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The Cochrane database of systematic reviews · 2026
Friedreich ataxia (FRDA) is a rare inherited autosomal recessive neurological disorder, characterised initially by unsteadiness in standing and walking, and slowly progressing to wheelchair dependency, usually in the late teens or early twenties. Scoliosis, pes cavus and cardiomyopathy are often present at diagnosis. As the disease progresses, individuals usually develop slurred speech, auditory impairment (especially in a noisy environment), urinary tract morbidity, diabetes, anxiety, depression, muscle spasticity and visual disturbances. Cardiac abnormalities cause premature death in 60% of people with FRDA. There is no easily defined clinical or biochemical marker to assess progression and no known curative treatment. This is the third update of a review published in 2009 and updated in 2012 and 2016. To assess the effects of pharmacological treatments for people with Friedreich ataxia (FRDA) after 12 months of treatment. To identify studies for inclusion in this review, we searched CENTRAL, MEDLINE, Embase, CINAHL Plus, TRIP, Orphanet, WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov. We also checked reference lists of relevant studies and contacted study authors. The most recent search was on 4 February 2025. We were interested in randomised controlled trials (RCTs) and quasi-RCTs of pharmacological treatments (including vitamins) in people with genetically-confirmed FRDA. To be included in the review, studies had to last at least 12 months. We assessed the following outcomes after 12 months of treatment: change in score on a validated ataxia rating scale; change in interventricular septal thickness in diastole (IVSTd) by cardiac magnetic resonance imaging or echocardiogram; change in activities of daily living (ADL) using a validated questionnaire; change in upper limb dexterity; and change in cardiopulmonary exercise testing (CPET). We also assessed treatment-related adverse events with medication continued for the study period, and treatment-emergent adverse events leading to cessation of medication or death during the study period. Using the Cochrane risk of bias tool RoB 2, we assessed the risk of bias in the seven outcomes reported in our summary of findings tables. We synthesised the results of the studies for each outcome using meta-analysis, where possible. We calculated the mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and the risk ratio (RR) for dichotomous outcomes, all with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for our prespecified outcomes as high, moderate, low or very low. We included eight RCTs in this updated review. We included seven of them in meta-analysis, and these studies enroled a total of 574 participants, with sample sizes ranging from 29 to 232 participants per study. One study was international, with centres in North America, Europe and Australia. There were four other multicentre studies (three in Europe and one in North America). Single-centre studies were conducted in the UK, Italy and France. Participants in the studies ranged from eight to 70 years of age at enrolment, with the mean age in each study being between 18 years and 35 years (with an unweighted pooled mean age across studies of 25.9 years). All of the studies enroled both males and females, with the proportion of female participants ranging from 21% to 58%. Sixty-eight per cent of participants had severe ataxia, while the other 32% had moderate ataxia. The studies tested epoetin alpha, CoQ10 and vitamin E, idebenone, leriglitazone, omaveloxolone, and RT001. One study tested pioglitazone but has not published any results. Four of the studies were pharmaceutical-industry-controlled. Meta-analysis of seven studies demonstrated that pharmacological treatment probably makes little or no difference to scores on the ataxia rating scale after 12 months of treatment (SMD 0.02, 95% CI -0.23 to 0.26; I² = 42%; 7 studies, 513 participants; moderate-certainty evidence). The evidence was very uncertain about the effects of treatment on IVSTd (MD -0.51, 95% CI -1.10 to 0.09; I² = 80%; 2 studies, 72 participants; very low-certainty evidence) and on ADL (MD -0.59, 95% CI -1.39 to 0.21; I² = 24%; 3 studies, 167 participants; very low-certainty evidence). Meta-analysis of three studies showed that treatment probably improves upper limb dexterity (SMD -0.42, 95% CI -0.73 to -0.11; I² = 0%; 3 studies, 166 participants; moderate-certainty evidence). We are very uncertain about the effect of pharmacological treatment on CPET (SMD -0.16, 95% CI -0.46 to 0.13; I² = 0%; 3 studies, 181 participants; very low-certainty evidence). We are very uncertain whether pharmacological treatment has any effect on treatment-related adverse events (RR 0.88, 95% CI 0.63 to 1.22; I² = 0%; 2 studies, 104 participants; very low-certainty evidence). There were only 104 participants in this analysis out of a total of 545 participants, so the result may have little relevance. Meta-analysis of six studies found that there may be little to no difference between pharmacological treatment and placebo in treatment-emergent adverse events leading to cessation of medication or death (RR 1.24, 95% CI 0.44 to 3.48; I² = 0%; 6 studies, 313 participants; low-certainty evidence). Our certainty in the evidence ranged from very low to moderate. We downgraded all outcomes by one or two levels for imprecision, with further downgrades for inconsistency (for the outcomes of IVSTd, ADL, CPET) and suspected publication bias (for the outcomes of IVSTd, ADL, CPET and adverse events). In this updated Cochrane systematic review, meta-analysis of results on the ataxia rating scale showed that pharmacological treatments probably make little or no difference compared with placebo after 12 months of treatment. Given this result, the probable improvement that we found in upper limb dexterity was unexpected. Treatment-emergent adverse events leading to cessation of medication or death may be no more common in treatment groups than placebo groups as there were few adverse events detected in the treated groups. However, the studies may not have detected all rare and serious adverse events. The authors in this review received no funding. Protocol (2009) DOI: 10.1002/14651858.CD007791 Original review (2009) DOI: 10.1002/14651858.CD99791.pub2 Update (2012) DOI: 10.1002/14651858.CD007791.pub3 Update (2016) DOI: 10.1002/14651858.CD007791.pub4.
