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Nieuwe meta-analyses, RCTs en systematic reviews die wij dagelijks monitoren in PubMed. Onafhankelijk geïndexeerd, niet redactioneel bewerkt.
Nutrients · 2026
Mild cognitive impairment (MCI), the prodromal stage of Alzheimer's disease, may be influenced by nutritional status and genetic susceptibility. This systematic review synthesised evidence on how nutritional biomarkers interact with genetic variants, particularly APOE ε4, to influence cognitive outcomes in individuals with MCI. Following PRISMA 2020 guidelines, seven studies were included (three longitudinal, two randomised controlled trials, and two cross-sectional) involving adults aged ≥55 years with MCI. Nutritional exposures comprised plasma or serum concentrations of vitamins A, D, E, the vitamin B group, lipids, selenium, and ketogenic medium-chain triglycerides. Genetic risk was assessed primarily through APOE ε4 status. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Due to heterogeneity in biomarkers, cognitive tools, and study designs, findings were synthesised narratively. Across nutrient categories, higher concentrations of vitamin D, selenium, and antioxidants were associated with better cognitive outcomes. kMCT supplementation improved episodic memory and brain energy metabolism. Evidence for nutrient-gene interactions was mixed: APOE ε4 modified responses to vitamin B group and selenium but showed limited influence on vitamin D, lipids, or kMCT effects. Heterogeneity in biomarker assays, cognitive tools, and genetic stratification limited comparability across studies. Nutritional biomarkers appear to influence cognitive trajectories in MCI, and some associations may differ by APOE ε4 status. However, small samples and limited genetic stratification constrain interpretation. Future research should prioritise standardised biomarker measurement, genetically stratified cohorts, and individual participant data meta-analyses to clarify nutrient-gene interactions in MCI.
PloS one · 2026
To investigate whether caffeine ingestion offsets the circadian-related decline in morning neuromuscular performance in females. Thirteen healthy females completed three experimental trials: i) evening placebo (PMPLAC), ii) morning placebo (AMPLAC), and iii) morning caffeine ingestion (6 mg·kg⁻¹; AMCAFF). A within-subject, repeated-measures, crossover, single-blind placebo design was used, with all subjects serving as their own controls. Each trial consisted of a maximal voluntary isometric contraction (MVIC) of the knee extensors, followed by intermittent isometric contractions (6 s contraction, 4 s rest) until task failure, and a post-fatigue MVIC. Time to exhaustion, torque and peak force, surface electromyography (RMS amplitude, MDF frequency), rate of perceived exertion, and tympanic temperature were all recorded across conditions. During PMPLAC, peak force and time to exhaustion were significantly greater (p < 0.05) than for AMPLAC. Peak force was higher (p < 0.01) in AMCAFF in both pre- (+33%) and post- (+45%) fatigue MVIC trials compared to PMPLAC. Similarly, RMS was higher (p < 0.01) during both AMCAFF and PMPLAC compared to AMPLAC, whereas MDF did not change (p > 0.05) across trials. AMCAFF also improved (p < 0.01) time to exhaustion by 43% compared to AMPLAC, and significantly reduced (p < 0.01) rate of perceived exertion, but without any change (p > 0.05) in temperature. Morning ingestion of 6 mg·kg⁻¹ of caffeine effectively reverses diurnal reductions in neuromuscular performance of females by enhancing peak force and time to exhaustion to evening levels. No change in MDF, but an increased RMS suggests a central rather than peripheral mechanism for caffeine's ergogenic effects.
BMC cardiovascular disorders · 2026
The association between coffee or caffeine intake and cardiovascular diseases (CVDs) and their risk factors has been extensively researched. However, there has been conflicting evidence. Therefore, the current updated meta-analysis assessed the relationship between coffee or caffeine with CVDs, such as coronary heart diseases (CHDs), myocardial infarction (MI), heart failure (HF), stroke, cardiac arrhythmias, and CVD mortality. Five electronic databases, namely PubMed, Web of Science, Cochrane Library, Embase, and Scopus, were extensively searched for all records published between January 2000 and December 2025. Studies were included if they examined the effects of coffee on any CVD and reported the associations in terms of the hazard ratio (HR), relative risk (RR), or odds ratio (OR). Moreover, quality appraisal was conducted using the Newcastle Ottawa Scale for cohort studies and the Joanna Briggs Institute tool for case-control studies. After exclusions, 38 studies involving 2,856,002 participants were reviewed and analyzed. The pooled analysis showed no significant associations between coffee consumption and total CHDs or HF, when comparing the highest and lowest coffee consumption categories (HR: 0.98; p = 0.80 and HR: 1.03; p = 0.62, respectively). In contrast, the pooled results showed a significant positive association between higher coffee consumption and the risk of developing MI (OR: 1.48; p < 0.0001). The pooled analysis also showed an inverse relationship between coffee consumption and stroke or cardiac arrhythmias (HR: 0.89; p = 0.01 and HR: 0.94; p = 0.04, respectively). Furthermore, we observed a non-linear relationship between caffeine intake and CVD mortality among hypertensive patients (HR: 0.68; p = 0.001). Higher coffee intake might increase the risk of MI, but can also offer protective effects against stroke and cardiac arrhythmias. Moreover, higher caffeine intake can reduce the risk of CVD mortality in hypertensive patients. PROSPERO: CRD420251073620.
