Research
Synephrine (Bitter Orange)
46 peer-reviewed studies curated from PubMed and Semantic Scholar.
Studies
Sorted by quality and recency
The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis
Systematic review and meta-analysis of 18 placebo-controlled human clinical trials evaluating the safety and efficacy of synephrine for weight loss. Synephrine was found to significantly increase both systolic and diastolic blood pressure, with no significant effect on weight loss or body composition.
Effect of Citrus Aurantium L. on pain and blood pressure in patients undergoing hand reconstructive surgery.
Double-blind, randomized clinical trial with 76 patients undergoing hand reconstructive surgery. The intervention group received Citrus Aurantium essential oil, showing significantly greater pain reduction and decreased systolic blood pressure compared to the control group.
The effect of aromatherapy with Citrus Aurantium essential oil on depression, stress and anxiety in pregnant women; a randomized controlled clinical trial.
RCT of 68 pregnant women assessing the effect of Citrus Aurantium essential oil aromatherapy on depression, stress, and anxiety. The intervention significantly reduced depression and anxiety scores compared to placebo, but the effect on stress was not statistically significant.
The Effect of Citrus Aurantium Aroma on the Sleep Quality in Postmenopausal Women: A Randomized Controlled Trial.
This double-blind randomized controlled trial studied the effect of Citrus aurantium aroma on sleep quality in 80 postmenopausal women with sleep disturbances. The intervention group used Citrus aurantium essential oil, showing significant improvement in sleep quality compared to the control group using almond oil.
Effect of a Combination of Citrus Flavones and Flavanones and Olive Polyphenols for the Reduction of Cardiovascular Disease Risk: An Exploratory Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects.
A randomized, double-blind controlled trial assessed the efficacy of a supplement combining grapefruit, bitter orange, and olive extracts over eight weeks in reducing cardiovascular risk in healthy volunteers. Significant improvements were observed in flow-mediated vasodilation, blood pressure, lipid profile, oxidative stress biomarkers, and inflammation-related biomarkers in the active group compared to placebo.
Essential Oil from Citrus aurantium Alleviates Anxiety of Patients Undergoing Coronary Angiography: A Single-Blind, Randomized Controlled Trial.
A single-blind, randomized controlled trial with 80 patients undergoing coronary angiography tested the inhalation of Citrus aurantium essential oil. The intervention group showed significant reductions in anxiety scores and vital signs compared to the control group, with no adverse reactions reported.
An evidence-based systematic review of bitter orange (Citrus aurantium) by the Natural Standard Research Collaboration.
Systematic review of bitter orange (Citrus aurantium) by the Natural Standard Research Collaboration, consolidating safety and efficacy data from clinical trials and expert opinions. Includes analysis of pharmacology, interactions, adverse effects, and dosing.
Effect of-Synephrine on Fat Oxidation Rate during Exercise of Increasing Intensity in Healthy Active Women.
This double-blind, randomized trial studied the effect of 3 mg/kg synephrine intake on fat oxidation during exercise in 18 healthy active women. Synephrine increased resting tympanic temperature but did not significantly affect fat oxidation rate, energy expenditure, or substrate oxidation during submaximal aerobic exercise.
Does the Time of Day Play a Role in the Acute Effect of-Synephrine on Fat Oxidation Rate during Exercise in Women? A Randomized, Crossover and Double-Blind Study.
This randomized, double-blind, placebo-controlled study evaluated the effect of acute ingestion of 3 mg/kg of synephrine on fat oxidation during exercise in 16 healthy women. The study found no significant effect of synephrine or time of day on maximum fat oxidation rate or the intensity that elicited maximum fat oxidation.
Bitter Orange (Citrus aurantium L.) Intake Before Submaximal Aerobic Exercise Is Safe for Cardiovascular and Autonomic Systems in Healthy Males: A Randomized Trial
A crossover, randomized, double-blind, placebo-controlled trial with 12 healthy male adults evaluated the cardiovascular safety of Citrus aurantium supplementation before submaximal aerobic exercise. Citrus aurantium ingestion accelerated the reduction in systolic blood pressure and improved heart rate variability indices post-exercise, with no adverse cardiovascular effects observed.
-Synephrine, the main protoalkaloid of, raises fat oxidation during exercise in elite cyclists.
