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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Molecular nutrition & food research · 2025
Iron deficiency anemia (IDA) affects over two billion people globally and is often treated with conventional iron supplements, which frequently have poor tolerability and limited bioavailability. This systematic review examines the potential of Arthrospira platensis (Spirulina) and Chlorella vulgaris as alternative, bioavailable iron sources. A systematic search was conducted by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying 32 in vivo studies (7 human, 25 animal) that evaluated iron-related outcomes of microalgae supplementation. Both A. platensis and C. vulgaris improved hematological parameters, including hemoglobin, serum ferritin, and red blood cell counts. A. platensis showed more vigorous erythropoietic activity, while C. vulgaris enhanced antioxidant defenses, increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity and reducing lipid peroxidation. Both microalgae reduced inflammation-induced hepcidin levels, thereby supporting improved iron absorption. No significant adverse effects or organ toxicity were reported in any of the included studies. A. platensis and C. vulgaris are safe and effective microalgal supplements that enhance iron status and antioxidant defense, presenting promising alternatives to conventional iron therapy. However, longer-term human clinical trials are needed to validate these findings and determine optimal dosing strategies.
Biological research for nursing · 2026
ObjectiveTo analyze various innovative approaches in the supportive therapy of patients with thalassemia and to summarize the efficacy of different biomedical interventions from Randomized Controlled Trials (RCT).MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and registered in PROSPERO (CRD420251163054). A comprehensive literature search was conducted across four major databases: Scopus, PubMed, ScienceDirect, and Sage Journals. The inclusion criteria for this review involve patients with thalassemia, focus on the supportive therapy of thalassemia, conducted in healthcare settings, and employ a RCT design. The literature quality was evaluated using the Joanna Briggs Institute (JBI) tool for RCT. The data were synthesized using a narrative synthesis approach.ResultsFrom 2,394 records, 13 articles were identified. Luspatercept and Thalidomide were found to be the most effective in reducing transfusion dependence and increasing hemoglobin levels. For iron overload, Amlodipine and Spirulina significantly improved cardiac T2*, contributing to cardioprotection. Furthermore, Curcumin supplementation was shown to improve lipid metabolism and inhibit systemic inflammation. Meanwhile, therapies using Green Tea and Vitamin E were effective in reducing markers of cellular oxidative damage, with Green Tea also demonstrating dual efficacy in reducing serum ferritin (SF) and liver iron concentration (LIC).ConclusionOverall, new and adjuvant supportive therapies significantly support the biological management of patients with thalassemia. Further studies are required to integration between pharmacological therapies and nutraceutical approaches should be further explored to optimize improvements in hematological status, oxidative stress, and patients' metabolic profiles.
Nutrition research (New York, N.Y.) · 2026
The present research assessed the efficacy of 12-week high-intensity interval training (HIIT) and blue-green algae (Spirulina) consumption on pro-inflammatory and anti-inflammatory factors (Dectin-1, IL-1β, and IL-10), along with lipid-associated signaling elements (ApoM and S1P) in obesity. We hypothesized that 12-week intervention combining HIIT and Spirulina consumption will demonstrate superior efficacy than HIIT or Spirulina alone on plasma concentrations of pro- and anti-inflammatory factors and lipid-associated signaling molecules in men with obesity. Sixty-four men with obesity (BMI ≥ 30 kg/m², 20-35 years) were randomly allocated to four treatment groups: control placebo (CP), blue-algae (BA), HIIT + placebo (HIIT+P), or HIIT + blue-algae (HIIT+BA). The treatment consisted of three weekly sessions of HIIT protocols, daily intake of 6 grams of capsulated Spirulina, or simultaneous implementation of both interventions. Plasma biomarkers (Dectin-1, IL-1β, IL-10, ApoM, and S1P), anthropometric measurements, cardiorespiratory assessments, and lipid profiles were examined at baseline and after the 12-week intervention. Statistical analyses demonstrated an elevation in plasma concentrations of IL-10 and ApoM, along with a reduction in concentrations of IL-1β in the BA, HIIT+P, and HIIT+BA groups (P< .05), with the most pronounced changes observed in the HIIT+BA. Also, an increase in S1P concentrations was observed in the HIIT+P and HIIT+BA groups (P = .03, P = .003, respectively). A decrease in Dectin-1 concentrations post-intervention was found only in the HIIT+BA group (P = .03). In conclusion, while HIIT and/or Spirulina have shown potential for targeting lipid- and inflammation-associated markers in obesity, combining these interventions demonstrates superior efficacy for certain parameters.