Nutrients · 2026
Background/Objectives: Dietary antioxidants are frequently utilized by breast cancer (BC) patients to mitigate treatment-related toxicities and enhance quality of life. However, their clinical efficacy remains highly controversial due to conflicting epidemiological and clinical data. This review aims to critically evaluate the molecular mechanisms, clinical outcomes, and translational challenges of antioxidant supplementation in BC management. Methods: A comprehensive evaluation of current literature-encompassing observational cohorts, randomized controlled trials, and mechanistic in vitro/in vivo models-was conducted. The analysis focused on the pharmacological interactions of diverse bioactive compounds (polyphenols, vitamins, carotenoids) with BC progression and standard antineoplastic regimens. Results: Current evidence demonstrates a paradoxical, double-edged role of antioxidants in oncology. While specific interventions (e.g., Coenzyme Q10, melatonin) effectively ameliorate treatment-induced toxicities without compromising therapeutic efficacy, the concurrent administration of antioxidants during cytotoxic chemotherapy can inadvertently neutralize essential reactive oxygen species (ROS), correlating with increased disease recurrence and mortality. Furthermore, clinical translation is severely hindered by the intrinsic hydrophobicity of natural compounds, the lack of whole-food matrix standardization, and dose-dependent hepatotoxicity. Emerging targeted delivery systems, such as lipid nanoformulations, show significant potential in overcoming these pharmacokinetic barriers. Conclusions: The therapeutic viability of antioxidant supplementation in BC is not universal; it is heavily dictated by intrinsic tumor biology, specific treatment modalities, and chronopharmacology. These findings underscore a critical biological imperative to transition from generalized dietary guidelines toward a rigorous paradigm of precision nutritional oncology, strictly avoiding concurrent antioxidant supplementation during active oxidative therapies.
Nutrients · 2026
Background/Objectives: Anabolic resistance is thought to underlie muscle loss in sarcopenia. Here, we investigated the adjuvant role of beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, on the acute muscle anabolic response to oral protein supplementation in older adults. Methods: A total of 24 community-dwelling older adults (68.5 ± 0.6 years; 13 men, 11 women) were randomized in a cross-over double-blind design to 40 g whey protein (Control) or 40 g whey protein with 3 g calcium-HMB (HMB). Subjects received a primed constant infusion of 13C6 phenylalanine to assess muscle protein synthesis (MPS, by tracer incorporation in myofibrils) and muscle protein breakdown (MPB, via arterio-venous dilution) at baseline and post supplementation. Fasted and 3 h fed-state plasma HMB, aminoacidemia, rates of MPS, MPB, limb and muscle blood flow were measured. Results: In all subjects, both interventions displayed significant increases in MPS in response to feeding [fasted to 3 h-fed change (mean ± SEM, standard error of the mean). Males: control, +0.032 ± 0.006%.h-1; HMB, +0.023 ± 0.004%.h-1; females: control, +0.023 ± 0.006%.h-1; HMB, +0.038 ± 0.006%.h-1, p < 0.05]. In older women, the addition of HMB further enhanced the MPS response (fasted to 3 h-fed change, p = 0.0495) and area under the curve (p = 0.0364) versus protein alone. During the late-fed period, MPB significantly decreased in HMB versus control (p = 0.0298), and this was also observed when subjects were separated by sex (p = 0.0012). Conclusions: High-dose protein bolus feeding increased MPS in older adults. Surprisingly, 40 g whey did not maximize the anabolic response in older women, and HMB further increased the MPS feeding response to protein. HMB further suppressed the MPB feeding response over a longer period of time. Further work is needed to understand the apparent sexual dimorphic MPS response to high protein.
