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One-carbon metabolism and chemotherapy-induced toxicities in patients with stage II-III colorectal cancer: a prospective cohort study.

BACKGROUND: One-carbon metabolism (OCM) is a target of the chemotherapeutic agent capecitabine. OBJECTIVES: We investigated OCM biomarker concentrations in relation to capecitabine-induced toxicities in patients with stage II-III colorectal cancer. METHODS: Within a prospective cohort, 297 patients receiving adjuvant capecitabine-based chemotherapy were included. Pretreatment plasma concentrations of the OCM biomarkers folate, vitamin B2, vitamin B6, vitamin B12, total homocysteine, methionine, serine, and glycine were determined. We also investigated whether associations differed according to methylenetetrahydrofolate reductase (MTHFR) C677T genotypes. Chemotherapy-induced toxicities were defined as toxicity-induced modifications of capecitabine treatment. To allow for inspection of shapes of the associations, restricted cubic splines and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and sex. RESULTS: In total, 156 (53%) patients experienced toxicity-induced modifications of capecitabine treatment. Folate was not associated with toxicities in the overall population. Higher folate concentrations were associated with a lower risk of toxicities in patients with MTHFR C677T CT/TT genotype (HRperdoubling: 0.75; 95% CI: 0.57, 0.98) but not in patients with CC genotype (HRperdoubling: 1.17; 95% CI: 0.84, 1.63). Higher concentrations of vitamin B2 were associated with a lower risk of toxicities (HRperdoubling: 0.81; 95% CI: 0.67, 0.99), whereas higher glycine concentrations were associated with a higher risk of toxicities (HRperdoubling: 1.87; 95% CI: 1.18, 2.94). The association between vitamin B6 and vitamin B12 and toxicities appeared nonlinear. Homocysteine, methionine, and serine were not associated with toxicities. CONCLUSIONS: Future studies investigating whether nutrition-guided optimization of OCM biomarkers will result in improved treatment tolerance are warranted.

Humans

Sugar rationing during the first 1000 days and early onset cancer: a natural experiment.

BACKGROUND: The "first 1000 days" of life is a critical window for metabolic programming, while the long-term oncological consequences of nutritional exposures during this period remain understudied. OBJECTIVES: We aimed to evaluate whether restricted sugar intake in utero and during early childhood reduces risk of early onset cancer diagnosis and mortality in adulthood, utilizing a natural experiment. METHODS: We analyzed 63,819 United Kingdom Biobank participants born between October 1951 and March 1956, spanning the end of United Kingdom sugar rationing (September 1953). Leveraging a quasi-experimental birth cohort design, we compared participants exposed to sugar rationing in utero and during infancy with those unexposed. Early onset cancer incidence (&#x2264;50 y) and mortality were ascertained via integrated national Cancer Registry and hospital inpatient records. Multivariable Cox proportional hazards models (including Gompertz distribution) were used to estimate hazard ratios (HRs), with exploratory site-specific analyses. RESULTS: Among 63,819 participants (56.3% female), 40,397 were exposed to rationing and 23,422 were unexposed. Early life sugar restriction significantly reduced early onset cancer risk (HR: 0.66; 95% confidence interval: 0.53, 0.81; P < 0.001). A dose-response relationship was observed, with peak protection in individuals exposed for &#x2264;24 mo postnatally. This protection was observed systemically across solid tumors, independent of specific cancer sites. Specificity was corroborated by null associations with negative controls (herpes zoster and cataract). No significant difference was found for cancer-specific mortality. CONCLUSIONS: Restricting sugar intake during the first 1000 days is associated with a reduced risk of early onset cancer, extending the disease-free lifespan. The divergence between reduced incidence and unchanged mortality suggests early life metabolic environments primarily influence tumor latency rather than biological aggressiveness. These findings highlight the potential long-term public health implications of early life dietary guidelines against the rising burden of early onset cancer.

