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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Molecular psychiatry · 2025
Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. The systematic review included 49 records documenting 50 studies (n = 2384) documenting 22 interventions. Citicoline (SMD =-1.05,95%CI = -1.85; -0.24), L-lysine (SMD = -1.04,95%CI = -1.84; -0.25), N-acetylcysteine (SMD = -0.87, 95%CI = -1.27; -0.47) and sarcosine (SMD = -0.5,95%CI = -0.87-0.13) outperformed placebo for total symptomatology. High heterogeneity (tau2 = 0.10, I2 = 55.9%) and global inconsistency (Q = 40.79, df = 18, p = 0.002) emerged without publication bias (Egger's test, p = 0.42). Sarcosine improved negative symptoms (SMD = -0.65, 95%CI = -1.10; -0.19). N-acetylcysteine improved negative symptoms (SMD = -0.90, 95%CI = -1.42; -0.39)/general psychopathology (SMD = -0.76, 95%CI = -1.39; -0.13). No compound improved total symptomatology within acute phase studies (k = 7, n = 422). Sarcosine (SMD = -1.26,95%CI = -1.91; -0.60), citicoline (SMD = -1.05,95%CI = -1.65;-0.44), and N-acetylcysteine (SMD = -0.55,95%CI = -0.92,-0.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD = -1.10, 95%CI = -1.75,-0.45), L-lysine (SMD = -1.05,95%CI = -1.55, -0.19), omega-3 fatty acids (SMD = -0.83,95%CI = -1.31, -0.34) and withania somnifera (SMD = -0.71,95%CI = -1.21,-0.22). Citicoline (SMD = -1.05,95%CI = -1.86,-0.23), L-lysine (SMD = -1.04,95%CI = -1.84,-0.24), N-acetylcysteine (SMD = -0.89,95%CI = -1.35,-0.43) and sarcosine (SMD = -0.61,95%CI = -1.02,-0.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU. Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.
Psychopharmacology · 2024
No drugs are currently validated to treat psychostimulant use disorder (PUD). Pathophysiological studies consistently highlight the contribution of cholinergic mechanisms in psychostimulant use, including the vulnerability to PUD, paving the way for potential therapeutic strategies. The aim of this systematic review is to describe and discuss the efficacy of cholinergic agents in drug trials for patients with PUD. A systematic review was conducted on April 4, 2024 in MedLine, Embase and Cochrane Library databases on controlled clinical drug trial of cholinergic agents in humans with PUD, psychostimulant abuse or dependence and psychostimulant use in recent year. Twenty-eight articles were included, twenty-one on cocaine and seven on amphetamines. Cholinergic agents used in these studies were biperiden (a muscarinic antagonist), mecamylamine (a nicotinic antagonist), nicotinic agonists, acetylcholinesterase inhibitors (AChEI), or citicoline. Two types of trials were identified. There were seventeen randomized controlled clinical trials evaluating cholinergic agents on psychostimulant use reduction in outpatients seeking treatment. Additionally, we retrieved eleven short-term «proof-of-concept» laboratory trials mainly with supervised psychostimulant administration and/or triggered craving challenges. Outpatient trials were heterogeneous and for most, inconclusive. Only two studies on galantamine (AChEI) and citicoline, reported a significant reduction of cocaine consumption. «Proof-of-concept» laboratory trials showed no evidence of efficacy on the selected outcomes, notably on craving. This review does not support the current prescription of cholinergic agents to treat PUD. Replication clinical trials notably on galantamine or other AChEI, and proof-of-concept trials on comedown symptoms will be necessary to identify a potential therapeutic indication for cholinergic agents in PUD.
Frontiers in pharmacology · 2024
This network meta-analysis aims to explore the efficacy and safety of neuroprotective agents in patients with ischemic stroke and attempts to identify which drug is the most effective in improving outcomes for patients with acute ischemic stroke (AIS) through a ranking method. We comprehensively searched the PubMed, Medline, Embase, Web of Science, and Cochrane library databases from their establishment to 30 June 2024. Data were extracted from the studies identified, and their quality was assessed using the Cochrane risk-of-bias tool or the Newcastle-Ottawa Scale (NOS). The outcome measures were for a favorable prognosis, based on the modified Rankin Scale score (mRS) or National Institutes of Health Stroker Scale (NIHSS) score, mortality, and adverse effect with different drug regimens. We utilized Stata version 16.0 and Review Manager (RevMan) version 5.3.0 for statistical analysis. A total of 35 studies were included: 25 randomized control trials, eight retrospective studies, and two prospective studies. The total sample size was 18,423 cases and included nine interventions: citicoline, edaravone (EDV), edaravone dexborneol, cinepazide maleate, cerebrolysin, minocycline, ginkgolide, ginkgo diterpene lactone meglumine (GDLM), and conventional (CON) treatment. Our analysis revealed that, except for edaravone dexborneol, the ginkgolide, EDV, cinepazide maleate, citicoline, cerebrolysin, minocycline, and GDLM treatment schemes reduced the mortality of patients with AIS compared with CON. Each drug regimen significantly improved the neural function of these patients compared with CON, which from highest to lowest was citicoline + vinpocetine, GDLM, citicoline, edaravone dexborneol, cinepazide maleate, ginkgolide, EDV, and CON. Moreover, we also found that, except for citicoline, the ginkgolide, EDV, edaravone dexborneol, GDLM, and cinepazide maleate treatment schemes had a high total treatment effective rate in these patients, the order from highest to lowest being ginkgolide, EDV, edaravone dexborneol, GDLM, cinepazide maleate, CON, and citicoline. In terms of the ineffective rate, we found that, compared with CON, the edaravone dexborneol, EDV, citicoline, GDLM, ginkgolide, and cinepazide maleate treatment schemes all had a lower ineffective rate. Finally, our analysis revealed that, except for cinepazide maleate and ginkgolide, the EDV, minocycline, edaravone dexborneol, GDLM, citicoline, and cerebrolysin schemes all had a higher rate of adverse effect on patients compared to CON. Based on the impact of the adverse effect with different surgical interventions, we further analyzed the effect of these drug treatments by the total treatment effective rate combined with adverse effect, revealing that EDV, ginkgolide, and edaravone dexborneol were the safest and most effective treatments. In patients with AIS, ginkgolide, EDV, cinepazide maleate, citicoline, cerebrolysin, minocycline, and GDLM were associated with a reduction in mortality rate. Moreover, ginkgolide, EDV, edaravone dexborneol, and GDLM treatment schemes revealed not only a high total treatment effective rate but also a low rate of treatment inefficacy. When considering the combination of the total treatment effective rate with adverse effect, EDV, ginkgolide, and edaravone dexborneol were revealed as the safest and most effective.