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition · 2026
Emerging evidence suggests that Spirulina may reduce inflammation by modulating key cytokines, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Accordingly, this study conducted a systematic review and meta-analysis to evaluate the effects of Spirulina supplementation on serum levels of inflammatory mediators in adults aged 18 years and older. Relevant randomized clinical trials (RCTs) were identified through searches of several databases, including the Cochrane Library, ClinicalTrials.gov, ISI Web of Science, Scopus, and PubMed up to August 2025. The pooled effects were calculated using the DerSimonian and Laird random-effects model. Statistical heterogeneity was assessed using I-squared statistics and Cochran's Q test. Eight studies met the inclusion criteria. The administered dosages of Spirulina varied from 1 g/day to 8 g/day, with intervention durations spanning 3 to 16 weeks. The pooled analysis demonstrated that Spirulina supplementation significantly reduced serum CRP concentrations compared with placebo group (weighted mean difference (WMD): -0.09 mg/L; 95% confidence interval (CI): -0.16 to -0.02). In contrast, Spirulina supplementation caused non-significant reduction in TNF-α concentration (WMD: -0.43 pg/mL; 95% CI: -1.44 to 0.59) and IL-6 (WMD: -0.44 pg/mL; 95% CI: -0.98 to 0.1). However, heterogeneity concerning all inflammatory mediators was significant. The findings of this study indicated that Spirulina supplementation significantly reduced serum CRP levels, whereas its effects on IL-6 and TNF-α were not statistically significant. Owing to the significant heterogeneity, further high-quality RCTs are needed to confirm these beneficial effects. PROSPERO Registration: The study was registered in PROSPERO (CRD42024606496).
Frontiers in nutrition · 2026
Spirulina, a nutrient-dense blue-green microalgae, has been proposed as a sustainable intervention to combat undernutrition in children and adolescents. Despite its nutritional benefits, evidence regarding its impact on overall growth in this population remains limited and inconsistent. This systematic review and meta-analysis synthesizes the available evidence on impact of Spirulina supplementation on the growth of children and adolescents. Following PRISMA (version 2020) guidelines, we systematically searched five databases [PubMed, Embase, CINAHL, CENTRAL and Google Scholar (till 16th July 2024)] for experimental studies published in English. Eligible studies assessed the impact of Spirulina supplementation on the growth of children and adolescents (<18 years), with growth-related outcomes such as changes in height, weight, etc. Data extraction and risk of bias assessment were conducted independently. A random-effects meta-analysis was performed using standardized mean differences (SMDs) to pool results. Of 208 identified studies, 5 met the inclusion criteria, and 2 were included in the meta-analysis. The pooled SMD for weight changes was -0.526 (95% CI, -1.289 to 0.236), indicating no statistically significant effect (p = 0.176). Heterogeneity was substantial (I2 = 99%). Variability in intervention dosage, duration and adherence to supplementation contributed to the observed heterogeneity. Spirulina supplementation did not show a statistically significant impact on growth outcomes in children and adolescents. Further high-quality studies are needed to explain its role as a nutritional intervention. https://www.crd.york.ac.uk/PROSPERO, identifier: CRD4202457183.
Behavioural brain research · 2026
This study assesses whether electroacupuncture (EA) is an effective treatment for post-stroke spasticity (PSS) and examines the mechanisms by which it modulates PSS. Clinical and mechanistic evidence are analyzed to clarify its therapeutic value and biological basis. A literature search was conducted in databases including PubMed, Web of Science (WOS), Embase，Medline and SinoMed. The quality was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) bias risk assessment tool and Collaborative Approach to Meta-analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Meta-analyses were performed using Stata 15.0 and Rstudio software. Twenty studies involving 388 animals were included, with quality scores ranging from 4 to 8 (mean: 6.1). Zea Longa and Modified Ashworth Scale (MAS) were selected as primary outcomes, while secondary outcomes included Bederson score, electrophysiological tracing, balance beam walking, cerebral water content, cerebral infarction degree, Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), gamma-aminobutyric acid (GABA), glutamate (Glu), gamma-aminobutyric acid transaminase (GABA-T), glutamate decarboxylase 67 (GAD67), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), BDNF messenger RNA (BDNF mRNA), TrkB messenger RNA (TrkB mRNA), glutathione (GSH), solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), SLC7A11 messenger RNA (SLC7A11 mRNA), and GPX4 messenger RNA (GPX4 mRNA).Meta-analysis demonstrated significant improvements in primary outcomes: Zea Longa score [MD = -1.05, 95 % CI (-1.30, -0.80), P < 0.001]，MAS score: [MD = -1.06, 95 % CI (-1.43, -0.69), P < 0.001]. EA therapy demonstrated significant efficacy in enhancing neurological recovery, alleviating limb spasticity, and improving postural balance. Furthermore, it effectively reduced cerebral infarct volume, mitigated cerebral edema severity, and modulated biochemical markers by decreasing serum levels of IL-6, TNF-α, MDA, Glu, and GABA-T (P < 0.05). Concurrently, therapeutic intervention upregulated multiple neuroprotective indicators including GSH, GABA, SLC7A11 mRNA, GPX4 (with its mRNA expression), GAD67, BDNF, TrkB (and its mRNA), along with enhancing GPX4 activity (P < 0.05). Heterogeneity analysis revealed publication bias in MAS assessments, while heterogeneity in intervention protocols (waveform parameters, acupoint selection, or treatment duration) potentially contributed to elevated heterogeneity across other outcome measures. EA modulates neurotransmitter levels and associated enzymatic, while concurrently suppressing microglia-mediated neuroinflammatory responses. This intervention mitigates oxidative stress byproducts, maintains tissue redox homeostasis, and enhances synaptic plasticity while promoting neuronal development. Collectively, our findings underscore EA's therapeutic potential in PSS management, necessitating further mechanistic investigations and optimization of clinical protocols.