Humans

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p&#xa0;<&#xa0;0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p&#xa0;=&#xa0;0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans

The relationship between food intake and outdoor temperature in a longitudinal study: a public health perspective in the context of global warming.

BACKGROUND: Climate change affects human health and nutrition. Rising temperatures may significantly impact diets, but research on their influence on dietary habits in large populations remains limited. OBJECTIVES: We aimed to study the link between outdoor temperature and energy-adjusted food consumption across profiles in a longitudinal study. METHODS: This study included 100,851 participants from the NutriNet-Sant&#xe9; study (2009-2023) with 1,716,046 24-h dietary records linked to daily maximum outdoor temperature at the residence, from the nearest M&#xe9;t&#xe9;o-France station. Associations were analyzed using linear mixed models with interactions tested for sex and 6 socioeconomic profiles (employees, privileged, intermediate, young, disadvantaged, and retirees) derived from clustering. RESULTS: Across all subgroups, higher outdoor temperature was associated with higher consumption of fruits, vegetables, processed meats, sweet products, water, alcoholic beverages, and sugar-sweetened beverages, whereas consumption of red meat, pulses, and dairy products decreased. From 25&#xb0;C to 35&#xb0;C, the increase in alcohol consumption with temperature was more pronounced in males {150 g/d [95% confidence interval (CI): 147 g/d, 153 g/d] to 166 g/d [95% CI: 162 g/d, 171 g/d], +11%} than in females [101 g/d (95% CI: 98 g/d, 103 g/d) to 107 g/d (95% CI: 104 g/d, 109 g/d), +6%]. Across socioeconomic profiles, changes shared similar directions, but some trends were more marked, notably for alcoholic beverages among employees (95% CI: 114 g/d, 130 g/d; +14%) and sugar-sweetened beverages in young (95% CI: 56 g/d, 72 g/d; +29%). Consumption of fruits increased more modestly in the young (95% CI: 227 g/d, 248 g/d; +9%) than in employees (95% CI: 194 g/d, 227 g/d; +17%). These changes, although variable in magnitude, were not accompanied by substantial modifications in energy intake or overall diet quality scores. CONCLUSIONS: These results emphasize the importance of targeted prevention messages when temperatures exceed 25&#xb0;C, especially concerning alcoholic and sugar-sweetened beverages, and offer insight into potential long-term food consumption patterns (beyond seasonal changes) in the context of global warming.

Humans

Childhood Economic Mobility and Systemic Inflammation Among Men Who Experienced Low Income in Toddlerhood: The Moderating Role of Trait Hostility.

OBJECTIVE: Childhood economic upward mobility (ie, increases in family income across childhood) may attenuate links between childhood poverty and systemic inflammation in adulthood, the extent of which may vary depending on inter-individual differences in personality characteristics, including hostility. METHODS: Men who experienced low income in toddlerhood (N=171) were followed prospectively into adulthood. Annual family income was collected 12 times when men were 1.5 to 17 years old. Men completed the Cook-Medley Hostility Scale and had their fasting blood drawn to measure circulating levels of C-reactive protein (CRP) at age 32. Multiple linear regression analyses examined main and moderation effects of childhood economic upward mobility and adult hostility on CRP levels adjusting for income at 1.5 years, race, parent educational attainment, and adult income, education, waist circumference, and smoking status. RESULTS: Main effects were nonsignificant, but an interaction effect emerged. Counter to expectations, childhood economic upward mobility related to greater adult CRP as trait hostility decreased ( &#x3b2; =-0.203, P =.018). Simple slope analyses further revealed that childhood economic upward mobility was positively associated with CRP among men lower in hostility ( &#x3b2; =0.23, SE=0.09, P =.020) but was unrelated to CRP among men higher in hostility. Results of post hoc sensitivity analyses are also discussed. CONCLUSIONS: Counterintuitive findings suggest that for men who experience poverty in toddlerhood, the association between childhood economic upward mobility and adult CRP may be nuanced and even in the positive direction for men low in hostility, which aligns with work on unintended health consequences of upward mobility.

