Search Results (978)

This pilot, randomized, double-blind, placebo-controlled trial investigated the effects of branched-chain amino acids (BCAAs)—provided in a 2:1:1 ratio of leucine:isoleucine:valine—combined with exercise on fatigue, physical performance, and quality of life in older adults. Twenty participants (63% female; BMI: 35 ± 2 kg/m²; age: 70.5 ± 1.2 years) were randomized to 8 weeks of either exercise + BCAAs (100 mg/kg body weight/d) or exercise + placebo. The program included moderate aerobic and resistance training three times weekly. Physical function was assessed using handgrip strength, chair stands, gait speed, VO₂ max, and a 400 m walk. Psychological health was evaluated using the CES-D, Fatigue Assessment Scale (FAS), Insomnia Severity Index (ISI), and global pain, fatigue, and quality of life using a visual analog scale (VAS). Significant group x time interactions were found for handgrip strength (p = 0.03), chair stands (p < 0.01), and 400 m walk time (p < 0.01). Compared to exercise + placebo, exercise + BCAAs showed greater improvements in strength, mobility, and endurance, along with reductions in fatigue (−45% vs. +92%) and depressive symptoms (−29% vs. +5%). Time effects were also observed for ISI (−30%), FAS (−21%), and VAS quality of life (16%) following exercise + BCAA supplementation. These preliminary results suggest that BCAAs combined with exercise may be an effective way to improve physical performance and reduce fatigue and depressive symptoms in older adults. Full article

Skin aging causes reduced hydration, elasticity, and increased wrinkles. Recent safety and compliance concerns over oral collagen supplements have increased interest in plant-based alternatives like Hibiscus sabdariffa with antioxidant and anti-aging properties. However, clinical evidence regarding its efficacy remains limited. We aimed to evaluate the effects of this plant-based collagen alternative (VC-H1, Hibiscus Enzyme Extract) supplement on skin hydration, transepidermal water loss (TEWL), desquamation, elasticity, and wrinkle reduction in photoaged individuals. A randomized, double-blind, placebo-controlled clinical trial was conducted with 98 participants (aged 35–60 years) presenting with dry skin and periorbital wrinkles. Participants randomly received 1.5 g/day of VC-H1 or placebo for 12 weeks. Skin hydration, TEWL, deep moisture, keratin index, elasticity, and wrinkle parameters were assessed at baseline, 6 weeks, and 12 weeks. VC-H1 supplementation significantly increased skin hydration, reduced the TEWL and keratin index, and improved deep moisture content for those receiving it compared with the controls. Wrinkle depth significantly decreased, and skin elasticity also improved. Those in the VC-H1 group showed greater overall improvement than those in the control group. Oral VC-H1 supplementation significantly improved skin hydration, elasticity, and wrinkle reduction, suggesting its potential as a plant-based alternative to traditional collagen supplements for skin rejuvenation. Full article

Background: Reducing cardiovascular risk markers is an essential target in chronic kidney disease (CKD). Thus, this study aimed to evaluate the effect of royal jelly plus green propolis supplementation on cardiovascular disease (CVD) risk factors in patients with CKD undergoing hemodialysis (HD). Methods: This randomized, double-blind, placebo-controlled trial involved HD patients allocated to receive either royal jelly plus green propolis EPP-AF^® (100 mg RJ + 500 mg GP) or placebo capsules daily for 2 months. Before and after the intervention period, the biochemical parameters, inflammatory cytokines, and uremic toxins were measured. Results: A total of 38 HD patients completed the 2-month supplementation study, with 19 patients in each group. After 2 months, the treated group showed a significant reduction in plasma levels of IL-6 (0.78 to 0.63 pg/mL, p = 0.008) and total cholesterol (138.60 to 111.85 mg/dL, p = 0.03), whereas no changes were observed in the placebo group. Uremic toxins did not change after intervention. Conclusion: Apitherapy with RJ + GP EPP-AF^® extract significantly reduced plasma IL-6 and total cholesterol in HD patients. This supplementation shows promise as a non-pharmacological strategy to reduce cardiovascular risk markers in this population. Full article

