Intervention Review

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Creatine for treating muscle disorders

  1. Rudolf A Kley1,*,
  2. Mark A Tarnopolsky2,
  3. Matthias Vorgerd3

Editorial Group: Cochrane Neuromuscular Group

Published Online: 5 JUN 2013

Assessed as up-to-date: 11 SEP 2012

DOI: 10.1002/14651858.CD004760.pub4


How to Cite

Kley RA, Tarnopolsky MA, Vorgerd M. Creatine for treating muscle disorders. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD004760. DOI: 10.1002/14651858.CD004760.pub4.

Author Information

  1. 1

    University Hospital Bergmannsheil, Ruhr University Bochum, Department of Neurology, Bochum, Germany

  2. 2

    McMaster University, Department of Neurology and Rehabilitation, Hamilton, Ontario, Canada

  3. 3

    Kliniken Bergmannsheil, Ruhr University Bochum, Department of Neurology, Bochum, Germany

*Rudolf A Kley, Department of Neurology, University Hospital Bergmannsheil, Ruhr University Bochum, Buerkle-de-la-Camp-Platz 1, Bochum, 44789, Germany. rudolf.kley@rub.de.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 5 JUN 2013

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Characteristics of included studies [ordered by study ID]
Banerjee 2010

MethodsRandomised, single-blind, placebo-controlled trial


Participants33 steroid-naive DMD boys (age range, 3 to 12 years)


InterventionsCreatine 5 g per day versus placebo (500 mg vitamin C) for 8 weeks


OutcomesManual muscle testing
Vignos' functional scale
Parents' overall response to intervention (change in the activity levels, falls, time taken for daily motor tasks)
P-31 MRS (right calf muscle)
Adverse events


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskInsufficient information to permit judgement

Allocation concealment (selection bias)High riskOne experimenter who was involved in recruitment, randomisation and treatment of participants was aware of the treatment group allocation

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants were blinded but one experimenter was not blinded (see above). Creatine and placebo (vitamin C) may be different in taste

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data were not balanced in numbers across intervention groups (5 dropouts in creatine group, 1 dropout in placebo group) but reasons were unlikely to be related to true outcome

Selective reporting (reporting bias)Unclear riskInsufficient information to permit judgement

Other biasLow riskThe study appears to be free of other sources of bias

Chung 2007

MethodsRandomised, double-blind, placebo-controlled trial


Participants37 participants with polymyositis (22 participants) or dermatomyositis (15 participants), mean age 59 years (creatine group) and 50 years (placebo group)


InterventionsCreatine (loading dosage of 20 g/day for 8 days followed by a maintenance dosage of 3 g/day) versus placebo,
6 months duration


OutcomesAggregate functional performance time (AFPT)
Functional index in myositis
Manual muscle testing using the Medical Research Council (MRC) extended scale
Serum creatine kinase (CK) levels
Health status using the Nottingham Health Profile (NHP)
Short Form McGill Pain Questionnaire
Hospital Anxiety and Depression Scales
Chalder fatigue score


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskSequence generation was organised by hospital pharmacies using random number lists

Allocation concealment (selection bias)Low riskCreatine and placebo were prepared by the hospital pharmacies and were provided in identical containers. Sequences were concealed until the study had ended and the statistical analysis had been completed

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants, supervising clinicians, and assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data unlikely to be related to true outcome. Intention-to-treat analysis

Selective reporting (reporting bias)Unclear riskInsufficient information to permit judgement

Other biasLow riskThe study appears to be free of other sources of bias

Escolar 2005

MethodsRandomised, double-blind, placebo-controlled, three-arm multicentre trial


Participants50 steroid-naive DMD boys aged 4 to 10 years recruited at 10 Cooperative International Neuromuscular Research Group (CINRG) Centres


InterventionsCreatine 5 g daily (15 participants) or glutamine 0.6 mg/kg daily (19 participants) or placebo (16 participants)
6 months duration


OutcomesQuantitative muscle testing (QMT) of bilateral elbow flexors and extensors, knee flexors and extensors, and grip
Combined QMT arm and leg scores
Manual muscle testing score of 34 muscle groups
Functional test
Pulmonary function testing