Frontiers in neuroscience · 2024
Ischemic stroke is the second leading cause of death and the third leading cause of combined disability and mortality globally. While reperfusion therapies play a critical role in the management of acute ischemic stroke (AIS), their applicability is limited, leaving many patients with significant neurological deficits and poor prognoses. Neuroprotective agents have garnered attention for their potential as adjunct therapies; however, their relative efficacy remains unclear. This study utilized a network meta-analysis (NMA) to systematically compare the efficacy of neuroprotective agents in improving neurological function and prognosis in stroke patients. This study adhered to PRISMA guidelines and the Cochrane Handbook for systematic reviews. Randomized controlled trials (RCTs) were identified through comprehensive searches of the PubMed, Embase, and Cochrane Library databases. Two independent reviewers conducted the selection process, data extraction, and quality assessment. Outcomes included 90-day modified Rankin Scale (90d-mRS), change of National Institutes of Health Stroke Scale score from baseline to 90-day/14-day/7-day (90d/14d/7d-NIHSS) and 90-day/14-day Barthel Index (90d/14d-BI). Data analyses were performed using RevMan 5.4 and Stata 14.0. A total of 42 RCTs involving 12,210 participants were included in this analysis. The interventions assessed included Cerebrolysin, Citicoline, Edaravone, Edaravone Dextranol, Human urinary kallidinogenase, Minocycline, Nerinetide, Butylphthalide, Vinpocetine, and Control. The NMA results demonstrated that NBP ranked highest for the 90d-mRS, 90d-NIHSS, 14d-NIHSS, and 14d-BI outcomes. Edaravone was found to be the most effective intervention for the 7d-NIHSS and 90d-BI outcomes. The findings of this study indicate that different neuroprotective agents exhibit distinct advantages at specific stages of recovery. NBP showed outstanding performance in improving 90d-mRS and 90d-NIHSS, underscoring its potential in long-term rehabilitation. Edaravone demonstrated significant superiority in 7d-NIHSS scores, highlighting its role in early neuroprotection. These results provide valuable insights for individualized clinical treatment. To further validate the efficacy and safety of neuroprotective agents, future studies should involve larger sample sizes and conduct multicenter, large-scale randomized controlled trials. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=601346, identifier CRD42024601346.
The British journal of nutrition · 2025
A randomised parallel intervention study was conducted with male patients diagnosed with CHD. Participants were assigned to three groups: Group A abstained from alcohol (n 20), Group B consumed red wine (n 21) and Group C (n 16) consumed an alcoholic beverage without wine micro-constituents. Biological samples were collected at baseline, 4 and 8 weeks. Enzyme activities of acetyl-CoA:lyso-platelet-activating factor (PAF) acetyltransferase, cytidine 5'-diphospho (CDP)-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-cholinephosphotransferase), PAF-acetylhydrolase in leukocyte homogenates, serum lipoprotein-associated phospholipase-A2 and plasma markers of thrombosis were measured. PAF-, ADP- and collagen-induced platelet aggregation was measured in human platelet-rich plasma. Red wine consumption led to a 15·3 % reduction in LysoPAF-acetyltransferase activity at 4 weeks (P= 0·008) compared with baseline and Group A (P= 0·01). PAF-cholinephosphotransferase activity was reduced by 11·1 % at 8 weeks (P= 0·04) compared with baseline and by 24·9 % compared with Group C (P= 0·02). PAF-acetylhydrolase activity was reduced by 36·2 % at 8 weeks compared with baseline (P= 0·001) and compared with Group A (P< 0·000) and Group C (P= 0·009). Fibrinogen levels in Group B reduced by 6-9 % at 4 (P= 0·04) and 8 weeks (P= 0·01) compared with baseline while D-dimer in Group C increased by 16·1 % at 8 weeks (P= 0·005) compared with baseline. Platelet aggregation against PAF and collagen was reduced in Group B (82·6 and 35·4 %, respectively), and in Group C (158·4 and 37·1 %, respectively) compared with baseline and Group A (P< 0·05). In conclusion, moderate wine consumption improved the activity of PAF-metabolism enzymes regardless of ethanol and reduced platelet aggregation, probably through mechanisms different from those of ethanol.