JAMA psychiatry · 2026
Psilocybin shows promise in treating depression, although limitations of previous research warrant further research. To investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in treatment-resistant depression (TRD). This was a 2-center, triple-blinded (investigator, participant, rater), phase 2b, active placebo-controlled randomized clinical trial. Participants were randomized to 4 groups in ratios 2:2:1:1, receiving 2 doses 6 weeks apart (week 0, week 6) as follows: (1) placebo (nicotinamide, 100 mg) then psilocybin, 25 mg; (2) psilocybin, 5 mg, then 25 mg; and (3) psilocybin, 25 mg, then 5 mg or psilocybin, 25 mg, twice embedded in psychotherapeutic sessions. Participants aged 25 to 65 years with TRD and withdrawn from antidepressant medication were recruited predominantly from 2 outpatient settings in Germany. Study data were analyzed from April 2024 to November 2025. Oral synthetic psilocybin, 25 mg; psilocybin, 5 mg; or nicotinamide, 100 mg administered with psychotherapeutic sessions. The primary end point was treatment response (≥50% reduction on the Hamilton Rating Scale for Depression [HAMD17]) at week 6 before the second dose. Key secondary end points were response on the Beck Depression Inventory II (BDI-II) and mean change from baseline on the HAMD17 and BDI-II at week 6. A total of 144 participants (mean [SD] age, 42.6 [10.8] years; 85 male [59.0%]) were randomized, and 142 were included in the primary efficacy analysis: psilocybin, 25 mg (n = 47), psilocybin, 5 mg (n = 48), and nicotinamide (n = 47). Response rates on the primary end point were 17.0% in the group receiving psilocybin, 25 mg; 12.5% in the group receiving psilocybin, 5 mg; and 10.6% in the group receiving nicotinamide. The first hierarchical comparison was nonsignificant (psilocybin, 25 mg vs nicotinamide, adjusted odds ratio [OR], 1.73; 95% CI, 0.53-6.23; P = .19; 1-sided α P = .03); consequently, further formal testing was not performed. Analyses of key secondary end points (mean changes from baseline on HAMD17 and BDI-II) provided exploratory evidence of a clinically meaningful effect of psilocybin, 25 mg. Psilocybin, 25 mg, was linked to adverse events, predominantly acutely, and was associated with higher reports of suicidal ideation on dosing days (4% vs 1%-2% in comparator conditions). Two serious adverse reactions were reported after psilocybin, 25 mg, including 1 case of hallucinogen persisting perception disorder. In this randomized clinical trial, psilocybin, 25 mg, with adjunct psychotherapy, was associated with a clinically meaningful reduction in depressive symptoms in individuals with TRD, although findings did not show a significant effect on the primary outcome. The treatment was well tolerated by most participants, although safety signals were observed. While overall this constituted an inconclusive trial, these results add to the existing evidence on the potential of psilocybin treatment for depression. ClinicalTrials.gov Identifier: NCT04670081.
Geriatrics & gerontology international · 2026
Nicotinamide mononucleotide (NMN) improves the pathogenesis of age-related changes and diseases by increasing intracellular nicotinamide adenine dinucleotide+. We aimed to evaluate retinal thickness changes after oral NMN administration according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Before and 24 weeks after the study initiated, 240 × 240 mm macular cube scan optical coherence tomography images were obtained from male patients with type 2 diabetes aged ≥ 65 years with physical frailty; changes in the automatically measured mean retinal thickness within the 9 ETDRS grid regions were compared between groups. Participants were randomly assigned to receive 250 mg/day NMN or placebo orally for 24 weeks. Retinal thickness changes at 24 weeks were compared between groups. Each group included 14 eyes of 7 patients; 8 eyes had ocular disease. Best-corrected visual acuity did not change significantly between baseline and 24 weeks for both groups. In the temporal subretinal field of the outer circle, the retinal thickness change from baseline to 24 weeks differed significantly between the NMN and placebo groups (+1.14 ± 2.85 μm and -2.77 ± 3.30 μm, respectively; p = 0.006). Among patients without ocular disease, the NMN group demonstrated a trend toward suppressed reduction in retinal thickness in the temporal region (+0.75 ± 3.20 μm and -2.45 ± 3.33 μm in the NMN and placebo groups, respectively; p = 0.07). Systematic and ophthalmic adverse events were not observed in the NMN group. The oral NMN administration was safe both systemically and locally in the eyes. Based on the retinal thickness results, NMN may be efficacious in mitigating age-related alterations in the retina.