Humans

Effects of cinnamon supplementation combined with exercise training on anthropometric indices and reproductive hormones in overweight and obese women.

BACKGROUND: The prevalence of obesity and increased fat in the chest and abdomen in women and hormonal changes, can affect female fertility. The present study aims to investigate the effect of exercise training combined with cinnamon supplementation on chest and abdominal circumference, as well as sex hormones, in overweight and obese women. METHODS: Twenty-six inactive overweight and obese women were randomly allocated to an exercise (E; n = 13) and exercise plus cinnamon supplementation (E+S; n = 13) group. Both groups completed a 4-week exercise program three times weekly, while the E+S group additionally received cinnamon supplementation three times weekly. Chest and abdominal circumferences and serum concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed before and after the intervention. RESULTS: Significant pre-to-post reductions in chest and abdominal circumference were observed in both groups (all p &#x2264; 0.005). Estradiol, progesterone, and FSH concentrations increased, whereas LH concentrations decreased significantly in both groups (all p &#x2264; 0.005). However, between-group comparisons revealed a significant difference only for chest circumference (p = 0.003), with no significant group differences in abdominal circumference or any reproductive hormone concentration (all p > 0.05). CONCLUSION: Both groups showed favorable changes in anthropometric and reproductive hormone measures following the 4-week study period. However, the significant between-group difference was limited to chest circumference, providing no clear evidence that cinnamon supplementation conferred additional benefits for abdominal circumference or reproductive hormone profiles beyond those observed with exercise. These findings highlight the potential relevance of exercise-based interventions while warranting confirmation in larger, adequately powered trials.

Humans

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPAR&#x3b1;, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPAR&#x3b1; expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

Animals

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1&#x3b1; axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans

Creatine formulations and repeated sprint training: effects on physical and physiological adaptations in soccer players during the short-term preparation phase.

BACKGROUND: This research examined the impact of various creatine (Cr) supplementation formulations during a 4-week preparatory phase on the efficacy of repeated sprint training (RST) and on improvements in physical and physiological performance in male soccer athletes. METHODS: A total of forty collegiate young soccer players volunteered for the study. They were randomly divided into four groups: creatine monohydrate (Cr-Mon, n&#x2009;=&#x2009;10), creatine ethyl ester (Cr-Ee, n&#x2009;=&#x2009;10), creatine hydrochloride (Cr-Hcl, n&#x2009;=&#x2009;10), and placebo (PL, n&#x2009;=&#x2009;10). All athletes engaged in a 4-week training intervention, three times a week (i.e. 12 sessions), and physical (countermovement vertical jump [CMVJ], 20-m sprint, and L-run) and physiological (Wingate anaerobic power and incremental exercise tests) performance were assessed both before and after the training period. RESULTS: All training groups improved physical and physiological performance following the 4-week intervention period (p&#x2009;<&#x2009;0.05). Additionally, the groups receiving the Cr supplement exhibited significantly greater changes (p&#x2009;=&#x2009;0.001) in physical performance, peak power output, and fatigue index compared to the PL group. However, no significant differences were found among the groups regarding mean power output and VO2max. Notably, the Ee and Hcl forms of Cr showed superior gains (p&#x2009;<&#x2009;0.05) in physical performance and peak power compared to the Mon form after the 4-week intervention. CONCLUSIONS: The results underscore the importance of Cr ingestion in enhancing adaptations for short-term physical performance tasks, highlighting the effectiveness of the Ee and Hcl forms in further improving the CMVJ, 20-m sprint, L-run, and peak power among soccer players during the short-term preparation phase.

Humans

Ketamine Plus Midazolam versus Fentanyl Plus Midazolam for Sedation and Analgesia during Image-guided Procedures in Interventional Radiology: Randomized Clinical Trial.