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025
Objective:This study aimed to evaluate the therapeutic effect of intratympanic injection of ganglioside in patients with refractory sudden deafness. Methods:A total of 120 patients with sudden deafness, aged 18-65 years, whose onset was within 11-42 days, failed to respond to conventional treatment, and had an average hearing threshold（500-4 000 Hz）>60 dB were selected. They were prospectively and randomly divided into a control group of 61 cases and an experimental group of 59 cases. The control group was treated according to the recommended protocol of the Chinese Medical Association（postauricular injection of methylprednisolone）, while the experimental group was treated with intratympanic injection of monosialotetrahexosylganglioside sodium+postauricular injection of methylprednisolone. Both groups were simultaneously administered oral ginkgo biloba extract and citicoline tablets. Hearing was re-examined two weeks after the completion of treatment, and the therapeutic effects of the two different treatment methods were compared and analyzed. Results:The effective rate was 29.51% in the control group and 54.24% in the experimental group（P<0.01）. The average hearing threshold improved by 11.57 dB HL in the control group and 22.50 dB HL in the experimental group（P<0.05）. Conclusion:The combination of postauricular injection of methylprednisolone and intratympanic injection of ganglioside is more effective than postauricular injection of methylprednisolone alone in the treatment of refractory sudden deafness. The earlier the treatment, the better the therapeutic effect. 目的：本研究旨在评价鼓室注射神经节苷脂在难治性突聋患者中的疗效。 方法：入选发病在11～42 d、经常规治疗无效、平均听阈（500～4 000 Hz）>60 dB的突发性聋、年龄18～65岁的患者120例，前瞻性平行随机分为对照组61例和试验组59例，对照组按照中华医学会推荐方案（耳后注射甲泼尼龙）治疗，试验组鼓室注射单唾液酸四己糖神经节苷脂钠+耳后注射甲泼尼龙治疗，2组同时口服银杏提取物和胞磷胆碱片。治疗结束2周后复查听力，对2种不同治疗方法的疗效进行比较分析。 结果：对照组有效率为29.51％，试验组有效率为54.24％（P<0.01）。对照组平均听阈改善了11.57 dB HL，试验组平均听阈改善22.50 dB HL（P<0.05）。 结论：耳后注射甲泼尼龙联合鼓室注射神经节苷脂较单纯耳后注射甲泼尼龙治疗难治性突发性聋疗效好，并且治疗越早，疗效更佳。.
Frontiers in pharmacology · 2025
Our group aimed to explore the effect of different dosages of citicoline on ischemic stroke (IS) patients and determine the most appropriate dosage for these patients. The databases of PubMed, Cochrane Library, Medline, Web of Science, and Embase were searched from their establishment to 15 October 2024. We assessed the quality of all included articles by using the Cochrane quality evaluation method or Newcastle-Ottawa Scale (NOS), which was based on the study type. Relative risk (RR) and 95% confidence interval (CI) were used for dichotomous data, and mean and standardized difference (SD) were used for continuous data. The outcome indicators were death, improvement in neurological function and daily living activities, and adverse effects. In this study, a total of 13 studies were included. Of these, 370 patients were treated with 500 mg citicoline, 502 patients were treated with 1,000 mg citicoline, 1,891 patients were treated with 2,000 mg citicoline, and 2,582 patients were treated in the group of control (CON). We evaluated the treatment effect of different outcome indicators by ranking. In terms of death, both 500 mg citicoline and 2,000 mg citicoline demonstrated lower mortality than CON, with 2,000 mg citicoline having the lowest mortality. In terms of neurological function improvement, we found that compared to CON, the rates of improvement were higher and the rates of ineffective results were lower in 500-mg citicoline, 2,000-mg citicoline, and 1,000-mg citicoline groups. In terms of improvement in daily living activities, the MBI scores for 500 mg citicoline and 2000 mg citicoline were both higher than CON, while the MBI score for 1,000 mg citicoline was not. Lastly, in the aspect of adverse effects, we found that the rate of adverse effects was lower for 1,000 mg citicoline than CON, while it was higher for 500 mg citicoline and 2,000 mg citicoline. Our research findings revealed that different dosages of citicoline significantly affect the neurological function, daily living activities, and adverse effects in patients with acute IS. Notably, 500 mg citicoline and 2,000 mg citicoline not only demonstrate higher rates of improvement in neurological function and daily living activities but also have lower mortality and ineffective results. However, this study does not specify the best one of the two dosages.
