N,N-Dimethylglycine 125mg tablets

PurposeMajor surgery under general anesthesia substantially alters physiologic homeostasis. Nevertheless, the intricate effects on the metabolome are poorly studied. Metabolic fingerprints may allow the identification of patients at risk for unfavourable outcomes.MethodsWe conducted a secondary, exploratory, targeted metabolomic analysis of 177 high-risk patients undergoing major abdominal surgery under general anesthesia enrolled in the Targeting preoperatively Assessed Personal cardiac Index in major abdominal suRgery patients (TAPIR) randomized controlled trial. We analyzed primary serum metabolites using liquid chromatography coupled with triple quadrupole mass spectrometry before surgery (on preoperative day 0) and on postoperative day 3 (POD3). Our primary aim was to investigate postoperative alterations in primary serum metabolites. Secondary objectives included analyses in different subgroups, including patients with postoperative complications (composite of complication, delirium, acute kidney injury, and infection) up to day 30. We applied regression analyses and calculated false discovery rate-adjusted P values to address multiplicity.ResultsOf the 37 metabolites analyzed, 20 were different on POD3 after comparison with before surgery (lower: 4-hydroxyproline, alanine, asparagine, citrulline, cystine, dimethylglycine, glutamine, glutamic acid, glycine, guanosine, histidine, niacinamide, serine, uric acid, and xanthine; higher: isoleucine, leucine, methionine, methionine sulfoxide, pyruvic acid; adjusted P values ConclusionMajor abdominal surgery under general anesthesia was associated with complex changes in primary metabolites. We identified alterations in certain metabolites that were associated with postoperative delirium. Future research may establish metabolic patterns allowing the identification of patients at risk for unfavourable postoperative outcomes.

Abstract licence: CC BY-NC

AbstractOral administration of N,N-Dimethylglycine (DMG), a tertiary amino acid, presumably enhances oxygen utilization by tissue and complex with free radicals. Beneficial effects are improved endurance performance and reduction fatigue in humans and animals. This pilot study reports the results over a one-year double-blind, placebo-controlled trial of DMG in 30 randomized patients with progressive multiple sclerosis. No treatment effects were found between the placebo group and the DMG group for disability, fatigue, cognitive, or gait parameters.

Abstract licence: CC BY 4.0

Abstract Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6 week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N=106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (False discovery rate (FDR) corrected P=0.043, d=0.74, N=83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR=0.004, d=1.13, N=60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR=0.006, r=-0.485, N=43) and deteriorations between 2 and 4 weeks (PFDR=0.032, r=0.415, N=37).Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood, and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-Methyl-D-Aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.Trial registration: A multicenter, parallel group, placebo-controlled, double blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders. (The date registered: 30th Oct 2020; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264)

Abstract licence: CC BY