Smartwatch Based Atrial Fibrillation Detection from Photoplethysmography Signals.

Our method achieves sensitivity, specificity and accuracy of 96.15%, 97.37% and 97.11%, respectively, which shows the potential of a practical and reliable AF monitoring scheme.


Electrodermal Activity Based Pre-surgery Stress Detection Using a Wrist Wearable.

Biometric Wearables (Sleep, HRV & Recovery)

The scheme yielded a classification accuracy of 85.06% on a new user dataset and proved to be more effective than the general supervised classification model.


Wearables measuring electrodermal activity to assess perceived stress in care: a scoping review.

Wearable EDA sensors are promising in detecting perceived stress. Field studies with relevant populations in a health or care context are lacking.


Examining Stress and Residual Symptoms in Remitted and Partially Remitted Depression Using a Wearable Electrodermal Activity Device: A Pilot Study.

Increased residual symptoms were associated with enhanced self-reported stress on the same day. Increased SCRs on one day predicted increased residual symptoms on the next day.


Perceived job insecurity as a risk factor for incident coronary heart disease: systematic review and meta-analysis.

Age adjusted relative risk of high versus low job insecurity was 1.32 (95% confidence interval 1.09 to 1.59).


Meta-analysis of perceived stress and its association with incident coronary heart disease.

Meta-analysis yielded an aggregate risk ratio of 1.27 (95% confidence interval 1.12 to 1.45) for the magnitude of the relation between high perceived stress and incident CHD.


Validation of the Withings ScanWatch as a Wrist-Worn Reflective Pulse Oximeter: Prospective Interventional Clinical Study.

We found a strong association and a high level of agreement between the measurements collected from the devices, with high Pearson correlation coefficients of r=0.944 and r=0.954 on the correlation plots.


Multidimensional Circadian Monitoring by Wearable Biosensors in Parkinson's Disease.

Our study demonstrates that a multichannel ACM device collects reliable and complementary information from motor (acceleration and time in movement) and common non-motor (sleep and skin temperature rhythms) features frequently disrupted in PD.


Heart rate variability in the prediction of mortality: A systematic review and meta-analysis of healthy and patient populations.

Lower HRV parameter values were significant predictors of higher mortality across different ages, sex, continents, populations and recording lengths.


Heart rate as a target of treatment of chronic heart failure.

In a long-term follow-up study in Framingham, the general population in this cohort showed an increase in all-cause mortality by 14% at every 10 bpm increase in HR.


Wrist-worn devices for the measurement of heart rate and energy expenditure: A validation study for the Apple Watch 6, Polar Vantage V and Fitbit Sense.

The Apple Watch 6 was the most accurate for measuring heart rate, whereas the Polar Vantage V and Fitbit Sense showed variable results dependent on the activity


Accuracy of the Multisensory Wristwatch Polar Vantage's Estimation of Energy Expenditure in Various Activities: Instrument Validation Study.

The Polar Vantage has a statistically moderate-to-good accuracy in EE estimation that is activity dependent.


Rationale and design of a large-scale, app-based study to identify cardiac arrhythmias using a smartwatch: The Apple Heart Study.

Smartwatch and fitness band wearable consumer electronics can passively measure pulse rate from the wrist using photoplethysmography (PPG). Identification of pulse irregularity or variability from these data has the potential to identify atrial fibrillation or atrial flutter (AF, collectively).


Effects of Continuous Glucose Monitoring on Metrics of Glycemic Control in Diabetes: A Systematic Review With Meta-analysis of Randomized Controlled Trials.

CGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes.


Effectiveness of Continuous Glucose Monitoring on Metrics of Glycemic Control in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Both rt-CGM and flash CGM led to modest but statistically significant declines in HbA1c among individuals with T2DM, with little heterogeneity in the results.


The Effectiveness of Continuous Glucose Monitoring in Patients with Type 2 Diabetes: A Systematic Review of Literature and Meta-analysis.

RT-CGM and P-CGM were associated with a modest but statistically significant reduction in HbA1c of 0.20% (95% confidence interval [CI] -0.31 to -0.09) compared with control. Patients who received FGM had a nonsignificant reduction of 0.02% (95% CI -0.07 to 0.04) compared with control.

no-difference-cue: "nonsignificant" | favorable-cue: "reduction in hba1c"


Continuous glucose monitoring in adults with type 2 diabetes: a systematic review and meta-analysis.

CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce.


Impact of flash glucose monitoring on hypoglycaemia in adults with type 1 diabetes managed with multiple daily injection therapy: a pre-specified subgroup analysis of the IMPACT randomised controlled trial.

At 6 months, mean time in hypoglycaemia was reduced by 46.0%, from 3.44 h/day to 1.86 h/day in the intervention group (baseline adjusted mean change, -1.65 h/day)


Flash Glucose-Sensing Technology as a Replacement for Blood Glucose Monitoring for the Management of Insulin-Treated Type 2 Diabetes: a Multicenter, Open-Label Randomized Controlled Trial.

Flash glucose-sensing technology use in type 2 diabetes with intensive insulin therapy results in no difference in HbA1c change and reduced hypoglycemia, thus offering a safe, effective replacement for SMBG.

no-difference-cue: "no difference" | favorable-cue: "effective"


IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): A randomized controlled trial.

The IMMEDIATE study has shown that among non-insulin-treated individuals with type 2 diabetes, use of isCGM is associated with an improvement in glycaemic outcomes.


Reduction in HbA1c using professional flash glucose monitoring in insulin-treated type 2 diabetes patients managed in primary and secondary care settings: A pilot, multicentre, randomised controlled trial.

Libre Pro can improve HbA1c and treatment satisfaction without increasing hypoglycaemic exposure in insulin-treated type 2 diabetes individuals managed in primary/secondary care centres.


Effect of Continuous Glucose Monitoring on Glycemic Control in Adolescents and Young Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Among adolescents and young adults with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in glycemic control over 26 weeks.


Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials.

The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51-78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25-56), for each 10 percentage points lower TIR


The Relationship of Hemoglobin A1C to Time-in-Range in Patients with Diabetes.

There is a good correlation between HbA1C and %TIR that may permit the transition to %TIR as the preferred metric for determining the outcome of clinical studies, predicting of the risk of diabetes complications, and assessing of an individual patient's glycemic control.


Effect of Flash Glucose Monitoring on Glycemic Control, Hypoglycemia, Diabetes-Related Distress, and Resource Utilization in the Association of British Clinical Diabetologists (ABCD) Nationwide Audit.

We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.


Improved well-being and decreased disease burden after 1-year use of flash glucose monitoring (FLARE-NL4).

Real world data demonstrate that use of FSL-FGM results in improved well-being and decreased disease burden, as well as improvement of glycemic control.


A review of flash glucose monitoring in type 2 diabetes.

Additional benefits associated with flash glucose monitoring versus SMBG include reductions in acute diabetes events, all-cause hospitalizations and hospitalized ketoacidosis episodes; improved well-being and decreased disease burden; and greater treatment satisfaction.


Cost Calculation for a Flash Glucose Monitoring System for Adults with Type 2 Diabetes Mellitus Using Intensive Insulin - a UK Perspective.

flash monitoring would cost an additional £585 per patient per year, offset by a £776 reduction in healthcare resource use, based on reductions in emergency room visits (41%), ambulance call-outs (66%) and hospital admissions (77%) observed in the REPLACE trial.


Combined assessment of stress hyperglycemia ratio and glycemic variability to predict all-cause mortality in critically ill patients with atherosclerotic cardiovascular diseases across different glucose metabolic states: an observational cohort study with machine learning.

Combined SHR and GV assessment serves as a critical prognostic tool for ASCVD mortality, providing enhanced predictive accuracy compared to individual metrics, particularly in NGR and Pre-DM patients.


Body fat and risk of all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

A total of 35 prospective cohort studies with 923,295 participants and 68,389 deaths were identified. The HRs of all-cause mortality for a 10% increment in BF were 1.11 (95%CI: 1.02, 1.20; I = 93%, n = 11) in the general adult populations, and 0.92 (95%CI: 0.79, 1.06; I = 76%, n = 7) in adults older than 60 years.


Change in body size associated with all-cause mortality in an older Chinese population.

Compared with participants with stable body size (change within 5%), those with more than a 10% decrease in BMI or BF% had 36% and 46% higher risks, respectively, of all-cause mortality (HR = 1.36, 95% CI: 1.17-1.59; and HR = 1.46, 95% CI: 1.25-1.72)


Body fat percentage, body mass index and waist-to-hip ratio as predictors of mortality and cardiovascular disease.