Background Opioid-benzodiazepine regimens remain common for radiologist-administered procedural sedation despite respiratory and analgesic effectiveness concerns. Purpose To compare intraprocedural pain and patient-reported experience between ketamine/midazolam and fentanyl/midazolam during image-guided procedural sedation. Materials and Methods This randomized clinical trial was conducted at a single academic center between June 2025 and February 2026. Adults undergoing image-guided lung or bone biopsy or abscess drainage were randomized to fentanyl/midazolam or ketamine/midazolam administered by interventional radiologists. Procedures were performed using US, CT, CT fluoroscopy, or combined CT and US guidance. The primary outcome was maximum intraprocedural pain (0-10 on the Numeric Rating Scale). Secondary outcomes included sedation depth, physiologic parameters, oxygen desaturation, patient-reported experience assessed using a modified Heidelberg questionnaire, and complications. Results Among 264 randomized procedures (132 procedures per group) in 260 participants (median age, 68 years [IQR, 61-75 years]; 135 [52%] female), ketamine/midazolam resulted in lower maximum intraprocedural pain than fentanyl/midazolam (mean difference, -1.4 points [95% CI: -2.0, -0.8]; P < .001). Pain scores greater than 4 occurred less frequently with ketamine/midazolam (2.3% vs 17%; absolute difference, 14 percentage points [95% CI: 8, 21]; P < .001). Ketamine/midazolam was associated with higher nadir oxygen saturation (mean difference, +1.4% [95% CI: 0.6, 2.2]; P = .001) and fewer oxygen desaturation events below 90% (three [2.3%] vs 13 [9.8%]; absolute difference, 7.6 percentage points [95% CI: 1.9, 13.3]; P = .02). Ketamine/midazolam produced deeper sedation and higher intraprocedural systolic blood pressure. Hallucinations occurred more frequently with ketamine/midazolam (15 [11.4%] vs five [3.8%]; absolute difference, 7.6 percentage points [95% CI: 1.3, 13.9]; P = .03), though overall procedural comfort, reduced recall, and perceived adequacy of sedation were improved. Procedure-related and sedation-related complications did not differ between groups. Conclusion Radiologist-administered ketamine/midazolam during image-guided procedural sedation improved analgesia and patient-reported experience with fewer hypoxemic events and no increase in complications compared with fentanyl/midazolam. Clinical trial registration no. NCT07040163

Aged

A 12-week, double-blind, quasi-randomized, placebo-controlled study to evaluate the efficacy and safety of Coleus forskohlii (Forcslim) on body weight loss.

BACKGROUND: Overweight and obesity have emerged as a global epidemic, significantly impacting human health. Traditional usage and growing scientific evidence suggest that Coleus forskohlii extract (Forcslim) may aid in reducing excess body weight and fat. This study aimed to evaluate the efficacy and safety of Forcslim supplementation in overweight individuals. METHODS: A quasi-randomized, double-blind, placebo-controlled clinical trial was conducted in 60 overweight subjects aged 20-70&#x2009;years over a period of 12&#x2009;weeks. The participants were assigned to receive either Forcslim or placebo. The key outcome measures included body weight, body mass index (BMI), body composition, and anthropometric parameters. Additionally, lipid profile parameters and safety markers (including metabolic, hepatic, and cardiovascular indicators) were assessed throughout the study duration. RESULTS: Compared to the placebo group, the Forcslim group showed significant reductions in waist circumference (-1.83&#x2009;cm; p&#x2009;<&#x2009;0.01) and body weight (-1.93&#x2009;kg; p&#x2009;<&#x2009;0.001). Significant improvements in anthropometric parameters were observed exclusively in the Forcslim group. Furthermore, triglyceride (TG) levels were significantly reduced (p&#x2009;<&#x2009;0.01), while high-density lipoprotein (HDL) levels showed a significant increase (p&#x2009;=&#x2009;0.001). No clinically significant changes were observed in metabolic markers, liver and muscle enzyme levels, heart rate, blood pressure, or reported adverse effects, indicating a favorable safety profile. CONCLUSIONS: Forcslim demonstrated significant anti-obesity effects, including reductions in body weight, waist circumference, and improvements in the lipid profile. These findings suggest that C. forskohlii extract supplementation may serve as a safe and effective alternative to synthetic anti-obesity drugs.

