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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
European journal of clinical nutrition · 2026
Caffeine, a performance-enhancing substance, affects haemostasis. However, the interplay between caffeine, exercise, and circadian rhythms on haemostatic responses remains unclear. This study aimed to investigate the effects of acute caffeine intake on exercise-induced haemostatic responses in sedentary young men at different times of day. Thirty caffeine-naïve sedentary men completed a randomized, double-blind, placebo-controlled crossover study. Each participant performed 4 combined exercise sessions-2 at 07:00 and 2 at 18:00-after ingestion of either caffeine or a placebo. Blood samples were collected pre-exercise, post-exercise, and after 60 minutes of recovery. Across all conditions, exercise elicited increases in platelet aggregation, thrombin generation, tPA activity, and clot lysis time. PAI-1 activity was unchanged post-exercise but declined during recovery. Caffeine further augmented exercise-induced increase in platelet aggregation, thrombin generation, and clot lysis time-most notably in the morning-without significantly altering tPA or PAI-1 activity. There was lower platelet aggregation, thrombin generation, PAI-1 activity, and clot lysis time, alongside higher tPA activity in the evening compared to the morning. These findings indicate that morning exercise triggers a greater prothrombotic status than evening exercise, and that acute caffeine intake exacerbates this effect. The enhanced fibrinolytic capacity in the evening may create a more favourable haemostatic setting for exercise and cardiovascular safety, a hypothesis that warrants confirmation with denser sampling protocols.
The Journal of nutrition · 2026
Supplementation with recombinant bovine β-lactoglobulin (rBLG), a precision-engineered mimetic of dairy-derived whey, supports similar resistance exercise (RE) training-induced muscle remodeling to whey protein (WHEY). However, the influence of rBLG on recovery indices and muscle protein synthesis rates after damaging exercise is unknown. To determine the influence of rBLG supplementation on indices of muscle recovery and integrated myofibrillar protein synthesis (iMyoPS) over 72 h following damaging RE, compared with WHEY and a carbohydrate placebo. In a randomized double-blind, placebo-controlled, parallel-group design, 27 healthy adults consuming a controlled diet (∼0.9 g/kg body mass/d of protein) were supplemented thrice daily with 0.3 g/kg body mass of rBLG, WHEY, or isocaloric carbohydrate placebo for 3 d following an acute bout of damaging lower-body RE (8 × 10 maximal, unilateral, eccentric knee extensions). Consumption of deuterated water combined with serial vastus lateralis muscle biopsies permitted the measurement of iMyoPS 72 h before (habitual) and after RE. Knee extensor maximum voluntary contraction (MVC), muscle soreness, and plasma concentrations of creatine kinase and lactate dehydrogenase (LDH) were also assessed post-RE to characterize muscle recovery. iMyoPS fractional synthetic rate (%/d) increased following damaging RE (P < 0.001), with no significant differences between groups. Knee extensor MVC decreased, and subjective muscle soreness and plasma LDH concentrations increased following strenuous exercise (P < 0.05 for all) with no significant differences between groups. At habitual dietary protein intakes ∼0.9 g/kg body mass/d, further rBLG or WHEY supplementation did not influence muscle recovery or iMyoPS rates, suggesting that protein supplementation, at the intakes studied, may have limited efficacy as a tool to enhance muscle recovery and remodeling from damaging exercise.
Nutrients · 2026
Objectives: The aim of this study was to explore the combined effects of resistance exercise and whey protein supplementation on plasma irisin levels in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) under a 30% calorie-restricted weight loss diet. Methods: Thirty adult patients with MASLD were randomized into the following three groups for a 4-week intervention: calorie restriction group (CR) (n = 8), CR with resistance exercise group (EX) (n = 11), and CR with resistance exercise and whey protein group (EX + P) (n = 11; 0.7 g/kg per day). All participants received boxed meals providing 70% of their total energy expenditure. The participants in the resistance exercise groups performed full-body resistance exercises 5 days/week (50-75% one-repetition maximum). Plasma irisin level, controlled attenuation parameter (CAP), and body composition were assessed before and after the intervention. Results: Plasma irisin levels significantly increased in the EX (+2.24 ng/mL, p = 0.016) and EX + P (+4.86 ng/mL, p = 0.004) groups but not in the CR group. Muscle mass increased significantly only in the EX + P group. The CAP decreased in all groups. The change in irisin level was negatively correlated with the change in CAP (r = -0.459, p = 0.032). Conclusions: Resistance exercise under calorie-restricted conditions effectively increased plasma irisin levels in patients with MASLD, whereas caloric restriction alone did not. Furthermore, a stronger increasing trend in the plasma irisin levels was observed with whey protein supplementation. An increase in irisin levels was significantly associated with hepatic fat reduction, suggesting that irisin may serve as a biomarker reflecting improvements in hepatic steatosis following lifestyle intervention.