Once BMI and WHR are taken into account, fat percentage does not add to prediction of mortality or CVD in middle-aged and older-aged adults.


Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement.

Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality.


Abdominal Visceral Adipose Tissue and All-Cause Mortality: A Systematic Review.

A high abdominal VAT area seems to be associated with increased all-cause mortality in individuals ≤ 65 years, possibly mediated by metabolic complications, and not through an independent effect.

unfavorable-cue: "increased all-cause mortality"


Low muscle mass in older adults and mortality: A systematic review and meta-analysis.

A reduced pooled ASMI in individuals who died as compared to those who survived (ASMI SMD = -0.18, CI95% -0.23 to -0.12, REM) was found.


Muscle mass, strength, and physical performance predicting activities of daily living: a meta-analysis.

Low muscle mass was associated with worsening ADL (pooled odds ratio (95% confidence interval) 3.19 (1.29-7.92)) and worsening IADL (1.28 (1.02-1.61)).


Recent sarcopenia definitions-prevalence, agreement and mortality associations among men: Findings from population-based cohorts.

Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I: 0.0%]; SDOC [2.75 (2.28, 3.31), I: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I: 58.3%].


Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis.

The pooled RRs of total CV events, CV mortality, and all-cause mortality were 2.26 (95% confidence interval: 1.89 to 2.70, 14 studies), 2.02 (95% confidence interval: 1.68 to 2.42, 10 studies), and 1.90 (95% confidence interval: 1.61 to 2.24, 11 studies), respectively, for high versus low aortic PWV subjects.


High aortic augmentation index predicts mortality and cardiovascular events in men from a general population, but not in women.

Our findings support that AIx relates to CVD in men but question the value in women.


Validity of Body-Composition Methods across Racial and Ethnic Populations.

For BIA, body-composition measures may be valid in a multi-ethnic sample, but the literature demonstrates disparate results between races/ethnicities.


Bioelectrical impedance analysis versus reference methods in the assessment of body composition in athletes.

The present systematic review suggests that BIA and BIVA can be used for assessing body composition in athletes, provided that foot-to-hand technology, predictive equations, and BIVA references for athletes are used.


Validity of total body water measured by multi-frequency bioelectrical impedance devices in a multi-ethnic sample.

The results suggest the BIS and IB devices evaluated can produce valid TBW estimates compared to DO in a multi-ethnic sample.


Bioelectrical phase angle and impedance vector analysis--clinical relevance and applicability of impedance parameters.

Numerous studies have proven the prognostic impact of PhA regarding mortality or postoperative complications in different clinical settings.


Weighing every day matters: daily weighing improves weight loss and adoption of weight control behaviors.

Daily weighers lost significantly more weight compared with those weighing less than daily (mean difference=-6.1 kg; 95% CI -10.2 to -2.1; P=0.004).


Frequent Self-Weighing and Visual Feedback for Weight Loss in Overweight Adults.

Daily self-weighing and visual feedback facilitated a minimal amount of weight loss and maintenance of this loss.


Self-monitoring in weight loss: a systematic review of the literature.

A significant association between self-monitoring and weight loss was consistently found; however, the level of evidence was weak because of methodologic limitations.


A Portable Gluten Sensor for Celiac Disease Patients May Not Always Be Reliable Depending on the Food and the User.

Of the 119 samples with gluten content ranging from 2 to 101,888 mg/kg tested in total, the sensor showed 80 positive (67.2%), 37 negative (31.1%) and 2 invalid results at the first of three consecutive measurements. The detection rate for samples containing ≥20 mg/kg of gluten was 90%.


Gluten contamination in labelled gluten-free, naturally gluten-free and meals in food services in low-, middle- and high-income countries: a systematic review and meta-analysis.

The results show that in the gluten-free foods analysed, the overall prevalence of gluten contamination was estimated at 15.12% (95% CI: 9.56%-21.70%), with more than 20 mg/kg of gluten.


Food Safety and Cross-Contamination of Gluten-Free Products: A Narrative Review.

It has been demonstrated that both natural and certified gluten-free foods can be heavily contaminated with gluten well above the commonly accepted threshold of 20 mg/kg.


Gluten contamination in food services and industry: A systematic review.

It indicates that foods labeled as "gluten-free" should not be considered safe for patients with GRD since information on the label regarding the presence/absence of gluten is unreliable.


Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy.

Gluten level was lower than 10 part per million (ppm) in 173 products (86.5%), between 10 and 20 ppm in 9 (4.5%), and higher than 20 ppm in 18 (9%), respectively.


Biomarkers to Monitor Gluten-Free Diet Compliance in Celiac Patients.

Therefore, the detection of gluten immunogenic peptides (GIP) in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients.


Detection of gluten immunogenic peptides and the Celiac Disease Adherence Test to monitor gluten-free diet: a pilot study.

Fecal GIP may be useful as a biomarker for ongoing gluten intake that is not possible to detect with current clinical methods to assess GFD adherence, and may play a role in the management of persistent gastrointestinal symptoms in celiac disease.


Challenges of Monitoring the Gluten-Free Diet Adherence in the Management and Follow-Up of Patients with Celiac Disease.

Cross-contamination of gluten-free products with gluten is a major cause of inadvertent non-adherence, while the limited availability, high costs, and poor quality of certified gluten-free products are responsible for intentionally breaking a GFD.


Biomarkers to Monitor Adherence to Gluten-Free Diet by Celiac Disease Patients: Gluten Immunogenic Peptides and Urinary miRNAs.

Gluten-free food contamination by other cereals during packaging and cooking or accidental ingestion of gluten may cause several intestinal and extraintestinal symptoms in CD patients.


Emerging Point-of-care Technologies for Food Safety Analysis.

POC devices, including paper- and chip-based devices, are typically rapid, cost-effective and user-friendly, offering a tremendous potential for rapid food safety analysis at POC settings.


A novel electrochemical mast cell-based paper biosensor for the rapid detection of milk allergen casein.

Therefore, a simple and novel electrochemical method for food allergens detection was developed, demonstrating its potential application in the food safety determination and evaluation.


Rapid label-free colorimetric dual-functional aptasensor for β-lactoglobulin detection based on a rational tailoring strategy.

Furthermore, the aptasensor offered advantages, such as cost-efficiency, simple operation, 40 min rapid detection, excellent specificity, and a sensitivity of a three-orders of magnitude linear range and an 8.23-fold linear curve slope, meeting the point-of-care testing (POCT) requirements for dairy analysis.


Accidental Reactions to Foods: Frequency, Causes, and Severity.

Despite best efforts by individuals, physicians, and legislative bodies to improve safety for food allergic individuals, accidental reactions to foods still occur and can result in fatalities.


Prospective Selective Mechanism of Emerging Senolytic Agents Derived from Flavonoids.

Among senolytic candidates, only dasatinib with quercetin and fisetin meet the rigorous criteria for senolytic drugs, according to a modified version of Koch's postulates.


Emerging senolytic agents derived from natural products.

In recent years, emerging natural compounds have been discovered to be effective senolytic agents, such as quercetin, fisetin, piperlongumine and the curcumin analog.


Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence in Skeletal Muscle With Aging: A Comparison to Genetic Clearance of Senescent Cells and Synthetic Senolytic Approaches.

We found that fisetin mitigated the adverse changes in frailty and grip strength with aging. Fisetin had no effects in young mice.


Endothelial senescent-cell-specific clearance alleviates metabolic dysfunction in obese mice.

the senolytic, fisetin, which targets senescent endothelial cells among other senescent cell types, reduced adipose tissue senescent endothelial cell abundance and improved glucose metabolism in obese mice or mice transplanted with senescent mouse endothelial cells.


IL-23R is a senescence-linked circulating and tissue biomarker of aging.

We discovered that age-dependent changes in plasma proteins, including IL-23R, CCL5 and CA13, were reversed by senotherapeutics, which corresponded to expression differences in tissues, particularly in the kidney. In plasma from humans across the lifespan, IL-23R increased with age.


Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review.

Fisetin has manifested several health benefits in preclinical models of neurodegenerative diseases such as Alzheimer's disease, Vascular dementia, and Schizophrenia.


Recent advances in potential of Fisetin in the management of myocardial ischemia-reperfusion injury-A systematic review.

Fisetin is reported to be effective in attenuating IR injury by delaying the clotting time, preserving the mitochondrial function, reducing oxidative stress, and inhibiting GSK 3β. But it failed to protect diseased cardiomyocytes challenged to IR.


Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle.

the senolytic ablation of these senescent cells with fisetin can be an effective therapeutic strategy for improving function of muscle stem cells and phenotypes of dystrophic muscles.


Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers.

Study results prove antiproliferative and proapoptotic properties of flavonols with regard to head and neck cancer.


Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.

Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases.


Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: Study protocol for a multicenter, randomized, adaptive allocation clinical trial.

We are conducting a multi-center, randomized, double-blinded, adaptive allocation phase 2 clinical trial to assess the efficacy of the senolytic drug fisetin in preventing clinical deterioration of elderly patients diagnosed with sepsis.


Polyphenols and Diets as Current and Potential Nutrition Senotherapeutics in Alzheimer's Disease: Findings from Clinical Trials.

Promising results with neuroprotective effects of senotherapeutic agents such as quercetin, resveratrol, Epigallocatechin-gallate, curcumin and fisetin were reported from preclinical studies. However, in-human trials remain limited, and findings were inconclusive.


Vascular Niches Are the Primary Hotspots in Cardiac Aging.

We treated mice with broad-spectrum senolytics dasatinib and quercetin, and endothelial-specific senolytic fisetin and studied their effects on senescence and macrophage populations.


Emerging Therapeutic Potential of Fisetin for Nephrotoxicity, Kidney Injury, and Nephropathy: A Systematic Review.

Preclinical studies revealed that FIS demonstrates promising protective effects against kidney toxicity, renal injury, diabetes, and lupus-induced nephropathy. However, more clinical studies are needed in this field to determine effective and safe doses.


Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.

Preliminary human studies involving FOXO4-axis modulators, such as high-dose fisetin, show a reduction in the senescence-associated secretory phenotype (SASP) and enhancements in cognitive and physical measures among older adults.


The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.

Urolithin A (Mitopure);Pomegranate Ellagitannin Extract

These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.


Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial.

These findings indicate that short-term UA supplementation modulates human immune cell composition and function, supporting its potential to counteract age-related immune decline and inflammaging.


Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study.

After 8 weeks of UA supplementation at 1 g/day, resistance-trained male athletes showed improvements in muscle strength and endurance. Additionally, UA supplementation was also associated with reduced oxidative stress levels and a decrease in inflammation response levels.


Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial.

The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF.


Targeting aging with urolithin A in humans: A systematic review.

UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function.

no-difference-cue: "no effect" | favorable-cue: "increased muscle"


Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.

We identified urolithin A (UA) as a first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption. In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan.


Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.

UA enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation.

unfavorable-cue: "detrimental" | favorable-cue: "enhances"


Mitophagy Activation by Urolithin A to Target Muscle Aging.

The natural postbiotic Urolithin A has been shown to promote mitophagy, mitochondrial function and improved muscle function across species in different experimental models and across multiple clinical studies.


Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer's disease.

mitophagy stimulation (through NAD supplementation, urolithin A, and actinonin) reverses memory impairment


Urolithin A promotes p62-dependent lysophagy to prevent acute retinal neurodegeneration.

UA alleviated neurodegeneration and preserved visual function in SI-treated mice.


Urolithin A Inactivation of TLR3/TRIF Signaling to Block the NF-kB/STAT1 Axis Reduces Inflammation and Enhances Antioxidant Defense in Poly(I:C)-Induced RAW264.7 Cells.

our results suggest that urolithin A inhibits TLR3-activated inflammatory and oxidative-associated pathways in macrophages, and that this inhibition is induced by poly(I:C).


Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress.

Urolithin A pretreatment reduced all the above renal damage parameters in a significant way.


Multi-Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo-Controlled Trial.

This multi-species synbiotic significantly increases diversity and abundance of key beneficial bacteria, enhances UroA production and butyrate levels, and is associated with lowered systemic inflammation.


A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy.

Urolithin A was detected in 21 of the 33 patients in the POMx group versus 12 of the 35 in the placebo group (P = 0.031).


Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial.

After 4 weeks, consumption of 10 g/d BSP resulted in a significant decrease in serum insulin concentration and HOMA-IR (p = 0.05 for treatment effect). Therefore, broccoli sprouts may improve IR in type 2 diabetic patients.


Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study.

No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.


Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects.

Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.


Dose-dependent detoxication of the airborne pollutant benzene in a randomized trial of broccoli sprout beverage in Qidong, China.

A statistically significant increase in benzene mercapturic acids in urine was found for the high-dose group (+63.2%) during the 10-d period.


Sulforaphane reprograms the metabolomic landscape of chronic kidney disease: insights from NMR-based metabolomics.

SFN supplementation tended to reduce 2-hydroxyisovalerate and glycerol levels, metabolites associated with insulin resistance and oxidative stress, and attenuated methanol elevation.


Potential efficacy of broccoli sprouts as a unique supplement for management of type 2 diabetes and its complications.

In hyperglycemic and oxidative conditions, sulforaphane has the potential to activate the NF-E2-related factor-2 (Nrf2)-dependent antioxidant response-signaling pathway, induces phase 2 enzymes, attenuates oxidative stress, and inactivates nuclear factor kappa-B (NF-κB), a key modulator of inflammatory pathways.


A mechanistic overview of sulforaphane and its derivatives application in diabetes and its complications.

Sulforaphane has been demonstrated to activate the PIK/AKT and AMP-activated protein kinase pathways and the glucose transporter type 4 to increase insulin production and reduce insulin resistance.


Sulforaphane alleviates high fat diet-induced insulin resistance via AMPK/Nrf2/GPx4 axis.

SFN was found to effectively reduce body weight, fasting blood glucose and hyperlipidemia, and improve liver function in HFD-fed mice.


Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism.

SFN intervention (SFN-I) alleviated hyperglycemia, dyslipidemia, HOMA-IR, serum MDA levels, and liver inflammation.


Sulforaphane attenuates aldose reductase-mediated platelet dysfunction in high glucose-stimulated human platelets via downregulation of the Src/ROS/p53 signaling pathway.

These findings suggest that by inhibiting the Src/ROS/p53 signaling pathway and mitigating AR-mediated platelet dysfunction, SFN may confer significant protection against atherothrombosis during hyperglycemia.


Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress.

by simultaneously activating macroautophagy/autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases.


Efficacy and safety of sulforaphane in schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

Sulforaphane led to significant reductions in metabolic markers, including LDL, triglycerides, and cholesterol. Discontinuation rates were lower in the sulforaphane group (RR = 0.68; 95% CI: 0.49 to 0.95; p = 0.02).


Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials.

CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02).

favorable-cue: "crp concentration was decreased"


Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials.

There was a significant decrease in the serum levels of IL-1 (WMD = -2.33 pg/ml, 95% CI = -3.33 to -1.34, P < 0.001) and TNF-α (WMD = -1.61 pg/ml, 95% CI = -2.72, -0.51, P < 0.001) compared to the placebo group following treatment.


The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.

The meta-analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL-6) (SMD -2.08; 95% CI [-3.90, -0.25]; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (SMD -0.65; 95% CI [-1.20, -0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD -3.14; 95% CI [-4.76, -1.53], p < 0.001).


Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials.

The credibility of the evidence was rated as high for fasting blood sugar (FBS), C-reactive protein (CRP), high-density lipoprotein (HDL), and weight.


Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity.


The effects of curcumin on anthropometric and cardiometabolic parameters of patients with metabolic related diseases: a systematic review and dose-effect meta-analysis of randomized controlled trials.

Nanocurcumin may have a greater effect on the reduction of FPG, INS, TC and LDL-C than other curcumin formulations.


An Investigation into the Effects of a Curcumin Extract (Curcugen) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study.

Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo.


Antioxidant Potential of Curcumin-A Meta-Analysis of Randomized Clinical Trials.

Pure curcumin has the potential to reduce MDA concentration and increase total antioxidant capacity.


Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials.

Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies.


The effects of curcumin-containing supplementations on inflammatory markers and lipid profiles in patients with chronic kidney diseases: a systematic review and meta-analysis of randomized controlled trials.

Curcumin intake significantly reduced total cholesterol (TC) (WMD=-13.77 mg/dL; 95% CI, -26.77, -0.77; p=0.04) and tumor necrosis factor alpha (TNF-α) (WMD=-18.87 pg/mL; 95% CI, -28.36, -9.38; p<0.001) compared with controls.

favorable-cue: "significantly reduced total cholesterol"


Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine.

After administration of co-amorphous CUR-PIP, the AUC of CUR significantly increased by 2.16- and 1.92-fold those in crystalline and amorphous CUR, respectively.


