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The theoretical alerts described in preclinical work concern a history of cancer, particularly vascularised solid tumours, pregnancy and breastfeeding, and proliferative retinopathies.
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One of the RCTs found significant mean improvements in Clinical Global Impressions-Improvement (CGI-I) score and cellular methylation capacity, but not in the Aberrant Behaviour Checklist (ABC), Social Responsiveness Scale (SRS) or GSH metabolism, with those who had the lowest methionine status at baseline (suggesting impaired methylation capacity) significantly more likely to respond to supplementation
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