American journal of respiratory and critical care medicine · 2026
Critical illness impairs the muscle protein synthetic response to protein administration. Whether increased protein dose can overcome this anabolic resistance is unknown. To assess the impact of a single intraduodenal bolus of 40 g protein compared to 20 g of protein in mechanically ventilated critically ill patients on the primary outcome of postprandial muscle protein synthesis rates. Mechanically ventilated patients were randomized to 40 or 20 g of whey protein isolate delivered intraduodenally over 1 h. Primed continuous intravenous L-[ring-13C6]-phenylalanine and L-[3,5-2H2]-tyrosine infusions were applied with repeated arterial blood and skeletal muscle tissue sampling over 2 h fasting and 6 h postprandial periods to assess plasma amino acid responses and rates of fasting and postprandial muscle protein synthesis (primary outcome). Data are mean ± SD and area under the curve (AUC), analyzed with ANCOVA adjusted for fasting rate and paired t-tests (P < .05). Twenty patients (n = 10/group: 40 g: 90% male, 49 ± 21 y and 20 g: 80% male, 51 ± 13 y) were studied. Postprandial muscle protein synthesis rates (primary outcome) did not differ between groups (40 g vs 20 g: 0.030 ± 0.012 vs 0.025 ± 0.010%·h-1; adjusted mean difference 0.007 (95% CI, -0.003 to 0.016) %·h-1; P = .152). Postprandial plasma leucine and tyrosine availability (AUC) were higher following 40 g vs 20 g protein (leucine: 263 ± 87 vs 194 ± 54 µmol·L-1, P = .005; tyrosine: 92 ± 24 vs 63 ± 17 µmol·L-1, P = .006). Fasting muscle protein synthesis rates did not differ between groups (40 g vs 20 g: 0.020 ± 0.012 vs 0.025 ± 0.023%·h-1; P = .558). The post hoc uncontrolled analysis of muscle protein synthesis rates from fasting to postprandial periods increased in the 40 g group only (P = .005). Higher enteral protein does not further augment postprandial muscle protein synthesis rates to overcome -anabolic resistance during critical illness, despite increased plasma amino acid availability. Australia New Zealand Clinical Trials Registry Identifier: ACTRN12620000776909.
Nutrients · 2026
Background/Objectives: Aging is closely associated with sarcopenia, which has a significant impact on muscle mass and its function. Protein supplementation (PS) brings benefits such as lean mass and strength gains during exercise training. This paper determined the optimal regimen among the composites of variate protein sources and training modalities for older individuals. Methods: We comprehensively searched the electronic databases, namely MEDLINE Complete, PEDro, the Cochrane Library, Google Scholar, EMBASE, and the China National Knowledge Infrastructure, from its inception until December 2025. We included randomized controlled trials (RCTs) that examined the effectiveness of any type of PS combined with one of three exercise types-resistance, aerobic, or multicomponent training-in untrained older adults. The main outcomes used to identify sarcopenia were assessed, including lean mass, handgrip and leg strength, and physical mobility measures. Network meta-analysis (NMA) was performed by a frequentist method using random-effects models. The estimated treatment effect was expressed as the standard mean difference (SMD) with a 95% confidence interval (CI). Any potential factor moderating the treatment effect was determined by the meta-regression analyses, including participant characteristics and methodological factors. Certainty of evidence (CoE) was assessed by the GRADE framework. Results: In total, we included 235 RCTs (20,980 participants) for analyses. A total of 10 protein sources (whey, soy, casein, milk, and the others) were identified, corresponding to 24 monotherapy and combined regimens of PS and exercise. Among the treatment arms, whey plus resistance training was ranked as the most effective treatment for muscle mass (large SMD, 1.29; CoE, moderate) and leg strength (large SMD, 1.16; CoE, moderate); additionally, whey plus multicomponent exercise training achieved the most promising effects on such sarcopenia-related physical indicators such as chair rise (large effect, SMD = 1.09; CoE: high), timed up and go (medium SMD, 0.70; CoE, high), and global mobility score (large SMD, 1.02; CoE, high). Conclusions: The treatment efficacy appears to be moderated by the participant's conditions, PS resource, and PS dose, particularly the outcome of muscle mass and strength. The present NMA results indicate that whey protein incorporated with resistance training is the optimal program to help combat sarcopenia in older adults.