The Effects of Quercetin Supplementation on Blood Pressures and Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

We found a significant reduction in systolic blood pressure (SBP) (WMD: -1.69; 95% CI: -3.22, -0.17) following the intake of quercetin supplements.


The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials.

Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I = 75.0%).


Quercetin reduces blood pressure in hypertensive subjects.

Blood pressure was not altered in prehypertensive patients after quercetin supplementation. In contrast, reductions in (P < 0.01) systolic (-7 +/- 2 mm Hg), diastolic (-5 +/- 2 mm Hg), and mean arterial pressures (-5 +/- 2 mm Hg) were observed in stage 1 hypertensive patients after quercetin treatment.


Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study.

In contrast to placebo, quercetin decreased systolic blood pressure (SBP) by 2.6 mmHg (P < 0.01) in the entire study group, by 2.9 mmHg (P < 0.01) in the subgroup of hypertensive subjects and by 3.7 mmHg (P < 0.001) in the subgroup of younger adults aged 25-50 years.


Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial.

In the subgroup of hypertensives, quercetin decreased 24 h systolic BP by -3·6 mmHg (P=0·022) when compared with placebo (mean treatment difference, -3·9 mmHg; P=0·049).

favorable-cue: "decreased 24 h systolic"


Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults with hypertension: a randomized, double-blind, placebo-controlled, crossover trial.

Systolic and diastolic blood pressure increased significantly over time, but were not affected by treatment (placebo or quercetin).


Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease.

EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025).


Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference.

no-difference-cue: "no difference" | favorable-cue: "improved"


Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors.


Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis.

Quercetin supplementation improved the antioxidant defence, indicated by the increased total plasma antioxidant capacity. Moreover, quercetin supplementation also reduced markers of oxidative stress and inflammation in the blood of sarcoidosis patients.


Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease.

Quercetin was safely tolerated up to 2000 mg/day as assessed by lung function, blood profile and COPD assessment test questionnaire.


Senolytics improve physical function and increase lifespan in old age.

The senolytic cocktail, dasatinib plus quercetin, which causes selective elimination of senescent cells, decreased the number of naturally occurring senescent cells and their secretion of frailty-related proinflammatory cytokines in explants of human adipose tissue.


Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.

Green tea consumption significantly lowered the TC concentration by 7.20 mg/dL (95% CI: -8.19, -6.21 mg/dL; P < 0.001) and significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: -3.16, -1.21 mg/dL; P < 0.001).

favorable-cue: "significantly lowered the ldl"


The effects of green tea on weight loss and weight maintenance: a meta-analysis.

Catechins or an epigallocatechin gallate (EGCG)-caffeine mixture have a small positive effect on WL and WM.


[Effects of green tea and its epigallocatechin (EGCG) content on body weight and fat mass in humans: a systematic review].

daily consumption of green tea with doses of EGCG between 100 and 460 mg/day has shown greater effectiveness on body fat and body weight reduction in intervention periods of 12 weeks or more.


Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.

Green tea consumption significantly changed systolic blood pressure, by -2.08 mm Hg (95% CI -3.06, -1.05), and diastolic blood pressure, by -1.71 mm Hg (95% CI -2.86, -0.56), compared to the control.


Effects of green tea catechin on the blood pressure and lipids in overweight and obese population-a meta-analysis.

in overweight and obese people green tea catechin could reduce waist circumference (WC) (pooled WMD = -1.37 cm, 95 % CI: -2.52 to -0.22 cm, p = 0.019), and triglyceride (TG) (pooled WMD = -0.18 mmol/L, 95 % CI: -0.35 to -0.02 mmol/L, p = 0.032)


Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 μU/mL; 95% CI: -0.36, 0.45 μU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not.


Effects of green tea consumption on glycemic control: a systematic review and meta-analysis of randomized controlled trials.

The pooled results showed that green tea significantly lowered fasting blood glucose by - 1.44 mg/dL (95%CI:-2.26, - 0.62 mg/dL; < 0.001) with no obvious heterogeneity

favorable-cue: "significantly lowered fasting blood glucose"


A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome.

These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.


Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome.

This study suggests that the daily consumption of green tea beverage or extracts for 8 wk was well tolerated but did not affect the features of metabolic syndrome.


The role of bioactives in energy metabolism and metabolic syndrome.

At present, the question 'Are bioactives effective in weight management and prevention of metabolic syndrome?' remains inconclusive.


Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study.

Green tea consumption is associated with reduced mortality due to all causes and due to cardiovascular disease but not with reduced mortality due to cancer.

favorable-cue: "associated with reduced"


Green tea (Camellia sinensis) for the prevention of cancer.

adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions.

unfavorable-cue: "raised blood pressure"


Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies.

Class I evidence: some lots of Polyphenon E have a high risk of hepatotoxicity.


Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in diversity outbred mice.

Within the DO population, an equal exposure to EGCG (50 mg/kg; daily for three days) was found to be tolerated in the majority of mice; however, a small fraction of the animals (16%; 43/272) exhibited severe hepatotoxicity (10-86.8% liver necrosis) that is analogous to the clinical cases.


Astaxanthin supplementation mildly reduced oxidative stress and inflammation biomarkers: a systematic review and meta-analysis of randomized controlled trials.

Compared with placebo, astaxanthin significantly reduced blood malondialdehyde concentration (standardized mean difference [SMD]: -0.95; 95% CI, -1.67 to -0.23; P = .01).


Exploring the benefits of astaxanthin as a functional food ingredient: Its effects on oxidative stress and reproductive outcomes in women with PCOS - A systematic review and single-arm meta-analysis of randomized clinical trials.

The findings indicate that while astaxanthin significantly improves markers of total antioxidant capacity (TAC) in follicular fluid, it does not show a consistent effect on other oxidative stress biomarkers such as malondialdehyde (MDA), catalase (CAT), or superoxide dismutase (SOD).


Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies.

The meta-analysis of clinical trials showed that AST significantly increased the oocyte maturation rate (MD: 8.40, 95% CI: 4.57 to 12.23, I: 0%) and the total antioxidant capacity levels in the follicular fluid (MD: 0.04, 95% CI: 0.02 to 0.06, I: 0%).


Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing.

Oral ASX supplementation significantly restored moisture content (SMD = 0.53; 95% CI = 0.05, 1.01; I= 52%;= 0.03) and improved elasticity (SMD = 0.77; 95% CI = 0.19, 1.35; I= 75%;= 0.009) but did not significantly decrease wrinkle depth (SMD = -0.26; 95% CI = -0.58, 0.06; I= 0%;= 0.11) compared to placebo.


Astaxanthin Influence on Health Outcomes of Adults at Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Results show marginal effects of astaxanthin on reduction in total cholesterol and systolic blood pressure, and a significant attenuating effect on low-density lipoprotein cholesterol.

favorable-cue: "reduction in total cholesterol"


Assessing the Effects of Moderate to High Dosage of Astaxanthin Supplementation on Lipid Profile Parameters-A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

The meta-analysis concludes positive effects of astaxanthin (6-20 mg/d) on HDL-C (0.4200; 95% CI: 0.1081 to 0.7319) and triglyceride (-0.3058; 95% CI: -0.5138 to -0.0978) levels.


The Effects of Astaxanthin Supplementation on Exercise Recovery Biomarkers and Exercise Performance: A Systematic Review and Meta-Analysis.

Astaxanthin significantly reduced creatine kinase levels (SMD = -0.45, 95% CI: -0.83 to -0.07). Lactate dehydrogenase also favored astaxanthin (SMD = -0.93, 95% CI: -1.39 to -0.48), although heterogeneity was substantial. No significant effects were observed for malondialdehyde or interleukin-6.

no-difference-cue: "no significant effects"


Carotenoids supplementation and inflammation: a systematic review and meta-analysis of randomized clinical trials.

For the individual carotenoids, astaxanthin, (WMD: -0.30 mg/L, 95% CI: -0.51, -0.09, = 0.005), lutein/zeaxanthin (WMD: -0.30 mg/L, 95% CI: -0.45, -0.15, < 0.001), and β-cryptoxanthin (WMD: -0.35 mg/L, 95% CI: -0.54, -0.15, < 0.001) significantly decreased CRP level.

favorable-cue: "significantly decreased crp"


Impact of astaxanthin on oxidative markers, uric acid, and clinical symptoms in heart failure: a randomized clinical trial.

