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Table 9 In vivo studies examining an association between metabolites of the γ-glutamyl cycle or trans-sulfation pathway and autism spectrum disorders

From: The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis

  

Study

Cases1

Controls1

P values

Overall

finding

Comments

Total glutathione (μmol/L)

     

Plasma

AD

Rose et al. 2008 [50]

5.69 ± 1.37

5.08 ± 1.38

7.53 ± 1.7

< 0.001

lower

ALAD CG + CC significantly lower than GG p = 0.007.

  

Pastural et al. 2009 [82]

Not provided

Not provided

< 0.05

lower

 

Erythrocyte

ASD

Adams et al. 2009 [65, 67]

501 ± 246

427-714

 

same

Paediatric values are lower than the reference range for adults provided by the laboratory.

Whole

AD

Pasca et al. 20094 [60]

161.16 ± 41.36

242.67 ± 118.77

0.02

lower

SEM converted to SD. Not treated to prevent oxidation

Blood

PDD-NOS

Pasca et al. 20094 [60]

209.96 ± 94.63

213.32 ± 98.55

ns

same

As above.

 

AS

Pasca et al. 20094 [60]

147.31 ± 74.26

171.29 ± 92.69

ns

same

As above.

Free glutathione (μmol/L)

     

Plasma

AD

James et al. 20063,4 [47]

1.4 ± 0.5

2.2 ± 0.9

< 0.0001

lower

 
  

Rose et al. 2008 [50]

1.60 ± 0.57

2.2 ± 0.9

< 0.001

lower

ALAD CG + CC significantly lower than GG P = 0.02

   

1.4 ± 0.48

   

Same controls as James et al. 2006.

  

James et al. 20093,4 [48]

1.5 ± 0.4

2.8 ± 0.8

0.008

lower

Cases with abnormal methylation or tGSH:GSSG only.

Reduced glutathione (μmol/L)

     

Plasma

ASD

Geier & Geier 2006 [66]

64% lower

 

< 0.01

lower

Sample preparation not provided.

  

Geier & Geier 2009 [90]

3.1 ± 0.53

4.2 ± 0.72

< 0.0001

lower

 
 

ASD

Geier & Geier 2009 [91]

3.14 ± 0.56

4.2 ± 0.72

< 0.0001

lower

 
  

Adams et al. 2011 [87]

3.23 ± 0.48

4.09 ± 0.79

< 0.0001

lower

 

Oxidised glutathione (μmol/L)

     

Plasma

AD

Rose et al. 2008 [50]

0.32 ± 0.127

0.32 ± 0.128

0.24 ± 0.1

< 0.001

higher

No significant difference between ALAD CG + CC and GG.

Total glutathione: oxidised glutathione

     

Plasma

AD

James et al. 20043 [46]

8.6 ± 3.5

25.5 ± 8.9

< 0.001

lower

 
  

James et al. 20063,4 [47]

14.7 ± 6.2

28.2 ± 7.0

< 0.001

lower

 
  

Rossignol et al. 20075 [49]

28.47 ± 4.599

28.2 ± 7.0

  

Cases more likely to be severe as requested

   

44.68 ± 14.1910

   

HBOT. Controls from James et al. 2006.

  

Rose et al. 2008 [50]

20.45 ± 8.77

28.2 ± 7.0

< 0.001

lower

ALAD CG + CC significantly lower than GG

   

17.4 ± 5.78

   

P = 0.03. Controls from James et al. 2006.

  

James et al. 20093,4 [48]

21 ± 6

47 ± 18

< 0.005

lower

Cases abnormal methylation or tGSH:GSSG only.

Free: oxidised glutathione

     

Plasma

AD

James et al. 20063,4 [47]

4.9 ± 2.2

7.9 ± 3.5

< 0.0001

lower

 
  

Rose et al. 2008 [50]

5.64 ± 2.67

4.81 ± 1.88

7.9 ± 3.5

< 0.001

lower

ALAD CG + CC significantly lower than GG P = 0.05

Reduced: oxidised glutathione

     

Plasma

ASD

Adams et al. 2011 [87]

8.0 ± 3.2

10.1 ± 4.5

0.01

lower

 
  

Al-Yafee et al. 2011 [85]

8.03 ± 2.46

26.07 ± 5.03

0.001

lower

 

Homocysteine (μmol/L)

     

Plasma

AD

Moretti et al. 2005 [54]

6

4-14

 

ns

Case study compared with reference values

  

Pastural et al. 2009 [82]

Not provided

Not provided

ns

ns

Result control normalised graph.