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2026
To evaluate the efficacy and safety of Cortexin in the comprehensive treatment of neurological complications in patients with type 2 diabetes mellitus (T2DM). This multicenter, parallel-group, randomized, clinical trial included 110 patients with neurological complications of T2DM including cognitive impairment, anxiety-depressive states, and a painless diabetic polyneuropathy (DPN). Of the participants, 70.6% were females and 29.4% were males, aged 45 to 70 years (mean age: 60.8±0.71 years). All patients received comprehensive treatment consisting of glycine and B-vitamin complexes for 30 days-administered parenterally for the first 10 days and orally for the subsequent 20 days. The patients were followed up until Day 90. Group 1 (n=55) patients received ten additional doses of Cortexin 10 mg i/m, while Group 2 patients received only comprehensive treatment. Changes in symptoms, glycemic hemoglobin (HbA1c) levels, cognitive deficit scores (Montreal Cognitive Assessment, MoCA), anxiety-depressive disorders (Hospital Anxiety and Depression Scale, HADS), and symptoms related to painless DPN (Neuropathy Symptom Score-9, Central Sensitization Index, CSI) were evaluated. The patients' condition and response to therapy were objectively assessed using the Clinical Global Impression (CGI) scale, and adverse events (AEs) were documented. The regression of cognitive symptoms in group 1 patients was superior to that in group 2 (6.0 times vs. 1.7 times), as confirmed by a 1.2-fold increase in the average MoCA score after 3 months of follow-up (p<0.001). In the Cortexin group, the mean HADS anxiety score decreased by 1.6 times, and the mean depression score decreased by 1.7 times, with minimal changes noted in the control group (p<0.001). Significant reductions in numbness were observed, with a 2.2-fold decrease in the Cortexin group compared to a 1.3-fold decrease in the control group. The mean NTSS-9 score dropped by 2.8 times in group 1 and by 1.3 times in group 2 (p<0.001); while the CSI decreased 1.8 times and 1.2 times, respectively (p<0.001). The reduction in HbA1c was also more significant in the Cortexin group (7.3±0.1% vs 7.8±0.1%, p<0.001). According to the CGI scale, 83.3% of patients in group 1 showed good or very good improvement, and a significant therapeutic effect was noted in 55.6% of patients. The proposed therapy demonstrated a high safety profile, with only 5 AEs reported (3 in Group 1 and 2 in Group 2), none of which were related to the study therapy. The comprehensive therapy with Cortexin proved to be highly effective, safe, and well-tolerated in patients with neurological complications of T2DM, and it is recommended for use in general clinical practice. Оценить эффективность и безопасность лекарственного препарата Кортексин в комплексной терапии неврологических осложнений у пациентов с сахарным диабетом (СД) 2 типа. В многоцентровое рандомизированное в параллельных группах клиническое исследование включено 110 пациентов с неврологическими осложнениями СД 2 типа в виде когнитивных нарушений (КН), тревожно-депрессивных расстройств и безболевой формы диабетической полинейропатии (ДПН), 70,6% женщин и 29,4% мужчин, возраст 45—70 лет (60,8±5,7 года), распределенных в 2 группы по 55 пациентов. Все пациенты получали комплексную базисную терапию в течение 30 дней, из них первые 10 дней — парентерально, последующие 20 дней — перорально, далее наблюдались до 90-го дня включительно. Пациенты 1-й группы дополнительно получали Кортексин 10 мг в/м (10 инъекций), пациенты 2-й группы — только комплексную терапию. Оценивались динамика жалоб, уровень гликированного гемоглобина (HbA1c), КН по Монреальской шкале оценки когнитивных функций (MoCA), тревожно-депрессивных нарушений (Госпитальная шкала тревоги и депрессии, HADS); симптомов безболевой формы ДПН (шкалы Общей оценки симптомов нейропатии, NTSS-9; центральной сенситизации, CSI), проводилась оценка состояния пациентов и реакции на терапию (шкала общего клинического впечатления, CGI), частоты нежелательных явлений (НЯ). Регресс жалоб со стороны когнитивной сферы у пациентов 1-й группы превосходил 2-ю группу в 6,0 раз против 1,7, что подтверждено увеличением среднего балла по шкале MoCA в 1,2 раза (p<0,001) через 3 мес наблюдения. В 1-й группе значения по шкале HADS снизились в 1,6 раза, депрессии — в 1,7 раза, в группе сравнения динамика была минимальной, p<0,001. Отмечено уменьшение жалоб на онемение конечностей в 1-й группе в 2,2 раза по сравнению со 2-й. Средний балл по шкале NTSS-9 снизился в 2,8 раза в 1-й группе и в 1,3 раза — во 2-й (p<0,001); по шкале CSI — в 1,8 раза против 1,2 соответственно (p<0,001). Отмечено большее снижение уровня HbA1c в 1-й группе по сравнению со 2-й (7,3±0,1% и 7,8±0,1%, p<0,001). По шкале CGI состояние 83,3% пациентов из 1-й группы расценено как сильное/очень сильное улучшение, а эффект от терапии у 55,6% пациентов — как значимый. Подтвержден высокий профиль безопасности предложенной схемы терапии, всего зарегистрировано 5 НЯ (3 — в 1-й группе, 2 — во 2-й), не связанных с приемом препаратов исследования. Комплексная терапия с Кортексином показала высокую эффективность, безопасность и хорошую переносимость у пациентов с неврологическими осложнениями СД 2 типа и может быть рекомендована к применению в широкой клинической практике.
Inflammopharmacology · 2026
To evaluate the clinical efficacy and safety of krill oil supplementation in patients with knee osteoarthritis (KOA) through a systematic review and meta-analysis. Potential mechanisms are discussed based on existing literature. A systematic search was performed across PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) investigating krill oil supplementation in patients with KOA. Studies were selected according to pre-defined inclusion and exclusion criteria. Data were independently extracted by two reviewers and pooled using RevMan 5.4. Risk of bias was assessed with the Cochrane Risk of Bias tool. Six RCTs with 971 participants were included. Krill oil supplementation significantly improved pain and physical function (WOMAC scores at week 4), with moderate effects observed on stiffness. Krill oil significantly increased HDL-C and omega-3 levels, but had no effect on LDL-C and CRP. No significant adverse events were reported. Krill oil is a promising functional food with a favorable safety profile for KOA symptom management, particularly for pain and physical function. The findings suggest potential mechanisms related to its anti-inflammatory and antioxidant effects, supporting its role in nutraceutical interventions for KOA.