In contrast, the ASX group demonstrated significantly greater reductions in MDA (-2.19 vs. -0.68 nmol/L, P < 0.001) and serum UA levels (-1.82 vs. -0.63 mg/dl, P = 0.003) compared to placebo.


Protective effects of Haematococcus astaxanthin on oxidative stress in healthy smokers.

Compared with baseline, the plasma malondialdehyde and isoprostane levels decreased, whereas superoxide dismutase level and total antioxidant capacity increased in all ASX intervention groups over the 3-week period.


Effects of astaxanthin on oxidative stress in overweight and obese adults.

Compared with baseline, the MDA (by 34.6% and 35.2%) and ISP (by 64.9% and 64.7%) levels were significantly lowered, whereas SOD (by 193% and 194%) and TAC (by 121% and 125%) levels were significantly increased in two dose groups after the 3 week intervention.


Astaxanthin Supplementation Increases Glutathione Concentrations but Does Not Impact Fat Oxidation During Exercise in Active Young Men.

Astaxanthin supplementation of 6 mg/day for 4 weeks increased whole blood levels of the antioxidant glutathione in active young men but did not affect oxidative stress markers or substrate utilization during exercise.


Effect of antioxidant supplementation on exercise-induced cardiac troponin release in cyclists: a randomized trial.

Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists.


Effect of astaxanthin-rich extract derived fromon cognitive function in middle-aged and older individuals.

The astaxanthin group experienced significantly larger increase in blood astaxanthin level than the placebo group. However, there were no significant intergroup differences in the results of the tests.

no-difference-cue: "no significant intergroup differences"


Astaxanthin supplementation modulates cognitive function and synaptic plasticity in young and aged mice.

We show that feeding astaxanthin to aged mice for 1 month improves performance on several hippocampal-dependent cognitive tasks and increases long-term potentiation.


Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study.

Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with the placebo group, which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain levels.

no-difference-cue: "no improvement" | favorable-cue: "improved"


Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics.

Lower plasma ET levels were associated with poorer baseline cognitive performance and faster rates of decline in function as well as in multiple cognitive domains including memory, executive function, attention, visuomotor speed, and language.


Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia.

Plasma ET concentrations were lowest in dementia (p < 0.001 vs. NCI and CIND), with intermediate levels in CIND (p < 0.001 vs. NCI).


Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.

we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, α-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma.


Prospective study of dietary mushroom intake and risk of mortality: results from continuous National Health and Nutrition Examination Survey (NHANES) 2003-2014 and a meta-analysis.

The meta-analysis of prospective cohort studies, including 601,893 individuals, showed that mushroom consumption was associated with a lower risk of all-cause mortality (pooled risk ratio: 0.94; 95% CI: 0.91, 0.98).

favorable-cue: "associated with a lower"


Effects of an ergothioneine-rich sp. on skin moisturizing functions and facial conditions: a randomized, double-blind, placebo-controlled trial.

At 12 weeks, wrinkle and texture scores were significantly better in the hiratake group than in the placebo group, and plasma EGT concentrations in the hiratake group were 4.7-fold higher than baseline (from 3.4 to 15.9 μM).


Ergothioneine for cognitive health, longevity and healthy ageing: where are we now?

Observational data consistently associate low blood ergothioneine levels with cognitive impairment, neurodegenerative diseases, cardiovascular disorders, frailty and mortality.


Prolonging healthy aging: Longevity vitamins and proteins.

the following 10 compounds as putative longevity vitamins, is reviewed: the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine


Decline of ergothioneine in frailty and cognition impairment.

In patients suffering from dementia, including Alzheimer's disease with hippocampal atrophy, deteriorating cognitive ability is correlated with declining ergothioneine levels.


Cardioprotective Effects and Antioxidant Mechanism of L-Ergothioneine in Experimental Type-2 Diabetic Rats.

L-egt protects against diabetes-induced cardiovascular injury via the upregulation of the Keap1-Nrf2 pathway and its downstream cytoprotective antioxidants.


Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Primordium Extract.

we disclosed a selective, preventive and neuroprotective effect of He2 on aged hippocampus, both on recognition memory as well on inflammation/oxidative stress/glutamate receptors expression.


Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III.

Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73-0.98)


Efficacy of olive leaf extracts in controlling blood pressure in hypertensive patients: a double-blind randomized clinical trial.

OLE can decrease 24-h BP, BPL, and diastolic BPV with improvement of lipid profile, systemic inflammation, and body weight in hypertensive patients.


Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril.

In conclusion, Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5-25 mg twice daily.


Effects of a combination of olive leaf extract and potassium on blood pressure in participants with mild to moderate hypertension: A double blind, randomized, placebo-controlled trial.

Supplementation also reduced total cholesterol by 11.1 mg/dL, LDL-cholesterol by 6.9 mg/dL, and triglycerides by approximately 22 mg/dL at Week 6, while HDL-cholesterol remained stable.

favorable-cue: "reduced total cholesterol"


Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial.

OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013).


Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats.

In the randomized clinical trial, the subjects treated with olive leaf extract exhibited significantly lower HbA1c and fasting plasma insulin levels; however, postprandial plasma insulin levels did not differ significantly by treatment group.

no-difference-cue: "did not differ" | favorable-cue: "significantly lower hba1c"


Effects of Olive Leaf Extract on Metabolic Response, Liver and Kidney Functions and Inflammatory Biomarkers in Hypertensive Patients.

The OLE tablets did not have significant effect on liver enzymes, total protein, albumin, urea and creatinine (p>0.05), but significantly decreased interleukin-6, interleukin-8 and tumor necrosis factor alpha as inflammatory biomarkers (p<0.05) in OLE group compared to the placebo group.


The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial.

Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels.

no-difference-cue: "were not significantly affected"


Antihypertensive potential of combined extracts of olive leaf, green coffee bean and beetroot: a randomized, double-blind, placebo-controlled crossover trial.

There was no significant effect of treatment on ABP or any other outcome measure. The failure to confirm prior evidence of the antihypertensive benefits of these extracts emphasises the importance of placebo control and the value of ABP monitoring.

no-difference-cue: "no significant effect" | favorable-cue: "benefits"


Efficacy and safety of olive leaf extract (Olea europaea L.) for glycaemic control in adults with type 2 diabetes mellitus (ESOLED): A pilot randomised controlled trial.

The ESOLED trial has provided preliminary evidence on the tolerability of OLE in adults with type 2 diabetes, but was inconclusive in determining whether OLE is effective at improving glycaemic control, insulin sensitivity, diabetes-related distress and quality of life.


No effect of fenugreek, bergamot and olive leaf extract on glucose homeostasis in patients with prediabetes: a randomized double-blind placebo-controlled study.

The administration of an agent containing fenugreek, olive leaf polyphenols and bergamot extract for 6 months did not improve glycemia or lipid parameters in patients with prediabetes.


Olive leaf extract effect on cardiometabolic risk factors: a systematic review and meta-analysis of randomized clinical trials.

The outcomes demonstrated a positive correlation between the intervention group and glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs).


The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials.

The present study revealed that supplementation with OLE yielded beneficial effects for blood pressure and lipid profile in adults, especially in patients with hypertension.


Efficacy of Olive Leaf Extract in Improving Blood Pressure in Pre-Hypertensive and Hypertensive Individuals: A Systematic Review and Meta-Analysis.

Olive leaf extract (1000 mg/day) may reduce systolic and diastolic blood pressure by -11.45 and -4.65 mmHg, respectively.


Cardioprotective potential of oleuropein, hydroxytyrosol, oleocanthal and their combination: Unravelling complementary effects on acute myocardial infarction and metabolic syndrome.

Conclusively, OL-HT-OC combination therapy exerts potent cardioprotective, antihyperglycemic and anti-atherosclerotic properties in vivo, with remarkable and clinically translatable cardiovascular benefits in high-risk patients.


Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases.

Thus, a protective action has been demonstrated in preclinical studies against several diseases, especially cardiovascular and metabolic disorders.


Consumption of Watermelon Juice Enriched in l-Citrulline and Pomegranate Ellagitannins Enhanced Metabolism during Physical Exercise.

the antioxidant pomegranate ellagitannins are precursors of urolithin A, which has been associated with mitophagy and increased muscle function.


Urolithin A: A Novel Postbiotic for inflammation, aging, and cancer: A Journey from Dietary ellagitannins to clinical use.

UA enhances muscle endurance, mitochondrial function indicators, and cardiometabolic health without side effects or adverse reactions in preliminary human trials, primarily including the elderly and sedentary individuals.


Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation.

Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora.


