Research
Hesperidin
52 peer-reviewed studies curated from PubMed and Semantic Scholar.
Studies
Sorted by quality and recency
The effects of hesperidin supplementation on insulin resistance and sensitivity in adults: a systematic review and meta-analysis of randomized controlled trials.
This systematic review and meta-analysis evaluated the effects of hesperidin supplementation on insulin resistance and sensitivity in adults, including 16 RCTs with 845 participants. Hesperidin significantly reduced HOMA-IR and increased the insulin sensitivity index, but no significant effects were observed on insulin, fasting blood glucose, or glycated hemoglobin A1c. The evidence does not support hesperidin as an effective intervention for insulin resistance or glycemic control.
Drug delivery and formulation development of hesperidin: a systematic review.
Systematic review of formulation strategies to improve hesperidin's bioavailability and solubility. The review included 69 studies on various delivery systems, with lipidic and polymeric nanosystems showing the most consistent improvements. The review highlights the need for further clinical trials to translate these findings.
Effects of Hesperidin Supplementation on Cardiometabolic Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Systematic review and meta-analysis of RCTs investigating hesperidin supplementation on cardiometabolic markers. Hesperidin significantly reduced fasting blood sugar, triglycerides, total cholesterol, LDL-C, systolic blood pressure, and TNF-alpha. No significant effects were observed on insulin, HOMA-IR, QUICKI, HDL-C, diastolic blood pressure, and hs-CRP. Interventions over 12 weeks and doses over 500 mg/day were particularly effective.
Hesperidin reduces systolic blood pressure in diabetic patients and has no effect on blood pressure in healthy individuals: A systematic review and meta-analysis.
Systematic review and meta-analysis of 14 studies with 656 patients examining the effect of hesperidin on blood pressure. Hesperidin reduced systolic blood pressure in diabetic patients but had no effect on blood pressure in healthy individuals.
Efficacy and molecular mechanisms of hesperidin in mitigating Alzheimer's disease: A systematic review.
Systematic review of preclinical studies on hesperidin's neuroprotective mechanisms in Alzheimer's disease. Hesperidin inhibits Aβ aggregation, enhances antioxidant defenses, reduces neuroinflammation, and promotes neurogenesis. Clinical trials suggest potential cognitive benefits, but further research is needed to confirm effects in humans.
Effects of hesperidin on anti-inflammatory and antioxidant response in healthy people: a meta-analysis and meta-regression.
Meta-analysis of 18 human intervention trials evaluating hesperidin supplementation on anti-inflammatory and antioxidant parameters. Hesperidin significantly lowered CRP, IL-6, IL-4, and MDA levels, contributing to inflammatory and antioxidant response independently of dosage.
The effects of hesperidin supplementation or orange juice consumption on anthropometric measures in adults: A meta-analysis of randomized controlled clinical trials.
Meta-analysis of 11 RCTs with 512 individuals assessing the effect of orange juice and/or hesperidin supplementation on anthropometric measures. The study found no significant effect on body weight, BMI, fat mass, percentage body fat, or waist circumference.
Impact of hesperidin in 100% orange juice on chronic disease biomarkers: A narrative systematic review and gap analysis.
This narrative systematic review analyzed the impact of hesperidin in 100% orange juice on chronic disease biomarkers. The review found that higher frequencies, doses, and concentrations of hesperidin had an impact on cognitive function, cardiac, insulin, inflammatory, antioxidant/phenolic, and oxidative stress outcomes. However, variability in study designs made the role of hesperidin unclear.
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.
Systematic review and meta-analysis of 10 RCTs with 577 participants evaluating hesperidin supplementation on lipid profile and blood pressure. The analysis found no significant effect of hesperidin on serum cholesterol, triglycerides, or blood pressure.
Hesperidin supplementation has no effect on blood glucose control: A systematic review and meta-analysis of randomized controlled clinical trials.
Systematic review and meta-analysis of six randomized controlled trials with 318 participants assessing the effect of hesperidin supplementation on blood glucose control. The study found no significant effect of hesperidin on serum fasting blood glucose, plasma insulin, glycated haemoglobin A1c, insulin resistance, or insulin sensitivity.
