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

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

Study Intervention Dose & duration Study size Findings Comments
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.  
  1. SAM s-adenosyl-methionine SAH s-adenosyl-homocysteine tGSH total glutathione GSSH Oxidised glutathione bd twice daily DMSA dimercaptosuccinic acid ADOS autism diagnostic observation schedule