麩醯胺酸 Glutamine × 免疫功能（重症／創傷／術後感染預防、運動員 URTI 預防、腸黏膜屏障與淋巴球功能）

結論：Heyland et al. NEJM 2013 multicenter blinded RCT in 1,223 critically ill adults with ≥2 organ failures across 40 ICUs (Canada/US/Europe). Glutamine supplementation was associated with INCREASED 28-day mortality (32.4% vs 27.2%, adjusted OR 1.28, 95% CI 1.00-1.64, p=0.05) and significantly increased in-hospital mortality (37.2% vs 31.0%, adjusted OR 1.31, 95% CI 1.04-1.65, p=0.02) and 6-month mortality (43.7% vs 37.2%, p=0.02). No reduction in infectious complications or organ failure. Antioxidants showed no benefit. Trial halted early for futility/safety on glutamine arm. Strongest available harm signal in glutamine literature.

結論：Andrews et al. BMJ 2011 multicentre 2x2 factorial blinded RCT in 502 adult ICU patients across 8 Scottish ICUs. Parenteral glutamine showed NO significant effect on new infections within 14 days (RR 0.93, 95% CI 0.79-1.10, p=0.40), 6-month mortality, antibiotic days, length of stay, or SOFA score. Selenium produced a borderline reduction in new infections only in patients receiving ≥5 days PN. Authors conclude routine parenteral glutamine supplementation cannot be recommended for short-duration ICU PN.

結論：Wernerman et al. Acta Anaesthesiol Scand 2011 pragmatic multicentre blinded RCT in 413 mixed Scandinavian ICU patients. Pre-specified primary endpoint of ICU mortality showed NO significant difference between glutamine and placebo. Some secondary analyses suggested a modest survival signal favoring glutamine in subgroups receiving longer-duration PN, but main analysis null. Reinforces that parenteral glutamine in standard ICU PN does not consistently improve hard outcomes; contrasts with earlier smaller Goeters/Griffiths trials.

結論：Systematic review and meta-analysis of glutamine RCTs in critically ill patients. Mixed results across inflammatory markers; some reduction in CRP and IL-6 in subgroups, but no consistent benefit on infectious complications or mortality. Heterogeneity high. When restricted to large high-quality trials (REDOXS, SIGNET, Scandinavian) effects on hard endpoints are null-to-harmful. Authors caution against routine high-dose combined parenteral + enteral glutamine in patients with multi-organ failure or renal/hepatic dysfunction.

結論：Singer/Blaser/Berger ESPEN ICU guideline (Clin Nutr 2019). Recommends AGAINST routine high-dose parenteral glutamine in unstable critically ill patients with multi-organ failure (Grade B, based on REDOXS harm signal). In stable surgical ICU patients on prolonged parenteral nutrition (>5 days, no organ failure), parenteral glutamine dipeptide 0.2-0.3 g/kg/day MAY be considered (Grade B). Enteral glutamine NOT recommended in critically ill patients except in burn (>20% BSA) and trauma. Captures the post-REDOXS paradigm shift: indication-restricted, not population-wide.

結論：Castell/Poortmans/Newsholme Eur J Appl Physiol 1996 open-label trial in 151 elite endurance athletes (marathon/ultra/middle-distance/rowing). URTI incidence over 7 days post-event was 19% in glutamine group vs 51% in placebo (p<0.001 reported). Founding study for the 'plasma glutamine drop → URTI risk' hypothesis. Subsequent better-controlled trials (Krzywkowski 2001, Walsh 2000s, Gleeson reviews) FAILED to replicate consistent URTI prevention or lymphocyte function rescue. Original effect now considered methodologically fragile (open-label, self-reported URTI, no plasma glutamine measurement at infection onset).

結論：Sandini/Nespoli/Oldani/Bernasconi/Gianotti World J Gastroenterol 2015 systematic review pooling 19 RCTs (n=1,462) of perioperative glutamine in abdominal/cardiac/colorectal surgery. Glutamine reduced postoperative infectious complications (RR 0.65, 95% CI 0.50-0.83, p<0.001) and shortened length of hospital stay by ~3 days. NO significant effect on mortality. Effect more pronounced with parenteral than enteral route. Quality of evidence rated low-to-moderate (heterogeneity, small individual trial sizes, publication bias risk). Stands in tension with REDOXS/SIGNET: surgical-elective context appears qualitatively different from multi-organ-failure ICU.