Psychiatry research · 2025
A substantial proportion of individuals with bipolar disorder (BD) show some degree of cognitive impairment. Emerging evidence suggests that lifestyle-based interventions (LBIs) can improve clinical outcomes in BD, although few studies have assessed their efficacy on cognition. To evaluate the methodological quality and efficacy of randomized controlled trials (RCTs) comprising LBIs for improving cognition in people with BD. A systematic search following PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, PsycINFO and ClinicalTrials.gov were searched from inception until February 1st, 2024. RCTs examining the effects of LBIs on cognition, assessed by validated neuropsychological tests, in individuals with BD (of any age, mood or comorbidity) were eligible. Risk of bias and methodological quality were assessed with the Cochrane RoB 2 tool and the PEDro scale, respectively. Results were narratively synthesized. Seven RCTs ( = 275) were included, each targeting one lifestyle domain. Six assessed nutraceuticals (e.g., vitamins B1/B6, DHA, NAC, citicoline, creatine) and one evaluated a mind-body intervention (Tai Chi/Qigong). Two RCTs reported pro-cognitive effects of nutraceuticals: citicoline was associated with improvements in declarative memory and verbal learning, and creatine with improved verbal fluency. Mean intervention duration was 12 weeks. Cognition was a primary outcome in three RCTs. Overall, methodological quality was high, and risk of bias was low. Specific nutraceuticals may offer pro-cognitive effects for BD. However, the evidence is limited by the small number of included studies and substantial heterogeneity in populations, interventions, and cognitive assessments. Future studies should examine whole-diet, physical activity/exercise and multimodal LBIs.
Journal of neurotrauma · 2026
Traumatic brain injury (TBI) is a global health problem. Amantadine and citicoline showed considerable effects on neurorecovery from TBI. In a randomized controlled trial, the effects of amantadine and citicoline and their combinations were compared on arousal and behavioral consequences in the early phase of moderate TBI. Patients were divided into three groups (15 patients each) with moderate TBI; group C (citicoline) received 1 g citicoline every 12 h for 7 days. Participants received 500 mg oral drops syrup twice a day or the same dose as oral drops syrup of citicoline through a nasogastric tube (NG) or percutaneous endoscopic gastrostomy (PEG) tube in a total dose of 1000 mg/day for a 30-day study period. Group A (amantadine) received 200 mg of amantadine sulfate in a 500 mL solution every 12 h for 7 days. Participants received two 100-mg tablets twice a day or through an NG or PEG tube as 400 mg for a 30-day study period. Group CA (Citicoline + Amantadine) received 1 g citicoline every 12 h and 200 mg of amantadine sulfate in a 500 mL solution every 12 h for 7 days, then 500 mg of citicoline syrup twice daily plus 200 tablets twice daily amantadine for a 30-day study period. Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), and mini-mental state (MMS) were used to assess the patient's conditions on the 1st, 4th, and 7th days (acute phase) in the intensive care unit (ICU), then 30 days after injury. The endpoints of the study were either the death of the patient or the completion of the study period of 30 days. The number of mechanically ventilated patients, the number of ventilated days, mortality, total ICU, and hospital length of stay were measured. GCS on days 4, 7, and 30 were significantly higher in group A and group CA compared with group C, with no significant differences between groups A and CA. DRS in days 4 and 7 became significantly lower in groups A and CA compared with group C, with no significant differences between groups A and CA. MMS in days 4, 7, and 30 became significantly lower in group C, with no significant differences between groups A and CA. The duration of mechanical ventilation, ICU, and hospital stay was significantly longer in group C, with no significant differences between groups A and CA. This study showed that amantadine alone or in combination with citicoline has a favorable effect on the recovery of consciousness and cognitive behavior in patients with moderate TBI and reduces the mechanical ventilation days, hospital, and ICU length of stay.
PloS one · 2025
Perinatal asphyxia (PA) is a major contributor to neonatal mortality and long-term neurodevelopmental impairment, particularly in low- and middle-income countries (LMICs), where the effectiveness of therapeutic hypothermia remains limited. Pharmacologic neuroprotective agents have shown potential as alternative treatments, but their efficacy in low-income and lower-middle-income countries (LILMICs) is not well established. This systematic review aimed to assess the effectiveness of pharmacologic interventions in neonates with PA in LILMICs. A systematic search of PubMed, Web of Science, CINAHL, and Google Scholar was conducted for randomised controlled trials (RCTs) published between 2000 and 2024. Eligible studies compared pharmacologic neuroprotective agents with placebo or standard care, excluding therapeutic hypothermia, among neonates diagnosed with PA in LILMICs. Data on survival and neurodevelopmental outcomes were extracted and synthesized; meta-analyses were conducted where appropriate. Twelve RCTs involving 1,008 neonates were included. The majority (91.7%) of studies were conducted in Asia, with only one study from Africa. Magnesium sulphate was the most frequently evaluated agent (66.7% of studies), followed by melatonin, topiramate, erythropoietin, and citicoline. Melatonin was associated with improved survival, and all agents showed improved short-term neurological outcomes. Neurodevelopmental outcomes at 3, 6, 12, and 19 months were generally favourable, though data remained limited. Pharmacologic neuroprotective agents show promise in improving survival and neurological outcomes in neonates with PA in LILMICs. However, more robust, multi-center RCTs are needed to confirm their efficacy and establish them as feasible alternatives to therapeutic hypothermia in these settings.