Humans

Immunomodulatory effects of palm-derived tocotrienol-rich fraction in healthy volunteers following influenza vaccination: A randomised clinical trial.

Most studies on vitamin E and immunity have focused on tocopherols, but the tocotrienol-rich fraction (TRF) from palm oil may exert stronger immunomodulatory effects. This study investigated the effect of various TRF doses on the immune response to influenza immunisation in healthy adults. We hypothesized daily supplementation with lower doses of TRF can boost immune response to the influenza vaccine in healthy Individuals. In a double-blind placebo-controlled trial, 150 participants (&#x2265;18 years) were randomised to receive placebo or TRF (50, 100, 200, or 400 mg) daily for 2 months, with vaccination on day 28. Blood samples collected on days 0, 28, and 56 were analyzed for humoral and cellular immunity, antioxidant status, and plasma concentrations of vitamin E. TRF significantly augmented anti-influenza antibody production across all doses, with the 400 mg group exhibiting the highest titers. A selective Th1-type immune response was observed, characterized by significant IFN-&#x3b3; production upon restimulation in all TRF-supplemented groups compared with placebo. Plasma IL-12 was elevated in the highest dose, whereas the amount of EBI3 produced increased across a broader range of doses compared to placebo. TRF supplementation was associated with increased antioxidant enzyme activities and stable malondialdehyde activity. Elevated &#x3b1;-tocopherol concentrations observed, primarily at higher doses. Supplementation with TRF can enhance immune response to influenza immunisation by modulating humoral, Th1 responses and improving antioxidant status. Critically, antibody production increased similarly across all TRF doses, suggesting that lower doses may offer a cost-effective strategy for supporting humoral immunity, while higher doses provide broader immunomodulatory benefits.

Humans

A GRADE-assessed systematic review and meta-analysis of randomized controlled trials evaluating the effects of olive leaf or olive pomace supplementation on cardiometabolic and anthropometric health markers.

AIMS: Cardiometabolic diseases (CMDs) are major contributors to global morbidity and mortality, and dietary bioactives such as polyphenols may modulate key risk factors. Olive by-products, particularly olive leaves (OL) and olive pomace (OP), are rich in phenolic compounds with antioxidant, anti-inflammatory, and cardiometabolic effects demonstrated across in vitro, preclinical, and clinical studies. DATA SYNTHESIS: This GRADE-assessed systematic review and meta-analysis included 30 randomized controlled trials (n&#x202f;=&#x202f;1726) evaluating OL or OP supplementation on 21 standardized biomarkers, encompassing inflammatory markers, lipid profile, glycemic control, insulin sensitivity, anthropometric measures, and blood pressure. Meta-analyses were conducted using random-effects models, with effect sizes calculated as mean differences (or standardized mean differences for oxLDL). Between-study heterogeneity was assessed with I2 statistics, and sensitivity and subgroup analyses explored potential sources of variability. Publication bias was evaluated using Begg's test and funnel plots where appropriate. OL supplementation significantly improved lipid parameters (total cholesterol, triglycerides, LDL-C, ApoB, oxLDL) and increased ApoA1, while reducing TNF-&#x3b1;, systolic and diastolic blood pressure, body weight, and BMI. No significant effects were observed on glycemic markers. OP supplementation showed no consistent cardiometabolic benefits and was associated with an increase in IL-8. Certainty of evidence ranged from very low to high, with several outcomes downgraded due to imprecision, heterogeneity, or limited study numbers. CONCLUSION: These findings support the targeted use of OL as an adjunctive strategy for cardiometabolic risk management. Evidence for OP supplementation remains limited, underscoring the need for well-powered, high-quality RCTs to clarify its clinical effects.