Endocrinology, diabetes & metabolism · 2026
Orforglipron (OFG), an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1 RA), has demonstrated significant weight loss and glycemic benefits in adults with or without type 2 diabetes (T2DM). However, its gastrointestinal (GI), hepatic and pancreatic safety profile has not been systematically evaluated. This network meta-analysis aimed to assess GI adverse events (AEs), hepatic and pancreatic outcomes, and enzyme changes across different OFG doses. A frequentist network meta-analysis was conducted in accordance with the PRISMA guidelines. PubMed, Embase, Scopus and Web of Science (WOS) were searched for randomized controlled trials (RCTs) that assess the GI effects of OFG in adults with or without T2DM. We considered random-effects models to express treatment effects as odds ratios (OR) and mean differences (MD) with 95% confidence intervals (95% CI). RStudio software (version 4.5.1) was used for analysis. All OFG doses (3, 12, 24, 36 and 45 mg) increased GI AEs compared to placebo, with a clear dose-response trend. High-dose OFG (45 mg) markedly increased nausea (OR 11.48, 95% CI: 6.52-20.21), vomiting (OR 11.48, 95% CI: 6.52-20.21), diarrhoea (OR 3.99, 95% CI: 2.07-7.70) and discontinuation due to GI AEs (OR 10.22, 95% CI: 4.99-20.94). No dose increased pancreatitis risk (p > 0.05). Higher doses significantly reduced ALT, with the most significant reduction observed at 24 mg (MD -11.19 IU/L, 95% CI: -19.18 to -3.21). Doses ≥ 12 mg increased lipase (e.g., 24 mg: +28.52 IU/L, 95% CI: 12.02-45.01) and pancreatic amylase (45 mg: +18.20 IU/L, 95% CI: 9.49-26.91), without corresponding increases in clinical events. AST and ALP levels remained similar to those of the placebo. Subgroup analyses showed consistent effects in patients with or without T2DM. Oral OFG showed dose-dependent GI adverse effects over 26 weeks. Higher doses improve ALT and elevate pancreatic enzymes without clinical manifestations. The safety profile aligns with established GLP-1 RAs.
BMC psychiatry · 2026
Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are thought to be significant global contributors to the burden of mental illness. According to recent WHO epidemiological estimates, 3.9% of people worldwide have experienced PTSD at some point in their lives; this number rises to roughly 5.6% among those who have experienced trauma. NAC has shown promise in reducing PTSD symptoms and cravings in veterans, according to recent trials. Our analysis aims to resolve the conflict between results and determine whether NAC is an effective add-on therapy for PTSD, AUD, and co-occurring PTSD/AUD. We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, following our protocol (CRD420251170956). We searched PubMed, Scopus, Cochrane CENTRAL, Embase, EBSCO, and the Web of Science for relevant studies. Only randomized placebo-controlled trials were included. The primary outcomes were severity of PTSD and alcohol craving, while secondary outcomes were anxiety, depression, and alcohol use patterns and biomarkers. Seven randomized, double-blind, placebo-controlled trials were included in this meta-analysis, enrolling a total of 566 participants. There were no significant differences between NAC and placebo in craving (SMD= -0.40, 95% CI [-1.05, 0.25], P = 0.22, I² = 56.1%). Regarding PTSD severity, the PCL scale pooled analysis demonstrated no significant difference between NAC and placebo (SMD = 0.04, 95% CI [-0.40, 0.48], P = 0.8) (I² = 65.9%, P = 0.05), while the CAPS scale pooled analysis demonstrated no significant difference between NAC and placebo (SMD = -0.13, 95% CI [-0.50, 0.24], P = 0.49) (I² = 54.8%, P = 0.109). Leave-one-out sensitivity analysis showed that exclusion of the Back et al. (2025) study resulted in a significant effect favoring NAC (SMD = -0.35, 95% CI [-0.70, -0.01], P = 0.04), with no observed heterogeneity (I² = 0%). Our meta-analysis indicates that N-acetylcysteine, when compared to placebo, does not demonstrate consistent efficacy in reducing the primary symptoms of AUD or PTSD in broad patient populations. However, the treatment is relatively safe. A noteworthy signal of potential efficacy for PTSD symptoms emerged in a sensitivity analysis, suggesting that the therapeutic promise of NAC should not be entirely dismissed. Not applicable.