The Cochrane database of systematic reviews · 2025
Alterations to the corneal nerves can lead to neurotrophic keratopathy (NK), which is marked by breakdown of the corneal epithelium and impaired healing. If untreated, NK can cause severe corneal damage and significant visual impairment. Etiologies include infection, inflammation, chemical or mechanical trauma, systemic disease (e.g. diabetes mellitus), drug toxicity, contact lens overuse, and ophthalmic, neurosurgical, or otolaryngologic surgery. Treatments are often clinician-dependent and include an array of topical medications and surgical techniques to promote re-epithelialization and preserve vision. There is no consensus on the "gold standard" treatment. To examine the efficacy and safety of medical and surgical interventions when compared with no treatment, placebo, standard care, or an alternative treatment, for people with neurotrophic keratopathy. We searched CENTRAL, MEDLINE, Embase, PubMed, LILACS, and trial registries on 10 January 2025. We included randomized controlled trials (RCTs) in which medical or surgical interventions were compared with no treatment, placebo (e.g. ophthalmic vehicle, normal saline), standard care (e.g. artificial tears, bandage contact lens (BCL)), or an alternative treatment. Our outcomes of interest were corneal re-epithelialization, visual acuity, corneal sensitivity, worsening or relapse of the disease, and adverse events as assessed by investigators. We analyzed most outcome data at one to three months post-intervention; we assessed disease progression at six months or longer, and non-serious and serious adverse events at the longest follow-up time point. Using Cochrane's risk of bias tool RoB 2, we assessed the risk of bias for outcomes reported in our summary of findings table. We performed separate comparisons for medical and surgical interventions. In addition to the qualitative synthesis of included studies, where possible, we conducted fixed-effect meta-analyses, calculating risk ratios (RRs) with 95% confidence intervals (CI) for dichotomous outcomes and mean differences (MDs) and 95% CIs for continuous outcomes. We checked continuous data for skewness. We assessed the certainty of evidence using the GRADE approach. We included seven parallel-group RCTs with a total of 494 participants (study sample size: 18 to 156 participants; mean age: 25 to 68 years; proportion of female participants: 60% to 77%). Follow-up duration in the studies ranged from 28 days to 18 months. Four studies (57.1%) were multicenter RCTs in the USA and Europe; three studies were conducted in Europe or Asia. Five studies (71.4%) that reported funding sources were industry-sponsored. Six studies compared medical interventions versus opthalmic vehicle or artificial tears; the medical interventions included two topical biologic interventions (20 μg/ml recombinant human nerve growth factor (rhNGF; two studies), and recombinant bovine basic fibroblast growth factor (rb-bFGF)), and three non-biologic interventions (0.1% RGN-259, topical citicoline and vitamin B12 (Cit-B12), and CACICOL20 (T4020)). One trial compared amniotic membrane transplantation with tarsorrhaphy or BCL for NK. Six studies evaluated medical interventions versus vehicle or artificial tears. Meta-analysis of two studies showed that rhNGF may slightly improve corneal re-epithelialization (defined as < 0.5 mm of corneal staining) (RR 1.88, 95% CI 1.37 to 2.58; I2 = 0%; 148 participants; low-certainty evidence). The same two studies assessed complete corneal re-epithelialization (defined as < 0.1 mm of corneal staining) and found similar results but with substantial heterogeneity in the meta-analysis (RR 2.75, 95% CI 1.82 to 4.16; I2 = 72%; 148 participants; low-certainty evidence). One trial of CACICOL20 found that it may not increase the proportion of participants with corneal re-epithelialization (RR 0.89, 95% CI 0.66 to 1.19; 148 participants; low-certainty evidence), while one trial of 0.1% RGN-259 found the same (RR 9.00, 95% CI 0.57 to 141.88; 18 participants; low-certainty evidence). Meta-analysis of two studies showed that rhNGF may not improve visual acuity (RR 0.07, 95% CI -0.58 to 0.71; I2 = 0%; 151 participants; low-certainty evidence). Meta-analysis of two studies suggested that medical interventions, specifically rb-bFGF, may improve corneal sensitivity (MD 8.43, 95% CI 1.90 to 14.97; I2 = 0%; 60 participants; very low-certainty evidence), but the evidence is very uncertain. One trial showed that rhNGF may not improve corneal sensitivity (MD 1.08, 95% CI -0.32 to 2.48; 33 participants; very low-certainty evidence), but the evidence for this result is also very uncertain. Two studies narratively reported lower rates of disease recurrence with rhNGF compared with the opthalmic vehicle. One trial of CACICOL20 found that it may result in little to no difference in risk of adverse events compared with control groups (RR 0.98, 95% CI 0.63 to 1.52; 152 participants; low-certainty evidence); similar results were found in meta-analysis of two studies of rhNGF (RR 1.08, 95% CI 0.62 to 1.86; I2 = 0%; 151 participants; low-certainty evidence). Only one trial evaluated surgical interventions, comparing amniotic membrane transplantation versus tarsorrhaphy or BCL. Amniotic membrane may have little to no effect on the proportion of participants with corneal re-epithelialization (RR 1.10, 95% CI 0.69 to 1.76; 30 participants; very low-certainty evidence) or improvements in visual acuity (RR 1.40, 95% CI 0.57 to 3.43; 30 participants; very low-certainty evidence), but the evidence is very uncertain. No other prespecified outcomes were reported in this comparison. Neurotrophic keratopathy is a rare condition with an array of etiologies, which poses challenges for research in terms of study design, participant recruitment, and consensus on objective outcome measures. Our review found low or very low certainty of evidence regarding the effects of medical or surgical interventions on corneal re-epithelialization, visual acuity, and corneal sensitivity. We downgraded the certainty of the evidence mostly because of imprecision, followed by indirectness, risk of bias, and inconsistency. Given the current evidence and lack of universal guidelines, clinicians should individualize treatment based on clinical judgment and available resources. We expect future studies examining a wider range of interventions will be able to offer higher quality evidence and produce more conclusive assessments. This review had no internal source of support. External sources: National Eye Institute, National Institutes of Health, USA; Public Health Agency, UK; Queen's University Belfast, UK; Birmingham Health Partners, UK. Protocol available via doi.org/10.1002/14651858.CD015723.