Serum

 

Geier & Geier 2006 [66]

62% lower

 

< 0.01

 

Does not state whether fasted or not.

CSF

AD

Moretti et al. 2005 [54]

0.424

0.032-0.114

 

high

Case study compared with reference values

Cysteine (μmol/L)

      

Plasma

AD

Pastural et al. 2009 [82]

Not provided

Not provided

< 0.05

lower

Result provided graphically as relative to homocysteine.

 

ASD

Geier & Geier 2006 [66]

81% lower

 

< 0.01

  

Serum

AD

Visconti et al. 19946 [69]

40.56 ± 5.6811

41.04 ± 15.5612

40.26 ± 12.72

ns

same

 

Cystine (mmol/L)

      

Plasma

AD

Khaleeluddin & Philpott 1980 [93]

5/6 low

   

Concentrations and reference range not provided.

  

D'Eufemia et al. 19953 [70]

78.3 ± 17.5

72.5 ± 19.9

ns

ns

Units incorrectly labelled mmol/L in Table 1. Correctly labelled μmol/L in Figure 3.

 

ASD

Adams et al. 2011 [87]

32.2 ± 8.2

34.8 ± 7.4

ns

ns

Fasted.

Cystathione (μmol/L)

      

Plasma

AD

Khaleeluddin & Philpott 1980 [93]

1/6 high

    

Serum

ASD

Geier & Geier 2006 [66]

68% low

 

< 0.05

 

Details of sample preparation not provided.

Cysteinylglycine (μmol/L)

     

Plasma

AD

James et al. 20064,5 [47]

38.9 ± 11

39.4 ± 7.3

0.78

ns

 
  

James et al. 20094,5 [48]

40 ± 9

45 ± 6

< 0.005

lower

Cases abnormal methylation or tGSH:GSSG only.

 

ASD

Suh et al. 2008 [77]

17.5 ± 6.8

10.5 ± 4.1

0.0008

higher

 

Serine (μmol/L)

     

Serum

AD

Visconti et al. 19946 [69]

130.59 ± 24.849

143.79 ± 30.08

ns

ns

 
   

151.45 ± 50.4310

143.79 ± 30.08

ns

ns

 
  

D'Eufemia et al. 19953 [70]

163.5 ± 32.1

169.1 ± 47.3

ns

ns

Units incorrectly labelled mmol/L in Table 1. Correctly labelled μmol/L in Figure 3.

  

Shinohe et al. 20064 [75]

  

ns

ns

Results presented graphically

Plasma

AD

Pasca et al. 20095 [60]

99.46 ± 13.56

125.23 ± 47.31

0.08

trend

SEM converted to SD.

 

ASD

Aldred et al. 2003 [88]

  

ns

ns

Results presented graphically.

  

Adams et al. 2011 [87]

104 ± 25

94.7 ± 21

0.04

high

 

(platelet poor)

Tirouvanziam et al. 2011 [86]

85.23 ± 26.5

112.30 ± 27.3

0.0013

low

Data obtained from author.

 

PDD-NOS

Pasca et al. 20095 [60]

113.31 ± 22.84

114.6 ± 38.23

ns

ns

SEM converted to SD.

 

AS

Pasca et al. 20095 [60]

96.2 ± 14.3

124.75 ± 49.07

ns

ns

SEM converted to SD.

Glycine (μmol/L)

      

Serum

AD

Visconti et al. 19946 [69]

225.88 ± 36.238

245.63 ± 60.19

ns

ns

 
   

225.06 ± 24.079

 

ns

ns

 
  

D'Eufemia et al. 19953 [70]

246.7 ± 52.2

257.7 ± 55.3

ns

ns

Units incorrectly labelled mmol/L in Table 1. Correctly labelled μmol/L in figures.