This study investigated the acute effects of synephrine ingestion on substrate oxidation during exercise in elite cyclists. In a double-blind, crossover, randomized, placebo-controlled trial, 15 elite cyclists ingested either a placebo or 3 mg/kg of synephrine. Synephrine increased the rate of fat oxidation during exercise compared to placebo, although it did not affect energy expenditure or heart rate.
Comparing acupressure with aromatherapy using Citrus aurantium in terms of their effectiveness in sleep quality in patients undergoing percutaneous coronary interventions: A randomized clinical trial.
RCT comparing aromatherapy using Citrus aurantium and acupressure on sleep quality in 85 patients undergoing percutaneous coronary interventions. Aromatherapy showed improvement in sleep quality, but acupressure had a more significant effect.
Investigation of the effect of aromatherapy with Citrus aurantium blossom essential oil on premenstrual syndrome in university students: A clinical trial study.
Double-blind clinical trial on 62 university students investigating the effect of aromatherapy with Citrus aurantium blossom essential oil on premenstrual syndrome. The intervention group showed significant improvement in overall and psychological symptoms of PMS compared to the control group.
Comparison of the effect of lavender and bitter orange on sleep quality in postmenopausal women: A triple-blind, randomized, controlled clinical trial.
This triple-blind, randomized controlled trial compared the effects of lavender and bitter orange on sleep quality in postmenopausal women. Both substances significantly improved sleep quality compared to the control group after eight weeks of treatment.
Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males.
RCT examining the effects of a pre-workout dietary supplement with and without synephrine on training adaptations in resistance-trained males over 8 weeks. Some evidence of improved cognitive function and 1RM strength in the PWS and/or PWS+S groups compared to placebo, but no significant additive benefits from synephrine.
Anxiolytic Effect of Citrus aurantium L. on Patients with Chronic Myeloid Leukemia.
RCT assessing the anxiolytic effect of Citrus aurantium essential oil inhalation in patients with chronic myeloid leukemia undergoing bone marrow aspiration. Inhalation of C. aurantium was associated with decreased anxiety scores and changes in physiological measurements, suggesting an anxiolytic effect.
To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome: a randomized group sequential comparative trial.
A randomized, group sequential, double-blinded, multicenter trial compared the efficacy of two kinds of Zhizhu pills on symptom changes in patients with functional dyspepsia of spleen-deficiency and qi-stagnation syndrome. The trial found that Zhizhu pills containing immature orange fruit of Citrus aurantium L. (IFCA) were superior to those containing Citrus sinensis Osbeck (IFCS), with cure-markedly effective rates of 67% for IFCA and 45% for IFCS.
Citrus aurantium blossom and preoperative anxiety.
RCT of 60 ASA I patients undergoing minor operation comparing Citrus aurantium blossom distillate to saline placebo for preoperative anxiety. The Citrus aurantium group showed significant reductions in anxiety as measured by STAI-state and APAIS scales.
Safety and efficacy of citrus aurantium for weight loss.
Systematic review examining the safety and efficacy of citrus aurantium for weight loss. Only one eligible RCT was identified, which followed 20 patients for 6 weeks and showed no statistically significant benefit for weight loss, with limited safety information.
Acute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax.
Double-blind, randomized trial with 14 healthy subjects assessing the effect of p-synephrine on substrate oxidation during 1 hour of cycling at Fatmax. p-Synephrine increased whole-body fat oxidation and reduced carbohydrate oxidation compared to placebo, though energy expenditure remained unchanged.
Citrus Aurantium and caffeine complex versus placebo on biomarkers of metabolism: a double blind crossover design.
Double-blind, randomized crossover study with 10 physically active males examining the metabolic response to Citrus Aurantium and Caffeine complex versus placebo. The study found significant time-dependent increases in plasma epinephrine and norepinephrine only in the CA+C trial, but no meaningful changes in glucose, insulin, or triglycerides during the ingestion period. No trial-dependent differences were observed in the recovery period.
Acute hematological and mood perception effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine: A placebo-controlled, double-blind study.
This placebo-controlled, double-blind study examined the acute hematological and mood perception effects of p-synephrine alone and in combination with caffeine in 16 subjects. The study found no significant differences in mood or blood parameters with p-synephrine alone, except for changes in hematocrit, triglycerides, and iron levels. Caffeine-containing supplements increased feelings of attention, excitement, energy, and vigor.
