and 12 from the placebo group for

additional per-protocol population analy-

ses of primary and all secondary efficacy

measures due to protocol violations or dis-

continuation of the study.”


tion were included in data analysis, and the

reasons were specified

The NINDS NET-PD 2007

Methods A randomized, double-blind, calibrated futility clinical trial of Co Q10 and GPI-1485

in early untreated PD using placebo data from the DATATOP study to establish the

futility threshold

Participants 213 randomized: 71 received Co Q10, 71 received GPI-1485, and 71 received placebo

Incl: Participants were men and women aged 30 and over who had a diagnosis of PD but

did not require any medications for the treatment of their symptoms at the time of study

entry. Two of three cardinal manifestations of PD (tremor, rigidity, and bradykinesia)

were required; these findings had to be asymmetric. The diagnosis of PD must have been



The NINDS NET-PD 2007 (Continued)

made within 5 years of randomization. Women of childbearing potential were required

to use adequate birth control and have a negative pregnancy test at baseline

Excl: Those who had any secondary causes of parkinsonism, such as drug-induced parkin-

sonism or structural lesions; atypical parkinsonian syndromes; gait freezing or impair-

ment in postural reflexes; prior stereotaxic surgery for PD; used GPI-1485 or Co Q10

or an investigational agent within 90 days prior to randomization; known hypersensitiv-

ity to Co Q10 or GPI-1485; or any clinically significant medical condition that could

interfere with the subject’s ability to safely participate in the study or to be followed

In Co Q10 group, Mean age 60.7yrs, 61% male, Mean total UPDRS score 22.5, Hoehn

and Yahr 1.49

In GPI-1485 group, Mean age 62.2yrs, 65% male, Mean total UPDRS score 22.0,

Hoehn and Yahr 1.54

In placebo group, Mean age 60.1yrs, 70% male, Mean total UPDRS score 22.6, Hoehn

and Yahr 1.41

Interventions The participants may receive 1) 2400 mg of Co Q10 and placebo for GPI-1485; 2)

placebo for Co Q10 and 4000 mg of GPI-1485; or 3) placebo for Co Q10 and placebo

for GPI-1485


UPDRS motor score

UPDRS mental score

UPDRS ADL score

Hoehn and Yahr scale

Serious adverse events and withdrawals due to adverse event

Notes Mean FU: 12 months

Risk of bias


Allocation concealment (selection bias) Low risk Quote: “The statistical center generated the

random allocations sequence, and the sites

accessed the blinded treatment assignment

via a secured web page.”

Comment: Adequate


bias)

All outcomes

Low risk Quote: “Subjects and investigators were

kept blinded to treatment group.”

Comment: Adequate


All outcomes

Low risk Quote: “There were few missed visits with

only three subjects in the GPI-1485 arm,

one subject in the Co Q10 arm, and no con-

trols having missing values requiring impu-

tation.”


tion were included in data analysis



Excl: excluded

FU: follow up

Incl: included

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Shults 2004 Not an RCT - open-label trial without matched controls

Strijks 1997 Not an RCT - open-label trial without matched controls

Characteristics of ongoing studies [ordered by study ID]

Phase III

Trial name or title Effects of coenzyme Q10 in Parkinson’s Disease - Phase III

Methods Treatment, randomized, double blind (participant, caregiver, investigator, outcomes assessor), parallel assign-

ment, safety and efficacy study

Participants Those people who has presence of all 3 of the cardinal features of PD (resting tremor, bradykinesia and

rigidity). The clinical signs must be asymmetric. The diagnosis of PD within 5 years prior to the screening

visit. Age 30 or older. Female subjects must not be of childbearing potential or must use an approved form

of contraception for the duration of the trial

Sample size: 600

Interventions Co Q10 2400 mg/day with vitamin E 1200 IU/day versus placebo with vitamin E 1200 IU/day

Outcomes Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Primary outcomes: Change in UPDRS total score (sum of parts I, II and III)

Secondary outcomes: Change in Modified Schwab and England Scale; modified Rankin Scale; PD qualify of

life scale; Symbol Digit Modalities Test; adverse experiences and abnormal lab values

Starting date August 22, 2008

Contact information Principal Investigator: M. Flint Beal, MD

Weill Medical College of Cornell University, New York Hospital Department of Neurology

Notes This study is currently recruiting participants.

Last Updated: October 14, 2009



D A T A A N D A N A L Y S E S

Comparison 1. Co Q10 versus placebo

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Total UPDRS score change 3 330 Mean Difference (IV, Fixed, 95% CI) 0.49 [-0.64, 1.63]

1.1 300-400mg/d VS Placebo 2 80 Mean Difference (IV, Fixed, 95% CI) 0.83 [-0.97, 2.63]

1.2 600mg/d VS Placebo 1 50 Mean Difference (IV, Fixed, 95% CI) 0.60 [-3.10, 4.31]

1.3 1200mg/d VS Placebo 1 58 Mean Difference (IV, Fixed, 95% CI) -0.25 [-2.18, 1.67]