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAn adaptive, biased-coin (urn) randomisation technique was applied

Allocation concealment (selection bias)Low riskCentral allocation by the Biostatistics Centre

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were given as powders of identical colour, texture and taste in predetermined proportions

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes described on http://clinicaltrials.gov that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Klopstock 2000

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants16 participants with mitochondrial cytopathies (mean age 46.4 ± SD 17.2 years)


InterventionsCreatine 20 g per day versus placebo (microcrystalline cellulose)
4-week treatment phases
Washout period of at least 29 days in all participants except two (24 and 26 days)


OutcomesMaximum isometric strength of biceps and quadriceps muscle
Isokinetic biceps and quadriceps contractions with 15% of MVC until muscular exhaustion
Manual muscle testing using MRC scale, Hammersmith motor ability score (HMAS), neuromuscular symptom score (NSS)
Function time test, function ranking test, ataxia score
Aerobic cycle ergometry with pre- and post-lactate measurements
Neuro-orthoptic examination
Subjective muscle weakness and general activity using a visual analogue scale


NotesTwo participants had muscle cramps during the creatine period


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskHospital pharmacy did the randomisation and distributed the study agents. Opaque, sealed envelopes and sealed drug containers of identical appearance were sequentially numbered and opened sequentially

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were undistinguishable

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes that are of interest in the review have been reported in the pre-specified way

Other biasUnclear riskWashout period may be too short in two participants

Kornblum 2005

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants15 participants with mitochondrial cytopathies (mean age 49 ± 9 years)


InterventionsCreatine 0.15 g/kg daily versus placebo
Each treatment phase lasted 6 weeks
4-week washout period


OutcomesIsometric maximum voluntary contraction of the calf muscles
Tensiometric hand grip test
P-31 MRS during calf muscle ergometric test (aerobic and ischaemic exercise at 30% of MVC)
Skeletal muscle function assessed by modified Boston score
Subjective endurance performance and general physical condition using individual rating scales
Creatine and creatinine plasma levels


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskCentral allocation by hospital pharmacy

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Capsules used for administration of creatine and placebo were identical in appearance

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data unlikely to be related to true outcome

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes that are of interest in the review have been reported

Other biasLow riskThe study appears to be free of other sources of bias

Louis 2003

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants15 participants with muscular dystrophy (mean age 10.8 ± 2.8 years):

  • 12 participants with DMD,
  • 3 participants with BMD


InterventionsCreatine 3 g daily versus placebo (maltodextrin)
3-month treatment phases
Washout period of 2 months


OutcomesMaximal voluntary contraction of isometric elbow flexion
Fatigue resistance at 75% MVC, total joint stiffness at 50% MVC
Intramuscular PCr/beta-ATP ratio at rest measured by P-31 MRS
Bone mineral density determined by dual energy X-ray absorptiometry
Body mass
Plasma creatine level, serum CK activity
Hepatic and renal function assessed by blood and urine studies


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCoin tossing was used for sequence generation

Allocation concealment (selection bias)Low riskSealed drug containers of identical appearance were sequentially numbered and opened sequentially

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll outcomes specified in the study protocol have been reported

Other biasLow riskThe study appears to be free of other sources of bias

Schneider-Gold 2003

MethodsRandomised, double-blind, placebo-controlled trial


Participants20 participants with PROMM (mean age 57.7 ± 8.7 years)


InterventionsCreatine 10 g per day (10 participants) versus placebo (10 participants),
3 months duration


OutcomesMaximum grip strength
Compound strength score of proximal arm and leg muscles calculated from hand-held dynamometry
MRC, NSS
Subjective assessment of activity in daily life using a visual analogue scale


NotesIn the creatine group, myalgia improved in two participants and chest pain resolved in another patient


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskCentral allocation by hospital pharmacy. Creatine and placebo were filled in coded boxes of identical appearance. Code numbers were broken only at the final data evaluation

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were administered in an identical powder form

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Tarnopolsky 1997

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants7 participants with mitochondrial cytopathies (mean age 42 ± 14 years)