Nutrients · 2026
Background: Nausea and vomiting in pregnancy affects up to 80% of pregnant women and may progress to hyperemesis gravidarum, leading to maternal morbidity and adverse pregnancy outcomes. Despite numerous pharmacological and non-pharmacological options, the comparative efficacy and safety of these interventions remain unclear. Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials assessing pharmacological and non-pharmacological interventions for nausea and vomiting in pregnancy. The databases searched included CENTRAL, PubMed, and EMBASE (up to 28 May 2024). Eligible trials compared interventions with a placebo in pregnant women with nausea and vomiting in pregnancy. The primary outcomes were symptom severity, assessed using validated tools. Safety outcomes included adverse effects. Data were pooled using frequentist pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool, and the certainty of evidence was evaluated using the CINeMA framework. Results: Of 9844 records screened, 24 randomized controlled trials (3017 participants) met the inclusion criteria, encompassing 16 intervention categories. Network analysis ranked quince, vitamin B6 with pomegranate and mint, acupressure P6, dimenhydrinate, and acupuncture combined with doxylamine-pyridoxine as the most effective interventions for reducing symptoms of nausea and vomiting in pregnancy, with considerable uncertainty and low-to-moderate quality of evidence. Reporting of adverse events was limited. Risk of bias was low to moderate. Discussion: Most interventions demonstrated significant benefit over a placebo. However, high heterogeneity and sparse reporting of adverse effects warrant caution when translating these results into clinical practice. Conclusions: This study indicates that both pharmacological (vitamin B6, metoclopramide, dimenhydrinate) and non-pharmacological (ginger, quince, acupressure, acupuncture) interventions might be effective in reducing symptoms of nausea and vomiting in pregnancy.
Dermatitis : contact, atopic, occupational, drug · 2026
Nutritional supplements and topical formulations are increasingly implicated in allergic contact dermatitis (ACD), yet their allergenic potential remains underrecognized due to inconsistent regulatory oversight, limited provider awareness, and the misconception that "natural" products are inherently safe. To identify emerging allergens in supplements and cosmetics, characterize associated ACD reactions, and highlight diagnostic and regulatory challenges. A systematic review of PubMed, Embase, MEDLINE, Web of Science, and CENTRAL databases was conducted to evaluate reports of ACD linked to dietary supplements and topical formulations. Key sensitizers include vitamin derivatives (tocopherol, phytonadione, ascorbic acid), herbal extracts (Ginkgo biloba, turmeric, St. John's Wort), and antioxidants (α-lipoic acid, resveratrol). Documented cases range from localized dermatitis to systemic reactions. Patch testing confirms sensitization, with cross-reactivity and oxidation-related allergenicity frequently observed. Patch testing may not always reveal the sensitizing agent, especially if the allergen is a contaminant, an unlisted ingredient, or undergoes chemical transformation during oxidation or formulation. The rising prevalence of supplement- and cosmetic-induced ACD underscores the need for standardized patch testing, improved ingredient labeling, and enhanced regulatory oversight, including mandated reporting of adverse reactions, premarket safety testing for allergens, and standardized labeling of known sensitizers and botanical components.
Chemistry & biodiversity · 2026
Traumatic brain injury (TBI) is a leading cause of mortality and long-term neurological disability, while effective pharmacological therapies for its neurobehavioral consequences remain limited. This systematic review evaluates the therapeutic potential of Ginkgo biloba (GB), particularly the standardized extract EGb 761, in TBI management. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to February 2026. Sixty-five studies met the inclusion criteria, including 42 in vivo experimental studies and 23 clinical trials examining neuroprotective, cognitive, behavioral, or functional outcomes following GB administration. Preclinical evidence consistently demonstrates that Ginkgo biloba (GB) exerts neuroprotective effects through attenuation of oxidative stress, as evidenced by increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, alongside reduced malondialdehyde (MDA) levels. These effects are accompanied by modulation of the Slc7a11-Eif4ebp1 signaling axis, suppression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and regulation of key molecular pathways. Specifically, GB inhibits JAK/STAT and TXNIP/NLRP3 signaling while activating PI3K/AKT-associated pathways and autophagy. Clinical studies indicate potential improvements in cognitive and functional outcomes. However, adverse events, particularly bleeding, have been reported, especially when GB is co-administered with anticoagulants or nonsteroidal anti-inflammatory drugs. This underscores the importance of careful patient monitoring. The current evidence supports the promising neuroprotective potential of GB in traumatic brain injury. Nevertheless, clinical data remain insufficient to justify routine therapeutic use. Large-scale, well-designed, randomized controlled trials are necessary to confirm efficacy, optimize dosing regimens, and establish long-term safety profiles.
Nutrients · 2026
Objective: Seaweed and microalgae provide antioxidants, polyunsaturated fatty acids, and bioactive compounds that may enhance exercise performance and accelerate recovery. However, evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of algae-derived supplementation on exercise performance and physiological recovery outcomes in healthy and athletic adults. Methods: This review was registered in PROSPERO (CRD420251166723) and conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Embase, Cochrane Library, EBSCO, and CNKI were systematically searched for randomized controlled trials (RCTs) evaluating algae supplementation in exercise contexts. Inclusion and exclusion criteria were defined based on the PICOS framework. Primary outcomes included VO2max, Time to exhaustion (TTE), maximal power output (WRmax), Time-Trial (TT) performance, and creatine kinase (CK). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were performed. Results: Twenty-two RCTs (n = 822) investigating Spirulina, Chlorella, brown-algal polysaccharides, or astaxanthin met inclusion criteria. Algae supplementation showed a suggestive improvement in VO2max (SMD = 0.88, 95% CI: 0.00-1.75) and significantly improved in TTE (SMD = 1.06, 95% CI: 0.16-1.96), with smaller effects on WRmax (SMD = 0.29, 95% CI: 0.03-0.55), and no significant benefit for TT performance (SMD = -0.27, 95% CI: -0.74 to 0.21). Regarding recovery, CK concentrations were significantly reduced (SMD = -0.78, 95% CI: -1.28 to -0.28). Subgroup analysis suggested greater effects for Chlorella supplementation, higher dosages, and aerobic training contexts; reductions in muscle-damage markers were more evident following resistance exercise. Sensitivity analyses supported the robustness of the main findings with minimal evidence of publication bias. Conclusions: Algae-derived supplements-particularly Spirulina and Chlorella-may modestly enhance aerobic exercise performance and attenuate exercise-induced muscle damage under certain conditions. Effects appear to depend on algae species, dosing strategies, intervention duration, and training modality. High-quality, multi-center RCTs incorporating mechanistic endpoints are needed to clarify optimal application and to develop athlete-specific recommendations.