2 Motor UPDRS 3 330 Mean Difference (IV, Fixed, 95% CI) -0.07 [-0.71, 0.58]

2.1 300-400mg/d VS Placebo 2 80 Mean Difference (IV, Fixed, 95% CI) -0.27 [-0.99, 0.45]




3 Mental UPDRS 2 302 Mean Difference (IV, Fixed, 95% CI) -0.07 [-0.30, 0.17]





4 ADL UPDRS 2 302 Mean Difference (IV, Fixed, 95% CI) -0.52 [-1.15, 0.11]



4.3 1200mg/d VS Placebo 1 58 Mean Difference (IV, Fixed, 95% CI) -1.65 [-3.01, -0.29]


5 Hoehn & Yahr 2 302 Mean Difference (IV, Fixed, 95% CI) 0.05 [-0.05, 0.15]





6 Schwab & England (investigator) 2 302 Mean Difference (IV, Fixed, 95% CI) 0.30 [-0.79, 1.39]





7 severe viral infection 2 211 Risk Ratio (M-H, Fixed, 95% CI) 0.55 [0.18, 1.68]

7.1 300mg/d VS Placebo 2 157 Risk Ratio (M-H, Fixed, 95% CI) 0.40 [0.10, 1.61]



8 Pharyngitis 1 80 Risk Ratio (M-H, Fixed, 95% CI) 1.04 [0.18, 5.89]




9 Sinusitis 2 222 Risk Ratio (M-H, Fixed, 95% CI) 0.75 [0.30, 1.92]





10 Flatulence 1 80 Risk Ratio (M-H, Fixed, 95% CI) 0.26 [0.06, 1.04]






11 Back pain 2 222 Risk Ratio (M-H, Fixed, 95% CI) 1.00 [0.43, 2.35]





12 Coughing 2 222 Risk Ratio (M-H, Fixed, 95% CI) 0.53 [0.21, 1.36]





13 Diarrhea 3 353 Risk Ratio (M-H, Fixed, 95% CI) 1.39 [0.62, 3.16]





14 Fall 2 222 Risk Ratio (M-H, Fixed, 95% CI) 0.55 [0.22, 1.35]





15 Fatigue 2 222 Risk Ratio (M-H, Fixed, 95% CI) 0.32 [0.12, 0.85]





16 Hypercholesterolemia 2 223 Risk Ratio (M-H, Fixed, 95% CI) 0.14 [0.04, 0.44]





17 Number of withdrawals due to

adverse effects

4 381 Risk Ratio (M-H, Fixed, 95% CI) 0.61 [0.23, 1.62]

Comparison 2. Long-term efficacy of Co Q10 versus placebo

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Total UPDRS score change 2 222 Mean Difference (IV, Fixed, 95% CI) -0.27 [-2.61, 2.07]





2 Motor UPDRS 2 222 Mean Difference (IV, Fixed, 95% CI) 0.33 [-1.41, 2.06]







3 Mental UPDRS 2 222 Mean Difference (IV, Fixed, 95% CI) -0.11 [-0.44, 0.21]





4 ADL UPDRS 2 222 Mean Difference (IV, Fixed, 95% CI) -0.45 [-1.30, 0.40]



4.3 1200mg/d VS Placebo 1 29 Mean Difference (IV, Fixed, 95% CI) -3.12 [-5.88, -0.36]


5 Hoehn & Yahr 2 222 Mean Difference (IV, Fixed, 95% CI) 0.08 [-0.04, 0.21]





6 Schwab & England (investigator) 2 222 Mean Difference (IV, Fixed, 95% CI) 1.11 [-0.75, 2.97]



6.3 1200mg/d VS Placebo 1 29 Mean Difference (IV, Fixed, 95% CI) 4.43 [0.05, 8.81]


Analysis 1.1. Comparison 1 Co Q10 versus placebo, Outcome 1 Total UPDRS score change.

Review: Coenzyme Q10 for Parkinson’s disease

Comparison: 1 Co Q10 versus placebo

Outcome: 1 Total UPDRS score change

Study or subgroup CoQ10 PlaceboMean

Difference WeightMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

1 300-400mg/d VS Placebo

Mueller 2003 14 2.29 (2.92) 14 1.21 (2.64) 30.4 % 1.08 [ -0.98, 3.14 ]

Shults 2002 21 8.81 (7.45) 5 11.99 (7.51) 2.4 % -3.18 [ -10.49, 4.13 ]

Shults 2002 21 1.35 (4.36) 5 0.22 (4.4) 7.0 % 1.13 [ -3.15, 5.41 ]

Subtotal (95% CI) 56 24 39.9 % 0.83 [ -0.97, 2.63 ]

Heterogeneity: Chi2 = 1.23, df = 2 (P = 0.54); I2 =0.0%

Test for overall effect: Z = 0.90 (P = 0.37)

2 600mg/d VS Placebo

Shults 2002 20 10.82 (7.34) 5 11.99 (7.51) 2.4 % -1.17 [ -8.50, 6.16 ]

Shults 2002 20 1.43 (4.31) 5 0.22 (4.4) 7.0 % 1.21 [ -3.08, 5.50 ]

-100 -50 0 50 100

Favours CoQ10 Favours Placebo

(Continued . . . )



