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