BMC pregnancy and childbirth · 2026
Poor pregnancy outcomes are still relatively high in developing countries. Deficiency in micronutrients is among the factors that play a role in developing adverse pregnancy outcomes. The present study aims to investigate the role of micronutrient deficiencies in poor pregnancy outcomes and their association with newborn health. For this review, a systematic search was done using the Harzing Perish and publish software, as well as separate searches in PubMed, Google Scholar, Web of Science, and Scopus for evidence on the association between maternal micronutrient status and/or micronutrient supplementation during pregnancy and adverse pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). We assessed heterogeneity using the I2 index, conducted the meta-analysis, and measured the overall effect size using the fixed-effect method. Overall, 49 articles were included in this systematic review, and 43 articles were included in the meta-analysis. Cumulative analysis of effect size showed that supplementation of vitamin D (d = 0.18), zinc (d = 0.39), iron with folic acid (d = 0.64) or multiple micronutrients (d = 0.059) plays positive role in reducing the risk of LBW and SGA. However, in all studies apart from iron with folic acid the effect of Multiple Micronutrient Supplementations (MMS) or other single micronutrient was assessed against the control group receiving iron with folic acid. Iron with folic acid showed the strongest and most consistent effect in reducing LBW and SGA; however, zinc, vitamin D, and multiple micronutrient supplementation were also associated with modest improvements in fetal growth outcomes. The topic and protocol were retrospectively registered in PROSPERO (ID: CRD42023451468).
Nutrients · 2026
Soccer aerial duels require rapid take-off, repeated-performance maintenance, and effective head-neck control under physically demanding conditions. This study examined the effects of caffeine (CAF), Rhodiola rosea (RHO), and their combination on repeated aerial duel performance and neck neuromuscular function in male collegiate soccer players. Ninety-six players were randomly assigned, in a double-blind, placebo-controlled, parallel design, to placebo control (CTR), RHO, CAF, or RHO + CAF groups (n = 24 each) for 4 weeks. CAF was acutely administered at 3 mg·kg-1 before testing, whereas RHO was chronically supplemented at 2.4 g·day-1. Outcome measures included countermovement jump height, early take-off impulse, repeated heading contact height, ball exit velocity, heading duel success rate, neck maximal voluntary isometric contraction, and session rating of perceived exertion (session-RPE). Significant group × time or group × repetition effects were observed for CMJ height (p = 0.0034), early take-off impulse (p = 0.0007), and post-intervention repeated heading contact height (p < 0.0001), with additional significant effects across heading-specific, neck strength, duel-success, and perceived-load outcomes. CAF was mainly associated with improved take-off-related explosive performance and duel success, whereas RHO was mainly associated with lower perceived exertion and better maintenance of heading contact height during the later repeated trials. Combined RHO + CAF supplementation produced the broadest pattern of benefits across explosive output, ball-contact performance, duel success, and multidirectional neck strength. These findings suggest that, in male collegiate soccer players, CAF and RHO may contribute differently to repeated aerial duel-related performance, and their combination may offer broader sport-specific benefits under repeated high-intensity demands.
Nutrients · 2026
Background/Objectives: Melatonin (MEL) promotes sleep and recovery, while caffeine (CAF) enhances alertness and performance. Despite their common use among athletes, their potential interaction remains underexplored. This study examined the effects of MEL and CAF, administered separately or in combination, on sleep, physical performance, physiological, biochemical, and perceptual responses in trained males. Methods: In a randomized double-blind placebo-controlled crossover study, fourteen trained males (22.4 ± 2.9 years) underwent four conditions, designed to isolate the effects of each substance and their interaction: (1) PLA + PLA: placebo before sleep and placebo in the morning; (2) PLA + CAF: placebo before sleep and caffeine (3 mg·kg-1) in the morning; (3) MEL + PLA: melatonin (6 mg) before sleep and placebo in the morning; and (4) MEL + CAF: melatonin before sleep followed by caffeine in the morning. One hour after the morning ingestion, participants performed the 5 m shuttle run test (5mSRT). Blood samples were collected pre- and post-exercise to assess markers of muscle damage (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) and inflammation (C-reactive protein). Peak heart rate (HRpeak) and rating of perceived exertion (RPE) were recorded throughout the test. Sleep was assessed only during the night following melatonin or placebo ingestion. Results: No differences were observed in sleep parameters between conditions (p > 0.05). Total distance in the 5mSRT increased following MEL + CAF and PLA + CAF conditions compared with PLA + PLA. Moreover, MEL + CAF reduced muscle damage and inflammation markers compared with PLA + PLA, MEL + PLA, and PLA + CAF conditions (p < 0.05). Conclusions: The ingestion of nocturnal MEL and next-day CAF was associated with improvements in certain high-intensity exercise performance outcomes, along with changes in muscle damage and inflammation.