(. . . Continued)



Difference


Subtotal (95% CI) 40 10 9.4 % 0.60 [ -3.10, 4.31 ]




Shults 2002 23 6.69 (7.4) 6 11.99 (7.51) 2.9 % -5.30 [ -12.03, 1.43 ]

Shults 2002 23 0.42 (4.32) 6 0.22 (1.2) 32.0 % 0.20 [ -1.81, 2.21 ]

Subtotal (95% CI) 46 12 34.9 % -0.25 [ -2.18, 1.67 ]

Heterogeneity: Chi2 = 2.36, df = 1 (P = 0.12); I2 =58%



The NINDS NET-PD 2007 71 7.52 (8.87) 71 6.31 (8.47) 15.9 % 1.21 [ -1.64, 4.06 ]

Subtotal (95% CI) 71 71 15.9 % 1.21 [ -1.64, 4.06 ]

Heterogeneity: not applicable


Total (95% CI) 213 117 100.0 % 0.49 [ -0.64, 1.63 ]



Test for subgroup differences: Chi2 = 0.95, df = 3 (P = 0.81), I2 =0.0%

-100 -50 0 50 100




Analysis 1.2. Comparison 1 Co Q10 versus placebo, Outcome 2 Motor UPDRS.



Outcome: 2 Motor UPDRS



Difference



Mueller 2003 14 0.29 (0.61) 14 0.64 (1.28) 75.1 % -0.35 [ -1.09, 0.39 ]

Shults 2002 21 1.54 (3.48) 5 0 (3.54) 3.5 % 1.54 [ -1.90, 4.98 ]

Shults 2002 21 5.88 (5.5) 5 6.54 (5.58) 1.4 % -0.66 [ -6.09, 4.77 ]

Subtotal (95% CI) 56 24 80.0 % -0.27 [ -0.99, 0.45 ]




Shults 2002 20 6.47 (5.43) 5 6.54 (5.58) 1.4 % -0.07 [ -5.51, 5.37 ]

Shults 2002 20 1.28 (3.44) 5 0 (3.54) 3.5 % 1.28 [ -2.17, 4.73 ]

Subtotal (95% CI) 40 10 4.9 % 0.89 [ -2.02, 3.81 ]




Shults 2002 23 4.61 (5.47) 6 6.54 (5.58) 1.7 % -1.93 [ -6.92, 3.06 ]

Shults 2002 23 1.29 (3.47) 6 0 (3.54) 4.1 % 1.29 [ -1.88, 4.46 ]

Subtotal (95% CI) 46 12 5.8 % 0.37 [ -2.31, 3.04 ]




The NINDS NET-PD 2007 71 4.73 (6.66) 71 3.79 (6.16) 9.3 % 0.94 [ -1.17, 3.05 ]

Subtotal (95% CI) 71 71 9.3 % 0.94 [ -1.17, 3.05 ]



Total (95% CI) 213 117 100.0 % -0.07 [ -0.71, 0.58 ]




-100 -50 0 50 100




Analysis 1.3. Comparison 1 Co Q10 versus placebo, Outcome 3 Mental UPDRS.



Outcome: 3 Mental UPDRS



Difference



Shults 2002 21 0.54 (0.89) 5 0.9 (0.89) 7.3 % -0.36 [ -1.23, 0.51 ]

Shults 2002 21 -0.29 (0.62) 5 -0.22 (0.61) 15.4 % -0.07 [ -0.67, 0.53 ]

Subtotal (95% CI) 42 10 22.7 % -0.16 [ -0.65, 0.33 ]




Shults 2002 20 -0.15 (0.62) 5 -0.22 (0.61) 15.2 % 0.07 [ -0.53, 0.67 ]

Shults 2002 20 0.35 (0.89) 5 0.9 (0.89) 7.2 % -0.55 [ -1.42, 0.32 ]

Subtotal (95% CI) 40 10 22.5 % -0.13 [ -0.62, 0.37 ]




Shults 2002 23 -0.27 (0.61) 6 -0.22 (0.61) 18.3 % -0.05 [ -0.60, 0.50 ]

Shults 2002 23 0.33 (0.89) 6 0.9 (0.89) 8.6 % -0.57 [ -1.37, 0.23 ]

Subtotal (95% CI) 46 12 26.8 % -0.22 [ -0.67, 0.24 ]




The NINDS NET-PD 2007 71 0.68 (1.49) 71 0.48 (1.18) 28.1 % 0.20 [ -0.24, 0.64 ]

Subtotal (95% CI) 71 71 28.1 % 0.20 [ -0.24, 0.64 ]



Total (95% CI) 199 103 100.0 % -0.07 [ -0.30, 0.17 ]




-100 -50 0 50 100




Analysis 1.4. Comparison 1 Co Q10 versus placebo, Outcome 4 ADL UPDRS.