InterventionsCreatine (10 g daily for 2 weeks followed by 4 g per day for 1 week) versus placebo
5-week washout period


OutcomesEvoked and voluntary isometric contraction strength of the dorsiflexors
Nonischemic, isometric, dorsiflexion torque (NIDFT, 2 min)
Ischaemic isometric handgrip strength (1 min)
Basal and postischemic exercise lactate
Aerobic cycle ergometry with pre- and post-lactate measurements
Activities of daily living assessed by a visual analogue scale
Lean body mass measured by DEXA scanning


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPieces of labelled paper were put into envelopes and shuffled

Allocation concealment (selection bias)Low riskAn independent person who was not a co-author allocated sequentially numbered, opaque, sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were administered in an identical and indistinguishable powder form

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Tarnopolsky 2004a

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants31 participants with DMD (mean age 10 ± 3 years)


InterventionsCreatine 0.1 g/kg daily versus placebo
4-month treatment phases
6-week washout period


OutcomesMaximal isometric handgrip strength
Manual muscle testing
Pulmonary function testing
Fat-free mass, body fat, bone mineral content and density measured by DEXA scanning
Functional tests and Activity Scale for Kids questionnaire
Serum CK activity, gamma glutamyl transferase activity, serum and urine creatinine concentration
DNA oxidative damage assessed by urinary 8-hydroxy-2-deoxy-guanosine
Bone breakdown measured by N-telopeptide excretion in urine


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPieces of labelled paper were put into envelopes and shuffled in blocks

Allocation concealment (selection bias)Low riskAn independent person who was not a co-author allocated sequentially numbered, opaque, sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were indistinguishable (flavoured tablets)

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Tarnopolsky 2004b

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants42 participants with DM1 (mean age 41 ± 10 years)


InterventionsCreatine 5 g per day versus placebo
4-month treatment phases
6-week washout period


OutcomesMaximum isometric strength (handgrip, foot dorsiflexion, knee extension)
Manual muscle testing
Pulmonary function assessed by spirometry
PCr/beta-ATP ratio measured by P-31 MRS
Functional tasks
Assessment of activities of daily living using a visual analogue scale
Body mass
Fat-free mass, body fat, bone mineral content and density measured by DEXA scanning
Side effects using a questionnaire
Serum activities of CK, aspartate aminotransferase, gamma glutamyl transferase
Serum bilirubin concentration, serum and urine creatinine concentration


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPieces of labelled paper were put into envelopes and shuffled in blocks

Allocation concealment (selection bias)Low riskAn independent person who was not a co-author allocated sequentially numbered, opaque, sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were indistinguishable (flavoured tablets)

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced in numbers across intervention groups. Reasons for missing data unlikely to be related to true outcome

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Vorgerd 2000

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants9 participants with glycogen storage disease type V (mean age 39.1 ± 17.9 years)


InterventionsCreatine 0.15 g/kg daily for 1 week followed by 0.06 g/kg daily for 4 weeks versus placebo
4-week washout period


OutcomesErgometer exercise test
Fatigue Severity Scale, muscle cramp scale
P-31 MRS and S-EMG during calf muscle ergometric test (aerobic and ischaemic exercise with 30% of MVC)
Serum creatine level and CK activity


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskHospital pharmacy did the randomisation and distributed the study agents. Drug containers of identical appearance were sequentially numbered and opened sequentially

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Capsules used for administration of creatine and placebo were identical in appearance

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Vorgerd 2002

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants19 participants with glycogen storage disease type V (mean age 33.8 ± 11.8)


InterventionsCreatine 0.15 g/kg daily versus placebo
Each treatment phase lasted 5 weeks
4-week washout period


OutcomesIsometric maximum voluntary contraction of the calf muscles
P-31 MRS and S-EMG during calf muscle ergometric test (aerobic and ischaemic exercise with 30% of MVC)
Exercise intolerance and adverse effects using a diary
Serum creatine level and CK activity
Body mass index


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskHospital pharmacy did the randomisation and distributed the study agents. Drug containers of identical appearance were sequentially numbered and opened sequentially

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Capsules used for administration of creatine and placebo were identical in appearance

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data unlikely to be related to true outcome