American journal of obstetrics & gynecology MFM · 2026
To assess whether high-dose folic acid supplementation (4-5 mg/day), initiated before conception, reduces the risk of miscarriage and improves pregnancy rates compared to standard-dose supplementation (0.4 mg/day). A comprehensive search was conducted in PubMed, Embase, Scopus, the Cochrane Library, and ClinicalTrials.gov from inception through May 16, 2025. Eligible studies were randomized controlled trials (RCTs) comparing high-dose (4-5 mg/day) versus standard-dose (0.4 mg/day) folic acid supplementation in nonpregnant women of reproductive age, with no restrictions on language or publication date. The primary outcome was miscarriage; the secondary outcome was clinical pregnancy. Data were pooled using random-effects meta-analysis models and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Risk of bias, study trustworthiness, and certainty of evidence were assessed using the RoB 2.0 tool, OGEIG criteria, and the GRADE framework, respectively. Three RCTs (n=5144) were included. Among these, 1488 women became pregnant during the study period and were included in the primary analysis of miscarriage risk. In this population, high-dose folic acid supplementation was associated with a statistically significant reduction in miscarriage risk (RR 0.73; 95% CI: 0.56-0.94; I2=0%). An additional intention-to-treat (ITT) analysis, which included all randomized participants regardless of pregnancy status, showed a nonsignificant reduction in miscarriage risk (RR 0.79; 95% CI: 0.61-1.04). Moreover, the pregnancy rate was significantly higher in the high-dose group compared to the standard-dose group (RR 1.10; 95% CI: 1.02-1.18). The certainty of evidence was rated as low to moderate. High-dose folic acid supplementation (4 mg/day) may reduce the risk of miscarriage and increase pregnancy rates in women trying to conceive. These findings may support consideration of revising current recommended dosage of folic acid in women trying to conceive. However, large-scale RCTs are needed to confirm these results. El resumen está disponible en Español al final del artículo.
BMJ open · 2026
To examine whether multiparous women have more or less folic acid uptake than primiparous women. Preconceptional, periconceptional and postconceptional folic acid use among all pregnant women and high risk pregnant women. Systematic review and meta-analysis. MEDLINE-Ovid, CINAHL Ultimate, Scopus and ProQuest Medical. Observational epidemiological studies comparing folic acid use between primiparous and multiparous women, published in English from January 1994 to June 2024. Two reviewers screened all papers meeting the eligibility criteria. One reviewer completed data extraction and assessed study quality using an adapted version of the Newcastle-Ottawa Scale. Three other reviewers independently assessed 10% of the studies as a quality check. Random-effects (DerSimonian and Laird) meta-analyses combined results for each outcome. Heterogeneity, risk of publication bias and certainty of evidence were assessed. Of the 10 982 records identified, 81 studies involving 826 855 women were included in the review. 27 studies were conducted in Europe, 22 in Asia, 11 in North America, 7 in Africa, 7 in Australia, 5 in the Middle East and 2 in South America. Multiparous women were consistently less likely to take folic acid before and during pregnancy than primiparous women. For preconceptional use, the odds were 29% lower among multiparous women (adjusted OR (aOR): 0.71; 95% CI 0.64 to 0.78; n=25 studies; I2=88.67%), and 58% lower in multiparous high-risk women (aOR: 0.42, 95% CI 0.27 to 0.64; n=3 studies; I2=27.28%). For periconceptional use, the odds were 32% lower among multiparous women (aOR: 0.68; 95% CI 0.63 to 0.74; n=28 studies; I2=85.46%). Postconception, the odds were 21% lower among multiparous women (aOR: 0.79; 95% CI 0.74 to 0.85; n=33 studies; I2=85.91%). By the second trimester, there was no significant difference between the two parity groups (aOR: 0.96; 95% CI 0.87 to 1.05; n=4 studies; I2=0.00%). The certainty of evidence was low for preconceptional, periconceptional and postconceptional uptake due to heterogeneity, and moderate for preconceptional uptake among high-risk women. Multiparous women were less likely to take folic acid preconceptional, periconceptional and postconceptionally, despite their previous pregnancy experience. Barriers to folic acid supplement uptake among multiparous women need to be identified, and strategies to address them in preconception, antenatal and interconception care should be investigated. CRD42024553241.