Placenta · 2026
Defective deep placentation contributes to major obstetric complications, including preterm birth, preeclampsia (PE), and severe fetal growth restriction (FGR). Docosahexaenoic acid (DHA) supplementation may improve placental function, but evidence from randomized trials remains inconsistent. To evaluate whether early DHA supplementation modifies clinical phenotypes associated with impaired placentation. In this multicenter, double-blind, placebo-controlled trial (NCT02336243), singleton pregnant women <16 weeks were randomized to receive DHA 600 mg/day (n = 404) or placebo (n = 405) until delivery. The primary outcome was a composite of preterm birth ≤34 weeks, early-onset PE, or severe FGR (<3rd percentile). Analyses were performed on an intention-to-treat basis. Of 844 women screened, 809 were randomized (404 DHA, 405 placebo). The trial did not reach the planned sample size, and the observed event rate was lower than expected. The primary outcome occurred in 3.47% of the DHA group and 2.96% of the placebo group (RR = 1.17; 95% CI 0.55-2.50; p = 0.685). No significant differences were observed for severe FGR (RR = 0.79; 95% CI 0.22-2.95) or early-onset PE (RR = 0.50; 95% CI 0.09-2.73). Secondary maternal and neonatal outcomes were similar. Adherence exceeded 90%, and no serious adverse events were recorded. Daily DHA supplementation (600 mg) from early pregnancy was safe and well tolerated but did not demonstrate a statistically significant effect on clinical phenotypes of impaired placentation. Given that the study was underpowered, definitive conclusions regarding efficacy cannot be drawn. Future studies should explore higher-dose or targeted supplementation strategies, particularly in women with low baseline omega-3 status. gov (NCT02336243).
Nutrients · 2026
Background: Supplementation with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may mitigate exercise-induced muscle damage (EIMD) and enhance post-exercise recovery. However, the systematic reviews/meta-analyses evaluating these effects across populations and exercise models are limited and do not provide dosing recommendations. Objective: This systematic review and meta-analysis aimed to evaluate the effects of LC n-3 PUFA supplementation on key post-exercise recovery outcomes, including muscle soreness, muscle function, and muscle damage biomarkers in healthy adults. Methods: Following the PRISMA guidelines, a comprehensive search of PubMed, Scopus, and clinical trial registry databases was conducted (to January 2025). All studies that met the inclusion criteria underwent appropriate methodological quality assessments using established tools. The data were extracted for inputting into random-effects models, with effect sizes reported as Hedges' g and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. Results: Among the 2539 records, 43 studies met the inclusion criteria for the systematic review, and nine met the inclusion criteria for the meta-analysis. The effect of LC n-3 PUFA supplementation on recovery outcomes was equivocal, with significant methodological limitations noted across the literature. However, the meta-analysis of nine placebo-controlled, eccentric exercise trials demonstrated that LC n-3 PUFA supplementation significantly reduced delayed onset muscle soreness (DOMS) (Hedges' g = -0.75; 95% CI: -1.14 to -0.36), creatine kinase (CK) (Hedges' g = -0.40; 95% CI: -0.70 to -0.10), and muscle swelling (Hedges' g = -0.45; 95% CI: -0.83 to -0.07), and significantly improved muscle strength (Hedges' g = 0.45; 95% CI: 0.07 to 0.83) and range of motion (ROM) (Hedges' g = 0.93; 95% CI: 0.33 to 1.53) at peak impairment compared with placebo. Conclusions: LC n-3 PUFA supplementation may support recovery from EIMD. However, due to the methodological limitations across the literature base it was not possible to assess effective dosing strategies. Future studies should address dose-response and duration requirements and incorporate objective assessments of omega-3 status (e.g., the Omega-3 Index [O3I] or comparable biomarkers) alongside standardized compliance measures. These approaches are necessary to determine effective dosing strategies and to test the relationship between omega-3 status and recovery outcomes.
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026
Breast milk ovalbumin concentrations have been measured with considerable inter-individual variation. Body mass index (BMI) and gestational diabetes mellitus (GDM) in humans, and fish oil supplementation in pigs, have been associated with breast milk protein concentrations. This study aimed to identify whether breast milk ovalbumin concentrations are associated with these maternal characteristics. This is a secondary analysis of data collected during a randomized trial. Breast milk ovalbumin concentrations were measured in 66 atopic women 2-6 h after consumption of one egg at 2, 4, and 6 weeks of lactation. Associations between ovalbumin concentrations and maternal characteristics (BMI, GDM and fish oil supplementation during pregnancy) were investigated. Participants with GDM (n = 6) had higher ovalbumin concentrations at 2 weeks of lactation (median = 0.87 [IQR 0.27-2.17] ng/mL) compared to participants without GDM (n = 60, median = 0.15 [IQR 0.05-0.67] ng/mL; p = .03). Participants who consumed fish oil supplements during pregnancy (n = 16) had higher ovalbumin concentrations at 4 weeks (median = 0.39 [IQR 0.07-1.20] ng/mL) and 6 weeks (median = 0.29 [IQR 0.15-0.86] ng/mL) compared to those who did not (n = 50, median = 0.05 [IQR 0.05-0.44] ng/mL at 4 weeks, p = .01; and 0.05 [IQR 0.05-0.40] ng/mL at 6 weeks, p = .01). Pre-pregnancy BMI was not associated with ovalbumin concentrations. GDM and pregnancy fish oil supplementation were associated with higher breast milk ovalbumin concentrations. Future, larger studies should further investigate associations between these maternal characteristics and breast milk food protein concentrations.
