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Bitter Orange Weight Loss - Synephrine HCL

What is Citrus Aurantium Extract (Advantra Z)

Bitter orange is also commonly referred to as Citrus Aurantium or Seville Bitter Orange. The citrus aurantium tree is native to Africa and Asia. It has been used for their essential oil in foods and perfumes. Citrus Aurantium is also used in herbal medicine as a stimulant and appetite suppressant. It has also been used in traditional Chinese medicine to treat nausea, indigestion, and constipation. However, what has made bitter orange well known and popularized is the claim that it replaces the banned ephedra stimulant, without the ephedra side effects. Because of this, Citrus Aurantium is a popular weight loss ingredient used in a wide variety of diet pills and fat burners such as Nutrex Lipo 6, Lean System 7, and Miracleburn (advantra-z) just to name a few.

Citrus Aurantium contains synephrine which is a stimulant with similar properties as caffeine and ephedrine. It claims to have similar effects by increasing energy expenditure, increasing metabolism, and suppressing appetite - and it has been labeled as the ephedra replacement. Banning of ephedra has paved the way for bitter orange to become a very widely used stimulant in fat burners. Although you'll se marketing material claiming citrus orantium to have similar benefits but none of the side effects of ephedra, clinical research and case reports have proven otherwise. There are reported cases of stroke [1] and angina [2].

Moreover, there is somewhat limited clinical evidence to show that bitter orange is an effective weight loss supplement. In writing reviews of all types of fat burners and diet pills, I have come across and researched upon citrus aurantium numerous times. From all the clinical trials that I've looked at, there are several studies that have demonstrated the effectiveness of synephrine for weight loss, and in cases where it was effective, it involved very high doses. However, there were also studies which found that there is little evidence to suggest that bitter orange is an effective weight loss stimulant since synephrine has lipolytic effects on human fat cells only at high doses. So the effectiveness of bitter orange is still debatable.

Bitter Orange Extract - Advantra Z   

Advantra Z is a weight loss ingredient used in numerous diet pills. Its main ingredient is bitter orange extract along with some protein, carbs, omega 3 & 6, sodium and Vitamins A & C. Advantra Z is not a weight loss in itself, but it is used as an active ingredient in various diet pills. While Advantra Z is billed as a safe and effective alternative to ephedra, there's little scientific evidence to support this. Whether Advantra Z is an effective weight loss aid is debatable, especially since its main ingredient citrus aurantium (Synephrine) is still relatively unproven.

On the other hand, a University of California study done on Advantra Z and Xenadrine EFX found that Advantra Z had little to no cardiovascular stimulant actions. In this study, ten healthy adults participated in a randomized, double-blind, placebo controlled, three arm crossover study involving Advantra Z, Xenadrine EFX, and a placebo for control. When the results were compared to placebo, the study found that only Xenadrine EFX increased blood pressure and heart rate. They stated that Ephedra-free weight loss supplements have significant cardiovascular stimulant actions, similar to ephedra, but these effects are not likely caused by citrus aurantium alone, where an eight fold higher dose of synephrine (Advantra Z) had no effect on blood pressure. They attributed this effect to caffeine and other stimulants. The aim of this study was not to test whether bitter orange is an effective weight loss aid, but whether it has health risks similar to ephedra. Based on their results, the only conclusion they could draw on was that Advantra Z had no apparent effect on blood pressure. [3] My interpretation of this is that while Advantra Z did not seem to have any effect on blood pressure, it's likely that it also has limited stimulant activities - as the study stated "...significant cardiovascular stimulant actions, similar to ephedra... are not likely caused by C. aurantium... but may be attributable to caffeine and other stimulants".

Citrus Aurantium - Synephrine HCL Studies

Citrus aurantium has a rare combination of 5 amines: synephrine, N-methyltyramine, hordenine, octopamine, and tyramine, which "stimulates beta-3 cell receptors" that could lead to increase in your metabolic rate without affecting heart rate or blood pressure.