Nutrients · 2026
The purpose of this study was to examine the effects of acute dietary nitrate (NO3-) and caffeine (CAF) supplementation on end power (EP) and work performed above EP (WEP) in trained male cyclists during a 3 min all-out test (3MT) on a cycle ergometer. Fifteen healthy, trained male cyclists (28.5 ± 5.3 years, 79.2 ± 9.1 kg, VO2peak 55.2 ± 5.6 mL·kg-1·min-1) completed four exercise trials in a randomized, double-blind, placebo-controlled, crossover study design separated by 3-7 days. The four experimental conditions were placebo beverage (nitrate-depleted) + placebo capsule, nitrate-rich beetroot juice + placebo capsule (BR), placebo beverage + caffeine capsule (CAF), and nitrate-rich beetroot juice + caffeine capsule (BR + CAF). Participants consumed nitrate-rich beetroot juice (~13 mmol NO3-) or nitrate-depleted placebo three hours before exercise, and caffeine (5 mg∙kg-1) or maltodextrin placebo one hour before testing. EP and WEP were determined from the 3MT. Secondary outcomes included peak and mean power output. Data were analyzed using a repeated-measures ANOVA with repeated measures on condition. A p-value of 0.05 was used to determine statistical significance. Effect size was evaluated using partial eta squared. No significant effect of condition was observed for EP (p = 0.401, ηp2 = 0.056), WEP (p = 0.580, ηp2 = 0.048), peak power (p = 0.642, ηp2 = 0.046), mean power (p = 0.212, ηp2 = 0.108), or total work (p = 0.217, ηp2 = 0.107). No statistically significant differences between conditions were detected under the conditions of the present study.
Biological trace element research · 2026
Metabolic Syndrome (MetS) is a complex disorder characterized by metabolic dysregulations. While chromium picolinate (CrPic) has shown beneficial effects on metabolic parameters, its comprehensive effects and safety in MetS patients remain unclear. This study aimed to investigate the effectiveness of CrPic supplementation on cardiometabolic indicators, DNA damage, and inflammatory markers in MetS patients. In this 12-week randomized, double-blind, placebo-controlled trial, 48 subjects with MetS (based on NCEP ATP III criteria) were randomized to receive either 400 µg CrPic daily (n = 24) or placebo (n = 24). Primary outcomes included glycemic control (fasting blood sugar, HbA1c), lipid profile, DNA damage index (8-hydroxydeoxyguanosine), and inflammatory markers (tumor necrosis factor-α (TNF-α) level and gene expression). Secondary outcomes were anthropometric measures and blood pressure. Forty participants (20 in each group) completed the study. CrPic supplementation significantly improved HbA1c (-0.68%, P = 0.005), HDL-c (+ 4.8 mg/dl, P = 0.008), and SBP (-4.8 mmHg, P = 0.012). After adjusting for confounding factors, improvements in HbA1c (-0.07 ± 0.02%, P = 0.001) and SBP (-8.84 ± 3.57 mmHg, P = 0.019) remained significant compared to placebo. CrPic showed no adverse effects on DNA damage markers or inflammatory cytokine expression. CrPic supplementation appears to be a safe intervention that can modestly improve glycemic control, HDL-c levels, and blood pressure in MetS patients. While these improvements were statistically significant, achieving clinically meaningful changes may require optimization of dosage and intervention duration.
Oecologia · 2026
Leersia hexandra, a perennial grass widely distributed in rice agroecosystems, presents a striking ecological paradox. It is simultaneously recognized as an asymptomatic reservoir for Xanthomonas spp. the causal agent of Bacterial Leaf Blight (BLB), and as a potent ecoremediation agent capable of hyperaccumulating heavy metals such as chromium. This hypothesis-driven systematic review, conducted in accordance with PRISMA guidelines, addresses this dual identity by integrating findings from phytopathology and environmental sciences through the lens of the cross-tolerance hypothesis. We propose that the physiological mechanisms enabling tolerance to chronic abiotic stress also modulate the plant's interaction with biotic pathogens. Based on a synthesis of 30 primary studies, we suggest that the physical traits of L. hexandra (e.g., iron plaque formation) and its internal biochemical defenses, primed by long-term abiotic exposure, may create a tightly regulated host-pathogen equilibrium. This containment does not eliminate the pathogen but may allow sustained, asymptomatic colonization, positioning L. hexandra as a potential cryptic reservoir. The very traits that enable pollutant remediation may inadvertently facilitate pathogen survival, rendering this species a persistent "green bridge" for BLB epidemics. These findings highlight the need for integrated management strategies that reconcile environmental resilience with disease risk and invite experimental validation of the proposed framework.
