AbstractIntroductionIn recent times, evidence from published reports; randomized clinical trial (RCT), human case-controls, metabolomics, animal and cell studies is gaining rapt significance on the ameliorative potential of histidine (His) in obesity/insulin resistance (IR)/ inflammation outcomes. This study aimed at systematically mining evidence from previously published studies on the vitality of His on metabolic disorder outcomes.MethodsUsing the MOOSE guidelines we searched PubMed and Cochrane library using the search words “histidine” and “obesity” or “diabetes” or “metabolic syndrome” and included articles on His intake/administration and obesity/diabetes/metabolic disorders involving human and/or animal experimentation.ResultsWe found low circulating His profile has been associated with metabolic disorders independent of ethnicity [1–4]. Similarly, two separate animal trials [5–6] found His to be significantly lower in diabetic Balb/cA mice and lean Zucker rat. Also, the endogenous absence of His disrupts mitochondrial membrane integrity thereby impairing energy production [7]. In addition, epidemiological report revealed higher dietary His was associated with lower overweight and obesity risk [8]. Though epidemiological reports from the diverse population to assert this observation are insufficient, reports from animal models [9–10] revealed similar conclusions. Also, some reports [11–12] have demonstrated the dose-dependent inhibitory effect of His on some inflammatory markers by assuaging the palmitic acid induced pAkt/Akt expression [12]. Also, His inhibits the up-production of free radicals to impede the extracellular signal-regulated kinase in neurons [13].ConclusionThese evidences are novel but primarily limited to mostly obesity. In our opinion, future multi-ethnic longitudinal cohort and trials should consider exploring effects of His on non-fatty alcoholic liver diseases and cardiovascular complications. His might as well be beneficial potentially offering significant hope and non-invasive alternatives in the management of metabolic disorders.Note:Complete citations available inMEDLINE;[1] PMID: 20834187 [2] PMID: 22266733 [3] PMID: 21996294 [4] PMID: 23697717 [5] PMID:15878720 [6] PMID:15389298 [7] PMID: 4621606 [8] PMID: 27409634 [9] PMID: 17372311 [10] PMID: 15561489 [11] PMID: 16107255 [12] PMID: 23361591 [13] PMID: 22101981