Nutrients · 2025
Background: Tribulus terrestris L. Zygophyllaceae (TT) is a plant that has been claimed to increase testosterone levels and improve sexual function, particularly erectile dysfunction, with potential benefits for male sexual health. Purpose: This systematic review aimed to evaluate the effectiveness of TT supplementation in improving sexual function and serum testosterone levels in men. Methods: We conducted a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After searching the literature (n = 162), 52 studies were selected for full-text reading, and 10 studies were eligible for this review, comprising 9 clinical trials and 1 quasi-experimental study (a study without a control). The Jadad score revealed low methodological quality for 50% of the studies. Results: The studies involved 15 to 172 participants (total = 483) aged between 16 and 70 years with different health conditions: healthy men (n = 5), oligozoospermia (n = 1), erectile dysfunction (n = 1), erectile dysfunction associated with hypogonadism (n = 2), and unexplained infertility (n = 1). TT supplementation at doses of 400 to 750 mg/d for 1 to 3 months improved erectile dysfunction in 3 of the 5 studies that assessed this parameter. Eight out of ten studies did not report significant changes in androgen profile following TT supplementation, but the subjects in the neutral studies did not have low androgen levels at baseline. Therefore, only 2 studies showed significant intra-group increase in total testosterone levels, which had low clinical magnitude (60-70 ng/dL) and involved subjects with hypogonadism. Conclusions: TT supplementation has a low level of evidence regarding its effectiveness in improving erectile function in men with erectile dysfunction, and no robust evidence was found for increasing testosterone levels.
International journal of impotence research · 2026
Tribulus terrestris is a medicinal herb purported to enhance reproductive function, particularly in instances of erectile dysfunction (ED). This study aims to assess the effectiveness and safety of administering Tribulus terrestris to patients with ED. We performed a systematic literature review in the Cochrane Library, Medline, Scopus, and Europe PMC databases utilizing particular keywords. The primary endpoint in this study is International Index of Erectile Function, that may be in abridged form (IIEF-5) or full form (IIEF-15). The outcomes of continuous variables were aggregated into the mean difference (MD) with corresponding 95% confidence intervals (95% CI) utilizing random-effects models. Eight studies were selected for inclusion. After the intervention with Tribulus terrestris, the IIEF-5 [MD 4.21, p < 0.00001] and IIEF-15 scores [MD 15.88, p = 0.0004] were markedly elevated compared to their pre-supplementation levels, as per our comprehensive analysis. Additionally, on both the IIEF-5 [MD 3.23 (95%CI 1.89, 4.58), p < 0.00001] and IIEF-15 [MD 14.44 (95%CI 5.75, 23.14), p = 0.001], Tribulus terrestris outperformed placebo. However, the two groups were not significantly different in terms of total testosterone levels. We observed no difference in the incidence of adverse events between Tribulus terrestris and placebo. Tribulus terrestris supplementation may offer benefits in improving erectile function among patients with ED with a relatively good safety profile.
African journal of reproductive health · 2026
Infertility affects 15% of couples worldwide, with male factors contributing to over half of the cases. Varicocele, present in 35% of men with primary infertility, impairs sperm quality. This study evaluates the effect of electroacupuncture (EA) on improving sperm motility and morphology in varicocele patients. A single-blind, randomized controlled trial was conducted with 14 participants divided into an EA group (n=7) and a control group (n=7). The intervention group received EA in combination with a herbal regimen and Tribulus Terrestris, while the control group received only the herbal regimen and Tribulus Terrestris without EA. Men aged 20-35 with ultrasound-confirmed varicocele and abnormal spermiograms were included. Statistical analysis used the paired t-test, Wilcoxon, and Mann-Whitney tests. The EA group showed significant improvements in sperm morphology (P=0.029) and motility (P=0.026) compared to the control group. These findings suggest that EA significantly enhances sperm quality in varicocele patients and may serve as an effective complementary treatment for male infertility. L'infertilité touche 15 % des couples dans le monde, les facteurs masculins contribuant à plus de la moitié des cas. La varicocèle, présente chez 35 % des hommes souffrant d'infertilité primaire, altère la qualité du sperme. Cette étude évalue l'effet de l'électroacupuncture (EA) sur l'amélioration de la motilité et de la morphologie des spermatozoïdes chez les patients atteints de varicocèle. Un essai contrôlé randomisé en simple aveugle a été mené auprès de 14 participants répartis en deux groupes: un groupe EA (n=7) et un groupe témoin (n=7). Le groupe d'intervention a reçu une combinaison d'EA, d'un traitement à base de plantes et de Tribulus Terrestris, tandis que le groupe témoin a reçu uniquement le traitement à base de plantes et le Tribulus Terrestris sans EA. Des hommes âgés de 20 à 35 ans, présentant une varicocèle confirmée par échographie et des anomalies au spermogramme, ont été inclus. L'analyse statistique a utilisé les tests t apparié, de Wilcoxon et de Mann-Whitney. Le groupe EA a montré une amélioration significative de la morphologie (P=0.029) et de la motilité des spermatozoïdes (P=0.026) par rapport au groupe témoin. Ces résultats suggèrent que l'EA améliore significativement la qualité du sperme chez les patients atteints de varicocèle et pourrait constituer un traitement complémentaire efficace contre l'infertilité masculine.