International journal of implant dentistry · 2026
This pilot randomized clinical trial compared peri-implant tissue health around milled cobalt-chromium (CoCr) versus polyether ether ketone (PEEK) secondary telescopic crowns in implant-retained mandibular overdentures over 12 months.  Twelve completely edentulous patients received two implants each. After randomization, secondary crowns were fabricated from milled CoCr (n = 6 patients) or PEEK (n = 6 patients). Assessor-blinded outcome assessments such as marginal bone loss (MBL), probing depth (PD), and plaque index (PI) were performed at baseline, 6, 9, and 12 months post-loading. Statistical analysis used the patient as the unit of analysis.  No statistically significant inter-group differences were found at any time point. At 12 months, mean MBL was 0.48 ± 0.15 mm for CoCr and 0.45 ± 0.16 mm for PEEK (p = 0.735). PD increased over time within groups but remained comparable between groups (CoCr: 2.58 ± 0.58 mm, PEEK: 2.33 ± 0.41 mm at 12 months; p = 0.411). PI scores also showed no significant inter-group differences (p > 0.05).  Over 12 months, milled PEEK and CoCr secondary telescopic crowns demonstrated comparable peri-implant tissue health. PEEK presents a viable metal-free alternative for this application. These preliminary findings warrant confirmation in larger, long-term studies.
Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026
Nicotinamide (NAM) and Polypodium leucotomos extract (PL) have demonstrated photoprotective effects, but their role in preventing UVA-induced DNA damage in humans remains unclear. To evaluate the effects of oral NAM and PL on UVA-induced erythema and thymidine dimer (TT-dimer) formation. In this intraindividual trial, 50 healthy volunteers (phototypes I-III) were randomized (1:1) to receive either NAM (2000 mg daily) or PL (Heliocare Advanced: 480 mg daily) for 30 days. UVA-induced erythema, assessed by minimal erythema dose (MED), and TT-dimers, quantified in urine and skin biopsies, were measured before and after treatment with NAM or PL. Both NAM and PL increased MED by 26%. With a median MED of 27.7 J/cm² (13.4-51.1 J/cm²) pre-NAM and 34.8 J/cm² (13.4-62.5 J/cm²) post-NAM (p = 0.0008). And A median MED of 27.7 J/cm² (13.4-51.1 J/cm²) pre-PL and 34.8 J/cm² (16.4-62.5 J/cm²) post-PL (p = 0.0002). Neither treatment reduced UVA-induced TT-dimers in skin (NAM: p = 0.15; PL: p = 0.15) or urine (NAM: p = 0.89; PL: p = 0.30). NAM and PL were not administered during the urine collection-period, which limited the assessment of the treatment's effect after radiation. UVA-induced erythema was significantly reduced by PL and NAM, but neither had measurable effects on TT-dimer induction. Further research should investigate the relation between these findings and the chemopreventive effect of NAM and PL on skin cancer.
Journal of cosmetic dermatology · 2026
Xerosis cutis is characterized by impaired epidermal barrier function, increased transepidermal water loss (TEWL), reduced hydration, and symptoms such as pruritus. To evaluate the efficacy, tolerability, and subjective perception of a topical formulation containing panthenol, niacinamide, and dipotassium glycyrrhizate in improving skin hydration and barrier function in subjects with dry, sensitive skin. In this randomized, intra-individual, split-leg clinical trial, subjects with xerosis applied the test emollient twice daily for 28 days to one pretibial area. The contralateral leg remained untreated as control. Assessments were performed at baseline (T0), 30 min, 24 h, 48 h, day 7 and day 28. Primary outcomes were corneometric stratum corneum hydration and TEWL. Secondary outcomes included deep skin conductance ("deep moisturization"), desquamation index, surface microrelief regularity (SEr), scaliness (SEsc), dermatologist-rated clinical signs, and participant self-assessment. Thirty-five participants (31 women; mean age 47.3 ± 2.0 years) were included. Compared with baseline (hydration: 21.3 ± 1.0 c.u., 95% CI: 19.3-23.3; TEWL: 9.2 ± 0.3 g/h/m2, 95% CI: 8.6-9.8) and untreated control, the treated leg showed greater corneometric hydration at all time points: 66.2% (33.9 ± 1.4 c.u., 95% CI: 31.1-36.7) at day 7 and 74.1% (35.2 ± 1.2 c.u., 95% CI: 32.8-37.6) at day 28 (all p < 0.001). TEWL decreased by 11.3% (8.2 ± 0.2 g/h/m2, 95% CI: 7.8-8.6) and 