Crosstalk between dietary pomegranate and gut microbiota: evidence of health benefits.

Uro contributes to strengthening intestinal barrier and reducing inflammatory processes. Yet, Uro production varies greatly among individuals and depend on GM composition.


Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages.

Urolithins A, B, and C decreased NO production via inhibition of the iNOS protein and mRNA expression. They decreased the expression of IL-1β, TNF-α, and IL-6 mRNA in LPS challenged RAW 264.7 murine macrophages.


Impacts of supplementation with pomegranate on cardiometabolic risk factors: A systematic review and dose-response meta-analysis.

PO supplementation substantially reduced body weight (standardized mean difference (SMD): -0.14 kg, 95 % CI: -0.25, -0.03; P = 0.01), diastolic blood pressure (DBP) (SMD: -0.39 mmHg, 95 % CI: -0.59, -0.18; P < 0.001)


Effects of pomegranate juice on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

Quantitative data synthesis from 8 RCTs showed significant reductions in both systolic [weighed mean difference (WMD): -4.96mmHg, 95% CI: -7.67 to -2.25, p<0.001) and diastolic BP (WMD: -2.01mmHg, 95% CI: -3.71 to -0.31, p=0.021) after pomegranate juice consumption.


Effects of pomegranate juice consumption on blood pressure and lipid profile in patients with type 2 diabetes: A single-blind randomized clinical trial.

It is concluded that PJ consumption could decrease systolic and diastolic blood pressure in patients with diabetes while having no effect on lipid profile.


Does Pomegranate intake attenuate cardiovascular risk factors in hemodialysis patients?

Regular PJ consumption by HD patients reduced systolic blood pressure and improved lipid profile. These favorable changes may reduce the accelerated atherosclerosis and high incidence of CVD among HD patients.


Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease.

After 3 months, the extent of stress-induced ischemia decreased in the pomegranate group (SDS -0.8 +/- 2.7) but increased in the control group (SDS 1.2 +/- 3.1, p <0.05).


Influence of gut microbiota-derived ellagitannins' metabolites urolithins on pro-inflammatory activities of human neutrophils.

Urolithins can specifically modulate inflammatory functions of neutrophils, and thus could contribute to the beneficial health effects of ellagitannin-rich medicinal plant materials and food products.


The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials.

Overall analyses found significant reductions for SBP (WMD = -6.077; 95% CI: -10.736 to -1.419; P = 0.011) and DBP (WMD = -2.803; 95% CI: -4.417 to -1.189; P = 0.001) after grape seed extract treatment.


The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials.

Based on the currently available literature, grape seed extract appears to significantly lower systolic blood pressure and heart rate, with no effect on lipid or CRP levels.

no-difference-cue: "no effect" | favorable-cue: "significantly lower systolic"


The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis.

In conclusion, GSE may be beneficial for individuals with or at risk of cardiovascular disease because it may have hypotensive and HR-lowering properties.


The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials.

This meta-analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.

favorable-cue: "significantly reduced fpg, tc, ldl"


The effect of grape seed extract supplementation on oxidative stress and inflammation: A systematic review and meta-analysis of controlled trials.

It appears that GSE supplementation can remarkably modulate the body's redox system, particularly through the inhibition of lipid peroxidation, but has neutral or mildly beneficial effects on inflammatory responses.


Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial.

GSE was found to be safe and to improve BP in people with pre-hypertension, supporting the use of GSE as a functional ingredient in a low-energy beverage for BP control.


A grape seed and bilberry extract reduces blood pressure in individuals at risk of developing type 2 diabetes: the PRECISE study, a double-blind placebo-controlled cross-over intervention study.

Long-term supplementation with bilberry and grape seed extract can improve systolic and diastolic blood pressure in individuals at risk of T2DM.


Effects of Acute Grape Seed Extract Supplementation on Hemodynamics in Normal Body Weight and Obese Males.

Our study suggests that acute supplementation with GSE reduced both SBP and MAP via a reduction in CO in obese individuals and decreased peripheral vasoconstriction in NBW group.


Effects of Grape Seed Extract Supplementation on Endothelial Function and Endurance Performance in Basketball Players.

We demonstrated that chronic supplementation with GSE improved endurance performance and these effects may partially be due to vasodilation in active skeletal muscle mediated by enhanced endothelial function.


Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects.

Thus sufficient polyphenols from GSE appear to be absorbed to influence endothelial nitric oxide production, and GSE has the potential to favourably influence vascular function.


Grape Seed Extract Supplementation Attenuates the Blood Pressure Response to Exercise in Prehypertensive Men.

FMD was augmented by GSE (18.9 ± 2.0 vs. 12.4% ± 2.0%).


Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity.

GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4-week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk.


Grape seed proanthocyanidin extracts enhance endothelial nitric oxide synthase expression through 5'-AMP activated protein kinase/Surtuin 1-Krüpple like factor 2 pathway and modulate blood pressure in ouabain induced hypertensive rats.

In conclusion, GSPE increase eNOS expression and NO production in an AMPK/SIRT1 dependent manner through KLF2 induction, and attenuate ouabain induced hypertension.


Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress.

ET-1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function.


Effects of oligomeric grape seed proanthocyanidins on heart, aorta, kidney in DOCA-salt mice: role of oxidative stress.

These findings suggest that administration of GSPs has the potential to attenuate DOCA-salt induced CR and KH and preserve NO activity and endothelial function, which mechanism may contribute to its antioxidant characteristic, at least in part.


Impact of Silymarin in individuals with nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Silymarin seems to be effective in reducing transaminase levels in individuals with NAFLD. Despite the statistical benefits, we call attention to potential flaws related to the quality of the included studies.


The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials.

SIL has positive efficacy to reduce transaminases levels in NAFLD patients. SIL can be an encouraging and considerable phytotherapy for NAFLD patients.


Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis.

Silymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.


Effects of silymarin use on liver enzymes and metabolic factors in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis.


Are alterations needed in Silybum marianum (Silymarin) administration practices? A novel outlook and meta-analysis on randomized trials targeting liver injury.

silymarin administration showed a significant reduction in AST (SMD [95% CI]: - 0.670 [- 0.931, - 0.408], p-value = 0.000), and ALT (SMD [95% CI]: - 0.912 [- 1.177, - 0.646], p-value = 0.000) levels.


Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

routine silymarin administration determines a significant reduction in fasting blood glucose levels (-26.86 mg/dL; 95% CI -35.42-18.30) and HbA1c levels (-1.07; 95% CI -1.73-0.40) and has no effect on lipid profile.

no-difference-cue: "no effect" | favorable-cue: "reduction in fasting blood glucose"


Effect of Medicinal Plants and Natural Products on Liver Enzymes in Non-alcoholic Fatty Liver Patients in Iran: A Systematic Review and Meta-Analysis.

silymarin had the highest effect on the reduction of AST (SMD = -2.68), cinnamon excreted the most profound effect on ALT (SMD = -2.69).


The efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trials.

Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor.


A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis.

Silymarin may reduce liver fibrosis but this remains to be confirmed in a larger trial. It appears to be safe and well tolerated.


Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight.


Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial.

This randomized double-blinded placebo-controlled clinical trial suggested a significant benefit of silymarin, pioglitazone, and vitamin E in improving liver aminotransferases in patients with NAFLD after only 3 months, without exerting any specific side effects.


Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial.

The results of this study indicate that silymarin has no effect on survival and the clinical course in alcoholics with liver cirrhosis.


Mechanistic Insights into the Pharmacological Significance of Silymarin.

Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity.


Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases.

Overall, literature data suggest that, despite encouraging preclinical data, further well-designed randomized clinical trials are needed to fully substantiate the real value of MT preparations in liver diseases.


Nutraceutical Approach to Non-Alcoholic Fatty Liver Disease (NAFLD): The Available Clinical Evidence.

Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium-long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters.


Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers

Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast.

no-difference-cue: "was not significantly affected"


Hesperidin displays relevant role in the nutrigenomic effect of orange juice on blood leukocytes in human volunteers: a randomized controlled cross-over study

This study shows that regular consumption of orange juice for 4 weeks alters leukocyte gene expression to an anti-inflammatory and anti-atherogenic profile, and hesperidin displays a relevant role in the genomic effect of this beverage.


Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men

Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed.


Orange juice-derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease

Despite increased plasma flavanone and phenolic metabolite concentrations, cardiovascular risk biomarkers were unaltered.