Zhonghua zhong liu za zhi [Chinese journal of oncology] · 2026
Objective: To investigate the efficacy and safety of 36 000 IU recombinant human erythropoietin (rhEPO) in the treatment of cancer-related anemia (CRA) and to evaluate whether 36 000 IU rhEPO can serve as a rational "reduced-dose alternative" to the 40 000 IU rhEPO regimen. Methods: The multicenter, open-label, non-inferiority, randomized controlled trial was conducted from March 2023 to July 2024 across 12 hospitals in China, including Liaoning Cancer Hospital. A total of 119 patients with CRA were enrolled and randomly assigned to receive the 36 000 IU rhEPO (n=61) or 40 000 IU rhEPO (n=58). The primary efficacy endpoint was the change in hemoglobin (Hb) levels from baseline at weeks 9-13. Secondary efficacy endpoints included hematologic and other biochemical parameters, transfusion requirements, quality of life (QOL), which was assessed by QOL scores and Karnofsky performance status (KPS) scores, and overall survival. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). Results: The least-squares mean changes in Hb from baseline to weeks 9-13 were (12.9±2.3) g/L in the 36 000 IU group and (13.4±2.4) g/L in the 40 000 IU group. Analysis of covariance showed no statistically significant difference between groups (F=-0.21, P=0.836), with a between-group difference of (-0.5±2.5) g/L (95% CI: -5.4 g/L, 4.4 g/L). The lower limit of the 95% CI (-5.4 g/L) exceeded the predefined non-inferiority margin of -10 g/L, indicating non-inferiority of the 36 000 IU dose compared to the 40 000 IU. At week 13, the proportions of patients with Hb increase ≥10 g/L were 82.0% (50/61) in the 36 000 IU group and 86.2% (50/58) in the 40 000 IU group, with no significant difference between groups (Qmh=0.40, P=0.527). The average weekly transfusion rate was 2.0% in both groups. No significantly significant differences were observed between the two groups in terms of changes in hematocrit, reticulocyte percentage, folate, vitamin B12, albumin, iron metabolism markers, QOL scores, KPS scores, or overall survival (all P＞0.05). Regarding safety, the incidence of TEAE was 80.3% (49/61) in the 36 000 IU group and 84.5% (49/58) in the 40 000 IU group, with nausea, fever, and fatigue being the most common symptoms (incidence＞5%). No drug-related serious adverse events were reported, and there were no significant differences between the groups (P＞0.05). Conclusions: The 36 000 IU dose of rhEPO is non-inferior to the 40 000 IU dose in terms of efficacy and has a favorable safety profile for the treatment of CRA. These findings support the use of 36 000 IU rhEPO as a reasonable clinical option for managing CRA. 目的： 探索36 000 IU重组人促红细胞生成素（rhEPO）治疗肿瘤相关性贫血（CRA）的有效性和安全性，评估36 000 IU rhEPO能否成为40 000 IU rhEPO的合理“减量替代”。 方法： 采用多中心、开放标签、非劣效、随机对照试验设计，于2023年3月至2024年7月在辽宁省肿瘤医院等中国12家医院开展。共纳入119例CRA受试者，根据rhEPO给药剂量规格随机分为36 000 IU组（n=61）和40 000 IU组（n=58）。主要疗效指标为第9～13周血红蛋白（Hb）水平较基线的变化值，次要疗效指标包括血细胞比容等血液生化指标、输血需求、生活质量［生活质量（QOL）评分和卡氏功能状态（KPS）评分］及总生存时间。安全性指标为治疗期不良事件（TEAE）发生率。 结果： 36 000 IU组和40 000 IU组受试者在第9～13周Hb较基线变化值的最小二乘均值分别为（12.9±2.3）g/L与（13.4±2.4）g/L，协方差分析显示组间差异无统计学意义（F=-0.21，P=0.836），组间差值为（-0.5±2.5）g/L（95% CI：-5.4～4.4 g/L），95% CI下限（-5.4 g/L）高于预设的非劣效界值（-10 g/L），表明36 000 IU组相对于40 000 IU组具有非劣效性。在第13周时，36 000 IU组和40 000 IU组Hb升高≥10 g/L的受试者比例分别为82.0%（50/61）和86.2%（50/58），差异无统计学意义（Qmh=0.40，P=0.527），且两组平均周输血率均为2.0%。两组受试者治疗前后的血细胞比容、网织红细胞百分比、叶酸、维生素B12、白蛋白、铁代谢指标、QOL评分、KPS评分以及总生存时间差异均无统计学意义（均P＞0.05）。在安全性方面，36 000 IU组和40 000 IU组TEAE发生率分别为80.3%（49/61）与84.5%（49/58），以恶心、发热和乏力症状为主（发生比例高于5%），均未报告任何药物相关严重不良事件，组间差异无统计学意义（均P＞0.05）。 结论： 36 000 IU rhEPO在治疗CRA方面对比40 000 IU rhEPO具有非劣效性，且安全性良好，36 000 IU剂量可作为临床治疗CRA的合理选择。.
