Several clinical research studies have found that bitter orange and multi-ingredient supplements containing bitter orange produce a significant increase in the resting metabolic rate and are effective in inducing weight loss and reducing body fat more than diet and exercise alone – without increasing heart rate or blood pressure or causing other adverse effects.
Below is a compilation of key research studies – most of which have used Advantra Z® (*) and or a multi-ingredient supplement containing Advantra Z (**) – rather than generic bitter orange extracts.
To review a study in its entirety, click on the link provided.
Mar 2008 ** Exercise was easier 83% of the time – and no significant adverse events occurred – following use of a performance-enhancing dietary supplement containing Advantra Z.
Human Pharmacology of a Performance-Enhancing Dietary Supplement Under Resting and Exercise Conditions – Haller, University of California, San Francisco, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY †
2006 ** A multi-ingredient supplement containing Advantra Z increased energy production and fat oxidation.
Metabolic and Physiological Effects of Ingesting Extracts of Bitter Orange, Green Tea and Guarana at Rest and During Treadmill Walking in Overweight Males – Sale, University of Chichester, INTERNATIONAL JOURNAL OF OBESITY †
Jan 2006 * Acute Advantra Z ingestion increased resting metabolic rate, but did not affect the cardiovascular indices of heart rate and blood pressure.
The Acute Effects of Citrus aurantium on Blood Pressure and Heart Rate – Seifert, St. Cloud State University †
Jul 2005 * Six-year longitudinal study, Gougeon, Nutrition and Food Science Centre, McGill University, OBESITY RESEARCH
Advantra Z increased energy expenditures up to 29% in certain populations.
Increase in the Thermic Effect of Food by Adrenergic Amines Extracted from Citrus aurantium
Advantra Z caused a measurable increase in the metabolic rate in obese subjects.
Thermic Effect of Citrus aurantium in Obese Subjects
Advantra Z increased the thermic effect of food in lean subjects after consumption of a meal, resulting in a measurable increase in metabolic rate without heart rate or blood pressure irregularities.
Thermic Effect of Beta-Sympathicomimetic Compounds Extracted from Citrus aurantium, in Humans
2005 ** A multi-ingredient supplement containing Advantra Z was more effective in inducing weight loss than diet and exercise alone.
Effect of a Multi-Ingredient Weight-Loss Product on Body Composition in Overweight Adult Men and Women – Zenk †
May 2004 ** A multi-ingredient supplement containing Advantra Z reversed the decrease in resting metabolic rate associated with calorie restriction in overweight adults without serious adverse events.
Effect of a Multi-Ingredient Weight-Loss Product on Metabolic Rate and Body Composition – Zenk, JOURNAL NUTRITION †
Aug 2003 * Advantra Z provides the “whole food footprint”: five naturally occurring adrenergic amines; generic bitter orange extracts often contain only synephrine.
The Difference Between Citrus aurantium Extract (Advantra Z) and Ephedra Extract – Jones
2003 ** A multi-ingredient supplement containing Advantra Z significantly enhanced metabolism without negatively affecting blood pressure.
Efficacy of a Commercial Green Tea Extract/Caffeine-Based Product to Increase Basal Metabolism in Healthy Adults – Kalman
2003 ** A multi-ingredient product containing Advantra Z reduced fatigue and curbed appetite in overweight adults without serious adverse events.
An Acute Clinical Trial to Evaluate the Safety and Efficacy of a Popular Weight Loss Supplement When Used with Exercise – Kalman †
2002 Citrus aurantium (e.g., Advantra Z) may be the best thermogenic substitute for ephedra.
Citrus aurantium as a Thermogenic, Weight Reduction Replacement for Ephedra: An Overview – Preuss, JOURNAL OF MEDICINE
Sep 2000 ** A multi-ingredient supplement containing Advantra Z aided weight loss – particularly during the first, frustrating weeks of dieting – without causing serious adverse events.
Study on the Effectiveness of a Multi-Ingredient Supplement for the Reduction of Body Weight – Kendall-Reed
Mar 1999 ** A multi-ingredient supplement containing Advantra Z was effective in promoting weight and fat loss – without significant changes in blood pressure and heart rate – when combined with diet and exercise.
Effects of Citrus aurantium Extract, Caffeine, and St. John's Wort on Body Fat Loss, Lipid Levels, and Mood States in Overweight Healthy Adults – Colker, CURRENT THERAPEUTIC RESEARCH †
Mechanism of Action
Apr 2007 Synephrine-rich orange peel induced lipolysis in fat cells.
Lipolysis Induced by Segment Wall Extract from Satsuma Mandarin Orange – Tsujita, Ehime University, JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY
Jun 2002 * Advantra Z primarily stimulates beta 3 receptors, which are responsible for triggering thermogenesis. It does not cross the blood/brain barrier, making minimal contact with the excitatory receptors that cause negative cardiovascular and central nervous systems side effects.
Advantra Z: Observation on its Effects and Mechanism of Action – Jones
Apr 1998 Activation of beta-3 adrenergic receptors stimulates lipolysis.
A Selective Human Beta-3 Adrenergic Receptor Agonist Increases Metabolic Rate in Rhesus Monkeys – Fisher, JOURNAL OF CLINICAL INVESTIGATION
2007 ** Daily supplementation with Advantra Z did not produce any cardiovascular risks in healthy adults.
Citrus aurantium Extract has No Effect on Blood Pressure or Heart Rate in Healthy Adults, – Talbott, EXPERIMENTAL BIOLOGY
Apr 2006 A single-dose bitter orange (e.g., Advantra Z) did not cause a false-positive response to the CEDIAs amphetamines assay.
Response of CEDIAs Amphetamines Assay After a Single Dose of Bitter Orange – Nguyen, University of California, San Francisco, DRUG MONIT
Nov 2005 * Advantra Z had virtually no impact on blood pressure or heart rate.
Absence of QTc Interval–Prolonging or Hemodynamic Effects of a Single Dose of Bitter-Orange Extract in Healthy Subjects – Min, University of Connecticut, PHARMACOTHERAPY †
Sep 2005 * Advantra Z had little or no effect on the central nervous system and did not cause any increase in blood pressure in doses relevant to dietary supplements on the market.
Hemodynamic Effects of Ephedra Free Weight Loss Supplements in Humans – Haller, University of California, San Francisco, AMERICAN JOURNAL OF MEDICINE †
Jun 2004 Bitter orange (e.g., Advantra Z) does not have ephedra’s negative cardiovascular and central nervous system side effects.
National Toxicology Study on Bitter Orange – National Institute of Health
2004 Long-term, daily administration of bitter orange extract (e.g., Advantra Z) does not cause negative herb drug interactions.
Pharmokenetics and Drug Disposition – Gurley, AMERICAN SOCIETY OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
2001 Cardiovascular indices were not significantly altered by Seville orange juice ingestion, even though the juice contained marked amounts of synephrine.
Seville (sour) Orange Juice: Synephrine Content and Cardiovascular Effects in Normotensive Adults – Penzak, JOURNAL OF CLINICAL PHARMACOLOGY
Jul 1997 * The acute oral LD50 toxicity test of Advantra Z was greater than 10,000 mg per kilogram.
An Acute Oral Toxicity Study in Rats with Advantra Z – Douds
† Double-blind, placebo-controlled clinical study