Frontiers in nutrition · 2026
Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, affecting a significant proportion of the elderly population. Non-pharmacological nutritional supplements, such as vitamins, omega-3 fatty acids, probiotics, and herbal extracts, have been proposed as potential interventions to mitigate cognitive decline and improve physiological biomarkers. However, evidence on their efficacy remains inconsistent. This systematic review and network meta-analysis (NMA) aimed to evaluate the effectiveness of various non-pharmacological nutritional supplements on cognitive function and key physiological indicators (e.g., BDNF, Aβ42, Aβ40) in elderly individuals with MCI. This systematic review followed PRISMA-NMA guideline and was registered in PROSPERO (CRD420251079079). We searched PubMed, Embase, Cochrane Library, Web of Science, and CNKI databases from inception to June 2025 for randomized controlled trials (RCTs) comparing dietary supplements to placebo or no intervention. Data extraction included cognitive scores (e.g., MMSE, MoCA, FSIQ) and physiological markers. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Pairwise meta-analyses and NMA were conducted using random-effects models, with standardized mean differences (SMD) for continuous outcomes. Heterogeneity was assessed via I 2 statistics, and sensitivity analyses were performed to test robustness. Thirteen trials involving 2,451 participants were included. PUFA supplements showed the greatest cognitive benefit (SMD 0.91; 95% CI 0.21-1.61) and ranked first according to SUCRA values. Supplementation significantly reduced Aβ42 levels, while effects on BDNF and Aβ40 were non-significant. Heterogeneity was substantial (I 2 = 96%), and sensitivity analyses demonstrated attenuated effect sizes after removing studies at high risk of bias. Dietary supplements may offer potential cognitive benefits in MCI, but evidence is limited by study quality and heterogeneity. High-quality RCTs are needed to confirm these findings. Identifier CRD420251079079.
BMC oral health · 2026
Systematically evaluate the clinical efficacy of systemically administered non-steroidal anti-inflammatory drugs (NSAIDs) as an adjunct to scaling and root planing (SRP) for periodontitis, assess the therapeutic effects of different drugs, and identify the most effective treatment regimen. This study is registered in PROSPERO under trial No. CRD420250651756. Randomized controlled trials (RCTs) examining systemic NSAIDs as SRP adjuncts were identified through systematic searches of PubMed, Embase, Web of Science, Cochrane Library and CNKI databases. Eligible studies were screened, followed by data extraction and risk-of-bias assessment using Cochrane criteria. Efficacy was assessed through changes in probing depth (PD) and clinical attachment loss (CAL). Statistical analyses were performed using Stata 18.0, and R 4.4.3 software. Thirteen RCTs involving 549 patients met inclusion criteria. The results of the Network meta-analysis (NMA) identified that, when NSAIDs are used as an adjuvant treatment for periodontitis, compared with using only SRP to treat periodontitis, ibuprofen + SRP [MD = 0.58, 95% CI (0.31, 0.85)] shows the most significant efficacy in improving PD and CAL after 1 - month follow - up. At 3 months, the ibuprofen-doxycycline combination [MD = 1.70, 95% CI (1.16, 2.24)] and omega-3 polyunsaturated fatty acids (PUFAs) combined with aspirin [MD = 0.82, 95% CI (0.57, 1.07)] demonstrated superior efficacy versus monotherapies. Current evidence suggests that systemic administration of NSAIDs as an adjunct to periodontal baseline therapy may provide clinically significant benefits in periodontitis management. However, further well-designed randomized controlled trials with larger sample sizes are required to validate and refine this conclusion.
BMC neurology · 2026
Migraine is a common, disabling neurological disorder affecting over one billion people worldwide, characterized by recurrent unilateral, pulsating headaches lasting 4-72 h. Caffeine, a widely consumed psychoactive alkaloid found in coffee, tea, and other beverages, is frequently implicated as both a trigger and a treatment for attacks. We aim to comprehensively evaluate the association between caffeine exposure and migraine by integrating observational evidence with Mendelian Randomization (MR) studies. A comprehensive search was conducted through PubMed, Scopus, Web of Science, and the Cochrane Library till August 2025. We included primary studies assessing the impact of caffeine exposure on migraine risk. 19 studies (nine cross-sectional, seven MR, and three cohort) were included in our review. MR studies included over one million participants, while cross-sectional studies involved over 43,000 participants, and the cohort studies included 421 migraine cases. MR reflected lifelong genetic liability (population-level, chronic exposure) and associated with a reduced risk with overall odds ratio (OR) ranging from 0.53 to 0.71, with stronger associations reported in migraine with aura (ORs as low as 0.37-0.39). Observational studies captured short-term, acute effects and showed that abrupt withdrawal or acute excessive intake (≥ 3 drinks/day) can trigger attacks in some people (P = 0.024). While habitual moderate use was generally not linked to higher average migraine burden. Lifelong genetic liability to higher coffee/caffeine intake is associated with a reduced risk of migraine especially for migraines with aura. However, acute excessive intake or sudden changes in caffeine habits can trigger attacks in some people. More future large, well prospective cohorts and carefully designed MR studies are needed to confirm our results and clarify the precise impact of caffeine on migraine risk.