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

Walter 2000

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants36 participants with muscular dystrophies (mean age 26 ± 16 years):

  • 12 participants with FSHD (37 ± 19 years)
  • 10 participants with BMD (23 ± 10 years)
  • 8 participants with DMD (10 ± 3 years)
  • 6 participants with sarcoglycan-deficient LGMD (30 ± 12 years)


InterventionsCreatine (adults 10 g/day, children 5 g/day) versus placebo,
8-weeks treatment phases,
washout period of 3 weeks


OutcomesMRC score

NSS
vital capacity,
subjective assessment of improvement


NotesOnly the placebo-creatine sequence was included in the final evaluation because of carryover effects in the creatine-placebo sequence


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskHospital pharmacy did the randomisation and distributed the study agents. Opaque, sealed envelopes and sealed drug containers of identical appearance were sequentially numbered and opened sequentially

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel. Creatine and placebo were administered in identical powder form

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data unlikely to be related to true outcome

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes have been reported in the pre-specified way

Other biasLow riskSmall carryover effects have been detected but this point was considered in the final evaluation (only data of placebo - creatine sequence was included). The study appears to be free of other sources of bias

Walter 2002

MethodsRandomised, double-blind, placebo-controlled cross-over trial


Participants34 participants with DM1 (mean age 44 ± 13 years)


InterventionsCreatine (10.6 g daily for 10 days followed by 5.3 g daily for 46 days) versus placebo,
6-week washout period


OutcomesMaximum isometric strength of biceps and quadriceps muscle
MRC, NSS
Body weight and lean body mass
Spirometry
Patients´ global assessment of improvement


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer random number generator was used

Allocation concealment (selection bias)Low riskHospital pharmacy did the randomisation and distributed the study agents. Opaque, sealed envelopes and sealed drug containers of identical appearance were sequentially numbered and opened sequentially

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of participants and study personnel

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll of the study's pre-specified outcomes have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Barisic 2002Case report (1 participant with MELAS)

Beurey 1967Case report (1 participant with polymyositis)

Borchert 1999Non-controlled trial (4 people with mitochondrial encephalomyopathies)

Duperrat 1972Case report (1 participant with dermatomyositis)

Felber 2000Case report (1 participant with DMD)

Freddi 1979Non-controlled trial (9 participants with myotonic dystrophy type 1)

Hagenfeldt 1994Case report (1 participant with MELAS)

Komura 2003Non-controlled trial (2 people with mitochondrial encephalomyopathy)

Matsumura 2004Open, non-controlled trial (22 muscular dystrophy participants)

Rodriguez 2007Combination therapy (creatine monohydrate, coenzyme Q10, lipoic acid; 16 participants with mitochondrial cytopathies)

Sejersen 2000Trial on 38 participants with DMD, published in abstract form. Necessary details could not be obtained

Stout 2001Case study (1 participant with myasthenia gravis)

Tarnopolsky 1999Study 1 (81 participants with neuromuscular disease): open, non-controlled trial; study 2 (n = 21): single-blinded, non-randomised trial

Tarnopolsky 2004Case report (1 participant with mitochondriopathy)

 
Characteristics of ongoing studies [ordered by study ID]
NCT01217320

Trial name or titleCreatine supplementation in pediatric rheumatology

MethodsRandomised, double-blind, placebo-controlled trial

ParticipantsEstimated enrollment of 40 participants (age 6 to 18 years) with juvenile systemic lupus erythematosus or juvenile dermatomyositis

InterventionsCreatine 5 g per day versus placebo (dextrose 5 g/day) for 12 weeks

OutcomesQuality of life, muscle function, kidney function parameters

Starting dateJanuary 2011

Contact informationBruno Gualano, PhD, University of Sao Paulo, Brazil, gualano@usp.br

Notes

 
Comparison 1. Creatine versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Maximum voluntary contraction (MVC) in muscular dystrophies6277changes in MVC [%] (Fixed, 95% CI)8.47 [3.55, 13.38]

    1.1 dystrophinopathies
3121changes in MVC [%] (Fixed, 95% CI)9.20 [3.52, 14.88]

