Table 11 In vivo studies involving interventions directed at normalising γ-glutamyl cycle or trans-sulfation pathway metabolites

Interventions involving folate cycle metabolites

Bertoglio et al. 2010 [64]

Methyl-cobalamin

64.5 μg/kg methyl-cobalamin or placebo injected every third day 6 wks washout period).

32+ cases started the trial of which 30 finished.

Overall, no significant difference in GSH, GSH: GSSG or behaviouraloutcomes. ↑ GSH, ↑GSH:GSSG and improved behavioural outcomes in 9/30 children.

Primary outcome behavioural response. Findings for GSH and tGSH:GSSG presented as bar charts for responder group only. Dispersion and units not provided.

James et al. 2009 [48]

Folinic acid + methyl-cobalamin

400 μg folinic acid bd + 75 μg/kg methyl-cobalamin injected every third day 3 mo.

48 cases selected for low SAM:SAH or GSH: GSSG.

↑ homocysteine, ↑ cystathione ↑ cysteine, ↑ tGSH & ↑tGSH: GSSG.

Excluded 26% of cases because normal SAM: SAH and/or tGSH: GSSG. Following the intervention, tGSH:GSSG was still significantly lower in cases than controls. There was no change in SAM or SAH levels.

James et al. 2004 [46]

Folinic acid + betaine

800 μg folinic acid + 1,000 μg betaine bd 3 mo.

8 cases

↑ homocysteine, ↑ cystathione ↑ cysteine, ↑ tGSH, ↑tGSH: GSSG, ↓SAH & ↓adenosine

Improved but did not normalise tGSH and GSSH.

Folinic acid + betaine +

As above + 75 μg/kg methyl-

8 cases

↑ homocysteine,

Normalised tGSH & tGSH:

methyl-cobalamin

cobalamin injected twice weekly 1 mo.

↑cystathionine, ↑cysteine, ↑ tGSH, ↑tGSH: GSSG, ↓GSSG

GSSG. Improved but did not normalise GSSG.

Moretti et al. 2005 [54]

Folinic acid

0.5 mg/kg/d folinic acid for 2 wk, 1.0 mg/kg/d thereafter 3 mo.

1 case

Normalised (↓) cerebral spinal fluid homocysteine.

Other interventions

Adams et al. 2009 [65, 67]

Chelation therapy

Glutathione (180 mg) or placebo cream daily for 7 days followed by 10 mg/kg DMSA in 3 doses/day for 3 days to screen for high urinary

64 cases

Significantly ↓ variance in erythrocyte glutathione levels 1-2 months after one round of DMSA treatment.

Topical glutathione had no effect on erythrocyte glutathione. Behavioural instruments not validated

excretion of metal ions. 'High

26 DMSA

No data provided for

for measurement of autism

excreters' from the topical

15 placebo

post intervention gluta-

severity. ADOS(diagnostic

glutathione arm given a further

thione.

test) administered pre and

6 rounds of DMSA and those

post second intervention,

from the topical placebo arm

but not at baseline.

given 6 rounds of a placebo.

Rossignol et al. 2007 [49]

Hyperbaric oxygen therapy (HBOT)

1.3 atm (n = 12) or 1.5 atm (n = 6) for 45 mins × 40 sessions (ie 4.6 times/wk × 9 wk)

18 cases

No significant difference in plasma tGSH:GSSG before or after either intervention.