  

Shinohe et al. 20064 [75]

  

ns

ns

Results presented graphically

Plasma

AD

Pasca et al. 2009 [60]

184.20 ± 46.67

217.23 ± 52.46

0.09

ns

SEM converted to SD

 

ASD

Aldred et al. 2003 [88]

  

ns

ns

Results presented graphically.

  

Adams et al. 2011 [87]

267 ± 81

273 ± 101

ns

ns

 

(platelet poor)

Tirouvanziam et al. 2011 [86]

192.8 ± 46.8

190.3 ± 49.5

ns

ns

Data obtained from author.

 

PDD-NOS

Pasca et al. 20095 [60]

207.94 ± 10.31

209.73 ± 42.31

ns

ns

SEM converted to SD.

 

AS

Pasca et al. 20095 [60]

188.6 ± 30.39

224.0 ± 49.81

ns

ns

SEM converted to SD.

Glutamate (μmol/L)

      

Serum

AD

Visconti et al. 19946 [69]

61.89 ± 22.698

77.16 ± 50.01

ns

ns

 
   

72.28 ± 44.429

77.16 ± 50.01

ns

ns

 
  

D'Eufemia et al. 19953 [70]

77.3 ± 24.5

72.4 ± 21.2

ns

ns

Units incorrectly labelled mmol/L in Table 1. Correctly labelled μmol/L in figures.

  

Shinohe et al. 20064 [75]

89.2 ± 21.5

61.1 ± 16.5

< 0.001

higher

High correlation with ADI-R social scores (r = 0.523, P = 0.026)

 

ASD

Adams et al. 2011 [87]

65 ± 15

55 ± 13

0.001

higher

 

Plasma

 

Arnold et al. 2003 [89]

51 ± 3213

48 ± 15

 

ns

 
   

42 ± 2314

48 ± 15

 

ns

 

Plasma (platelet poor)

 

Tirouvanziam et al. 2011 [86]

104.06 ± 33.85

82.71 ± 34.20

0.039

higher

Data obtained from authors.

Glutamate (nmol/10 8 )

      

Platelets

AD

Rolf et al. 19934 [68]

4.8 ± 1.2

6.0 ± 1.2

< 0.02

lower

Findings presented graphically.

Vitamin B6 (nmol/L)

      

Plasma

AD

Sankar 19797 [92]

753.6 ± 31.7

Reference

Not

higher

 
    

Range (147.8-254.2)

provided

  
  

Khaleeluddin & Philpott

4/9 high

 

Not

higher

 
  

1980 [93]

  

provided

higher

 
 

ASD

Adams et al. 2004 [73]

224.55 ± 30.35

129.47

< 0.001

higher

 
  

Adams et al. 2006 [76]

226.58 ± 84.97

145.66 ± 35.60

0.001

higher

 

Vitamin B6 as pyridoxyl-5-phosphate (nmol/L)

     

Erythrocyte

ASD

Adams et al. 2011 [87]

72.44 ± 64.75

61.51 ± 21.45

ns

ns

 

Selenium (μmol/L)

      

Erythocytes

AD

Jory and McGinnis 20074,5 [78]

3.12 ± 0.54

3.67 ± 0.38

0.0006

lower

 

Whole blood

ASD

Adams et al. 2011 [87]

2.63 ± 0.36

2.67 ± 0.25

ns

ns

 

Selenium (μg/g)

      

Erythrocytes

ASD

Adams et al. 2011 [87]

0.24 ± 0.04

0.23 ± 0.03

ns

ns

 
  1. 1Mean ± standard deviation 2 Cases relative to controls 3 Free from relevant medications 4 Free from supplementation5 Most on folinic acid or methyl-cobalamin 6One case, one control on thioridazine 7 ALAD GG polymorphism 8 ALAD CG + CC polymorphism 9Prior to 40 sessions HBOT at 1.3 atm 10Prior to 40 sessions HBOT at 1.5 atm 11 Normal EEG 12Abnormal EEG13 Normal diet 14Gluten/caseine free diet ns not significant AD Autistic disorder
  2. ASD Autism spectrum disorder PDD-NOS Pervasive developmental disorder- not otherwise specified. GSH Reduced glutathione GSSG Oxidised glutathione tGSH Total glutathione ALAD Delta aminolevulinic acid dehydratase HBOT Hyperbaric oxygen therapy SEM Standard error of the mean SD standard deviation