PloS one · 2024
Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom. This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens. In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment. Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27). LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models.
Journal of neural transmission (Vienna, Austria : 1996) · 2025
Levodopa remains central to Parkinson's disease (PD) treatment, but long-term use can cause motor complications, highlighting the need for additional therapies. Mucuna pruriens (MP), a natural source of levodopa, shows potential in managing these complications. Further research is needed to compare its pharmacokinetics (PK) and clinical outcomes with traditional levodopa formulations. This randomised, single-blind, crossover trial compared the PK, clinical outcomes, and safety of MP powder against levodopa/benserazide dispersible tablets (Levodopa DT) in PD patients with motor complications. Twelve participants were recruited to receive either 30 g of MP powder or two 100/25 levodopa DT in separate sessions with a two-week washout between sessions. Key PK parameters (AUC, Cmax, Tmax, and t½) were measured. Clinical assessments used standard rating scales and adverse events were recorded. Data from 11 participants were analysed after one withdrawal. MP powder demonstrated significantly higher overall drug exposure, with a geometric mean AUC0-∞ of 12,424.81 compared to 7981.69 ng·h/mL for levodopa DT. The geometric mean ratio was 155.67% (90% CI 134.59-180.04), exceeding the bioequivalence acceptance range of 80-125%. However, the two treatments exhibited similar Tmax and t₁/₂ values, indicating comparable rates of absorption and elimination. Clinically, MP provided a longer ON state without dyskinesia-232.2 min versus 161.8 min for levodopa DT (p = 0.01). Mild and transient adverse events, such as nausea and dizziness, were more frequently associated with MP. MP offers superior drug exposure and extends the ON state without increasing dyskinesia, positioning it as a promising alternative to synthetic levodopa for managing motor symptoms. These findings support MP's potential role in alleviating motor complications in PD treatment.
Journal of Parkinson's disease · 2026
BackgroundParkinson's disease (PD) causes disability and premature mortality if untreated. Limited access to levodopa in low- and middle-income countries leaves many patients undertreated. Mucuna pruriens (MP) is a leguminous plant that contains high concentrations of levodopa.ObjectiveTo demonstrate the non-inferiority of long-term intake of MP powder in terms of safety and efficacy compared to standard levodopa plus dopa-decarboxylase inhibitor (LD + DDCI).MethodsIn this 12-month, multicenter, randomized, open-label phase 2 trial, thirty-two untreated PD patients received levodopa monotherapy with MP powder -derived from roasted seeds without pharmacological processing- or standard LD + DDCI. Dosing was adjusted for body weight and disease stage, with MP doses further calibrated to account for the absence of a DDCI. We measured quality of life using the 39-item PD Questionnaire, motor and non-motor disability using the Movement Disorders Society updated version of the Unified PD Rating Scale (MDS-UPDRS) (parts I to IV) and the Non-Motor Symptoms Questionnaire. Safety measures included recording any adverse event and laboratory test.ResultsMP powder improved quality of life, motor and non-motor symptoms over 12 months, demonstrating similar outcome to LD + DDCI on all endpoints. Adverse events were more frequent with MP (56% vs. 37.5%, p = 0.48), though the difference was not statistically significant. Most were mild, with only 12.5% leading to discontinuation.ConclusionsMP could be a cost-effective alternative for PD individuals with limited access to commercial levodopa formulations. To confirm long-term safety and efficacy, larger international multicenter, double-blind trials with extended follow-up (e.g. 24-36 months) and ethnically diverse cohorts are needed.Registered at PACTR201611001882367.