Human brain mapping · 2025
Cognitive control, which is critical for goal-directed behavior, involves resolving conflicts between competing stimuli and is influenced by neurotransmitter interactions within cortico-subcortical areas. This study investigated the relationship between baseline amino acid transmitter levels and interference control, focusing on the effects of experimentally enhancing catecholaminergic signaling. Using a double-blind, placebo-controlled crossover design with two dosage groups, n = 71 healthy human adults underwent proton magnetic resonance spectroscopy once to assess baseline GABA+ and Glx levels in the anterior cingulate cortex (ACC), striatum, and supplementary motor area (SMA). Participants then performed a subliminally primed flanker task inducing different scales of conflict twice while EEG was recorded: once after receiving a placebo (lactase) and once more under either low (0.25 mg/kg) or medium (0.50 mg/kg) doses of methylphenidate (MPH), which modulates the catecholaminergic and amino acid transmitter systems driving cognitive and interference control. Medium MPH doses were more effective than low doses at reducing subliminal interference effects, highlighting dose-specific behavioral improvements. Higher striatal GABA+ levels led to better interference control at low doses, while lower ACC GABA+ and GABA+/Glx levels were associated with better interference control at medium doses, suggesting a dose-dependent shift from striatal to ACC dominance in conflict resolution. Neurophysiological (EEG data) analyses revealed increased theta-band (TBA) and alpha-band activity (ABA) overlapping in the mid-superior-frontal and inferior-frontal clusters under conditions of heightened cognitive control demands. The findings highlight that whether and how amino acid transmitter levels in cognitive control-relevant regions modulate interference conflicts depends on the degree of catecholaminergic signaling.
Journal of clinical anesthesia · 2026
To evaluate if opioid-free anaesthesia (OFA), is non-inferior to standard of care (SOC), in patients at low risk for acute postoperative pain (APOP). Patient- and assessor-blinded, non-inferiority, randomised, controlled trial. Single centre between March 2022 to February 2024. 154 adult patients, ASA I - II, planned for elective laparoscopic surgery and risk-classified as low risk for APOP based on perceived pain during venous cannulation (VAS < 2.0). Patients were randomised to receiving OFA, including sevoflurane, dexmedetomidine, esketamine and lidocaine, or standard of care (SOC), a traditional GABAA and opioid-based strategy. Patients were subjected to the intervention from time to arrival at the day of surgery until discharge from the PACU. Primary outcome: worst pain intensity in the PACU. worst pain, and proportion having NRS ≥ 4, at 24 h (during rest and movement), worst pain and proportion having NRS ≥ 1, at 3- and 6-months (during rest and movement), postoperative recovery at 24 h, PONV in the PACU and at 24 h. Rescue dose opioids in the PACU was an exploratory outcome. Pain scores were 4.8 in the OFA group and 4.6 in SOC group (P = 0.67). At 24 h, worst pain at rest was 5.7 vs 5.0 (P = 0.11), and during movement 5.6 vs 5.3 (P = 0.43). Proportion of patients with NRS ≥ 4 in the PACU was 66 % vs 69 % (P = 0.65) and at 24 h 76 % vs 60 % at rest (P = 0.042) and 73 % vs 69 % during movement (P = 0.65). There was no significant difference in PPOP at 3 or 6 months, either at rest (P = 0.51, P = 0.56) or movement (P = 0.72, P = 0.48), PONV (PACU: P = 0.93), at 24 h: (P = 0.52) or postoperative recovery at 24 h (99 vs 102, P = 0.44). OFA group required less rescue opioids in the PACU (3.4 mg vs 5.1 mg, P = 0.039). When individualising anaesthesia based on predicted risk for APOP, OFA is non-inferior to a traditional GABAA and opioid-based anaesthesia strategy, for patients with a low risk for APOP undergoing laparoscopic surgery. No secondary advantages, i.e. lower PONV, less PPOP, better quality of recovery, was associated with OFA.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