The Effect of a Citrus and Pomegranate Complex on Physical Fitness and Mental Well-Being in Healthy Elderly: A Randomized Placebo-Controlled Trial

After four weeks of CPC supplementation, handgrip strength significantly improved (p=0.019), compared to placebo. Moreover, the thinking, memory, learning, and concentration facets were improved (p=0.042), compared to placebo, and plasma malondialdehyde decreased, compared to placebo (p=0.033).


8-Week Supplementation of 2S-Hesperidin Modulates Antioxidant and Inflammatory Status after Exercise until Exhaustion in Amateur Cyclists

Chronic 2S-hesperidin supplementation increased endogenous antioxidant capacity (↑SOD) after maximal effort and decreased oxidative stress (↓AUC-GSSG) during the rectangular test, decreasing inflammation (↓MCP1) after the acute recovery phase.

favorable-cue: "decreased oxidative stress"


Effects of Citrus Flavanone Hesperidin Extracts or Purified Hesperidin Consumption on Risk Factors for Cardiovascular Disease: Evidence From an Updated Meta-analysis of Randomized Controlled Trials

intercellular adhesion molecule 1 (WMD: -13.60 ng/mL; 95% CI: -23.72, -3.48 ng/mL), vascular cell adhesion molecule 1 (WMD: -15.60 ng/mL; 95% CI: -30.13, -1.06 ng/mL), and C-reactive protein (WMD: -0.56 mg/L; 95% CI: -1.11, -0.01 mg/L), whereas no effects were found for other CVDRFs.


Effect of hesperidin on blood pressure and lipid profile: A systematic review and meta-analysis of randomized controlled trials

the outcomes of this meta-analysis suggest that hesperidin administration could benefit patients with CVD by reducing LDL, TC, and TG.


Effects of Hesperidin Supplementation on Cardiometabolic Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

The results of this study demonstrate that hesperidin supplementation had a significant impact on reducing FBS, TG, TC, LDL-C, SBP, and TNF-α. However, there was no significant effect observed on insulin, HOMA-IR, QUICKI, HDL-C, DBP, and hs-CRP.

no-difference-cue: "no significant effect"


The effects of hesperidin supplementation on cardiovascular risk factors in adults: a systematic review and dose-response meta-analysis

The results showed that hesperidin supplementation had a significant effect on reducing serum triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL), tumor necrosis factor-alpha (TNF-α), and systolic blood pressure (SBP), whereas weight was increased.


Hesperidin reduces systolic blood pressure in diabetic patients and has no effect on blood pressure in healthy individuals: A systematic review and meta-analysis

However, hesperidin reduced systolic blood pressure in patients with type 2 diabetes (WMD = -4.32, 95% CI: - 7.77 ~ - 0.87, Z = 2.45, p = 0.01), and had a tendency to reduce diastolic blood pressure in diabetic patients (WMD = -3.72, 95% CI: -7.63 ~ 0.18, Z = 1.87, p = 0.06).


Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials

Hesperidin supplement also had no effect on systolic (WMD = -0.85 mmHg; 95% CI [-3.07, 1.36]) and diastolic blood pressure (WMD = -0.48 mmHg; 95% CI [-2.39, 1.42]). Hesperidin supplementation might not improve lipid profile and blood pressure.


Effects of hesperidin consumption on cardiovascular risk biomarkers: a systematic review of animal studies and human randomized clinical trials

In the human studies, endothelial function improved with flavonoid consumption, whereas no conclusive results were observed for the other biomarkers.


Hesperidin, hesperidin methyl chalone and phellopterin from Poncirus trifoliata (Rutaceae) differentially regulate the expression of adhesion molecules in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells

hesperidin, hesperidin methyl chalone and phellopterin reduce TNF-alpha-induced VCAM-1 expression through regulation of the Akt and PKC pathway, which contributes to inhibit the adhesion of monocytes to endothelium.


Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites

Hp7GA enhanced nitric oxide (NO) release by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) activity in a human umbilical vein endothelial cell culture system, indicating that plasma hesperetin metabolites can improve vasodilatation in the vascular system.


Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis.

Our findings suggest that apigenin is a promising phytochemical for reducing the impact of senescent cells in age-related lung diseases such as COPD.


Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages.

These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels.


NAD+ and sirtuins in aging and disease.

NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies.


Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion.

Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression.


The NADase CD38 is a central regulator in gouty inflammation and a novel druggable therapeutic target.

Mouse air pouch inflammatory responses to MSU crystals were blunted by CD38 KO and apigenin.


Targeting CD38 to Suppress Osteoarthritis Development and Associated Pain After Joint Injury in Mice.

CD38 deficiency exerts OA disease-modifying effects. Inhibition of CD38 has the potential to be a novel therapeutic approach for OA treatment.


CD38 Coordinates with NF-kappaB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

apigenin significantly reduce the threshold shift of hearing by inhibiting the expression of NF-κB and CD38 can be a promising target for protecting against noise-induced hearing loss.


Apigenin: a natural molecule at the intersection of sleep and aging.

Cumulatively, a large body of evidence positions apigenin as a unique molecule capable of influencing both aging and sleep.


Efficacy and safety of Matricaria chamomilla intervention in managing menopausal symptoms: a triple-blind clinical trial.

Notable differences were found between the intervention and control groups in the overall scores on the symptom scorecard from baseline to 12 weeks' postintervention (-10.36; 95% confidence interval [CI], -13.84 to -6.92; P < 0.001).


Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo.

we found that the apigenin-containing cream increased dermal density and elasticity, and reduced fine wrinkle length.

favorable-cue: "increased dermal density"


Apigenin potentiates glucose-stimulated insulin secretion through the PKA-MEK kinase signaling pathway independent of K-ATP channels.

Apigenin exerts glucose-stimulated insulin secretion by modulating the PKA-MEK kinase signaling cascade independent of K-ATP channels.


Luteolin Could Improve Cognitive Dysfunction by Inhibiting Neuroinflammation.

luteolin prevented the increase of TNF-α and IL-1β, IL-6, and MDA, improved the activity of SOD and GPx, inhibited microglia over-activation and astrogliosis (particularly in the hippocampus and cortex), and ameliorated learning and short-term memory dysfunction, and LTP deficit.


Luteolin and Exercise Combination Therapy Ameliorates Amyloid-β1-42 Oligomers-Induced Cognitive Impairment in AD Mice by Mediating Neuroinflammation and Autophagy.

Luteolin (100 mg/kg/d) combined with exercise could significantly improve the performance of AD model mice in novel object recognition test, and the improvement was greater than that of monotherapy.


Luteolin Suppresses Microglia Neuroinflammatory Responses and Relieves Inflammation-Induced Cognitive Impairments.

these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.

unfavorable-cue: "impairment" | favorable-cue: "effective"


Co-ultraPEALut in Subjective Cognitive Impairment Following SARS-CoV-2 Infection: An Exploratory Retrospective Study.

Neuro-post-COVID-19 patients treated with co-ultraPEALut scored better than controls in MoCA and PRMQ questionnaires after 10 months: this may support the importance of neuroinflammation modulation for neuro-long-COVID-19.


Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.

At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA-LUT alone, and 41.6% receiving once daily um-PEA-LUT alone (p < 0.00001).


Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial.

The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls.


Efficacy of Palmitoylethanolamide and Luteolin Association on Post-Covid Olfactory Dysfunction: A Systematic Review and Meta-Analysis of Clinical Studies.

CoUltraPEALut demonstrated significant efficacy in the overall recovery of the olfactory function, compared to the conventional therapy, suggesting that it could represent a possible future adjuvant treatment for PCOD.


A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (), Luteolin, and Fisetin ().

Luteolin did not decrease symptom severity more than placebo at either the lower (= 0.718) or higher dosages (= 0.492).


An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders.

There was a significant improvement in adaptive functioning as measured by using the VABS age-equivalent scores (8.43 months in the communication domain, 7.17 months in daily living skills, and 8 months in the social domain; P < 0.005)


Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6.

the mean serum IL-6 and TNF levels decreased significantly (P=0.036 and P=0.015, respectively) at the end of the treatment period (26 weeks) as compared with levels at the beginning


Luteolin prevents liver from tunicamycin-induced endoplasmic reticulum stress via nuclear factor erythroid 2-related factor 2-dependent sestrin 2 induction.

luteolin significantly decreased Tm- or thapsigargin-mediated C/EBP homologous protein (CHOP) expression. In addition, luteolin reduced the activation of three canonical signaling pathways related to the unfolded protein response


Preclinical evidence for luteolin in ulcerative colitis: a meta-analysis and systematic review.