Endocrinology, diabetes & metabolism · 2026
The use of metformin among children and adolescents has risen in the past decade; however, its effect on vitamin B12 has been unclear. To address this gap, we conducted this first systematic review and single-arm meta-analysis. To investigate the effect of metformin on vitamin B12 levels. PubMed, Scopus and Web of Science were systematically searched until April 2025. The primary outcomes were the effect of metformin on vitamin B12 levels after 6 and 12 months of duration, and vitamin B12 deficiency after at least 12 months of usage. We conducted the risk-of-bias assessment using the NOS and Cochrane ROB2 tool. The mean difference (MD) and standard error (SE) were calculated and used for analysis. We assessed the heterogeneity of the studies using the chi-squared test and measured it with the I2 statistic. A fixed effects model was applied to calculate the pooled MD in the absence of significant heterogeneity. The registration number in PROSPERO 2025 is CRD420251045023. A total of five articles were included in this systematic review and meta-analysis. The pooled rate of vitamin B12 deficiency in RCT studies after at least 12 months of use was 1.4% [95% CI: -0.012, 0.040] with mild heterogeneity (I2 = 30.87%, p = 0.235). While in observational studies the pooled rate was 18.7% [95% CI: -0.212, 0.586] with substantial heterogeneity (I2 = 87.93%, p = 0.004). Vitamin B12 levels decreased after 6 and 12 months of using metformin; however, it was neither statistically nor clinically significant (p > 0.05). More trials with larger sample sizes and longer durations of follow-up are needed to better understand the risk of vitamin B12 deficiency among the paediatric population. PROSPERO (CRD420251045023).
The Journal of nutrition · 2026
Prediabetes is potentially recognized as a stage of heightened risk not only for diabetes but also for early cognitive decline, driven by insulin resistance, oxidative stress, and low-grade inflammation. The aim of this study was to evaluate the effect of daily almond supplementation on cognitive performance and biochemical markers in middle-aged Asian Indians with prediabetes, who are at high risk for metabolic and cognitive decline. This 24-wk, open-label, parallel-arm randomized controlled trial was conducted at a tertiary care center in New Delhi. A total of 60 adults aged 40-60 y with prediabetes were randomly assigned to an almond group (n = 29; almonds providing 20% of daily energy with diet and exercise) or a control group (n = 31; isocaloric diet and exercise without almonds). Cognitive function was assessed at baseline and 24 wk using the Cambridge neuropsychological test automated battery (CANTAB), covering executive function, memory, attention, processing speed, and working memory. Anthropometry, glycemia, plasma α-tocopherol, thiobarbituric acid reactive substances (TBARS), and high-sensitivity C-reactive protein were also measured. At 24 wk, the almond group showed significant improvements in executive function [One Touch Stockings of Cambridge; β = -2.5, 95% confidence interval (CI): -4.4, -0.6, P = 0.01] and in processing speed (reaction time; β = 73.8, 95% CI: 25.7, 122.0, P = 0.003; β = 39.3, 95% CI: 9.4, 69.1, P = 0.011) compared with controls. There were also significant reductions in weight, body mass index, waist circumference, fasting and postprandial glucose, glycosylated hemoglobin, and TBARS, along with increased plasma α-tocopherol (all P < 0.05). Six months of almond supplementation improved executive function, processing speed, and overall cognition, reduced oxidative stress (TBARS), and improved plasma α-tocopherol and glycemia in Asian Indians with prediabetes. These findings suggest that almonds provide dual cognitive and metabolic benefits in this high-risk population. However, the moderate sample size and 24-wk duration warrant confirmation in larger and longer-term trials. This trial was registered at clinicaltrials.gov as NCT05322304.
Depression and anxiety · 2026
Mood disorders (MDs), including depressive disorder (DD) and bipolar disorder (BD), represent a major global health burden, yet the absence of objective biomarkers has persistently hindered their accurate clinical diagnosis. The niacin skin flushing response (NSFR) has shown promise as a potential biomarker; however, inconsistencies in diagnostic efficacy and response characteristics across studies have limited its utility. This meta-analysis aims to systematically evaluate the NSFR in MD patients to address these discrepancies. A comprehensive search of PubMed, Embase, Cochrane Library, and Scopus databases was conducted for articles published through May 2025, identifying 18 eligible case-control studies involving 1848 participants (888 MD patients and 960 HC). Random-effects models were used to assess the degree, speed, and sensitivity of NSFR, while subgroup analyses and meta-regression explored potential sources of heterogeneity. MD patients exhibited markedly blunted NSFR, characterized by reduced degree and speed of response (standardized mean difference [SMD] = -0.59, 95% confidence interval [CI]: [-1.12; -0.05] and SMD = 0.72, 95% CI: [0.35; 1.10]), while no statistically significant difference in NSFR sensitivity was observed (SMD = 0.51, 95% CI: [-0.18; 1.20]). Subgroup analyses identified substantial heterogeneity across detection methods, geographical regions, and control sources, highlighting the need for standardized protocols. Meta-regression analyses indicated that sample size, publication year, gender distribution, and age did not significantly affect outcomes, further strengthening the robustness of our findings. This study reinforces the potential of NSFR as a biomarker for MD and highlights the critical need to address heterogeneity through standardized methodologies in future research to enhance its diagnostic reliability.