The effect of hesperidin supplementation on inflammatory markers in human adults: A systematic review and meta-analysis of randomized controlled clinical trials.
Systematic review and meta-analysis of six RCTs with 296 participants examining hesperidin supplementation on inflammatory markers. Hesperidin significantly reduced VCAM-1 levels but had no significant effect on CRP, E-selectin, interleukin 6, and ICAM-1 levels.
Enhanced skin photoprotection integrating a spray-dried hesperetin nanocapsules semisolid formulation: Development of the formulation and clinical trial study.
The study developed a cosmetic formulation containing spray-dried hesperetin nanocapsules for skin photoprotection. The formulation showed high photoprotective capacity, stability, and safety, with an SPF value of 12.71 and similar protection to an SPF 30 sunscreen in a pilot clinical study.
Lemon flavonoids nutraceutical (Eriomin®) attenuates prediabetes intestinal dysbiosis: A double‐blind randomized controlled trial
Double-blind RCT assessing the effect of Eriomin®, a nutraceutical with 70% eriocitrin, on the microbiota of prediabetic patients. Eriomin® supplementation led to a 6% decrease in hyperglycemia and a 22% increase in GLP-1 blood levels, with changes in microbiota composition, including increased Ruminococcaceae and reduced Blautia genus.
The Effect of Hesperidin and Diosmin Individually or in Combination on Metabolic Profile and Neuropathy among Diabetic Patients with Metabolic Syndrome: A Randomized Controlled Trial.
RCT of 129 T2DM patients with MetS and neuropathy comparing hesperidin, diosmin, and their combination to oral hypoglycemics alone over 12 weeks. Both hesperidin and diosmin groups showed significant reductions in blood glucose, triglycerides, and LDL. The combination was more effective, also improving MNSI scores significantly.
Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).
RCT assessing the effects of orange juice with natural and enriched hesperidin on blood and pulse pressures in mildly hypertensive individuals. A single dose of hesperidin-enriched orange juice reduced systolic and pulse pressures, with greater reductions after sustained consumption. Hesperidin also decreased homocysteine levels and altered gene expression related to hypertension.
Effects of hesperidin consumption on cardiovascular risk biomarkers: a systematic review of animal studies and human randomized clinical trials.
Systematic review of 12 animal studies and 11 human randomized clinical trials evaluating the effects of hesperidin on cardiovascular risk biomarkers. Animal studies showed reductions in glucose, total and LDL cholesterol, and triglyceride levels, while human studies showed improved endothelial function but inconclusive results for other biomarkers.
Radioprotective Effect of Hesperidin: A Systematic Review.
Systematic review evaluating the radioprotective effect of hesperidin against ionizing radiation-induced damage. The review included 24 studies involving rats, mice, and cultured human and animal cells, showing that hesperidin reduced oxidative stress and inflammation, increased survival rates, and protected against DNA damage.
The Effectiveness of Hesperidin, Diosmin and Proanthocyanidins Nutritional Supplementation on Cognitive and Motor Functions in Older Adults: A Pilot Randomized Control Study.
Pilot randomized controlled study evaluating the effects of Altermor, a supplement containing hesperidin, diosmin, and proanthocyanidins, on cognitive and motor functions in older adults. The study found significant improvements in cognitive function, particularly attention, and reduced fall risk in the experimental groups compared to the control group.
Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization-A Randomized, Crossover and Double-Blind Clinical Trial.
This randomized, crossover, and double-blind clinical trial evaluated the effects of micronization and diastereoisomer ratios on hesperidin bioavailability in healthy individuals. The study found that the bioavailability of 2S-hesperidin extract was higher compared to the standard mixture of 2S-/2R-hesperidin extract, and that the micronization process increased hesperidin bioavailability.
Effect of the consumption of hesperidin in orange juice on the transcriptomic profile of subjects with elevated blood pressure and stage 1 hypertension: A randomized controlled trial (CITRUS study).
RCT investigating the effects of hesperidin in orange juice on the transcriptomic profile of 37 subjects with elevated blood pressure and stage 1 hypertension. A single dose and 12-week treatment of hesperidin decreased systolic blood pressure and downregulated proinflammatory genes, suggesting protective effects against insulin resistance and inflammation.
Hesperidin improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial.