The meta-analysis revealed that LUT significantly ameliorated colon length, reduced the disease activity index, alleviated body weight loss, and decreased histological scores.


Cardioprotective Effects and Possible Mechanisms of Luteolin for Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis of Preclinical Evidence.

Pooling of the data demonstrated that luteolin exerts cardioprotective effects against MIRI through different signaling pathways. As possible mechanisms, luteolin exerts anti-apoptosis, anti-oxidation, and anti-inflammation effects against MIRI.


Focal brain inflammation and autism.

The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.


The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer's disease: a narrative review.

Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer's disease.


Paving Luteolin Therapeutic Potentialities and Agro-Food-Pharma Applications: Emphasis on Pharmacological Effects and Bioavailability Traits.

luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored.


Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial.

daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function.


Cocoa flavanols alleviate early diastolic dysfunction by decreasing left atrial volume in a randomized double blinded trial in healthy older individuals.

Flavanol intake counteracted subclinical cardiac dysfunction, evidenced by a 12.6 ± 3.5% reduction in maximal LA volume


The overlooked impact of background diet and adherence in nutrition trials.

Taking these factors into account resulted in a larger effect size for all observed endpoints


Effect of cocoa on blood pressure.

This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.


Does chocolate reduce blood pressure? A meta-analysis.

Our meta-analysis suggests that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension.


Chocolate and prevention of cardiovascular disease: a systematic review.

Our updated meta-analysis indicates that intake of flavonoids may lower risk of CHD mortality, RR = 0.81 (95% CI: 0.71-0.92) comparing highest and lowest tertiles.


Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial.

Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate.


Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial.

Consumption of DP1-10, but not of either DP2-10 or the control capsule, significantly increased flow-mediated vasodilation (primary endpoint) and the concentration of structurally related (-)-epicatechin metabolites (SREMs) in the circulatory system while decreasing pulse wave velocity and blood pressure.


Cocoa Flavanols Improve Vascular Responses to Acute Mental Stress in Young Healthy Adults.

Flavanols are effective at counteracting mental stress-induced endothelial dysfunction and improving peripheral blood flow during stress.


Cocoa flavanols lower vascular arginase activity in human endothelial cells in vitro and in erythrocytes in vivo.

erythrocyte arginase activity was lowered in healthy humans following consumption of a high flavanol beverage in vivo.


(-)-epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways.

Together, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (-)-epicatechin, which may mediate its cardiovascular effects.


Cocoa Flavanols Protect Human Endothelial Cells from Oxidative Stress.

Our results demonstrate for the first time that a polyphenolic extract from cocoa and its main flavonoid protect human endothelial cells against an oxidative insult by modulating oxygen radical generation and antioxidant enzyme and non-enzyme defences.


Changes in endothelial function, arterial stiffness and blood pressure in pregnant women after consumption of high-flavanol and high-theobromine chocolate: a double blind randomized clinical trial.

Chronic HFHT intake increased plasma theobromine, though it did not have positive impacts on endothelial function, arterial stiffness or BP when compared to LFLT in pregnant women at risk of PE.


[Cacoa and dark chocolate in cardiovascular prevention?].

An increase of endothelial NO production following the ingestion of the antioxidant cocoa flavanols catechin and epicatechin seems to be the leading mechanism causing these effects.


Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.

In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051).


Endothelium-dependent vascular effects of Pycnogenol.

These results indicate that P, in addition to its antioxidant activity, stimulates constitutive endothelial NOS (eNOS) activity to increase NO levels, which could counteract the vasoconstrictor effects of E and NE.


A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology.

PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of endothelial nitric oxide synthase.


Effect of pycnogenol supplementation on blood pressure: A systematic review and meta-analysis of clinical trials.

Pooled analysis suggested that pycnogenol supplementation can reduced systolic blood pressure (SBP) of (-3.22 mmHg; 95% CI [-5.52, -0.92]) and diastolic blood pressure (DBP; -1.91 mmHg; 95% CI [-3.64, -0.18]).


Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis.

Compared with the control, the pooled estimate of change in systolic and diastolic BPs were -3.22 mmHg (95% CI: -6.20, -0.24) and -3.11 mmHg (95% CI: -4.60, -1.62), respectively.


Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies.

Therefore, the present meta-analysis does not suggest any significant effect of pycnogenol on BP.


Pine bark (Pinus spp.) extract for treating chronic disorders.

Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.


Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial.

Intake of Pycnogenol for 1 month restored erectile function to normal. Intercourse frequency doubled. e-NOS in spermatozoa and testosterone levels in blood increased significantly.


Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized, double-blind, placebo-controlled, parallel-arm study.

This study shows that Prelox is effective for improving erectile function, and that this effect persists on continuous therapy for up to 6 months.


Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation.

After 12 weeks of supplementation, Pycnogenol resulted in improved diabetes control, lowered CVD risk factors, and reduced antihypertensive medicine use vs controls.


Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II.

Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function.


Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55.

Pycnogenol® supplementation for 12 weeks appears to improve cognitive function and oxidative stress in healthy professionals.


Pycnogenol® supplementation in minimal cognitive dysfunction.

In the Pycnogenol® group MMSE score at inclusion was on average 21.64±1.5; after 8 weeks of supplementation, the average MMSE score increased significantly to 25.64±1.4 (P<0.05).


Pleiotropic Effects of French Maritime Pine Bark Extract to Promote Healthy Aging.

The extract reduces oxidative stress and improves endothelial health. Its antithrombotic properties are based on inhibition of platelet aggregation.


The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects.

Pycnogenol (PYC) is a natural compound that could control inflammation and oxidative stress.


Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality.

There were significant increases in time in bed, total sleep time and sleep efficiency total (P < 0.05) with cherry juice supplementation.


Effects of a tart cherry juice beverage on the sleep of older adults with insomnia: a pilot study.

When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo.


The Effect of Tart Cherry on Sleep Quality and Sleep Disorders: A Systematic Review.

Three studies reported significant improvements in sleep indicators such as sleep duration, sleep efficiency, or sleep onset time. Three studies also reported an increase in melatonin levels after tart cherry consumption.


Efficacy, acceptability, and tolerability of all available treatments for insomnia in the elderly: a systematic review and network meta-analysis.

The limited evidence on non-pharmacological interventions suggested that acupressure, auricular acupuncture, mindfulness-based stress reduction program, and tart cherry juice were better than their control interventions.


Sleep and Nutrition Interactions: Implications for Athletes.

Various nutritional interventions have been shown to improve sleep including high carbohydrate, high glycaemic index evening meals, melatonin, tryptophan rich protein, tart cherry juice, kiwifruit and micronutrients.


Sleep Hygiene and Recovery Strategies in Elite Soccer Players.

Consuming high-electrolyte fluids such as milk, high-glycemic index carbohydrates, some forms of protein immediately prior to sleep, as well as tart cherry juice concentrate and tryptophan may promote rehydration, substrate stores replenishment, muscle-damage repair and/or restorative sleep.


Montmorency cherry juice reduces muscle damage caused by intensive strength exercise.

Montmorency cherry juice consumption improved the recovery of isometric muscle strength after intensive exercise perhaps owing to the attenuation of the oxidative damage induced by the damaging exercise.


Influence of a montmorency cherry juice blend on indices of exercise-induced stress and upper respiratory tract symptoms following marathon running--a pilot investigation.

The CRP increase at 24 and 48 h post-Marathon was lower (P < 0.01) in the CJ group compared to PL group.


Effects of powdered Montmorency tart cherry supplementation on acute endurance exercise performance in aerobically trained individuals.

Results revealed that short-term supplementation of Montmorency powdered tart cherries surrounding an endurance challenge attenuated markers of muscle catabolism, reduced immune and inflammatory stress, better maintained redox balance, and increased performance in aerobically trained individuals.

favorable-cue: "reduced immune and inflammatory"


Montmorency tart cherry juice does not reduce markers of muscle soreness, function and inflammation following professional male rugby League match-play.

These data suggest MC does not affect the modest changes observed in cytokine responses and markers of recovery from RL match-play.


The role of cherries in exercise and health.

Reported to be high in anti-inflammatory and anti-oxidative capacity, cherries and their constituents are proposed to provide a similar but natural alternative akin to over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) or analgesics.


Dose-dependent effect of tart cherry on blood pressure and selected inflammation biomarkers: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Regarding the 21 included trials, Tart cherry didn't affect blood pressure, heart rate, high-sensitive C-reactive protein, and interleukin-6 (P > 0.05).