In a clinical review of various studies done on citrus aurantium, the researchers reviewed numerous available clinical weight loss trials, physiological studies, and case reports of bitter orange. From their review of synephrine studies, they found some promising evidence for synephrine in treatment of obesity, but concluded that more rigorous studies are needed to draw adequate conclusions. [4] There are several such types of clinical reviews performed on citrus aurantium studies [5], and they all post similar conclusions of needing more studies to draw more concrete conclusions. I wonder why they did not just design a weight loss study themselves and test it out? Food for thought.

Below is another citrus aurantium study conducted by the department of physiology, medicine and pathology at the Georgetown university that had favorable findings:


There are also studies which found no evidence to show that bitter orange (synephrine) is an effective weight loss aid, and that synephrine is only effective at high doses. In a another Georgetown University study, the researchers concluded that: "there is little evidence that products containing C. aurantium are an effective aid to weight loss. Synephrine has lipolytic effects in human fat cells only at high doses, and octopamine does not have lipolytic effects in human adipocytes." [7]

Citrus Aurantium Synephrine Side Effects

Most of the marketing material you read about citrus aurantium and bitter orange will state that it is a safe replacement for ephedra with similar weight loss benefits, but little to no side effects. However this is not the case. In a severe (but rare) case, a 38 year old patient had a stroke associated with a diet supplement containing synephrine and caffeine. [1] Another study also reported a possible incidence of myocardial infarction (heart attack) associated with the use of citrus aurantium. It involved a 55 year old woman who was admitted to the emergency room for chest pains. The patient had ingested a diet pill containing 300mg of bitter orange. So there may be some cardiovascular risks from using synephrine. [8] Other studies have also found that consuming bitter orange synephrine led to a increase in blood pressure and heart rate for up to 5 hours after a single dose of bitter orange. [9]




1. Mayo Clin Proc. 2005 Apr;80(4):541-5.
Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine.
Bouchard NC, Howland MA, Greller HA, Hoffman RS, Nelson LS.

2. Mayo Clin Proc. 2006 Apr;81(4):545-8
Variant angina associated with bitter orange in a dietary supplement.
Gange CA, Madias C, Felix-Getzik EM, Weintraub AR, Estes NA 3rd.
Division of Cardiology, Tufts-New England Medical Center, Boston, MA, USA.

3. Am J Med. 2005 Sep;118(9):998-1003.
Haller CA, Benowitz NL, Jacob P 3rd.
Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California

4. Obes Rev. 2006 Feb;7(1):79-88.
Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update.
Haaz S, Fontaine KR, Cutter G, Limdi N, Perumean-Chaney S, Allison DB.
Division of Rheumatology, Johns Hopkins University School of Medicine

5. Am J Cardiol. 2004 Nov 15;94(10):1359-61.
Safety and efficacy of citrus aurantium for weight loss.
Bent S, Padula A, Neuhaus J.
Osher Center for Integrative Medicine at the University of California

6. Preuss HG, DiFerdinando D, Bagchi M, Bagchi D.
Department of Physiology, Medicine and Pathology, Georgetown University Medical Center

7. Exp Biol Med (Maywood). 2004 Sep;229(8):698-704.
Fugh-Berman A, Myers A.
Department of Physiology & Biophysics, Georgetown University

8. Ann Pharmacother. 2004 May;38(5):812-6. Epub 2004 Mar 16.
Possible association of acute lateral-wall myocardial infarction and bitter orange supplement.
Nykamp DL, Fackih MN, Compton AL.
Department of Clinical and Administrative Services, School of Pharmacy, Mercer University, Atlanta, GA

9. Ann Pharmacother. 2006 Jan;40(1):53-7. Epub 2005 Nov 29.
Blood pressure and heart rate effects following a single dose of bitter orange.
Bui LT, Nguyen DT, Ambrose PJ.
School of Pharmacy, University of California, San Francisco, CA, USA.


July 2009