JAMA network open · 2026
Psilocybin has been proposed as a rapid-acting antidepressant (onset <2 weeks) with sustained effects (>6 weeks), but evidence from randomized clinical trials remains limited, particularly in the broader major depressive disorder (MDD) population. To assess short-term and long-term antidepressant effects of psilocybin therapy in patients with MDD. This double-blind, placebo-controlled randomized clinical trial of participants diagnosed with moderate to severe recurrent MDD was conducted at the Northern Stockholm Psychiatric Clinic between January 26, 2021, and February 19, 2024. Statistical analysis was performed from February 20, 2024, to June 20, 2025. Participants received a single dose of psilocybin (25 mg) or active placebo (niacin, 100 mg) and 5 psychotherapeutic support sessions during 17 days. The primary end point was between-group difference in change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 8. Secondary end points included MADRS scores on days 15, 42, and 365, as well as monthly self-reports (MADRS-S) of depressive symptoms, disability, quality of life, and anxiety throughout the 365-day follow-up. The study included 35 participants (21 [60%] female; mean [SD] age, 41.0 [10.1] years) diagnosed with moderate to severe recurrent MDD, with 17 randomized to the psilocybin group and 18 to the niacin group. The study met its primary end point with a significant mean between-group difference (model estimated) in change in MADRS score on day 8 (-7.27; 95% CI, -12.89 to -1.65; P = .01) in favor of psilocybin. The between-group difference was significant also on days 15 (mean difference, -11.03; 95% CI, -16.65 to -5.42; P < .001) and 42 (mean difference, -8.33; -13.94 to -2.71; P = .004) but no longer on day 365 (mean difference, -3.68; -9.30 to 1.94; P = .20). For MADRS-S, the psilocybin group had a significantly greater reduction beginning at day 2 (mean difference, -9.58; 95% CI, -16.05 to -3.11; P = .004), with group differences persisting through day 102 (mean difference, -6.60; 95% CI, -13.01 to -0.19; P = .04) and then isolated effects at days 283 and 343. Most reported treatment-emergent adverse events were transient and of mild to moderate severity. No drug-related serious adverse events were reported. Two participants in the psilocybin group reported persistent, severe anxiety that required medical attention. In this randomized clinical trial of MDD, a single dose of psilocybin was associated with rapid antidepressant effects, observed by day 2 and persisting for more than 3 months on secondary outcomes; psilocybin was generally well tolerated, but some individuals required additional support after dosing due to anxiety. These results suggest that psilocybin may provide a rapid and relatively long-lasting antidepressant effect on major depressive disorder, warranting further investigation into repeated dosing or adjunctive treatment strategies. ClinicalTrials.gov Identifier: NCT04630964.
Journal of the International Society of Sports Nutrition · 2026
PAPE is a physiological phenomenon that temporarily enhances muscular strength and responsiveness following high-intensity muscle activity. This study aimed to investigate the acute effects of a PAPE protocol combined with taurine supplementation on anaerobic performance, blood lactate levels, and neuromuscular fatigue in highly trained male wrestlers. Twenty elite male wrestlers participated in a double-blind, crossover design comprising three separate sessions: (i) control with no supplementation or PAPE protocol (CON), (ii) PAPE protocol with placebo (PAPE*PLA), and (iii) PAPE protocol with taurine supplementation (PAPE*TAU). In the PAPE*PLA and PAPE*TAU conditions, participants completed 3 sets of 8 repetitions of squat and hip thrust exercises at 85% of their one-repetition maximum. Either a taurine supplement or a sucrose placebo was administered 60 minutes before the protocol. Five minutes after the PAPE protocol, the Wingate anaerobic power (WanT) test was conducted, while CMJ tests were performed before (CMJ-pre), immediately after (CMJ-post), and five minutes following (CMJ-post-5) the WanT. The PAPE*TAU condition resulted in significantly higher peak power output (16.76% increase; p = 0.048) and power relative to body mass (22.24% increase; p = 0.028) compared to PAPE*PLA and CON. Additionally, post-test blood lactate levels were significantly lower in the PAPE*TAU condition (p < 0.05), and CMJ performance was significantly better post-exercise (p < 0.05), indicating reduced neuromuscular fatigue. In conclusion, the combination of the PAPE protocol with taurine supplementation enhances anaerobic performance, supports neuromuscular function, and promotes metabolic recovery following high-intensity exercise. These findings suggest a synergistic effect that may benefit athletes engaged in explosive and anaerobic sports such as wrestling.