Outcome: 4 ADL UPDRS



Difference



Shults 2002 21 0.12 (1.72) 5 0.52 (1.74) 14.0 % -0.40 [ -2.09, 1.29 ]

Shults 2002 21 2.54 (3.08) 5 4.74 (3.08) 4.4 % -2.20 [ -5.20, 0.80 ]

Subtotal (95% CI) 42 10 18.4 % -0.83 [ -2.31, 0.64 ]




Shults 2002 20 0.37 (1.71) 5 0.52 (1.74) 13.9 % -0.15 [ -1.85, 1.55 ]

Shults 2002 20 4.02 (3.03) 5 4.74 (3.08) 4.4 % -0.72 [ -3.73, 2.29 ]

Subtotal (95% CI) 40 10 18.3 % -0.29 [ -1.77, 1.19 ]




Shults 2002 23 -0.66 (1.72) 6 0.52 (1.74) 16.5 % -1.18 [ -2.74, 0.38 ]

Shults 2002 23 1.62 (3.04) 6 4.74 (3.08) 5.3 % -3.12 [ -5.88, -0.36 ]

Subtotal (95% CI) 46 12 21.8 % -1.65 [ -3.01, -0.29 ]




The NINDS NET-PD 2007 71 2.15 (3.05) 71 2.04 (2.93) 41.5 % 0.11 [ -0.87, 1.09 ]

Subtotal (95% CI) 71 71 41.5 % 0.11 [ -0.87, 1.09 ]



Total (95% CI) 199 103 100.0 % -0.52 [ -1.15, 0.11 ]



Test for subgroup differences: Chi2 = 4.50, df = 3 (P = 0.21), I2 =33%

-100 -50 0 50 100




Analysis 1.5. Comparison 1 Co Q10 versus placebo, Outcome 5 Hoehn & Yahr.



Outcome: 5 Hoehn % Yahr



Difference



Shults 2002 21 0.16 (0.29) 5 0.02 (0.29) 12.0 % 0.14 [ -0.14, 0.42 ]

Shults 2002 21 0.04 (0.27) 5 0.01 (0.28) 13.1 % 0.03 [ -0.24, 0.30 ]

Subtotal (95% CI) 42 10 25.1 % 0.08 [ -0.11, 0.28 ]




Shults 2002 20 0.15 (0.29) 5 0.02 (0.29) 11.9 % 0.13 [ -0.15, 0.41 ]

Shults 2002 20 -0.02 (0.29) 5 0.01 (0.28) 12.6 % -0.03 [ -0.31, 0.25 ]

Subtotal (95% CI) 40 10 24.5 % 0.05 [ -0.15, 0.25 ]




Shults 2002 23 0.13 (0.29) 6 0.02 (0.29) 14.2 % 0.11 [ -0.15, 0.37 ]

Shults 2002 23 0.02 (0.28) 6 0.01 (0.28) 15.2 % 0.01 [ -0.24, 0.26 ]

Subtotal (95% CI) 46 12 29.4 % 0.06 [ -0.12, 0.24 ]




The NINDS NET-PD 2007 71 0.32 (0.65) 71 0.31 (0.65) 21.0 % 0.01 [ -0.20, 0.22 ]

Subtotal (95% CI) 71 71 21.0 % 0.01 [ -0.20, 0.22 ]



Total (95% CI) 199 103 100.0 % 0.05 [ -0.05, 0.15 ]




-100 -50 0 50 100




Analysis 1.6. Comparison 1 Co Q10 versus placebo, Outcome 6 Schwab & England (investigator).



Outcome: 6 Schwab % England (investigator)



Difference



Shults 2002 21 -4.89 (4.81) 5 -7.98 (4.89) 5.3 % 3.09 [ -1.66, 7.84 ]

Shults 2002 21 -0.57 (2.43) 5 -0.12 (2.47) 20.7 % -0.45 [ -2.85, 1.95 ]

Subtotal (95% CI) 42 10 25.9 % 0.27 [ -1.87, 2.41 ]




Shults 2002 20 -7.03 (4.78) 5 -7.98 (4.89) 5.2 % 0.95 [ -3.82, 5.72 ]

Shults 2002 20 -0.53 (2.4) 5 -0.12 (2.47) 20.6 % -0.41 [ -2.82, 2.00 ]

Subtotal (95% CI) 40 10 25.8 % -0.13 [ -2.28, 2.01 ]




Shults 2002 23 -3.55 (4.8) 6 -7.98 (4.89) 6.2 % 4.43 [ 0.05, 8.81 ]

Shults 2002 23 0.28 (2.42) 6 -0.12 (2.47) 24.4 % 0.40 [ -1.81, 2.61 ]

Subtotal (95% CI) 46 12 30.6 % 1.22 [ -0.75, 3.19 ]




The NINDS NET-PD 2007 71 -5.5 (8.16) 71 -4.9 (7.63) 17.6 % -0.60 [ -3.20, 2.00 ]

Subtotal (95% CI) 71 71 17.6 % -0.60 [ -3.20, 2.00 ]



Total (95% CI) 199 103 100.0 % 0.30 [ -0.79, 1.39 ]




-100 -50 0 50 100

Favours Placebo Favours CoQ10



Analysis 1.7. Comparison 1 Co Q10 versus placebo, Outcome 7 severe viral infection.