13.5% (7.9 ± 0.2 g/h/m2, 95% CI: 7.5-8.3), respectively (all p < 0.05). Deep moisturization increased by 5.7% (39.5 ± 0.9 μS at day 7, 95% CI: 37.7-41.3) and 7.3% (41.1 ± 0.8 μS at day 28, 95% CI: 39.5-42.7) (p < 0.05). The desquamation index decreased by 13.0% (29.50% ± 1.67% at day 7, 95% CI: 26.1-32.9) and 15.8% (26.77% ± 1.25% at day 28, 95% CI: 24.2-29.3), SEr increased by 46.9% (3.38 ± 0.15 a.u. at day 7, 95% CI: 3.08-3.68) and 54.2% (3.47 ± 0.15 a.u. at day 28, 95% CI: 3.17-3.77), and SEsc decreased by 67.0% (0.81 ± 0.12 a.u. at day 7, 95% CI: 0.57-1.05) and 76.3% (0.51 ± 0.07 a.u. at day 28, 95% CI: 0.37-0.65), respectively (all p < 0.05). Dermatologist assessments at all time points showed significant clinical improvement in dryness and pruritus in all participants (p < 0.001). Complete resolution was observed in all participants according to the 5-point scale, though this may reflect a floor effect given mild baseline scores. The topical formulation appeared to be an effective and well-tolerated emollient; however, the absence of a vehicle control precludes attribution of effects specifically to the active ingredients. Patient-reported outcomes should be interpreted with caution due to the unblinded design.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
Iron deficiency, with or without anemia, remains a major public health concern among young children in Myanmar. While iron supplementation is widely recommended, its potential adverse effects on growth and gut microbiota warrant investigation, particularly in contexts of poor complementary feeding. To assess the effects of iron supplementation, with or without complementary feeding recommendations (CFRs), on micronutrient status, linear growth and gut microbiota composition among Myanmar children aged 12-23 months, a 24-week randomized controlled trial was conducted in Ayeyarwady Region of Myanmar. Fourteen clusters (villages/wards) were randomized to receive CFRs or not, and children within the clusters were randomized to receive daily aqueous iron or placebo, creating four arms: Placebo (n = 104), CFR (n = 112), Fe (n = 105) and CFRFe (n = 112) totalling 433 children. All intervention groups (CFR, Fe, CFRFe) improved haemoglobin and reduced anaemia risk compared with Placebo (AOR = 0.31 (0.15-0.62), 0.15 (0.07-0.32), 0.14 (0.07-0.31), respectively). CFR and CFRFe also improved zinc status. However, iron-alone (Fe) increased the stunting risk (AOR= 2.74 (1.04-7.23)), while CFRFe did not. No significant effects were observed on gut microbiota composition. Aqueous iron supplementation may impair linear growth when diets are not optimized; combining supplements with optimized complementary feeding may support healthier outcomes. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.
International journal of molecular sciences · 2026
Coronary artery disease (CAD), including acute coronary syndromes, frequently co-occurs with depression and is associated with adverse outcomes. Trace elements may influence shared biological pathways, including oxidative stress, inflammation, and neurovascular signaling. This study evaluated the association between trace element status and depressive symptoms in CAD. A systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251231129). PubMed, Scopus, and the Cochrane Library were searched from inception to 2 December 2025. Studies assessing trace element concentrations in adults with CAD and depressive symptoms were eligible. Due to limited direct evidence, partially aligned and indirect studies were also included. Data were synthesized narratively. Of 699 records, four studies were included. No studies fulfilled Tier 1 criteria. The available evidence consisted of partially aligned (Tier 2) and indirect (Tier 3) studies. Lower zinc and magnesium levels and higher copper concentrations were suggested to be associated, based exclusively on Tier 2-3, low-certainty, predominantly indirect evidence. Interventional studies reported modest improvements following zinc or combined magnesium and zinc supplementation, although not in CAD-specific populations. Evidence directly addressing trace elements and depression in CAD is extremely limited and largely indirect. Current data do not support causal inference or clinical recommendations. Findings should be considered exploratory and hypothesis-generating.