    1.2 myotonic dystrophy type 1
2136changes in MVC [%] (Fixed, 95% CI)4.39 [-8.61, 17.39]

    1.3 myotonic dystrophy type 2
120changes in MVC [%] (Fixed, 95% CI)8.8 [-6.12, 23.72]

 2 MVC in metabolic myopathies366changes in MVC [%] (Fixed, 95% CI)-2.26 [-6.29, 1.78]

    2.1 mitochondrial diseases
238changes in MVC [%] (Fixed, 95% CI)-3.65 [-11.17, 3.86]

    2.2 glycogen storage disease
128changes in MVC [%] (Fixed, 95% CI)-1.69 [-6.48, 3.09]

 3 Global assessment of improvement in muscular dystrophies4183Risk Ratio (M-H, Fixed, 95% CI)4.51 [2.33, 8.74]

 4 Neuromuscular Symptoms Score (NSS) in muscular dystrophies3120Mean Difference (IV, Fixed, 95% CI)0.83 [-0.43, 2.08]

 5 Percentage change in MRC sum score in muscular dystrophies6275Mean Difference (IV, Fixed, 95% CI)1.10 [0.37, 1.82]

    5.1 dystrophinopathies
291Mean Difference (IV, Fixed, 95% CI)0.93 [-0.39, 2.26]

    5.2 myotonic dystrophy type 1
2132Mean Difference (IV, Fixed, 95% CI)0.68 [-0.38, 1.73]

    5.3 myotonic dystrophy type 2
120Mean Difference (IV, Fixed, 95% CI)1.40 [-0.32, 3.12]

    5.4 mixed muscular dystrophies
132Mean Difference (IV, Fixed, 95% CI)5.0 [1.75, 8.25]

 6 PCr/beta-ATP ratio in metabolic myopathies368changes [%] (Fixed, 95% CI)2.00 [-1.76, 5.76]

 7 ATP consumption during aerobic exercise in metabolic myopathies254ATP consumpt. [%PCr] (Fixed, 95% CI)-1.75 [-2.98, -0.51]

 8 ATP consumption during ischaemic exercise in metabolic myopathies254ATP consumpt. [%PCr] (Fixed, 95% CI)-0.77 [-2.13, 0.59]

 9 tau after aerobic exercise in metabolic myopathies250changes in tau [s] (Fixed, 95% CI)11.30 [-7.97, 30.57]

 10 tau after ischaemic exercise in metabolic myopathies254changes in tau [s] (Fixed, 95% CI)-2.18 [-21.79, 17.43]

 11 Lean body mass (LBM) in muscular dystrophies3196changes in LBM [kg] (Fixed, 95% CI)0.63 [0.02, 1.25]

 
Summary of findings for the main comparison. Creatine for treating muscular dystrophies

Creatine for treating muscular dystrophies

Patient or population: patients with muscular dystrophies
Settings: outpatient treatment
Intervention: creatine
Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

placebocreatine

Maximum voluntary contraction in dystrophinopathies
%
The mean maximum voluntary contraction in dystrophinopathies in the control groups was
30.8 N (mean value of combined testing)1
The mean maximum voluntary contraction in dystrophinopathies in the intervention groups was
9.2 higher
(3.52 to 14.88 higher)
121
(3 studies)
⊕⊕⊕⊕
high

Maximum voluntary contraction in myotonic dystrophy type 1
%
The mean maximum voluntary contraction in myotonic dystrophy type 1 in the control groups was
104.4 Nm (knee extension)2
The mean maximum voluntary contraction in myotonic dystrophy type 1 in the intervention groups was
4.39 higher
(8.61 lower to 17.39 higher)
76
(2 studies)
⊕⊕⊕⊝
moderate3

Maximum voluntary contraction in myotonic dystrophy type 2
%
The mean maximum voluntary contraction in myotonic dystrophy type 2 in the control groups was
52.4 kPa (grip strength)4
The mean maximum voluntary contraction in myotonic dystrophy type 2 in the intervention groups was
8.8 higher
(6.12 lower to 23.72 higher)
10
(1 study)
⊕⊕⊕⊕
high

Adverse eventsSee commentSee comment261
(8 studies)
⊕⊕⊕⊕
high
Differences in side effect profiles of creatine and placebo treatment were not detected. No trial reported any clinically relevant adverse event.