Outcome: 7 severe viral infection

Study or subgroup CoQ10 Placebo Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI


Shults 2002 1/21 0/5 9.6 % 0.82 [ 0.04, 17.64 ]

Storch 2007 2/64 6/67 71.5 % 0.35 [ 0.07, 1.67 ]

Subtotal (95% CI) 85 72 81.1 % 0.40 [ 0.10, 1.61 ]

Total events: 3 (CoQ10), 6 (Placebo)




Shults 2002 1/20 0/5 9.5 % 0.86 [ 0.04, 18.45 ]

Subtotal (95% CI) 20 5 9.5 % 0.86 [ 0.04, 18.45 ]





Shults 2002 2/23 0/6 9.4 % 1.46 [ 0.08, 26.97 ]

Subtotal (95% CI) 23 6 9.4 % 1.46 [ 0.08, 26.97 ]




Total (95% CI) 128 83 100.0 % 0.55 [ 0.18, 1.68 ]





0.01 0.1 1 10 100




Analysis 1.8. Comparison 1 Co Q10 versus placebo, Outcome 8 Pharyngitis.



Outcome: 8 Pharyngitis




Shults 2002 1/21 0/5 33.6 % 0.82 [ 0.04, 17.64 ]

Subtotal (95% CI) 21 5 33.6 % 0.82 [ 0.04, 17.64 ]





Shults 2002 1/20 0/5 33.3 % 0.86 [ 0.04, 18.45 ]

Subtotal (95% CI) 20 5 33.3 % 0.86 [ 0.04, 18.45 ]





Shults 2002 2/23 0/6 33.1 % 1.46 [ 0.08, 26.97 ]

Subtotal (95% CI) 23 6 33.1 % 1.46 [ 0.08, 26.97 ]




Total (95% CI) 64 16 100.0 % 1.04 [ 0.18, 5.89 ]





0.01 0.1 1 10 100




Analysis 1.9. Comparison 1 Co Q10 versus placebo, Outcome 9 Sinusitis.



Outcome: 9 Sinusitis

Study or subgroup CoQ10 Placebo Risk Ratio Risk Ratio



Shults 2002 2/21 0/5 1.36 [ 0.08, 24.76 ]

Subtotal (95% CI) 21 5 1.36 [ 0.08, 24.76 ]





Shults 2002 0/20 0/5 0.0 [ 0.0, 0.0 ]

Subtotal (95% CI) 20 5 0.0 [ 0.0, 0.0 ]



Test for overall effect: Z = 0.0 (P < 0.00001)


Shults 2002 2/23 0/6 1.46 [ 0.08, 26.97 ]

Subtotal (95% CI) 23 6 1.46 [ 0.08, 26.97 ]





The NINDS NET-PD 2007 5/71 8/71 0.63 [ 0.21, 1.82 ]

Subtotal (95% CI) 71 71 0.63 [ 0.21, 1.82 ]




Total (95% CI) 135 87 0.75 [ 0.30, 1.92 ]





0.01 0.1 1 10 100




Analysis 1.10. Comparison 1 Co Q10 versus placebo, Outcome 10 Flatulence.



Outcome: 10 Flatulence




Shults 2002 0/21 1/5 42.5 % 0.09 [ 0.00, 1.96 ]

Subtotal (95% CI) 21 5 42.5 % 0.09 [ 0.00, 1.96 ]





Shults 2002 2/20 1/5 28.9 % 0.50 [ 0.06, 4.47 ]

Subtotal (95% CI) 20 5 28.9 % 0.50 [ 0.06, 4.47 ]





Shults 2002 1/23 1/6 28.6 % 0.26 [ 0.02, 3.59 ]

Subtotal (95% CI) 23 6 28.6 % 0.26 [ 0.02, 3.59 ]




Total (95% CI) 64 16 100.0 % 0.26 [ 0.06, 1.04 ]





0.01 0.1 1 10 100




Analysis 1.11. Comparison 1 Co Q10 versus placebo, Outcome 11 Back pain.



Outcome: 11 Back pain




Shults 2002 2/21 1/5 18.4 % 0.48 [ 0.05, 4.27 ]

Subtotal (95% CI) 21 5 18.4 % 0.48 [ 0.05, 4.27 ]





Shults 2002 1/20 1/5 18.2 % 0.25 [ 0.02, 3.34 ]

Subtotal (95% CI) 20 5 18.2 % 0.25 [ 0.02, 3.34 ]





Shults 2002 4/23 1/6 18.0 % 1.04 [ 0.14, 7.70 ]

Subtotal (95% CI) 23 6 18.0 % 1.04 [ 0.14, 7.70 ]





The NINDS NET-PD 2007 6/71 4/71 45.4 % 1.50 [ 0.44, 5.09 ]

Subtotal (95% CI) 71 71 45.4 % 1.50 [ 0.44, 5.09 ]




Total (95% CI) 135 87 100.0 % 1.00 [ 0.43, 2.35 ]





0.01 0.1 1 10 100

Favours experimental Favours control



Analysis 1.12. Comparison 1 Co Q10 versus placebo, Outcome 12 Coughing.