Metformin, a well-established antidiabetic agent, has emerging neuroactive properties extending beyond glycemic control. Evidence suggests effects on neurotransmission, neuroprotection, and neuroinflammatory pathways, offering potential in neurodegenerative disorders. Following PRISMA 2020 guidelines and PROSPERO registration (CRD420251105355), we systematically searched PubMed, Scopus, Web of Science, and Google Scholar (November 2024-July 2025) for in vivo and clinical studies in humans or animals reporting CNS-related outcomes. Two reviewers independently screened and extracted data; risk of bias was assessed with validated tools appropriate to study design. A total of 166 studies met inclusion criteria, including animal models, mechanistic experiments, and clinical observations. Metformin crosses the blood-brain barrier and modulates CNS pathways through anti-inflammatory and mitochondrial-supportive actions. Crucially, it regulates major neurotransmitter systems - serotonin, dopamine, glutamate, GABA, acetylcholine, and norepinephrine - restoring excitatory/inhibitory balance and enhancing synaptic plasticity. Most of the current evidence arises from preclinical studies, which consistently demonstrate neuroprotective and neuromodulatory effects of metformin in models of Alzheimer's disease, Parkinson's disease, stroke, and fragile X syndrome. Clinical data, while promising, remain limited and heterogeneous, mainly suggesting potential cognitive benefits. Metformin shows promise for repurposing in CNS disorders via direct neurotransmitter regulation alongside mitochondrial and anti-inflammatory effects. Given that the majority of available data are preclinical, translational studies and well-designed clinical trials are essential to establish efficacy, dosing, and target populations. These findings underscore the metabolic-neurological interface and suggest a shift from viewing metformin solely as a metabolic therapy to recognizing its neurotherapeutic potential. Long-term use warrants vitamin B12 monitoring.
Psychiatry research · 2026
Individuals with 22q11.2 deletion syndrome are susceptible to psychosis and cognitive impairments. These symptoms have been linked to a disruption in the balance of glutamate (excitatory) to GABA (inhibitory) transmission. This clinical trial aimed to determine whether the glutamate and GABA-modulating drug riluzole reduces psychotic or cognitive symptoms within 22q11.2 deletion syndrome. 32 participants with a 22q11.2 deletion and psychotic and/or cognitive symptoms were enrolled in this placebo-controlled, fixed-order crossover trial. Participants received placebo for 8 weeks, followed by 8 weeks of 100mg/day riluzole. The Positive and Negative Syndrome Scale (PANSS) and Pennsylvania Computerized Neurocognitive Battery (CNB) were used to assess psychotic and cognitive symptoms, with PANSS total and subscale scores and CNB accuracy and reaction time as primary outcome measures. Correcting for family-wise error rate, riluzole improved performance on executive function (p = 0.036), social cognition (p = 0.041), and non-verbal reasoning (p = 0.005) tasks in comparison to baseline. Following correction, no significant effects of riluzole were found on the PANSS total score and subscales, or on accuracy and reaction time on the CNB compared to placebo. Exploratory analyses of individual PANSS items indicated that riluzole reduced anxiety (p = 0.001) and impairments in abstract thinking (p = 0.039) compared to baseline. Our results suggest riluzole may have beneficial effects on mental health and cognition. Further research is needed to confirm these findings and establish a responsive phenotype.