Global assessment of improvement
felt better
98 per 1000442 per 1000
(228 to 857)
RR 4.51
(2.33 to 8.74)
183
(4 studies)
⊕⊕⊕⊕
high5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Mean value of combined quantitative muscle testing (QMT) of elbow flexors and extensors, knee flexors and extensors, and grip at the end of placebo treatment (Escolar 2005).
2 Measurement at the end of placebo treatment (Tarnopolsky 2004b).
3 Quality of evidence was decreased due to inconsistency: one trial reported an increase in MVC (MD 8.4%, 95% CI -7.7 to 24.5; Walter 2002) and one trial showed a decrease in MVC (MD -3.1%, 95% CI -25 to 19.0; Tarnopolsky 2004b).
4 Measurement at the end of placebo treatment (Schneider-Gold 2003).
5 One single blinded study was included (Banerjee 2010) but result would also be significant and similar if this study would not be considered (RR 4.71, 95% CI 2.22 to 10.00).
 
Summary of findings 2. Creatine for treating metabolic myopathies

Creatine for treating metabolic myopathies

Patient or population: patients with metabolic myopathies
Settings: outpatient treatment
Intervention: creatine
Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

placebocreatine

Maximum voluntary contraction in mitochondrial diseases
%
The mean maximum voluntary contraction in mitochondrial diseases in the control groups was
693.43 N (foot plantar flexion)1
The mean maximum voluntary contraction in mitochondrial diseases in the intervention groups was
3.65 lower
(11.17 lower to 3.86 higher)
38
(2 studies)
⊕⊕⊕⊕
high

Maximum voluntary contraction in glycogen storage disease type V
%
The mean maximum voluntary contraction in glycogen storage disease type v in the control groups was
942.71 N (foot plantar flexion)
The mean maximum voluntary contraction in glycogen storage disease type V in the intervention groups was
1.69 lower
(6.48 lower to 3.09 higher)
28
(1 study)
⊕⊕⊕⊕
high

Impairment of activities of daily living (ADL) in glycogen storage disease type V
Visual numeric scale. Scale from: 1 to 10.
The mean impairment of activities of daily living (ADL) in glycogen storage disease type v in the control groups was
2.8 2,3
The mean impairment of activities of daily living (ADL) in glycogen storage disease type V in the intervention groups was
0.54 higher
(0.14 to 0.93 higher)3
19
(1 study)
⊕⊕⊕⊕
high

Adverse events in mitochondrial diseasesSee commentSee comment38
(3 studies)
Two patients reported muscle cramps during creatine treatment.

Adverse events in glycogen storage disease type VSee commentSee comment28
(2 studies)
Significant increase in muscle pain episodes in one trial.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Data obtained from the study by Kornblum et al. (Kornblum 2005).
2 Additional data from the study by Vorgerd et al. (Vorgerd 2002).
3 Higher values indicate more impairment.
 
Summary of findings 3. Creatine for treating idiopathic inflammatory myopathies

Creatine for treating idiopathic inflammatory myopathies

Patient or population: patients with idiopathic inflammatory myopathies
Settings: outpatient treatment
Intervention: creatine
Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

placebocreatine

Aggregate functional performance time (AFPT), intention-to-treat analysis
%
The mean aggregate functional performance time (AFPT), intention-to-treat analysis in the control groups was
28 s
The mean aggregate functional performance time (AFPT), intention-to-treat analysis in the intervention groups was
8.4 lower
(15.4 to 1.49 lower)
37
(1 study)
⊕⊕⊕⊕
high

AFPT, valid compliant completer analysis
%
The mean AFPT, valid compliant completer analysis in the control groups was
28 s
The mean AFPT, valid compliant completer analysis in the intervention groups was
11.6 lower
(19.59 to 3.6 lower)
29
(1 study)
⊕⊕⊕⊕
high

Adverse eventsSee commentSee comment37
(1 study)
See commentNo clinically relevant adverse events were associated with creatine treatment.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.