Outcome: 12 Coughing




Shults 2002 1/21 1/5 16.5 % 0.24 [ 0.02, 3.19 ]

Subtotal (95% CI) 21 5 16.5 % 0.24 [ 0.02, 3.19 ]





Shults 2002 1/20 1/5 16.3 % 0.25 [ 0.02, 3.34 ]

Subtotal (95% CI) 20 5 16.3 % 0.25 [ 0.02, 3.34 ]





Shults 2002 1/23 1/6 16.2 % 0.26 [ 0.02, 3.59 ]

Subtotal (95% CI) 23 6 16.2 % 0.26 [ 0.02, 3.59 ]





The NINDS NET-PD 2007 4/71 5/71 51.0 % 0.80 [ 0.22, 2.86 ]

Subtotal (95% CI) 71 71 51.0 % 0.80 [ 0.22, 2.86 ]




Total (95% CI) 135 87 100.0 % 0.53 [ 0.21, 1.36 ]





0.01 0.1 1 10 100




Analysis 1.13. Comparison 1 Co Q10 versus placebo, Outcome 13 Diarrhea.



Outcome: 13 Diarrhea




Shults 2002 2/21 0/5 8.4 % 1.36 [ 0.08, 24.76 ]

Storch 2007 5/64 1/67 10.5 % 5.23 [ 0.63, 43.59 ]

Subtotal (95% CI) 85 72 18.9 % 3.51 [ 0.68, 18.19 ]





Shults 2002 1/20 0/5 8.3 % 0.86 [ 0.04, 18.45 ]

Subtotal (95% CI) 20 5 8.3 % 0.86 [ 0.04, 18.45 ]





Shults 2002 2/23 0/6 8.3 % 1.46 [ 0.08, 26.97 ]

Subtotal (95% CI) 23 6 8.3 % 1.46 [ 0.08, 26.97 ]





The NINDS NET-PD 2007 5/71 6/71 64.4 % 0.83 [ 0.27, 2.61 ]

Subtotal (95% CI) 71 71 64.4 % 0.83 [ 0.27, 2.61 ]




Total (95% CI) 199 154 100.0 % 1.39 [ 0.62, 3.16 ]





0.01 0.1 1 10 100




Analysis 1.14. Comparison 1 Co Q10 versus placebo, Outcome 14 Fall.



Outcome: 14 Fall




Shults 2002 3/21 1/5 15.3 % 0.71 [ 0.09, 5.51 ]

Subtotal (95% CI) 21 5 15.3 % 0.71 [ 0.09, 5.51 ]





Shults 2002 0/20 1/5 22.1 % 0.10 [ 0.00, 2.05 ]

Subtotal (95% CI) 20 5 22.1 % 0.10 [ 0.00, 2.05 ]





Shults 2002 1/23 1/6 15.1 % 0.26 [ 0.02, 3.59 ]

Subtotal (95% CI) 23 6 15.1 % 0.26 [ 0.02, 3.59 ]





The NINDS NET-PD 2007 4/71 5/71 47.5 % 0.80 [ 0.22, 2.86 ]

Subtotal (95% CI) 71 71 47.5 % 0.80 [ 0.22, 2.86 ]




Total (95% CI) 135 87 100.0 % 0.55 [ 0.22, 1.35 ]





0.01 0.1 1 10 100




Analysis 1.15. Comparison 1 Co Q10 versus placebo, Outcome 15 Fatigue.



Outcome: 15 Fatigue




Shults 2002 2/21 1/5 11.9 % 0.48 [ 0.05, 4.27 ]

Subtotal (95% CI) 21 5 11.9 % 0.48 [ 0.05, 4.27 ]





Shults 2002 1/20 1/5 11.8 % 0.25 [ 0.02, 3.34 ]

Subtotal (95% CI) 20 5 11.8 % 0.25 [ 0.02, 3.34 ]





Shults 2002 0/23 1/6 17.2 % 0.10 [ 0.00, 2.13 ]

Subtotal (95% CI) 23 6 17.2 % 0.10 [ 0.00, 2.13 ]





The NINDS NET-PD 2007 3/71 8/71 59.1 % 0.38 [ 0.10, 1.36 ]

Subtotal (95% CI) 71 71 59.1 % 0.38 [ 0.10, 1.36 ]




Total (95% CI) 135 87 100.0 % 0.32 [ 0.12, 0.85 ]





0.01 0.1 1 10 100




Analysis 1.16. Comparison 1 Co Q10 versus placebo, Outcome 16 Hypercholesterolemia.



Outcome: 16 Hypercholesterolemia




Shults 2002 1/21 2/5 22.5 % 0.12 [ 0.01, 1.07 ]

Subtotal (95% CI) 21 5 22.5 % 0.12 [ 0.01, 1.07 ]





Shults 2002 0/21 2/5 27.4 % 0.05 [ 0.00, 0.99 ]

Subtotal (95% CI) 21 5 27.4 % 0.05 [ 0.00, 0.99 ]





Shults 2002 1/23 2/6 22.1 % 0.13 [ 0.01, 1.21 ]

Subtotal (95% CI) 23 6 22.1 % 0.13 [ 0.01, 1.21 ]





The NINDS NET-PD 2007 1/71 4/71 27.9 % 0.25 [ 0.03, 2.18 ]

Subtotal (95% CI) 71 71 27.9 % 0.25 [ 0.03, 2.18 ]




Total (95% CI) 136 87 100.0 % 0.14 [ 0.04, 0.44 ]





0.01 0.1 1 10 100




Analysis 1.17. Comparison 1 Co Q10 versus placebo, Outcome 17 Number of withdrawals due to adverse

effects.