Effects of p-Synephrine and Caffeine Ingestion on Substrate Oxidation during Exercise.
Double-blind randomized experiment with 13 healthy subjects testing the effects of caffeine, p-synephrine, and their combination on fat oxidation during exercise. All treatments increased the maximal rate of fat oxidation compared to placebo, but did not alter total energy expenditure or heart rate. No additive effect was observed with the combination.
The influence of citrus aurantium and caffeine complex versus placebo on the cardiac autonomic response: a double blind crossover design.
This double-blind crossover study examined the effects of a Citrus aurantium and caffeine complex on cardiac autonomic response in 10 physically active males. The complex increased sympathetic activity during resting conditions but did not affect parasympathetic activity or cardiac autonomic recovery following high-intensity exercise.
Effects of acute ingestion of a pre-workout dietary supplement with and withoutsynephrine on resting energy expenditure, cognitive function and exercise performance.
RCT with 25 healthy participants examining the effects of a pre-workout supplement with and without synephrine on energy expenditure, cognitive function, and exercise performance. The supplement increased resting energy expenditure and improved perceptions of readiness and cognitive function, but had limited effects on muscular endurance and anaerobic capacity.
Dose-Response Effects of p-Synephrine on Fat Oxidation Rate During Exercise of Increasing Intensity.
This study investigated the effects of different doses of p-synephrine on maximal fat oxidation during exercise in 17 healthy subjects. The ingestion of p-synephrine increased the maximal rate of fat oxidation during exercise, with the highest effects observed at doses of 2 and 3 mg/kg.
Acute p-synephrine ingestion increases fat oxidation rate during exercise.
This study investigated the effects of acute p-synephrine ingestion on fat oxidation at rest and during exercise in 18 healthy subjects. The results showed that p-synephrine increased the fat oxidation rate during exercise without affecting energy expenditure, although it did not change energy consumption or fat oxidation rate at rest.
Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.
This randomized placebo-controlled cross-over clinical trial assessed the cardiovascular effects of bitter orange extract (49-mg p-synephrine) in 18 healthy subjects. No significant changes were observed in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts. A small decrease in diastolic blood pressure was noted in the p-synephrine group at 60 minutes. No adverse effects were reported.
The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise.
RCT examining the effects of p-synephrine alone and in combination with caffeine on metabolic, lipolytic, and cardiovascular responses during resistance exercise in 12 healthy men. Supplementation increased lipolysis at rest and enhanced oxygen consumption, energy expenditure, and fat oxidation rates post-exercise. Heart rate changes were observed only with caffeine addition.
Acute consumption of p-synephrine does not enhance performance in sprint athletes.
RCT with 13 experienced sprinters testing the acute effects of p-synephrine (3 mg/kg) versus placebo on performance. P-synephrine did not enhance performance in sprint tests or alter the prevalence of side effects.
The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance.
RCT examining the effects of p-synephrine and p-synephrine with caffeine on resistance exercise performance in 12 healthy men. Both supplements increased repetitions and volume load compared to control and placebo, with SCF also enhancing power and velocity.
Clinical and mycological evaluation of an herbal antifungal formulation in canine Malassezia dermatitis.
RCT evaluating the effectiveness of Malacalm, an herbal antifungal formulation, in treating canine Malassezia dermatitis. The treatment showed significant clinical improvement and no recurrence of skin disorders at follow-up, compared to conventional therapy.
Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects.
Two Phase I studies assessed the effects of grapefruit and Seville orange juices on the pharmacokinetics of colchicine in healthy volunteers. Grapefruit juice did not significantly affect colchicine pharmacokinetics, while Seville orange juice reduced colchicine absorption and increased T(max). Both juices were well tolerated with no significant treatment-related adverse events.
Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes.
Double-blinded, randomized, placebo-controlled study assessing the thermogenic effects of p-synephrine alone and with flavonoids naringin and hesperidin. The study found that p-synephrine alone increased resting metabolic rate (RMR) by 65 kcal, while combinations with naringin and hesperidin further increased RMR without affecting heart rate or blood pressure.
Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans.