European journal of clinical pharmacology · 2026
This research sought to systematically evaluate the effects of pentoxifylline on renal function, anemia parameters, inflammatory status, and safety among individuals with chronic kidney disease (CKD). PubMed, Embase, Cochrane Library, and Web of Science were searched up to April 9, 2026 for RCTs of pentoxifylline in CKD. Two reviewers independently performed study selection, data extraction, and quality assessment. Meta-analysis was conducted using Stata 15; continuous outcomes were pooled as MD or SMD with 95% CIs. Heterogeneity was evaluated using the I² statistic. In total, 19 studies involving 1166 patients were included. Meta-analysis showed that, compared to the control group, pentoxifylline significantly increased the estimated glomerular filtration rate (7 studies, N = 547, MD = 4.59 mL/min/1.73 m², 95% CI: 2.57-6.61) and reduced the urinary albumin excretion rate (6 studies, N = 494, SMD = -0.57, 95% CI: -1.01--0.12), C-reactive protein (10 studies, N = 594, SMD = -0.70, 95% CI: -1.08--0.31), and tumor necrosis factor-α levels (5 studies, N = 246, SMD = -0.68, 95% CI: -1.19--0.18). Regarding anemia and nutritional indicators, pentoxifylline increased hemoglobin levels (9 studies, N = 424, SMD = 0.51, 95% CI: 0.08-0.94) and potentially improved serum albumin levels (7 studies, N = 355, MD = 0.19 g/dl ,95% CI: 0.00-0.38). Nevertheless, the effects of pentoxifylline on serum ferritin, transferrin saturation, and urinary albumin-to-creatinine ratio were not significant. Regarding safety, the main adverse events included gastrointestinal symptoms, and overall tolerability appeared promising. In patients with CKD, pentoxifylline safely improves renal function and reduces inflammation and anemia, with its efficacy potentially linked to the dosage and duration of treatment.
Journal of the International Society of Sports Nutrition · 2026
High-intensity judo bouts induce oxidative stress and muscle damage, impairing recovery. This randomized, double-blind, placebo-controlled pilot trial examined whether acute β-hydroxy-β-methylbutyrate free acid (HMB-FA) supplementation influences muscle damage, oxidative stress, and antioxidant biomarkers in elite judoka. Twenty-two male elite judoka were randomized to HMB-FA (1.0 g BetaTOR®) or placebo. Supplements were ingested after four simulated Olympic judo bouts. Blood was sampled pre-exercise, post-fourth bout, and 2 h post-bout for creatine kinase (CK), lactate dehydrogenase (LDH), catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC). Twenty-one completed the protocol (one placebo dropout due to injury). Data were analyzed via 2 × 3 mixed ANOVA with partial η². No group differences were seen for CK, MDA, or TAC (p > 0.05). Significant group × time interactions were observed for CAT (p < 0.001), GPX (p = 0.031), and SOD (p = 0.025), indicating greater enzyme increases in HMB-FA (CAT + 54%, GPX + 38%, and SOD + 16%) than placebo (+7-14%). LDH declined in both groups (interaction, p = 0.001), but more so in the placebo group (-29.9%) than in the HMB-FA group (-18.6%). Acute post-exercise HMB-FA supplementation in elite judo athletes did not significantly influence muscle damage or oxidative stress markers but transiently increased antioxidant enzyme activities (CAT, GPX, and SOD). These findings suggest an enzyme-specific effect and highlight the need for future studies using more precise oxidative-stress markers and cellular assays to better evaluate antioxidant responses; however, these effects should be interpreted with caution due to potential limitations related to assay sensitivity and the timing of measurements.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2026
Preliminary evidence indicates that theacrine, a naturally occurring stimulant, improves feelings of energy without impacting heart rate, blood pressure, or cognitive performance after consumption. The limited effects of theacrine consumption on blood pressure, heart rate, and cognitive performance could be due to the low doses (e.g., 200 mg) used in previous studies. Therefore, the purpose of this study was to investigate the effect of theacrine doses greater than those previously tested on heart rate, blood pressure, subjective feelings of energy, and cognitive performance. This is also the first study to investigate the impact of a theacrine-exclusive supplement on salivary cortisol and alpha-amylase. Nineteen healthy men (n = 5) and women (n = 14) who were habitual caffeine consumers completed this randomized, double-blind, crossover-design study. Participants completed a baseline visit and four experimental visits, with a 7-day washout period. They were randomly assigned one of four treatments each visit: placebo, 3 mg/kg theacrine, 6 mg/kg theacrine, or 9 mg/kg theacrine. Measurements were completed pre-treatment and at 60, 90, 120, 150, and 180 min post-treatment. Repeated measures ANOVA results indicated greater salivary cortisol concentration in the theacrine conditions versus the placebo condition at 120 and 180 min post-treatment. The effect of greater theacrine doses on subjective feelings of energy is unclear, as energy only improved in the placebo treatment. Overall, greater theacrine doses increased salivary cortisol with no significant impacts on heart rate, blood pressure, subjective feelings of energy, alpha-amylase, and cognitive performance. ClinicalTrials.gov Identifier: NCT07376564.