Background: Peritoneal stretching from CO₂ insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on postoperative pain reduction and associated changes in peritoneal gene expression after laparoendoscopic single-site (LESS) surgery for benign gynecologic disease. Methods: In this randomized, double-blind, placebo-controlled pilot study, 70 patients were randomly assigned to receive either celecoxib or placebo (400 mg) 40 min before surgery. Peritoneal tissues were collected before and after CO₂ insufflation. We analyzed changes in expressions of prostaglandin I₂ synthase, prostaglandin E synthase (PTGES), PTGES3, aldo-keto reductase family 1 member C1, and 15-hydroxyprostaglandin dehydrogenase (HPGD). Numeric Rating Scale (NRS) pain scores were also compared between groups. Results: A total of 62 patients completed the study: 30 in the celecoxib group and 32 in the placebo group. The mean CO₂ exposure time was 60.4 min. In a quantitative real-time polymerase chain reaction analysis, HPGD mRNA expression significantly increased after surgery in patients exposed to CO₂ for more than 60 min. Patients treated with celecoxib showed a significantly higher rate of grade 3 expression (83.3% vs. 37.5%; p = 0.01) and a level 2 increase in HPGD expression on in situ hybridization (58.3% vs. 12.5%; p = 0.01), despite no significant difference on immunohistochemistry. Moreover, celecoxib effectively reduced NRS pain scores compared to placebo. Conclusions: In this pilot study, celecoxib appeared to reduce postoperative pain and was associated with increased HPGD mRNA expression in the peritoneal tissue of patients with prolonged CO₂ exposure during LESS surgery. These exploratory findings warrant confirmation in larger trials with functional validation of HPGD expression (ClinicalTrials.gov, NCT03391570). Full article

Background: Pre-season training is critical for developing tolerance to high physical demands in professional soccer, and nitric oxide (NO) precursors such as dietary nitrate (NO₃⁻) and citrulline malate (CM) can support performance and recovery during this demanding phase. This study aimed to examine the effects of a four-week supplementation protocol combining 500 mg of NO₃⁻ from amaranth extract and 8 g of CM (NIT + CM) on external training load and post-match recovery in professional female soccer players during pre-season. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 34 female soccer players who received either the NIT + CM product or a placebo for four weeks during pre-season. Global positioning system (GPS)-derived external load was recorded throughout the intervention. Performance tests—a countermovement jump (CMJ) test and the Wingate anaerobic test (WAnT)—and blood sampling for plasma NO₃⁻ and nitrite (NO₂⁻) concentrations were conducted at baseline and the day after a competitive match. Results: The supplementation with NIT + CM increased maximal speed (Vmax) throughout training and match play. During post-match testing, the NIT + CM group exhibited a significantly smaller decline in mean (P_mean) and minimum (P_min) power during the WAnT, along with reduced power loss in both the first (0–15 s) and second (15–30 s) intervals. Plasma NO₃⁻ concentrations significantly increased from baseline in the NIT + CM group and remained elevated 24 h after the final dose, confirming sustained systemic exposure. Conclusions: Chronic NIT + CM supplementation may enhance Vmax and help preserve anaerobic performance the day after a match. These effects could reflect improved tolerance to high training loads and sustained NO₃⁻ availability during recovery. Full article

Background: Cannabidiol (CBD) has demonstrated potential as a therapeutic agent for muscle tension, pain, and sleep bruxism, yet its broader impact on comorbid conditions such as sleep disturbance and migraine disability remains underexplored. This study aimed to assess the effects of topical CBD on sleep quality and migraine-related disability in patients with bruxism-associated muscular pain. Methods: In a randomized, double-blind clinical trial, 60 participants with bruxism were allocated equally into three groups: control (placebo gel), 5% CBD gel, and 10% CBD gel. Participants applied the gel intraorally to the masseter muscles nightly for 30 days. Sleep quality and migraine-related disability were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Migraine Disability Assessment Scale (MIDAS), respectively. Surface electromyography (sEMG) and the Bruxoff^® device were used for objective evaluation of muscle tension and bruxism intensity. Results: Both CBD treatment groups demonstrated statistically significant improvements in PSQI and MIDAS scores compared to the control group (p < 0.001). No significant differences were observed between the 5% and 10% CBD groups, suggesting comparable efficacy. The sEMG findings corroborated a reduction in muscle tension. Improvements in sleep and migraine outcomes were positively correlated with reductions in muscle activity and pain. Conclusions: Topical CBD gel significantly improved sleep quality and reduced migraine-related disability in patients with bruxism-associated muscular pain, supporting its role as a multifaceted therapeutic option in the management of TMD and related comorbidities. Further research is needed to confirm long-term benefits and determine optimal dosing strategies. Full article