RCT investigating the cardiovascular effects of a dietary supplement containing bitter orange extract (p-synephrine), caffeine, and green tea extract in mildly overweight individuals. No effects on heart rate, systolic and diastolic blood pressure, or mean arterial pressure were observed. A small decrease in resting respiratory exchange ratio was noted in low caffeine users, suggesting potential increased fat oxidation.
Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian traditional medicine.
Randomized, double-blinded pilot clinical trial investigating the anti-diabetic efficacy of Rauvolfia-Citrus tea in 23 Danish type 2 diabetes patients. The treated group showed significant improvements in glycaemic control markers, including reductions in postprandial plasma glucose, HbA1c, and fasting plasma glucose, compared to placebo. Modifications to the fatty acid profile of skeletal muscle were also observed.
Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions.
A three-arm, double-blind, placebo-controlled, crossover study with 10 healthy adults examined the effects of a performance-enhancing dietary supplement containing synephrine and caffeine under resting and exercise conditions. The study found that exercise did not affect the pharmacokinetics of synephrine and caffeine. The supplement increased post-exercise blood pressure and plasma glucose levels but made exercise feel less strenuous.
Auricular acupressure may improve absorption of flavanones in the extracts from Citrus aurantium L. in the human body.
RCT with 10 healthy male volunteers comparing oral administration of Citrus aurantium L. extracts with and without auricular acupressure. Plasma concentrations of naringenin and hesperetin were significantly higher in the group receiving acupressure.
Dietary herbal supplements with phenylephrine for weight loss.
Two pilot studies evaluated the efficacy and safety of a dietary herbal supplement containing citrus aurantium and phenylephrine for weight loss in subjects with BMI 25-40 kg/m². The first study showed a slight weight gain in the citrus aurantium group compared to placebo, with increased resting metabolic rate at baseline but not at 8 weeks. The second study showed no significant weight loss in the phenylephrine group, though resting metabolic rate increased. No significant safety issues were observed.
Metabolic and physiological effects of ingesting extracts of bitter orange, green tea and guarana at rest and during treadmill walking in overweight males.
This study examined the acute effects of a commercial formula containing extracts of bitter orange, green tea, and guarana on metabolic rate and substrate utilization in overweight males at rest and during treadmill walking. The results showed no significant effect on total ATP utilization, but there was an increase in ATP production from carbohydrates and a decrease from NEFA.
Response of CEDIA amphetamines assay after a single dose of bitter orange.
Study tested the response of the CEDIA Amphetamines Assay after ingestion of bitter orange in 6 healthy adult male volunteers. A single dose of Nature's Way Bitter Orange did not cause a false-positive response to the assay.
Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects.
Randomized, double-blind, placebo-controlled, crossover study evaluating the hemodynamic and electrocardiographic effects of a single dose of bitter-orange dried-fruit extract in 18 healthy volunteers. The study found no significant changes in QTc interval or blood pressure compared to placebo.
Blood pressure and heart rate effects following a single dose of bitter orange.
Prospective, randomized, double-blind, placebo-controlled, crossover study of 15 healthy adults receiving a single dose of bitter orange. Systolic and diastolic blood pressure, as well as heart rate, were significantly increased compared to placebo for up to 5 hours after administration.
Hemodynamic effects of ephedra-free weight-loss supplements in humans.
RCT of 10 healthy adults assessing the cardiovascular effects of ephedra-free weight loss supplements containing Citrus aurantium. Xenadrine EFX increased systolic and diastolic blood pressure and heart rate, while Advantra Z did not affect blood pressure. The cardiovascular effects may be due to caffeine and other stimulants in the multi-component formulation.
Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects
Open-label, three-way crossover study in nine healthy male volunteers to evaluate the effects of lemon and Seville orange juices on the pharmacokinetics of sildenafil. Seville orange juice significantly increased sildenafil's plasma concentration and reduced its oral clearance, while lemon juice had no significant effects.
Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine
This review examines the safety, efficacy, and mechanisms of action of bitter orange extracts and p-synephrine, focusing on human, animal, in vitro, and mechanistic studies. It concludes that p-synephrine and bitter orange extracts are safe for use in dietary supplements and foods at commonly used doses, with no cardiovascular effects or stimulant actions observed in approximately 30 human studies.