Nutrients · 2025
Background: Exercise and nutritional interventions are often recommended to help manage risk related to metabolic syndrome (MetSyn). The co-ingestion of Phyllanthus emblica (PE) with trivalent chromium (Cr) has been purported to improve the bioavailability of chromium and enhance endothelial function, reduce platelet aggregation, and help manage blood glucose as well as lipid levels. Shilajit (SJ) has been reported to have anti-inflammatory, adaptogenic, immunomodulatory, and lipid-lowering properties. This study evaluated whether dietary supplementation with Cr, PE, and SJ, or PE alone, during an exercise and diet intervention may help individuals with risk factors to MetSyn experience greater benefits. Methods: In total, 166 sedentary men and women with at least two markers of metabolic syndrome participated in a randomized, placebo-controlled, parallel-arm, and repeated-measure intervention study, of which 109 completed the study (48.6 ± 10 yrs., 34.2 ± 6 kg/m2, 41.3 ± 7% fat). All volunteers participated in a 12-week exercise program (supervised resistance and endurance exercise 3 days/week with walking 10,000 steps/day on non-training days) and were instructed to reduce energy intake by -5 kcals/kg/d. Participants were matched by age, sex, BMI, and body mass for the double-blind and randomized supplementation of a placebo (PLA), 500 mg of PE (PE-500), 1000 mg/d of PE (PE-1000), 400 µg of trivalent chromium (Cr) with 6 mg of PE and 6 mg of SJ (Cr-400), or 800 µg of trivalent chromium with 12 mg of PE and 12 mg of SJ (Cr-800) once a day for 12 weeks. Data were obtained at 0, 6, and 12 weeks of supplementation, and analyzed using general linear model multivariate and univariate analyses with repeated measures, pairwise comparisons, and mean changes from the baseline with 95% confidence intervals (CIs). Results: Compared to PLA responses, there was some evidence (p < 0.05 or approaching significance, p > 0.05 to p < 0.10) that PE and/or Cr with PE and SJ supplementation improved pulse wave velocity, flow-mediated dilation, platelet aggregation, insulin sensitivity, and blood lipid profiles while promoting more optimal changes in body composition, strength, and aerobic capacity. Differences among groups were more consistently seen at 6 weeks rather than 12 weeks. While some benefits were seen at both dosages, greater benefits were more consistently observed with PE-1000 and Cr-800 ingestion. Conclusions: The results suggest that PE and Cr with PE and SJ supplementation may enhance some exercise- and diet-induced changes in markers of health in overweight individuals with at least two risk factors to MetSyn. Registered clinical trial #NCT06641596.
International journal of obesity (2005) · 2024
Gut dysbiosis that resulted from the alteration between host-microbe interaction might worsen obesity-induced systemic inflammation. Gut microbiota manipulation by supplementation of prebiotic inulin may reverse metabolic abnormalities and improve obesity. This study aimed to determine whether inulin supplementation improved intestinal microbiota and microbial functional pathways in children with obesity. Children with obesity whose BMI above median + 2SDs were recruited to a randomized, double-blinded placebo-controlled study. The participants aged 7-15 years were assigned to inulin supplement extracted from Thai Jerusalem artichoke (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received similar monthly conventional advice and follow-up for 6 months. Fecal samples were collected for gut microbiome analysis using 16S rRNA sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was performed to infer microbial functional pathways. One hundred and forty-three children with available taxonomic and functional pathway abundance profiles were evaluated. A significant increase in alpha-diversity was observed in the inulin group. Inulin supplementation substantially enhanced Bifidobacterium, Blautia, Megasphaera, and several butyrate-producing bacteria, including Agathobacter, Eubacterium coprostanoligenes, and Subdoligranulum, compared to the other groups. The inulin group showed a significant difference in functional pathways of proteasome and riboflavin metabolism. These changes correlated with clinical and metabolic outcomes exclusively in the inulin group. Inulin supplementation significantly promoted gut bacterial diversity and improved gut microbiota dysbiosis in children with obesity. The modulation of functional pathways by inulin suggests its potential to establish beneficial interactions between the gut microbiota and host physiology. Inulin supplementation could be a strategic treatment to restore the balance of intestinal microbiota and regulate their functions in childhood obesity.
Multiple sclerosis and related disorders · 2024
Dietary supplements can modulate the gut microbial ecosystem and affect the immune system. This has potential implications for autoimmune diseases, including multiple sclerosis (MS). Prior studies explored tolerability, symptomatic improvement, and immunologic effects of probiotics in people with MS (pwMS), but no study has examined prebiotics in this population or compared prebiotics with probiotics. This is a randomized, open-label trial of participants with relapsing-remitting MS on B-cell depletion therapy from two MS centers. 22 participants enrolled in the original cross-over study in which probiotic (Visbiome, containing Lactobacillus, Bifidobacterium and Streptococcus species) or prebiotic (Prebiotin, containing oligofructose enriched inulin) supplementation for 6 weeks was randomized, each followed by a washout period. Due to pandemic-related interruptions and expiration of the study supply of probiotics, another 15 participants enrolled in a single-arm study to receive prebiotic supplementation for 6 weeks followed by a washout period. We assessed supplement tolerability and patient-reported outcomes (PRO) relevant to MS (disability, fatigue, mood, and bowel symptoms) before and after each supplement administration period and each washout period. We bio-archived plasma, serum, peripheral blood mononuclear cells and stool samples at each timepoint for future multi-omic assessment. Prebiotics and probiotics had comparable adherence rates and both supplements were well tolerated in pwMS. Participants on either supplement reported minor adverse events, most of which were mild and self-limited. There was a subjective preference for prebiotics over probiotics. Comparing supplement-associated changes in PRO scores from baseline to 6 weeks post-supplementation, there were significant difference between prebiotics and probiotics for the change in patient-reported global symptom burden (MSRS-R Total) and bowel control (BWCS), but only probiotics statistically improved bowel control from baseline to post-supplementation. Supplementation with either prebiotics or probiotics is reasonably well-tolerated and safe. Probiotics improved bowel control, but did not improve other PROs in a 6-week time frame. These data regarding feasibility, tolerability, adherence, and adverse events of supplements will inform future clinical trial designs to definitively compare the efficacy and safety of prebiotics and probiotics. The biological data that will be generated from this study in the future will provide mechanistic insights into the effects of these dietary supplements on MS pathophysiology.