Background and Objectives: Preliminary studies indicate that dihydrogen (H₂) may affect molecular pathways involved in appetite regulation; however, its role in influencing patient-reported appetite outcomes in individuals with obesity remains uncertain. This randomized, placebo-controlled, double-blind trial aimed to evaluate the effects of H₂ supplementation on appetite, body composition, sleep quality, obesity-specific quality of life, and related biomarkers in obese men and women. Materials and Methods: The study included 36 participants (24 females; age 42.1 ± 13.2 years; BMI 30.8 ± 4.2 kg/m²) randomized to receive either 1.0 L of hydrogen-rich water (15 mg of H₂) or 1.0 L of control water (0 mg of H₂) daily for eight weeks. Results: The results demonstrated that hydrogen-rich water significantly mitigated cravings (p = 0.05), improved subjective sleep quality (p = 0.05), reduced total cholesterol (p = 0.02) and LDL cholesterol (p = 0.04), and increased plasma glucagon-like peptide-1 levels (p = 0.05) compared to the control. No severe adverse effects were reported throughout the trial. Conclusions: These findings suggest that hydrogen-rich water may serve as a safe and effective dietary strategy to address appetite regulation and related metabolic indices in individuals with obesity. The study is registered at ClinicalTrials.gov (NCT06722326). Full article

Background/Objectives: Colorectal cancer (CRC) patients undergoing chemotherapy often experience anemia, oxidative stress, and immune suppression, significantly impacting their quality of life and treatment outcomes. Normobaric oxygen (NBO) therapy, which delivers oxygen at atmospheric pressure with an elevated oxygen concentration, has shown the potential to enhance erythropoiesis, reduce oxidative stress, and modulate immune function. However, its efficacy in CRC patients remains underexplored. This study aims to evaluate the effects of NBO exposures on (1) supporting erythropoiesis by measuring erythropoietin (EPO) levels and hypoxia-inducible factor 1-alpha (HIF-1α), (2) reducing oxidative stress and improving stress and emotional well-being, and (3) modulating immune function by assessing cytokine profiles. Secondary objectives include assessing the impact of NBO on patient-reported outcome measures (PROMs) such as stress, anxiety, depression, and quality of life. Methods: This is a prospective, randomized, double-blind, placebo-controlled clinical trial. A total of 254 CRC patients undergoing chemotherapy will be randomized 1:1 to receive either active NBO therapy (n = 127, study group) or placebo NBO therapy (n = 127, control group). The intervention will consist of 10 NBO sessions over five weeks. Primary outcomes include biomarkers of erythropoiesis, oxidative stress, and immune response. Secondary outcomes assess quality of life and psychological well-being. Data will be collected at baseline, mid-intervention, post-intervention, and during two follow-up visits (3 and 6 months post-intervention). Results: The study hypothesizes that NBO therapy will improve erythropoiesis, reduce oxidative stress, and enhance immune function in CRC patients, leading to improved quality of life and clinical outcomes. Conclusions: Findings from this trial may establish NBO as a novel supportive therapy for CRC patients undergoing chemotherapy. Full article

Background/Objectives: Anorexia nervosa (AN) is a severe disorder with limited treatment efficacy. This interim analysis aimed to assess the preliminary efficacy and safety of transcranial direct current stimulation (tDCS) in reducing core AN symptoms, stress, depression, low self-esteem, and BMI in adolescent females, to determine the rationale for continuing the study. Methods: A single-center, randomized, double-blind, placebo-controlled trial included 20 adolescent females with AN assigned to an active tDCS group (n = 10) or a sham group (n = 10). The intervention involved 30 sessions over three weeks, targeting the dorsolateral prefrontal cortex. Outcomes were assessed at baseline, post-treatment, and follow-up using the Eating Attitudes Test (EAT-26) for eating disorder symptoms, the Perceived Stress Scale (PSS-10) for stress, the Beck Depression Inventory (BDI) for depression, the Rosenberg Self-Esteem Scale (SES) for self-esteem, and body mass index (BMI) measurements. Safety and tolerability were assessed using the tDCS Side Effects Questionnaire. Results: Eating disorder symptoms significantly decreased in the active tDCS group at study end (p = 0.003) and follow-up (p = 0.02), while no significant changes were observed in the sham group. Although BMI increased more in the active group (13.78%) than in the sham group (7.31%), this difference was not statistically significant (p = 0.10). Conclusions: Adverse effects were mild and transient, with no serious safety concerns reported. Based on the results of this interim analysis, the study will proceed due to promising efficacy outcomes and good treatment tolerability. Full article

Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves and husks, is rich in polyphenols and 1-deoxynojirimycin (DNJ) and may suppress postprandial glucose spikes, but evidence regarding its short-term daily intake is limited. This study aimed to evaluate the postprandial glycemic response and safety of two-week MW tea consumption using continuous glucose monitoring (CGM). Methods: We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial involving 31 participants. Each intervention period lasted two weeks, separated by a one-week washout. Participants consumed either MW tea or a placebo before meals. Interstitial glucose levels were measured every 15 min using CGM. Postprandial glucose responses were recorded every 15 min for 180 min after a standardized meal on the first day of each period. The primary outcome was the coefficient of variation (CV) in glucose levels, calculated using data from the central 10 days of each intervention period. Safety was assessed using CGM-derived hypoglycemia metrics and blood test results. Results: The CV of glucose levels during the MW tea period was significantly lower than during the placebo period (mean difference: 0.02, p = 0.0006). A significant reduction in 1 h postprandial glucose area under the curve was also observed. No significant differences were found in hypoglycemia occurrence, liver/renal/inflammatory markers, or self-reported adverse symptoms. Notably, 1,5-anhydroglucitol (1,5-AG) levels significantly increased during MW tea intake, suggesting improved glycemic control. Conclusions: Short-term consumption of Kanzaki MW tea effectively suppressed postprandial glucose variability without safety concerns. These findings support MW tea as a promising natural supplement for glycemic management and the prevention of diabetes. Full article

Background: Modulating ethanol metabolism and attenuating alcohol-induced oxidative stress are promising therapeutic strategies for reducing the severity of hangovers and alleviating their associated physiological burden. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effects of the probiotic strain Leuconostoc mesenteroides VITA-PB2 on ethanol metabolism, oxidative stress, and hangover-related symptoms in 28 healthy adults. The participants consumed either VITA-PB2 or a placebo before standardized alcohol intake, with a 7-day washout period and subsequent crossover. Primary outcomes included blood ethanol, acetaldehyde levels, and aldehyde dehydrogenase (ALDH) activity. Secondary outcomes measured hangover severity assessed by the Acute Hangover Scale (AHS), liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), oxidative stress indicators reactive oxygen species (ROS) and nitric oxide (NO), and antioxidant responses measured by glutathione peroxidase (GPx), catalase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity. Results: VITA-PB2 supplementation led to a sustained reduction in blood ethanol concentrations beginning at 0.5 h post-ingestion compared with the placebo group, indicating more efficient ethanol clearance. Additionally, VITA-PB2 significantly reduced acetaldehyde levels at 1 h post-ingestion (p < 0.05) and increased ALDH activity by 42.15% at 30 min (p < 0.05). It also markedly reduced ROS levels at 1 h (p < 0.05), enhanced glutathione peroxidase (GPx) activity at 2 h (p < 0.01), and significantly improved the subjective hangover symptoms, particularly thirst (p < 0.05). Conclusions: No adverse effects were reported during the trial, indicating that Leuconostoc mesenteroides VITA-PB2 is a safe probiotic. These findings suggest its efficacy in mitigating alcohol-induced oxidative stress and alleviating hangover-related symptoms. Full article

Many dogs suffer from pruritus, which is commonly caused by atopic dermatitis and associated with skin inflammation. The immune system and inflammatory response, and in particular the gut–skin axis, are central to the pathogenesis of atopic dermatitis. Managing atopic dermatitis involves complex, iterative treatment plans; early strategies supporting gut–skin health are needed to prevent elevated itching from progressing toward a disease condition requiring drug therapy. This double-blind, placebo-controlled, randomized trial evaluated the ability of a novel, indole-rich canine immune health postbiotic (CIHP) to reduce itching and promote a healthy gut microbiome in dogs with subclinical, but elevated itching behavior. Thirty dogs were stratified into two groups based on baseline scratching frequency, receiving either CIHP or placebo as a powder topper for 28 days. Canine itching was evaluated through accelerometer-based tracking and the Pruritus Visual Analog Scale (PVAS) score on Days 0, 7, 14, 21, and 28. Skin and coat health was assessed on Days 0, 14, and 28, and the gut microbiome was sequenced from fecal samples on Days 0 and 28. CIHP reduced scratching by 20% relative to the baseline (p = 0.032) and PVAS score by 27% compared to the placebo (p = 0.02). CIHP improved skin and coat quality compared to the placebo at Day 14 (p = 0.01) and increased Shannon diversity by 4.6% (p = 0.043), shifting gut microbiome composition. These findings validate this postbiotic’s ability to reduce itching in dogs with subclinical, but elevated itching behavior, provide evidence of promoting a healthy gut–skin axis, and suggest potential as an early intervention in the context of pruritic conditions, as well as for broader immune-related benefits. Full article