Journal of the International Society of Sports Nutrition · 2026
Esports has become a globally popular competitive activity. The performance of esports athletes depends not only on daily skill training but also on cognitive function, reaction speed, and psychological mood. In recent years, nutritional supplements have attracted widespread attention as a potential adjunctive treatment. However, their actual effects lack systematic evaluation. Objective: The primary aim of this study is to comprehensively review existing evidence and assess the impact of nutritional supplements on the performance of esports athletes, including cognitive, psychological, and gaming aspects. As of June 17, 2025, randomized controlled trials (RCTs) or randomized crossover trials investigating the effects of nutritional supplements on cognitive function, psychological mood, and competitive performance in esports players were retrieved from the PubMed, Scopus, Web of Science, and Embase databases. Two researchers independently extracted key information and data from the literature. The methodological quality of the included studies was assessed using the Physical Therapy Evidence Database (PEDro) scale. A total of 13 randomized controlled trials were included, comprising 10 randomized crossover trials and 3 randomized controlled trials. The study population comprised 466 participants. The methodological quality of the studies, assessed by the PEDro scale (score range 6-10), was good to excellent. The studies included 18 nutritional supplement protocols, with 14 protocols involving pure caffeine or caffeine-containing supplements. Other protocols included active substances such as inositol-enhanced arginine silicate (ASI + I), γ-aminobutyric acid (GABA), and microalgae extracts. Based on existing evidence, some nutritional supplements are associated with three aspects of competitive performance among esports players: 1) Esports players demonstrate significant improvements in attention and executive function, which are closely related to gaming. 2) Improvements in esports players' psychological mood are manifested as increased vitality and reduced fatigue/negative emotions. 3) Improvements in gaming performance are primarily focused on shooting performance, such as increased shooting scores and accuracy, as well as reduced reaction times. Specific nutritional supplements may improve esports players' cognitive function, psychological mood, and gaming performance.However, these findings represent preliminary evidence based on the heterogeneity of the included studies and raise concerns regarding the overall risk of bias in over half of the research. Furthermore, the small sample sizes and focus on amateur players limit the generalizability of the results. Consequently, caution is warranted when interpreting these findings.Future clinical studies are needed to standardize supplementation protocols, dosage, and measurement methods to confirm the benefits of nutritional supplements for esports players.
BMC medicine · 2025
Postoperative delirium (POD) represents a significant challenge in perioperative care, particularly among older surgical patients. This acute neuropsychiatric syndrome is associated with prolonged hospitalization, increased mortality, and long-term cognitive decline. Sleep disturbance has emerged as a significant modifiable risk factor for POD. Sodium oxybate (SO), a gamma-aminobutyric acid B (GABAB) receptor agonist with established sleep-enhancing properties, presents a promising therapeutic approach for POD prevention. The objective of this trial was to investigate whether prophylactic intraoperative sodium oxybate reduces POD incidence in older patients (≥ 65 years) undergoing major orthopedic surgery. This randomized, double-blind, placebo-controlled trial enrolled 332 older patients undergoing elective spine and joint replacement surgery. Participants received either sodium oxybate (30 mg kg-1) or saline after anesthetic induction. Stratified randomization allocated equal numbers to morning and afternoon surgery groups. The primary outcome was POD incidence within seven postoperative days, assessed using the Confusion Assessment Method (CAM). POD incidence showed no significant difference between groups in unstratified population (10.3% vs. 13.5%, P = 0.372). However, subgroup analysis revealed protective effects in morning surgery patients (7.3% vs. 18.5%, relative risk (RR) = 0.395, 95% confidence intervals (CI) = 0.161-0.968, P = 0.033), while no effect was observed in the afternoon surgery group (13.3% vs. 8.5%, P = 0.318). Among patients with delirium, no significant differences were observed in delirium severity, onset timing, delirium duration, or subtype distribution after false discovery rate (FDR) correction. No significant differences were found in sleep quality, maximal pain score, or safety parameters between groups after FDR correction. Intraoperative sodium oxybate demonstrates possible time-specific efficacy, significantly reducing POD incidence exclusively in older patients undergoing morning orthopedic surgery, while demonstrating an acceptable safety profile with no significant adverse effects on anesthesia recovery or hemodynamic parameters, suggesting a potential chronotherapeutic approach to POD prevention. Chinese Clinical Trial Registry, ChiCTR2300078594. Registered on 2023-12-13.
The Journal of clinical psychiatry · 2026
Pregabalin is a gabapentinoid. It does not act on GABA receptors; rather, it inhibits calcium influx into neurons by acting on the α2δ-1 subunit of voltage-gated calcium channels. This reduces release of excitatory neurotransmitters, thereby, perhaps, explaining the sedative, anxiolytic, anticonvulsant, and other properties of the drug. Pregabalin has been approved for neuropathic pain, fibromyalgia, partial-onset seizures, and generalized anxiety disorder, and is used, off-label, for pain in many other contexts and for alcohol use disorder, pruritus, restless legs syndrome, and sleep disorders. It may also be abused. About 0.04%-0.14% of women may use pregabalin during pregnancy. This article examines outcomes of pregnancies that were exposed to pregabalin. A meta-analysis of 7 cohort studies found that, even in unadjusted analysis, pregabalin was not associated with an increased risk of major congenital malformations. This finding was confirmed in later studies; or, if the unadjusted risk was significantly elevated, it was no longer so in adjusted analysis. Many studies found that anytime gestational exposure to pregabalin was not associated with a significantly elevated risk of other important birth outcomes such as stillbirth, low birth weight, preterm birth, small for gestational age, low Apgar score, and microcephaly; or the risks were elevated before but not after adjustment for covariates and confounds; or the risks were not significant relative to disease controls. Similarly, studies found that anytime gestational exposure to pregabalin was associated with no increase in risk, or with a significantly increased risk of attention-deficit/ hyperactivity disorder and related disorders, autism spectrum disorder and related disorders, and intellectual disability before but not after adjustment for covariates and confounds. As a limitation, pregabalin-exposed pregnancy sample sizes were small in all studies. On the positive side, safety impressions were obtained despite negligible adjustment for genetic, illness behavior, and environmental confounds.