Outcome: 17 Number of withdrawals due to adverse effects

Study or subgroup CoQ10 Placebo Risk Ratio Risk Ratio


Mueller 2003 0/14 0/14 0.0 [ 0.0, 0.0 ]

Shults 2002 0/64 0/16 0.0 [ 0.0, 0.0 ]

Storch 2007 2/64 3/67 0.70 [ 0.12, 4.04 ]

The NINDS NET-PD 2007 4/71 7/71 0.57 [ 0.17, 1.87 ]

Total (95% CI) 213 168 0.61 [ 0.23, 1.62 ]




Test for subgroup differences: Not applicable

0.01 0.1 1 10 100




Analysis 2.1. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 1 Total UPDRS score

change.


Comparison: 2 Long-term efficacy of Co Q10 versus placebo

Outcome: 1 Total UPDRS score change

Study or subgroup Experimental ControlMean


Difference



Shults 2002 21 8.81 (7.45) 5 11.99 (7.51) 10.3 % -3.18 [ -10.49, 4.13 ]

Subtotal (95% CI) 21 5 10.3 % -3.18 [ -10.49, 4.13 ]




Shults 2002 20 10.82 (7.34) 5 11.99 (7.51) 10.2 % -1.17 [ -8.50, 6.16 ]

Subtotal (95% CI) 20 5 10.2 % -1.17 [ -8.50, 6.16 ]




Shults 2002 23 6.69 (7.4) 6 11.99 (7.51) 12.1 % -5.30 [ -12.03, 1.43 ]

Subtotal (95% CI) 23 6 12.1 % -5.30 [ -12.03, 1.43 ]




The NINDS NET-PD 2007 71 7.52 (8.87) 71 6.31 (8.47) 67.4 % 1.21 [ -1.64, 4.06 ]

Subtotal (95% CI) 71 71 67.4 % 1.21 [ -1.64, 4.06 ]



Total (95% CI) 135 87 100.0 % -0.27 [ -2.61, 2.07 ]




-100 -50 0 50 100




Analysis 2.2. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 2 Motor UPDRS.



Outcome: 2 Motor UPDRS



Difference



Shults 2002 21 5.88 (5.5) 5 6.54 (5.58) 10.2 % -0.66 [ -6.09, 4.77 ]

Subtotal (95% CI) 21 5 10.2 % -0.66 [ -6.09, 4.77 ]




Shults 2002 20 6.47 (5.43) 5 6.54 (5.58) 10.2 % -0.07 [ -5.51, 5.37 ]

Subtotal (95% CI) 20 5 10.2 % -0.07 [ -5.51, 5.37 ]




Shults 2002 23 4.61 (5.47) 6 6.54 (5.58) 12.1 % -1.93 [ -6.92, 3.06 ]

Subtotal (95% CI) 23 6 12.1 % -1.93 [ -6.92, 3.06 ]




The NINDS NET-PD 2007 71 4.73 (6.66) 71 3.79 (6.16) 67.6 % 0.94 [ -1.17, 3.05 ]

Subtotal (95% CI) 71 71 67.6 % 0.94 [ -1.17, 3.05 ]



Total (95% CI) 135 87 100.0 % 0.33 [ -1.41, 2.06 ]




-100 -50 0 50 100




Analysis 2.3. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 3 Mental UPDRS.



Outcome: 3 Mental UPDRS



Difference



Shults 2002 21 0.54 (0.89) 5 0.9 (0.89) 14.2 % -0.36 [ -1.23, 0.51 ]

Subtotal (95% CI) 21 5 14.2 % -0.36 [ -1.23, 0.51 ]




Shults 2002 20 0.35 (0.89) 5 0.9 (0.89) 14.1 % -0.55 [ -1.42, 0.32 ]

Subtotal (95% CI) 20 5 14.1 % -0.55 [ -1.42, 0.32 ]




Shults 2002 23 0.33 (0.89) 6 0.9 (0.89) 16.8 % -0.57 [ -1.37, 0.23 ]

Subtotal (95% CI) 23 6 16.8 % -0.57 [ -1.37, 0.23 ]




The NINDS NET-PD 2007 71 0.68 (1.49) 71 0.48 (1.18) 54.9 % 0.20 [ -0.24, 0.64 ]

Subtotal (95% CI) 71 71 54.9 % 0.20 [ -0.24, 0.64 ]



Total (95% CI) 135 87 100.0 % -0.11 [ -0.44, 0.21 ]




-100 -50 0 50 100




Analysis 2.4. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 4 ADL UPDRS.