Frontiers in pharmacology · 2026
Ginseng berry saponin (GBS), the primary bioactive constituent of Panax ginseng C.A. Mey (known as "Renshen" in Chinese) berries, exhibits cardioprotective properties, including anti-inflammatory, antioxidant, and anti-fibrotic effects. In traditional Chinese medicine, they are widely used to treat various cardiovascular diseases. Several randomized controlled trials (RCTs) have shown its efficacy for heart failure (HF). To assess the clinical efficacy and safety of GBS as an adjunct therapy for HF through systematic review and meta-analysis. A comprehensive and systematic literature search was conducted across seven electronic databases, with no language restrictions, from their respective inception dates through 31 March 2025. These databases included PubMed, the Cochrane Library, EMBASE, Web of Science China National Knowledge Infrastructure China Science and Technology Journal Database (VIP), and Wanfang Data. For quality assessment, the Cochrane Risk of Bias (ROB 2.0) tool was employed, and meta-analyses were performed using Review Manager (RevMan, version 5.4). Under a random-effects model, mean differences and their corresponding 95% confidence intervals (CI) were calculated. Additionally, the certainty of evidence for each outcome was systematically assessed using the GRADE methodology (GRADEpro software v3.6). The study has been registered in PROSPERO, with the registration number CRD420251003193. The final analysis integrated 32 RCTs, comprising 3,476 HF patients for efficacy and safety assessment. Meta-analysis results indicated that adjunctive GBS therapy significantly improved the following outcomes compared with the control group (all P < 0.01): LVEF (MD = 8.91, 95%CI [6.78, 11.04]), 6MWTD (MD = 63.11, 95%CI [43.27, 82.95]), FS (MD = 2.63, 95%CI [2.04, 3.22]), SV (MD = 6.68, 95%CI [5.56, 7.80]), Cardiac Index (MD = 0.51, 95%CI [0.33, 0.70]), CO (MD = 0.68, 95%CI [0.38, 0.99]), NO (MD = 10.82, 95%CI [7.49, 14.15]), FMD (MD = 2.42, 95%CI [1.45, 3.39]), and NMD (MD = 2.13, 95%CI [1.04, 3.21]). Conversely, adjunctive GBS therapy significantly reduced the following parameters (all P < 0.01): LVEDD (MD = -5.71, 95%CI [-7.59, -3.82]), LVESD (MD = -6.30, 95%CI [-10.00, -2.59]), BNP (MD = -159.86, 95%CI [-199.17, -120.56]), NT-proBNP (MD = -529.13, 95%CI [-673.92, -384.33]), CRP (MD = -1.98, 95%CI [-2.25, -1.71]), hs-CRP (MD = -1.61, 95%CI [-2.66, -0.56]), TNF-α (MD = -20.42, 95%CI [-32.58, -8.26]), MMP-9 (MD = -34.76, 95%CI [-54.96, -14.56]), ET-1 (MD = -20.08, 95%CI [-30.18, -9.98]), SAS score (MD = -7.49, 95%CI [-11.43, -3.55]), SDS score (MD = -14.53, 95%CI [-17.26, -11.80]), HAMA score (MD = -4.48, 95%CI [-6.77, -2.20]), and HAMD score (MD = -5.79, 95%CI [-8.89, -2.68]). This systematic review suggests that adjunctive GBS therapy may be associated with improvements in surrogate cardiac function measures and patient-reported outcomes in patients with HF. However, these findings should be considered preliminary, as they are derived predominantly from low- and very low-certainty evidence, with no data on hard clinical endpoints such as mortality or hospitalization. Given these substantial limitations, the available evidence does not support the routine clinical use of GBS in HF management. Individualized application may be considered only in the context of shared decision-making and acknowledgment of the underlying evidence uncertainty. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251003193.
Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
The phase II ARROW study was designed to evaluate radioligand therapy (RLT) with 131I-LNTH-1095, an iodine-131-labeled small molecule targeting prostate-specific membrane antigen (PSMA), in combination with enzalutamide in subjects with metastatic castration-resistant prostate cancer after progression on prior abiraterone therapy. Men ≥18 years with PSMA-positive prostate cancer (PSMA PET tracer uptake >1× liver SUVmean in all CT-measurable lesions) were randomly assigned 2:1 to 131I-LNTH-1095 (4 cycles of 3.7 GBq/dose every 8 weeks) + enzalutamide (160 mg orally once daily) versus enzalutamide alone. The primary endpoint was PSA50 response. Secondary endpoints included radiographic progression-free survival (rPFS), objective response rate, overall survival (OS), and safety. Of 177 screened subjects, 120 were randomly assigned (80: 131I-LNTH-1095 + enzalutamide; 40: enzalutamide monotherapy). PSA50 response was 62.9% [95% confidence interval (CI), 50.5-74.1] for 131I-LNTH-1095 + enzalutamide versus 31.3% (16.1-50) for enzalutamide alone (P = 0.003). The median rPFS was 14.0 months (95% CI, 8.64-18.20) for 131I-LNTH-1095 + enzalutamide versus 11.5 months (2.79-18.43) for enzalutamide alone (P = 0.10). The incidence of grade ≥3 treatment-emergent adverse events (TEAE) was 65.8% for 131I-LNTH-1095 + enzalutamide versus 41% for enzalutamide monotherapy; the most frequent TEAEs were fatigue (75% vs. 53.8%), nausea (59.2% vs. 33.3%), thrombocytopenia (51.3% vs. 0%), and decreased appetite (48.7% vs. 17.9%), respectively. Two deaths in the 131I-LNTH-1095 + enzalutamide group were considered treatment-related. The study was not powered to detect rPFS and OS differences. 131I-LNTH-1095 + enzalutamide was associated with a statistically significant improvement in PSA50 response compared with enzalutamide alone despite a lower dosing schedule (4 cycles of 3.7 GBq/dose every 8 weeks) than the other approved PSMA RLT agents. Grade ≥3 adverse events were more frequent with combination therapy, particularly hematologic toxicity.