Nutrients · 2026
Caffeine is the most widely consumed psychoactive stimulant worldwide and acts primarily through antagonism of adenosine A1 and A2A receptors, thereby reducing sleep pressure and promoting wakefulness. Although its alerting and performance-enhancing effects are well established, its influence on sleep-related electroencephalography (EEG) has been investigated across diverse paradigms with substantial methodological heterogeneity. This systematic and mechanistic review aimed to synthesize human evidence on how caffeine affects sleep architecture, quantitative sleep EEG, and neurophysiological markers of sleep homeostasis, and to interpret these findings within current models of adenosine-mediated sleep-wake regulation. A systematic search of PubMed/MEDLINE, Web of Science, Scopus, Embase, PsycINFO, ResearchGate, and Google Scholar was conducted for studies published between January 1980 and January 2026, with the final search performed on 10 January 2026. Eligible studies were original human investigations examining caffeine exposure or administration and reporting sleep-related EEG outcomes, including polysomnographic sleep staging, spectral EEG analyses, or other EEG-derived sleep metrics. Two reviewers independently screened records and assessed eligibility, with disagreements resolved by consensus. Data on study design, participant characteristics, caffeine interventions, EEG methodology, and outcomes were extracted using a predefined form. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Owing to marked heterogeneity across studies, findings were synthesized narratively within a mechanistic interpretive framework. Thirty-two studies were included. Across highly heterogeneous paradigms-including acute bedtime or evening dosing, daytime or repeated caffeine use before nocturnal sleep, administration during prolonged wakefulness followed by recovery sleep, withdrawal protocols, and ambulatory/home EEG monitoring-the most consistent finding was suppression of low-frequency NREM EEG activity, particularly slow-wave activity and the lowest delta frequencies. Caffeine frequently increased faster EEG activity, including sigma/spindle and beta ranges, producing a lighter, more aroused, and more wake-like sleep EEG profile. These effects were especially prominent during early-night NREM sleep and in recovery sleep after sleep deprivation, where caffeine attenuated the expected homeostatic rebound in low-frequency power. REM-related effects were less consistent, but some studies reported delayed REM timing and subtler alterations in REM EEG. Emerging evidence further suggests that caffeine increases EEG complexity and shifts sleep dynamics toward a more excitation-dominant state. Several studies indicated that quantitative EEG measures were more sensitive than conventional sleep-stage variables in detecting caffeine-related sleep disruption. Dose, timing, habitual caffeine use, withdrawal state, age, circadian context, and adenosinergic genetic variation, particularly involving ADORA2A, moderated the magnitude of effects. We also highlighted the connection between current results and sports and sports science. Caffeine reliably alters the neurophysiological architecture of human sleep in a direction consistent with reduced sleep depth and weakened homeostatic recovery. The overall evidence supports a mechanistic model centered on adenosine receptor antagonism, attenuation of sleep-pressure build-up and expression, and a shift toward greater cortical arousal during sleep. Sleep EEG appears to be a sensitive marker of these effects, often revealing physiological disruption even when conventional sleep architecture changes are modest. Future research should prioritize larger and more diverse samples, pharmacokinetic and pharmacogenetic characterization, and ecologically valid high-resolution sleep monitoring to clarify the real-world and functional consequences of caffeine-induced EEG changes.
The American journal of clinical nutrition · 2026
Maternal periconceptional nutrition is important for birth outcomes, but few studies examine long-term effects on offspring growth and development. We assessed the impact of weekly preconception multiple micronutrients (MM) or iron and folic acid (IFA) supplements compared to folic acid (FA) alone, on cognitive function and nutritional status at 10-11 y. We also examined associations with early-life biological and socioenvironmental factors. We conducted a follow-up study of 1599 children from a preconception randomized trial in Vietnam, in which females received weekly FA, IFA, or MM before conception and daily IFA during pregnancy. We assessed cognitive function, academic achievement, and nutritional status at ages 10-11 y. Early biological factors included maternal nutritional status, birth characteristics, and postnatal linear growth; socioenvironmental variables were maternal schooling, ethnicity, depression, infant feeding, socioeconomic status (SES), and home environment. Analyses used intention-to-treat and per protocol comparisons with inverse-probability-of-censoring weights to account for loss to follow-up. Offspring in the MM and IFA groups had higher perceptual reasoning scores than the FA group {mean difference [95% confidence interval (CI): MM: 1.68 (0.01, 3.35); IFA: 2.04 (0.33, 3.74)]}. The IFA groups also had higher reading scores [0.78 (0.11, 1.44)] and lower anemia prevalence [-4.26 (-7.60, -0.91)]. No differences were observed in full-scale intelligence quotient (FSIQ) or anthropometric measures. Maternal underweight was negatively associated with FSIQ [β (95% CI): -1.62 (-3.06, -0.18)] and reading scores [-0.59 (-1.12, -0.06)] whereas postnatal linear growth was positively associated with FSIQ [1.67 (0.91, 2.43)], mathematics [0.36 (0.12, 0.61)], and reading scores [0.47 (0.21, 0.74)]. Maternal schooling, home environment, SES, were also linked to improved cognitive and academic outcomes [β range: 0.64 (0.01, 1.27) to 8.89 (5.20, 12.58)], and exclusive breastfeeding was linked with higher mathematics scores [0.73 (0.27, 1.19)]. Preconception MM and IFA supplementation improved certain aspects of cognitive functioning at 10-11 y compared with FA alone, whereas early-life biological and socioenvironmental factors were positively associated with cognitive and academic outcomes. This study was registered at clinicaltrials.gov as NCT01665378 (https://clinicaltrials.gov/ct2/show/NCT01665378).