Background: Oral mucositis (OM) is a common and debilitating complication of cancer therapy, particularly in patients undergoing chemotherapy and radiotherapy. It significantly impairs quality of life and may necessitate the interruption of cancer treatment. This study aimed to evaluate the efficacy and safety of OROSOL, an oral spray device, in managing oral mucositis in pediatric patients undergoing chemotherapy or radiotherapy. Methods: This randomized, double-blind, placebo-controlled clinical trial compared OROSOL to a placebo in children with oral mucositis aged 3 to 17 years. Participants were followed for 28 days with regular medical visits. The primary endpoints were changes in the Oral Assessment Guide (OAG) scores and key symptoms (mucositis score, difficulty in oral feeding, ulceration and erythema, and pain sensation). Safety was assessed via adverse events and local tolerability. Results: Both groups were demographically balanced at baseline (p > 0.6). OROSOL demonstrated significantly greater improvements in the mucositis score beginning on Day 7 (p = 0.0122) and maintained superiority through Day 28 (p = 0.0007). Notable reductions in mucositis severity were observed, with significantly faster relief in the OROSOL group compared to the placebo (p < 0.001 for most timepoints). Oral feeding difficulty also showed a marked decline, with significant improvements starting from Day 5 (p = 0.0153). Ulceration and erythema scores significantly decreased from Day 14 onwards (p = 0.0188). Pain sensation showed a marked reduction from Day 14 (p = 0.0014). No serious adverse events were reported, and tolerability was consistent across all participants. Conclusions: OROSOL has a significant impact on reducing mucositis severity, oral feeding difficulty, ulceration, erythema, and pain. Coupled with its excellent safety profile, it is a valuable therapeutic option. This treatment is particularly beneficial for pediatric patients, ensuring improved comfort and recovery without notable adverse effects. Full article

This randomized, double-blind, placebo-controlled, three-arm clinical trial evaluated the effects of a proprietary bioactive fucoidan-rich extract derived from Saccharina latissima (SLE-F) on gut microbial composition and function in healthy adults. The objective of the study was to assess the potential of SLE-F to beneficially modulate the gut microbiome, with this paper specifically reporting on microbial diversity, taxonomic shifts, and functional pathway outcomes. Ninety-one participants received either a low dose (125 mg), high dose (500 mg), or placebo twice daily for four weeks. The primary endpoint was the microbiome composition assessed via 16S rRNA sequencing (V3–V4 region), with secondary outcomes including surveys, adverse event monitoring, and clinical evaluations. High-dose supplementation resulted in dose-dependent improvements in the microbial diversity; increased abundance of beneficial taxa, including Bifidobacterium, Faecalibacterium, and Lachnospiraceae; and reductions in inflammation-associated taxa, such as Enterobacteriaceae and Pseudomonadota. A functional pathway analysis showed enhancement in short-chain fatty acid biosynthesis and carbohydrate metabolism. The low-dose group showed modest benefits, primarily increasing Bifidobacterium, with limited functional changes. In vitro colonic simulations further demonstrated a dose-dependent increase in short-chain fatty acids and postbiotic metabolite production following SLE-F exposure. SLE-F was well tolerated, with only mild, nonspecific adverse events reported. These findings support the potential of SLE-F as a safe and effective microbiome-modulating agent, warranting further study of the long-term use and synergy with dietary interventions. Full article

Background/Objectives Lettuce is known to contain compounds that promote sleep. This study aims to evaluate the effects of lettuce extract on Korean adults experiencing poor sleep quality. Methods In this randomized, double-blind, placebo-controlled trial, participants aged 30–65 with poor sleep quality (Pittsburgh Sleep Quality Index (PSQI) > 5) were recruited. Over 4 weeks, participants took two capsules daily of either the test extract or placebo. Sleep quality and quantity were assessed using the PSQI, actigraphy and polysomnography, and analyzed using ANCOVA adjusting for baseline, age, and sex. Results The adjusted final PSQI scores showed greater improvement in the test group than in the placebo group for both the global scores (6.48 ± 0.63 vs. 7.41 ± 0.57, p = 0.0462). Regarding actigraphy measurements, the adjusted final means showed significant improvements in the test group compared to the placebo group for total sleep time (TST) (421.68 ± 13.29 vs. 386.57 ± 12.27 min, p = 0.0023) and sleep efficiency (SE) (83.90 ± 1.6 vs. 81.01 ± 1.50%, p = 0.0342). Polysomnography results also favored the test group, with higher adjusted final means TST (358.90 ± 19.75 vs. 322.11 ± 17.66 min, p = 0.0457) and SE (86.86 ± 3.31 vs. 79.60 ± 2.99%, p = 0.0182), and lower wake after sleep onset (39.26 ± 10.57 vs. 68.15 ± 9.60 min, p = 0.0042). Conclusions Heukharang extract may enhance sleep quality and quantity and is deemed safe, suggesting its potential as a functional food for improving sleep. Full article