Nutrients · 2025
Background: Insomnia is prevalent and difficult to treat safely over the long term. Given the role of the microbiota-gut-brain axis in melatonin and hypothalamic-pituitary-adrenal (HPA) regulation, and preclinical evidence for Limosilactobacillus fermentum PS150, we evaluated whether a heat-treated formulation (HT-PS150) could improve sleep and modulate endocrine/circadian markers in adults with poor sleep. Methods: In a randomized, double-blind, placebo-controlled trial, 84 adults aged 20-60 years with PSQI ≥ 5 and ISI < 22 were assigned to receive either placebo or HT-PS150 for eight weeks. Outcomes included patient-reported sleep (PSQI, ISI), anxiety/depression (GAD-7, PHQ-9), quality of life (QLESQ-SF), gastrointestinal symptoms (VAS-GI), wrist actigraphy (Fitbit Inspire 3), and sleep-relevant biomarkers measured from urine, saliva, and/or blood samples (melatonin, cortisol, orexin, serotonin, GABA, and/or norepinephrine). Repeated measures were analyzed using generalized estimating equations. An exploratory proportional regulation analysis classified individual biomarker changes as up- or down-regulated and compared proportions between study arms. Per-protocol analyses required ≥80% compliance. Results: Improvements in the primary outcomes, PSQI and ISI, were observed over time in both groups, while no significant group × time interactions were detected. In exploratory proportional analyses, a higher proportion of participants in the HT-PS150 group exhibited up-regulated nocturnal melatonin secretion and improved daytime plasma orexin levels, as well as a tendency toward greater reductions in nocturnal salivary cortisol compared with placebo. In subgroup analyses with higher baseline insomnia severity (ISI ≥ 8), HT-PS150 was associated with greater improvements in PSQI (notably sleep duration and efficiency) and reduction in anxiety (GAD-7) upon post hoc testing. Conclusions: Although group mean scores on sleep symptom scales did not differ significantly in the full cohort, HT-PS150 appeared to modulate sleep-wake regulation by enhancing nocturnal melatonin secretion, attenuating HPA-axis activity, and stabilizing wakefulness. Clinical benefits were most evident among participants with greater baseline symptom burden, suggesting potential utility in more symptomatic populations.
Scientific reports · 2026
Gamma-aminobutyric acid, or GABA, the major inhibitory neurotransmitter, acts both through the central nervous system and via microbial production in the gut. Strains able to augment gut GABA production could be novel targets for modulation of sleep and mood. We previously demonstrated that Lactiplantibacillus plantarum Lp815 improves symptoms of anxiety. The current study investigates the impact of Lp815 on subjective sleep, mood, digestion and objective wearable sleep data over 6 weeks in adults with self-reported sleep disturbance. The trial was decentralized, double-blind, randomized and placebo controlled. Participants were screened for at least moderate symptoms of insomnia and blindly assigned to receive either a placebo capsule or 5 billion CFU of Lp815 per day. 139 Individuals (5 billion CFU Lp815 n = 70, placebo n = 69) were evaluated, aged 44 ± 13 years, 51.1% female and 55.4% Caucasian. A sub cohort (n = 17, 5 billion CFU Lp815 n = 9, Placebo n = 8) submitted a urinary time series for neurotransmitter analysis. Participants who received 5 billion CFU Lp815 exhibited significantly lower insomnia severity index scores at 6 weeks compared to placebo (p < 0.05). This result was clinically meaningful, with 77.3% of participants in the 5 billion CFU Lp815 cohort exhibiting improvement by 4 + points in their insomnia severity index at week 6, compared to 57.8% in the placebo group (p = 0.02). Anxiety scores were significantly reduced compared to placebo (p < 0.05), with a more pronounced effect among women (p < 0.01). Additionally, subjective night sweat severity decreased, and objective measures of sleep duration were increased in the 5 billion CFU Lp815 cohort compared to placebo (p < 0.05). Finally, the 5 billion CFU Lp815 cohort exhibited an increase in urinary GABA compared to placebo during the first week of use (p < 0.05) and urinary GABA was inversely correlated with insomnia and anxiety scores at week 2 (r2=-0.30 and - 0.48, respectively). All adverse events potentially related to product use were mild. A daily probiotic containing 5 billion CFU Lp815 significantly improved subjective symptoms of insomnia and anxiety, as well as objective measures of sleep after 6 weeks. Elevation of systemic GABA may contribute to these effects.Trial Registration. The trial was approved by Sterling IRB (12481-NACraft) and registered with ClinicalTrials.gov (NCT06789718).