Outcome: 4 ADL UPDRS



Difference



Shults 2002 21 2.54 (3.08) 5 4.74 (3.08) 8.0 % -2.20 [ -5.20, 0.80 ]

Subtotal (95% CI) 21 5 8.0 % -2.20 [ -5.20, 0.80 ]




Shults 2002 20 4.02 (3.03) 5 4.74 (3.08) 8.0 % -0.72 [ -3.73, 2.29 ]

Subtotal (95% CI) 20 5 8.0 % -0.72 [ -3.73, 2.29 ]




Shults 2002 23 1.62 (3.04) 6 4.74 (3.08) 9.5 % -3.12 [ -5.88, -0.36 ]

Subtotal (95% CI) 23 6 9.5 % -3.12 [ -5.88, -0.36 ]




The NINDS NET-PD 2007 71 2.15 (3.05) 71 2.04 (2.93) 74.6 % 0.11 [ -0.87, 1.09 ]

Subtotal (95% CI) 71 71 74.6 % 0.11 [ -0.87, 1.09 ]



Total (95% CI) 135 87 100.0 % -0.45 [ -1.30, 0.40 ]




-100 -50 0 50 100




Analysis 2.5. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 5 Hoehn & Yahr.



Outcome: 5 Hoehn % Yahr



Difference



Shults 2002 21 0.16 (0.29) 5 0.02 (0.29) 20.3 % 0.14 [ -0.14, 0.42 ]

Subtotal (95% CI) 21 5 20.3 % 0.14 [ -0.14, 0.42 ]




Shults 2002 20 0.15 (0.29) 5 0.02 (0.29) 20.1 % 0.13 [ -0.15, 0.41 ]

Subtotal (95% CI) 20 5 20.1 % 0.13 [ -0.15, 0.41 ]




Shults 2002 23 0.13 (0.29) 6 0.02 (0.29) 24.0 % 0.11 [ -0.15, 0.37 ]

Subtotal (95% CI) 23 6 24.0 % 0.11 [ -0.15, 0.37 ]




The NINDS NET-PD 2007 71 0.32 (0.65) 71 0.31 (0.65) 35.6 % 0.01 [ -0.20, 0.22 ]

Subtotal (95% CI) 71 71 35.6 % 0.01 [ -0.20, 0.22 ]



Total (95% CI) 135 87 100.0 % 0.08 [ -0.04, 0.21 ]




-100 -50 0 50 100




Analysis 2.6. Comparison 2 Long-term efficacy of Co Q10 versus placebo, Outcome 6 Schwab & England

(investigator).



Outcome: 6 Schwab % England (investigator)



Difference



Shults 2002 21 -4.89 (4.81) 5 -7.98 (4.89) 15.3 % 3.09 [ -1.66, 7.84 ]

Subtotal (95% CI) 21 5 15.3 % 3.09 [ -1.66, 7.84 ]




Shults 2002 20 -7.03 (4.78) 5 -7.98 (4.89) 15.2 % 0.95 [ -3.82, 5.72 ]

Subtotal (95% CI) 20 5 15.2 % 0.95 [ -3.82, 5.72 ]




Shults 2002 23 -3.55 (4.8) 6 -7.98 (4.89) 18.1 % 4.43 [ 0.05, 8.81 ]

Subtotal (95% CI) 23 6 18.1 % 4.43 [ 0.05, 8.81 ]




The NINDS NET-PD 2007 71 -5.5 (8.16) 71 -4.9 (7.63) 51.3 % -0.60 [ -3.20, 2.00 ]

Subtotal (95% CI) 71 71 51.3 % -0.60 [ -3.20, 2.00 ]



Total (95% CI) 135 87 100.0 % 1.11 [ -0.75, 2.97 ]




-100 -50 0 50 100




H I S T O R Y

Protocol first published: Issue 4, 2009

Review first published: Issue 12, 2011

C O N T R I B U T I O N S O F A U T H O R S

Liu J took the lead role in searching, identifying and assessing studies, in data extraction and analyses, and in writing up the full review.

Liu J and Wang L formulated the idea and developed the basis for the review.

Wang L gave general advice for this review.

Zhan S supervised the methodology.

Wang L, Xia Y identified trials, assessed studies and extracted data.

Xia Y gave great help with the statistics.

All authors were involved in writing or revising the full review.

D E C L A R A T I O N S O F I N T E R E S T

None known

S O U R C E S O F S U P P O R T

Internal sources

• Department of Geriatric Neurology, Chinese PLA General Hospital, China.

External sources

• No sources of support supplied

D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W

None

I N D E X T E R M S



Medical Subject Headings (MeSH)

Activities of Daily Living; Diarrhea [chemically induced]; Neuroprotective Agents [adverse effects; ∗therapeutic use]; Parkinson Disease

[∗drug therapy]; Pharyngitis [chemically induced]; Randomized Controlled Trials as Topic; Ubiquinone [adverse effects; ∗analogs &

derivatives; therapeutic use]; Vitamins [adverse effects; ∗therapeutic use]

MeSH check words

Humans



Coenzyme Q10 for Parkinson's disease

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Transcript of Coenzyme Q10 for Parkinson's disease