This randomized, double-blind, placebo-controlled clinical trial evaluated the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) in 50 patients. Hesperidin supplementation significantly reduced hepatic enzymes, cholesterol, triglycerides, hepatic steatosis, and inflammatory markers compared to placebo, suggesting benefits in managing NAFLD.
Hesperidin reduces adverse symptomatic intracerebral hemorrhage by promoting TGF-β1 for treating ischemic stroke using tissue plasminogen activator.
RCT assessing the impact of hesperidin on symptomatic intracerebral hemorrhage (SIH) in ischemic stroke patients treated with rt-PA. Hesperidin improved outcomes by reducing SIH incidences and enhancing recovery, potentially through elevation of TGF-β1 and reduction of MMP-2 and MMP-9 levels.
Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial.
This randomized double-blind controlled clinical trial examined the effects of 500 mg/day hesperidin supplementation on blood pressure and inflammatory markers in 64 patients with type 2 diabetes over 6 weeks. The hesperidin group showed significant reductions in systolic blood pressure, mean arterial blood pressure, IL-6, and hs-CRP, and an increase in total antioxidant capacity compared to baseline and the placebo group.
A Critical Evaluation of In Vitro Hesperidin 2S Bioavailability in a Model Combining Luminal (Microbial) Digestion and Caco-2 Cell Absorption in Comparison to a Randomized Controlled Human Trial.
The study evaluated the bioavailability of hesperidin 2S using an in vitro model combining microbial digestion and Caco-2 cell absorption, compared to a human trial. In vitro, hesperidin was resistant to degradation in the stomach and small intestine but degraded in the colon. In humans, hesperetin-glucuronide levels increased significantly, indicating different bioavailability patterns between in vitro and in vivo models.
Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid Peroxidation in Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Clinical Trial.
This randomized double-blind placebo-controlled clinical trial examined the effects of 500 mg/day hesperidin supplementation on glycemic parameters, oxidative DNA damage, and lipid peroxidation in 64 patients with type 2 diabetes over 6 weeks. Hesperidin improved total antioxidant capacity and reduced serum froctoseamin, 8-OHDG, and MDA levels compared to baseline and placebo.
Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals.
RCT investigating the effect of hesperidin 2S supplementation on endothelial function in 68 overweight individuals. No significant change in fasting or postprandial FMD was observed, but there was a trend for reduction in adhesion molecules and blood pressure. In subjects with baseline FMD ≥3%, hesperidin improved postprandial endothelial dysfunction and reduced adhesion molecules.
Hesperidin supplementation modulates inflammatory responses following myocardial infarction.
RCT of 75 myocardial infarction patients comparing 600mg/day hesperidin supplementation to placebo for 4 weeks. Hesperidin significantly decreased serum levels of E-selectin and increased adiponectin and HDL-C concentrations, suggesting potential cardioprotective and anti-inflammatory benefits.
Gastrointestinal absorption and metabolism of hesperetin-7-O-rutinoside and hesperetin-7-O-glucoside in healthy humans.
The study investigated the gastrointestinal absorption and metabolism of hesperetin-7-O-rutinoside (hesperidin) and hesperetin-7-O-glucoside in healthy humans using a single-blind, randomized crossover design. Hesperetin-7-O-glucoside was rapidly hydrolyzed and absorbed, while hesperetin-7-O-rutinoside showed minimal hydrolysis and absorption.
Pharmacokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans.
This study analyzed the pharmacokinetics of flavanone glycosides, hesperidin and narirutin, in humans after consuming fresh-squeezed versus commercially processed orange juice. No significant differences were found in the pharmacokinetic parameters between the two juice types.
Correlation between improvement in functional signs and plethysmographic parameters during venoactive treatment (Cyclo 3 Fort).
Open-label clinical trial in 65 women with venous insufficiency assessing the effects of Cyclo 3 Fort (Ruscus aculeatus, hesperidin methylchalcone, and ascorbic acid). Treatment improved venous refilling time and functional symptoms, showing a significant correlation between subjective and objective improvements.
The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women.
RCT with 204 moderately hypercholesterolemic men and women evaluating the LDL-C-lowering efficacy of hesperidin and naringin. Participants consumed capsules with either placebo, 800 mg hesperidin, or 500 mg naringin daily for 4 weeks. Hesperidin and naringin did not affect serum TC, LDL-C, HDL-cholesterol, or triglyceride concentrations.
Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion.
Randomised cross-over study examining the absorption, metabolism, and excretion of flavanones from orange fruit and juice in 129 subjects. Flavanone conjugates were detected in plasma and urine, with no difference in absorption or excretion between fruit and juice. A small decrease in hesperetin excretion was observed with increasing age.
Solubility of hesperidin drug in aqueous biodegradable acidic choline chloride-based deep eutectic solvents
The study investigates the solubility of hesperidin in water and various choline chloride-based deep eutectic solvents at different temperatures. The solubility data was analyzed using Van’t Hoff–Jouyban–Acree and Modified Apelblat–Jouyban–Acree models, and Hansen solubility parameters were estimated for the dissolution processes.
Nanoemulsion for improving the oral bioavailability of hesperetin: formulation optimization and absorption mechanism.
The study aimed to prepare a nanoemulsion vehicle to improve the oral bioavailability of hesperetin. The nanoemulsion increased the AUC0-t and Cmax of hesperetin by 5.67-fold and 2.64-fold, respectively, and enhanced lymphatic transport and intestinal permeability.
The effect of hesperidin supplementation on metabolic profiles in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.
This randomized, double-blind, placebo-controlled clinical trial evaluated the effects of 500-mg hesperidin supplementation twice daily for 12 weeks in 49 patients with metabolic syndrome. Hesperidin significantly decreased fasting glucose, triglycerides, systolic blood pressure, and TNF-α levels compared to placebo, indicating improvements in metabolic abnormalities and inflammatory status.
Acute Effects of Hesperidin in Oxidant/Antioxidant State Markers and Performance in Amateur Cyclists.
RCT using a crossover design in 15 amateur cyclists to assess the acute effects of 500 mg of 2S-Hesperidin (Cardiose) on antioxidant status, metabolism, and athletic performance. Significant improvements were found in anaerobic performance metrics such as average power, maximum speed, and total energy in the sprint test after Cardiose intake compared to placebo.
Effect of the flavonoid hesperidin on glucose and fructose transport, sucrase activity and glycaemic response to orange juice in a crossover trial on healthy volunteers.
Crossover trial on healthy volunteers examining the effect of hesperidin on glucose and fructose transport, sucrase activity, and glycaemic response to orange juice. Hesperidin attenuated glucose transport across cell monolayers and affected fructose transport by inhibiting GLUT5. In vivo, hesperidin modulated postprandial glycaemic response, with effects depending on sugar and hesperidin concentrations.
Effect of Daily Consumption of Orange Juice on the Levels of Blood Glucose, Lipids, and Gut Microbiota Metabolites: Controlled Clinical Trials.
Controlled clinical trial with 10 healthy women consuming commercial pasteurized orange juice for 2 months. The study found improvements in blood biochemical parameters, such as LDL-cholesterol, glucose, and insulin sensitivity, and positive modulation of gut microbiota, increasing Bifidobacterium spp. and Lactobacillus spp. populations.
Urinary excretion of Citrus flavanones and their major catabolites after consumption of fresh oranges and pasteurized orange juice: A randomized cross-over study.
Randomized cross-over study comparing bioavailability and colonic catabolism of flavanones from fresh oranges and pasteurized orange juice in 12 healthy subjects. Despite a 2.4-fold higher dose from fresh oranges, urinary excretion of flavanones did not differ significantly from that following orange juice consumption.
Effect of Hesperidin With and Without a Calcium (Calcilock) Supplement on Bone Health in Postmenopausal Women.
Double-blind, placebo-controlled, randomized-order crossover study of 500 g hesperidin with or without 500 mg calcium supplement in 12 healthy postmenopausal women. Calcium plus hesperidin improved bone calcium retention by 5.5%, while hesperidin alone did not.
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.
A randomized, placebo-controlled crossover trial in 16 men at moderate cardiovascular disease risk examined the effects of orange juice or a hesperidin supplement on cardiovascular risk biomarkers. Despite increased plasma flavanone and phenolic metabolite concentrations after orange juice intake, no effects were observed on cardiovascular risk biomarkers.
Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men.
Randomized cross-over trial with 25 mild hypercholesterolemic men comparing blond orange juice to a control beverage. Orange juice intake led to a marked antioxidant effect, correlated with hesperetin plasma levels, and showed a tendency towards reduced endothelial dysfunction and increased plasma apoA-I concentration.
Orange juice and its major polyphenol hesperidin consumption do not induce immunomodulation in healthy well-nourished humans.
Randomized crossover study in 24 healthy men assessing the effects of orange juice and hesperidin on immune cell functions. No significant changes were observed in leukocyte distributions, ROS production, NK cell activity, or cytokine production, indicating no immunomodulatory effect.
Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome.
A randomized, placebo-controlled, double-blind, crossover trial examined the effects of oral hesperidin (500 mg daily for 3 weeks) on endothelial function in individuals with metabolic syndrome. Hesperidin treatment increased flow-mediated dilation and reduced circulating inflammatory biomarkers compared to placebo, suggesting vasculoprotective actions.
Controlling for sugar and ascorbic acid, a mixture of flavonoids matching navel oranges significantly increases human postprandial serum antioxidant capacity.
A placebo-controlled crossover trial with 16 participants tested the effects of orange flavonoids on postprandial serum antioxidant capacity. The mixture of hesperidin, luteolin, and naringenin significantly increased serum oxygen radical absorbance capacity and lipoprotein oxidation lag time, suggesting a positive effect on postprandial oxidative protection.
Hesperidin displays relevant role in the nutrigenomic effect of orange juice on blood leukocytes in human volunteers: a randomized controlled cross-over study.
Randomized controlled crossover study in healthy volunteers assessing the effect of orange juice and hesperidin on leukocyte gene expression. Both orange juice and hesperidin significantly affected gene expression, suggesting anti-inflammatory and anti-atherogenic effects.
Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers.
Randomized crossover study in 24 healthy, overweight men investigating the effects of orange juice and hesperidin on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers. Orange juice and hesperidin significantly lowered diastolic blood pressure and improved postprandial microvascular endothelial reactivity compared to placebo.
Effects of alpha-glucosylhesperidin, a bioactive food material, on collagen-induced arthritis in mice and rheumatoid arthritis in humans.
The study evaluated the effects of alpha-glucosylhesperidin (Hsp-G) on collagen-induced arthritis in mice and rheumatoid arthritis in humans. In mice, oral administration of Hsp-G improved arthritis symptoms. In a 12-week double-blind, placebo-controlled trial with 19 human patients, 3 of 9 patients in the Hsp-G group showed improvement compared to 1 of 10 in the placebo group, suggesting Hsp-G may be effective as a complementary treatment for rheumatoid arthritis.
Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial.
This randomized, double-blind, crossover trial in 16 healthy volunteers compared the bioavailability of hesperidin in different forms. The study found that enzymatic conversion of hesperidin to hesperetin-7-glucoside significantly improved its bioavailability, with higher plasma concentrations and faster absorption compared to natural hesperidin.
Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables.
This study investigated the fasting plasma concentrations of quercetin, hesperetin, and naringenin in 37 healthy females consuming habitual diets and diets high or low in fruit and vegetables. The high-vegetable diet increased plasma hesperetin and naringenin concentrations, but these flavanones were poor biomarkers of intake. Quercetin levels remained stable across diets.
Hesperidin, a Bioflavonoid in Cancer Therapy: A Review for a Mechanism of Action through the Modulation of Cell Signaling Pathways
The review discusses the potential of hesperidin, a flavonoid found in citrus fruits, in cancer therapy. It highlights hesperidin's antioxidant, anti-inflammatory, and anticancer properties, focusing on its modulation of cell signaling pathways such as apoptosis, cell cycle, and angiogenesis. The article also explores hesperidin's synergistic effects with anticancer drugs.
The Effect of Dietary Antioxidant Supplementation in Patients with Glaucoma.
Prospective single-arm study of 30 Japanese glaucoma patients given a supplement containing hesperidin and crocetin for 8 weeks. In patients with high oxidative stress, 8-OHdG levels were significantly reduced and BAP was elevated, suggesting potential benefits of antioxidant supplementation in oxidative stress-related conditions.