Communications biology · 2026
Differences in the ϒ-aminobutyric acid (GABA) system contribute to an excitatory-inhibitory imbalance in autism, particularly affecting sensory processing. However, the brain's broader response to interventions targeting GABA pathways in individuals with autism remains poorly understood. This study tested the hypothesis that GABAergic control of information transfer across large-scale brain functional networks is altered in autism. We conducted a phase-amplitude coupling (PAC) analysis of resting-state EEG signals within and between these networks. Responses were compared after double-blind, randomized oral administration of either a placebo or 15/30 mg of arbaclofen, a GABAB receptor agonist. Twenty-four non-autistic (9 males; 19-53 years) and 15 autistic participants (9 males; 20-51 years) completed 93 study visits. Autistic participants exhibited significantly higher theta-beta PAC, especially within the limbic network. High-dose arbaclofen shifted PAC metrics in visual and somatomotor networks towards non-autistic levels, but had minimal effects on networks related to higher cognitive functions. Interestingly, altered PAC within and between networks in the limbic system of autistic participants was normalized by low-dose arbaclofen, yet reemerged after high-dose administration. These findings provide compelling evidence for altered GABAergic responsivity in autism, helping explain some of the challenges in prescribing medications for autistic individuals, such as paradoxical reactions and dose sensitivity.
The Journal of pharmacy and pharmacology · 2026
Ziziphus jujuba var. spinosa, commonly known as sour jujube, has been utilized for millennia in traditional Chinese medicine and functional foods. This review comprehensively summarizes the phytochemistry, pharmacology, and resource utilization of its multiple medicinal-edible parts, aiming to bridge research gaps and promote integrated applications. A systematic literature search was conducted across PubMed, Web of Science, Google Scholar, and CNKI, using keywords such as "Sour jujube" and "Z. jujuba var. spinosa," covering publications up to December 2024. Phytochemical analysis identified 354 bioactive compounds, including 164 flavonoids and 74 triterpenoids, underlying the plant's broad-spectrum pharmacological activity. The seeds, a well-documented herbal medicine, are used alone, in polyherbal formulations, or as an adjuvant to acupuncture, with sedative-hypnotic effects extensively studied via neurotransmitter regulation, specifically by upregulating GABA receptor expression and inhibiting 5-HT degradation and signaling pathway modulation. Nonseed tissues, such as fruits, leaves, and roots, exhibit underutilized potential due to their high content of antioxidants and nutrients, yet remain understudied, leading to resource waste. This review highlights the need to prioritize research on nonseed parts to maximize their medicinal and nutritional value. The findings provide a scientific basis for advancing sour jujube's applications in healthcare and functional food industries.
Frontiers in psychiatry · 2025
This study investigated the intervention effects of different physical exercise programs on multidimensional health outcomes in patients with substance use disorders. Through systematic categorization of intervention types, duration, frequency, and outcome indicators, this research aimed to provide evidence-based exercise prescriptions for rehabilitation treatment of patients with substance use disorders. A systematic search was conducted across six databases: PubMed, Web of Science, Cochrane Library, EMBASE, SCOPUS, and ScienceDirect, retrieving 11,689 articles related to substance use disorders. The search period was limited from database inception to July 1, 2025. Data extraction and quality assessment were performed using Review Manager 5.4 software, ultimately including 33 articles meeting inclusion criteria, encompassing 2,922 participants. Subsequently, network meta-analysis was conducted using Stata 16.0, with results presented as standardized mean differences (SMD) and 95% confidence intervals (CI). A total of 33 randomized controlled trial articles were included, comprising 57 randomized controlled trials with 2,922 subjects. Network meta-analysis results demonstrated that aerobic exercise and mind-body exercise exhibited significantly different advantages: aerobic exercise performed optimally in physiological health indicators (SUCRA = 0.874), followed by substance use outcomes (SUCRA = 0.468) and sleep quality (SUCRA = 0.446); mind-body exercise showed the greatest advantage in improving sleep quality (SUCRA = 0.884), with cognitive function (SUCRA = 0.608) and mental health (SUCRA = 0.588) ranking second and third, respectively. In pairwise comparisons, substance use outcomes in the mind-body exercise network showed significant advantages compared to sleep quality (effect size 44.58, 95% CI: 3.30-85.85), while all comparisons in the aerobic exercise network did not reach statistical significance. Different types of exercise exert therapeutic effects in their respective advantage domains through unique molecular biological mechanisms. Aerobic exercise primarily improves physiological health indicators through AMPK signaling pathways and anti-inflammatory mechanisms, while mind-body exercise optimizes sleep quality and cognitive function through HPA axis regulation and GABA receptor upregulation. These findings provide important evidence-based medical evidence for developing personalized exercise prescriptions for substance use disorders, contributing to the establishment of evidence-based rehabilitation treatment guidelines. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251144089.