The American journal of clinical nutrition · 2026
Anemia affects more than two-thirds of children aged <5 y in India, despite biweekly iron folic acid (IFA) supplementation under the Anemia Mukt Bharat national program. Multiple micronutrient (MMN) deficiencies may also contribute to the presence of anemia, but the incremental benefit of MMN supplementation in addition to IFA remains unclear. We aimed to compare the efficacy of biweekly preventive supplementation with MMNs plus IFA compared with IFA alone on hemoglobin concentrations and prevalence of anemia in children aged 6-59 mo. In this individually randomized, open-label trial, eligible children received biweekly supplementation with either MMN plus IFA (intervention) or IFA alone (control) for 100 doses over 50 wk. Primary outcomes were mean hemoglobin concentration and anemia prevalence. Secondary outcomes included serum ferritin, soluble transferrin receptor, vitamin B12, folate, and zinc. Among 1300 children enrolled (648 intervention and 652 control), supplementation compliance exceeded 75%. At the endline, the mean hemoglobin was slightly higher in the intervention group [adjusted mean difference, 0.12 g/dL; 95% confidence interval (CI): 0.00, 0.25]. The prevalence of anemia was 17.6% in the intervention group and 24.0% in the control group (adjusted relative risk, 0.72; 95% CI: 0.58, 0.90). No significant differences were observed in serum biomarkers of iron status or other micronutrients. Biweekly supplementation with MMN plus IFA resulted in a modest increase in hemoglobin concentrations and a relative reduction in anemia prevalence compared with IFA alone, particularly in older children. Lack of improvement in biochemical markers and a small rise in hemoglobin concentrations suggest that a reduction in the prevalence of anemia may be driven by shifts near diagnostic thresholds, rather than meaningful physiological benefits. MMN adds minimal value where IFA adherence is already high. The study was registered at Clinical Trial Registry of India as #CTRI/2020/10/028299 (https://ctri.nic.in/Clinicaltrials/login.php).
The American journal of clinical nutrition · 2026
Aging is accompanied by reduced muscle protein synthesis and increased circulating acid, both of which contribute to declines in muscle health. To determine the effects of whey protein (WP) and alkali (potassium bicarbonate, KHCO3) supplementation on muscle performance and mass in healthy older adults. In this randomized, 2 × 2 factorial, placebo-controlled study, healthy adults aged ≥65 years were assigned to either WP (1.5 g/kg/d) plus KHCO3 (81 mmol/d), WP plus placebo-KHCO3, placebo-WP plus KHCO3, or double placebo. Double leg press muscle power (primary outcome), physical performance, lean mass by dual energy x-ray absorptiometry, muscle mass by D3-creatine dilution, and serum insulin-like growth factor 1 (IGF-1) were measured at baseline and 24 weeks. Primary analyses estimated main effects of WP compared with placebo-WP and KHCO3 compared with placebo-KHCO3 using factorial comparisons "at-the-margins," following CONSORT/SPIRIT recommendations for factorial trials. Between-group differences in the 24-wk outcomes were estimated using analysis of covariance adjusted for baseline value, age, and sex. In the intention-to-treat sample (n = 128), 47.7% were female, mean ± SD age was 74 ± 6 y, and baseline protein intake was 0.85 ± 0.30 g/kg/d. Neither WP nor KHCO3 affected muscle power compared with their respective placebo {WP to placebo-WP difference 4.7 watts [95% confidence interval (CI): -21.1,30.5; P = 0.72]; KHCO3 to placebo-KHCO3 difference -13.6 watts [95% CI: -39.6, 12.4; P = 0.30]}. No group differences were noted in physical performance or muscle mass. However, 24-wk mean IGF-1 level was higher in the WP and KHCO3 groups compared with their respective placebo [WP to placebo-WP difference 14.2 ng/mL (95% CI: 7.5, 21.0; P < 0.01); KHCO3 to placebo-KHCO3 difference 7.2 ng/mL (95% CI: 0.4, 13.9; P = 0.04)]. In healthy free-living older adults reporting a protein intake at the current recommended daily allowance, neither increasing protein to 1.5 g/kg/d with WP nor adding a KHCO3 supplement for 24 wk improved measures of muscle power, physical performance, or muscle mass despite achieving higher circulating IGF-1 levels. This trial was registered as NCT04048616 at https://clinicaltrials.gov/study/NCT04048616?term=ceglia&rank=1.
Advances in nutrition (Bethesda, Md.) · 2025
The composition of total protein and free amino acids (FAA) in preterm human milk (HM) is crucial for optimizing infant growth and development. The objective of this systematic review and meta-analysis is to quantify the amount of true, crude, and unspecified protein and FAA in preterm HM. EBSCO, PubMed, and Scopus databases were searched up to July 2023 measuring total protein and FAA in preterm HM. Two reviewers, working independently, screened all titles and abstracts using Covidence software to identify studies meeting inclusion criteria [preterm <37 wk; Human Development Index >0.8; cross-sectional, case-controlled (n > 1), prospective cohort, and randomized clinical trials; English language]. Random-effects models were used to estimate mean protein and FAA content across studies. Data were aggregated for studies reporting multiple estimates (e.g. across time). Heterogeneity was estimated using I2 and publication bias using Kendall tau rank correlation coefficient. Of the 884 articles identified, a total of 66 original studies were included for the meta-analysis comprising an estimated 30,421 preterm HM samples. Preterm colostrum (<4 d) contained the highest mean (95% confidence interval) true protein at 2. 32 (1. 96, 2. 68) g/100 mL, followed by transition preterm HM (5-14 d) mean true protein of 1. 77 (1. 60, 1.93) g/100 mL. Mature (>14 d) preterm HM had the lowest mean true protein content at 1.46 (1.34, 1.59) g/100 mL. Glutamate was the most prevalent FAA reported. This systematic review provides updated estimates of protein and FAA concentrations in preterm HM. There was significant variability in the quality of studies, completeness of the reported results, and analytical methodologies across studies. This trial was registered at PROSPERO as CRD42023445191.