Interventions involving folate cycle metabolites
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Bertoglio et al. 2010 [64]
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Methyl-cobalamin
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64.5 μg/kg methyl-cobalamin or placebo injected every third day 6 wks washout period).
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32+ cases started the trial of which 30 finished.
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Overall, no significant difference in GSH, GSH: GSSG or behaviouraloutcomes. ↑ GSH, ↑GSH:GSSG and improved behavioural outcomes in 9/30 children.
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Primary outcome behavioural response. Findings for GSH and tGSH:GSSG presented as bar charts for responder group only. Dispersion and units not provided.
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James et al. 2009 [48]
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Folinic acid + methyl-cobalamin
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400 μg folinic acid bd + 75 μg/kg methyl-cobalamin injected every third day 3 mo.
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48 cases selected for low SAM:SAH or GSH: GSSG.
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↑ homocysteine, ↑ cystathione ↑ cysteine, ↑ tGSH & ↑tGSH: GSSG.
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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.
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James et al. 2004 [46]
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Folinic acid + betaine
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800 μg folinic acid + 1,000 μg betaine bd 3 mo.
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8 cases
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↑ homocysteine, ↑ cystathione ↑ cysteine, ↑ tGSH, ↑tGSH: GSSG, ↓SAH & ↓adenosine
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Improved but did not normalise tGSH and GSSH.
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Folinic acid + betaine +
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As above + 75 μg/kg methyl-
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8 cases
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↑ homocysteine,
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Normalised tGSH & tGSH:
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methyl-cobalamin
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cobalamin injected twice weekly 1 mo.
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↑cystathionine, ↑cysteine, ↑ tGSH, ↑tGSH: GSSG, ↓GSSG
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GSSG. Improved but did not normalise GSSG.
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Moretti et al. 2005 [54]
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Folinic acid
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0.5 mg/kg/d folinic acid for 2 wk, 1.0 mg/kg/d thereafter 3 mo.
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1 case
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Normalised (↓) cerebral spinal fluid homocysteine.
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Other interventions
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Adams et al. 2009 [65, 67]
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Chelation therapy
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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
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64 cases
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Significantly ↓ variance in erythrocyte glutathione levels 1-2 months after one round of DMSA treatment.
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Topical glutathione had no effect on erythrocyte glutathione. Behavioural instruments not validated
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excretion of metal ions. 'High
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26 DMSA
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No data provided for
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for measurement of autism
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excreters' from the topical
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15 placebo
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post intervention gluta-
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severity. ADOS(diagnostic
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glutathione arm given a further
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thione.
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test) administered pre and
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6 rounds of DMSA and those
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post second intervention,
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from the topical placebo arm
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but not at baseline.
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given 6 rounds of a placebo.
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Rossignol et al. 2007 [49]
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Hyperbaric oxygen therapy (HBOT)
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1.3 atm (n = 12) or 1.5 atm (n = 6) for 45 mins × 40 sessions (ie 4.6 times/wk × 9 wk)
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18 cases
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No significant difference in plasma tGSH:GSSG before or after either intervention.
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