Journal of psychiatric research · 2026
Approximately 80% of individuals diagnosed with major depressive disorder (MDD) report symptoms of insomnia. Glutamatergic modulators, such as ketamine, are reported to be effective for the treatment of depressive symptomatology in adults with MDD. Disrupted glutamate homeostasis is linked to poor sleep quality and sleep disorders. Herein, we sought to systematically determine the effect of glutamatergic modulators on sleep mechanisms in preclinical and clinical studies. In accordance with the PRISMA guidelines, a systematic search was performed using the following electronic databases: PubMed, Medline, Cochrane Library, PsycInfo, Embase, Scopus, and Web of Science. Databases were searched from inception to November 27, 2024. Study screening and selection was performed by three reviewers (K.V., B.S., and W.C.). Included studies reported on the effects of glutamatergic modulators on sleep behaviors, architecture, and mechanisms. Preclinical studies reported that glutamatergic modulators, notably ketamine impact mechanistic pathways known to subserve sleep. Including serotonergic, dopaminergic, and GABAergic systems. It was reported that ketamine effects on electroencephalogram (EEG) delta power during non-rapid eye movement (NREM) sleep, and normalizes clock suppressor gene expression. Furthermore, while esketamine enhances delta power during NREM sleep, arketamine does not exhibit a similar effect. Separately, mGlu2/3 activators are suggested to reduce rapid eye movement (REM) sleep. Clinical studies indicate that improved sleep in patients with MDD can mediate ketamine's antidepressant effects. Our findings indicate that glutamatergic modulators, primarily ketamine, are associated with improvement across several sleep behaviors commensurate in MDD, suggesting that mechanisms subserving sleep are potential targets for depression treatment.
Alpha psychiatry · 2026
Schizophrenia, one of the most disabling mental disorders, affects approximately seven per 1000 individuals worldwide and has an estimated heritability of around 80%; however, its pathophysiology remains incompletely understood. The disorder has been linked to dysregulation of multiple neurotransmitter systems, including dopamine, serotonin, γ-aminobutyric acid (GABA), and glutamate. GABA, the primary inhibitory neurotransmitter in the central nervous system, is synthesized by the enzymes glutamic acid decarboxylase 67 (GAD67) and glutamic acid decarboxylase 65 (GAD65), encoded by the GAD1 and GAD2 genes, respectively. The genes (SST) and parvalbumin (PVALB) encode somatostatin and parvalbumin, which are characteristic markers of specialized GABAergic interneuron subpopulations involved in maintaining excitatory-inhibitory balance and supporting cortical circuit function. While reduced GAD1 expression has been consistently reported in schizophrenia, findings regarding GAD2 expression have been inconsistent. In this study, we examined the expression of GAD1, GAD2, SST, and PVALB across three biological levels: postmortem brain tissue, peripheral blood samples, and patient-derived induced pluripotent stem cell (iPSC)-derived brain organoids, compared with healthy controls. The meta-analysis of brain tissue included seven independent datasets (295 samples: 151 individuals with schizophrenia and 144 healthy controls) and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patient-derived iPSC organoids were used to investigate early neurodevelopmental alterations, while a separate meta-analysis of peripheral blood gene expression included 293 samples (160 schizophrenia, 133 controls) to explore biomarker potential. Both GAD1 and GAD2 were significantly downregulated in postmortem brain samples (meta-analytic effect sizes <-0.5) and in iPSC-derived organoids, supporting the hypothesis that reduced expression of these genes emerges prior to clinical onset and may contribute to disease development. In contrast, decreased expression of SST and PVALB was observed in brain tissue but not in organoids, suggesting that alterations in these interneuron markers may occur at later stages of the disease. Notably, reduced PVALB expression was also detected in peripheral blood samples, indicating its potential utility as a peripheral biomarker for schizophrenia. Further studies are required to clarify the causal role of reduced GABAergic activity in schizophrenia pathogenesis and to evaluate the clinical relevance of PVALB expression for diagnosis and treatment monitoring.