Glycine for Schizophrenia
For schizophrenia, glycine does not work: early small trials suggested it eased negative symptoms, but the largest, highest-quality trial found no benefit, and added to clozapine it can make positive symptoms worse.
Why this grade7-layer evidence engine
Early enthusiasm came from very small crossover RCTs. A 1999 trial (PMID 9892253, n=22) reported a roughly 30% drop in PANSS negative symptoms with high-dose glycine (0.8 g/kg/day) added to standard antipsychotics, with response strongest in patients who started with low serum glycine. But with only ~22 patients, these findings were preliminary and not generalizable.
Larger, better-designed studies overturned this. The NIMH-funded multisite CONSIST trial (PMID 17898352, n=157, 16 weeks) was the highest-quality study and found no benefit of glycine over placebo on negative symptoms or cognition. A pooled meta-analysis of NMDA modulators (PMID 21936588, n=1,253) showed only a small overall effect, and importantly glycine added to clozapine worsened positive symptoms (SMD +0.56). Trials adding glycine to clozapine (PMID 10784481), a later pilot (PMID 30633660), and a GlyT1-inhibitor study (PMID 37141764) were all negative.
Authorities do not support glycine for schizophrenia. The FDA treats it only as a food additive/excipient (it is no longer 'generally recognized as safe' in human food), and EFSA found 'a cause and effect relationship has not been established' for amino-acid health claims. Cleveland Clinic does not mention glycine in its schizophrenia guidance; Harvard's McLean acknowledges the glycine-site target only as a research hypothesis, not a clinical recommendation. This earns a weak/counter-evidence grade: an early positive signal refuted by larger trials, with a real safety concern when combined with clozapine.
Scoring transparency
All scores computed by a 7-layer evidence engine — fully auditable▸View the full decision path (audit trail)
- compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.465
- tier_from_score — 依分數區間映射至 tier letter
- apply_hec_rules — 高品質 SR/MA 顯示 positive (1 篇 > 0 negative)
- tier_strict_requirement_check — Tier 條件達標，未降階
- detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
- decide_status — 依 tier + dispute 結果決定 status