Humans

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of &#x2265;200 subjects, and had &#x2265;1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans

Dietary approaches for glycemic management in type 1 diabetes: A systematic review of Mediterranean and low-carbohydrate diets.

BACKGROUND/OBJECTIVES: Specific dietary approaches for better management of type 1 diabetes (T1D) have not been thoroughly investigated. We conducted a systematic review to evaluate the Mediterranean and low-carbohydrate diets for glycemic management in people with T1D. METHODS: We examined longitudinal studies (cohort studies and clinical trials) including individuals with T1D who followed low-carbohydrate diets (<26% calories from carbohydrates and/or <130&#x202f;g of carbohydrates per day) and/or a Mediterranean diet, while hemoglobin A1c (HbA1c) and/or time in range (TIR) were measured. Additional eligibility criteria included publication in English and availability of a full-text primary research article. Non-longitudinal studies, abstracts, and studies published in languages other than English were excluded. Results were synthesized narratively, and the GRADEpro Guideline Development Tool was used to assess article quality. RESULTS: A total of 565 studies were identified from PubMed, the Web of Science, and citation chasing. After removal of duplicates and further evaluation, 22 studies (6 cohort studies and 16 clinical trials; total n&#x202f;=&#x202f;3284) were included in this review. The search was initially completed in May 2024, and updated February 2026. Low-carbohydrate diets were associated with better glycemic management when compared to usual diets or baseline glycemic parameters. Studies using CGM were overall underpowered. The impact of Mediterranean diets was less clear, but generally appeared to be less effective at improving glycemic management than low-carbohydrate diets. DISCUSSION: Although structured dietary interventions for T1D hold promise for improving glycemic outcomes, further research is needed to determine exactly which dietary intervention is most beneficial for this population. The evidence provided by included studies is limited by small sample sizes and short durations; better powered, longer-term studies are required to inform clinical recommendations.

Humans

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB

Impact of creatine supplementation alone or combined with exercise on inflammatory and clinical outcomes in chronic musculoskeletal pain treated in the rheumatological field: a systematic review.

Creatine supplementation has demonstrated ergogenic and anabolic effects in healthy and clinical populations. However, its potential therapeutic role in individuals with chronic musculoskeletal pain treated in rheumatological contexts remains unclear. The aim was to evaluate the efficacy and safety of creatine supplementation on pain, physical function/disability, quality of life, muscle strength, skeletal muscle mass, and inflammatory markers in people with chronic musculoskeletal pain usually treated from the rheumatological field. A systematic review was conducted following PRISMA guidelines. Searches were performed in MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE up to July 2026. Eligible studies were randomized or nonrandomized clinical trials that provided creatine supplementation alone or in combination with exercise as a treatment compared to a control or placebo group. Eight studies (n = 189) were included, encompassing fibromyalgia, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis. Creatine dosages varied from chronic low-dose to loading protocols (20 g/d, 2-5 g/d). Combined creatine plus resistance training may improve strength, skeletal muscle mass, and quality of life beyond exercise alone in osteoarthritis. Trials on fibromyalgia suggest an increase in muscle strength, but inconsistent effects on pain. Rheumatoid arthritis studies suggest gains in skeletal muscle mass and, in pilot studies, reduced disease activity. No major adverse events were reported. In conclusion, creatine supplementation alone may be insufficient to obtain clinical benefits, while combined with resistance exercise it could offer potential benefits for muscle strength, skeletal muscle mass and certain aspects of quality of life in these clinical conditions. However, evidence on pain and inflammation remains limited; Furthermore, the response across different clinical conditions is heterogeneous, highlighting the need for larger, high-quality trials.

Humans