Nutrients · 2026
Background: Nutritional psychiatry increasingly links diet quality and specific bioactive nutrients to depression and anxiety outcomes. Mechanistic evidence implicates neuroimmune activation, inflammation, altered neurotransmitter synthesis, and microbiota-derived metabolites. Objective: The objective of this study is to synthesize evidence on omega-3 polyunsaturated fatty acids (n-3 PUFAs), the microbiota-gut-brain axis, and vitamins and minerals that influence neurotransmitter synthesis, inflammation, and brain function and to translate these findings into food-based strategies. Methods: This study consisted of a focused synthesis of randomized controlled trials (RCTs), meta-analyses, and systematic reviews indexed in PubMed, Scopus and Web of Science, selected for relevance to omega-3s, probiotics/prebiotics, dietary patterns, and micronutrients (folate/B-vitamins, vitamin D, magnesium, zinc, and vitamin C/copper pathways). Results: RCT and meta-analytic evidence suggest modest benefits of omega-3 supplementation for anxiety severity and depressive symptoms, with heterogeneity by dose, EPA: DHA composition, and baseline inflammatory status. The gut-brain axis literature supports bidirectional effects of stress and microbiota, and meta-analyses of probiotics/prebiotics show small improvements in depressive and anxiety symptoms, likely dependent on strain and host phenotype. Micronutrients serve as enzymatic cofactors for monoamine and GABA synthesis and modulate immune signaling; clinical effects are the most consistent when correcting insufficiency or in biomarker-defined subgroups. A whole-diet RCT demonstrates that structured dietary improvement can reduce depressive symptoms as adjunctive therapy. Conclusions: A food-first approach emphasizing Mediterranean-style dietary patterns, omega-3-rich seafood, a diverse array of fiber, and micronutrient density is the most defensible. Supplementation may be considered selectively, guided by clinical context and nutritional status.
Nutrients · 2026
Background/Objectives: Oral iron supplementation is widely used to treat iron deficiency but frequently causes gastro-intestinal side effects that limit treatment adherence. Unabsorbed luminal iron has been proposed to influence intestinal microbial communities, yet the effects of different oral iron doses on the human gut microbiome remain insufficiently characterized. Methods: In this randomized open-label study, 30 healthy premenopausal women with iron deficiency without anaemia received either low-dose oral iron supplementation (6 mg twice daily) administered under fasting conditions or standard-dose iron supplementation (100 mg once daily) taken with a meal for four weeks. Stool samples were collected before and after treatment and analyzed using 16S rRNA sequencing to evaluate microbiome composition. Results: Baseline characteristics, including age, body mass index, hemoglobin concentration and serum ferritin, were comparable between groups. After four weeks of treatment, distinct alterations in gut microbiome composition were observed between the low-dose and standard-dose groups. The genera Colidextribacter and GCA-900066575 decreased in the low-dose group but increased in the standard-dose group, whereas Oscillospira showed the opposite pattern. Gastrointestinal adverse events were reported by 87% of participants receiving standard-dose iron supplementation compared with 7% receiving low-dose iron supplementation (p < 0.0001). Conclusions: Oral iron supplementation induces dose-dependent changes in the intestinal microbiome and higher doses are associated with substantially increased gastrointestinal intolerance. These findings suggest that lower iron doses may reduce microbiome disruption and improve treatment tolerability.
Inflammopharmacology · 2024
This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be due to the limited trials that are available on the combination of the sulfate forms of the intervention. Hence, there is a scope for conducting multicentric randomised controlled trials to evaluate and conclude the therapeutic role of CS and GS combination in the management of KOA.
Explore (New York, N.Y.) · 2026
Amiodarone, widely used in arrhythmia management, often causes phlebitis when administered via peripheral infusion. This study evaluated the effects of Nigella sativa oil and sesame oil in preventing amiodarone-induced phlebitis. The study was a randomized controlled trial with three parallel groups. This study included 108 patients who received amiodarone infusion in the coronary intensive care unit between November 2023 and August 2024. This three-arm, block-randomized controlled trial was conducted in line with CONSORT guidelines. Patients were randomly assigned to one of three groups: sesame oil (n = 36), Nigella sativa oil (n = 36), or control (n = 36). In the intervention groups, five drops of the respective oil were applied topically to a 10-cm area around the catheter site. The application was performed once before the infusion and then every 6 hours thereafter. The control group received no intervention. Patients were monitored hourly during the 26-hour infusion and every six hours for 48 hours after the infusion, for a total monitoring period of 74 hours. Phlebitis was assessed using the Visual Infusion Phlebitis Scale. This study was prospectively registered on ClinicalTrials.gov (NCT06030141) on November 15, 2023. Phlebitis was observed in 25% of patients in the sesame oil group, 33.3% in the Nigella sativa oil group, and 80.6% in the control group. A significant difference in phlebitis severity was observed between the groups (p < 0.001), with the highest severity in the control group, the lowest in the sesame oil group, and moderate levels in the Nigella sativa oil group. This study demonstrated that sesame and Nigella Sativa oils were effective in both preventing and reducing the severity of amiodarone-induced phlebitis. The use of sesame oil and Nigella sativa oil in peripheral intravenous catheter care may help reduce amiodarone-induced phlebitis, maintain vascular access integrity, and improve patient comfort. As natural, safe, and cost-effective agents, these oils can be readily incorporated into clinical nursing practice to enhance patient safety and quality of care.