Bitter Orange (Citrus Aurantium) Herbal Monograph

Bitter Orange – Common Uses

Citrus aurantium extract and its primary protoalkaloidal constituent p-synephrine are extensively used in weight management products and as thermogenic agents. They are also used in sports performance products to enhance stamina. Citrus aurantium extract is widely known as Bitter Orange extract, a product that is derived from the immature (green) fruits of the Seville Orange. It is also known as “Chih-shi” or “Zhi shi” in traditional Chinese medicine. Bitter Orange extract is used in weight management products due to its purported effects on metabolic processes, including an increase in basal metabolic rate and lipolysis as well as mild appetite suppression. (1)

Bitter Orange Active Constituents

P-synephrine is the primary protoalkaloid in Citrus aurantium (Bitter Orange) and other Citrus species. In addition to its consumption in dietary supplements, p-synephrine is daily consumed in various foods and juices derived from Citrus species as Seville Oranges, Mandarin Oranges, clementines, Marrs sweet Oranges, Nova tangerines, grapefruits and other Orange-related species containing p-synephrine. (2)

Bitter Orange Pharmacology

Various studies indicate that the lipolytic activity of p-synephrine is due to binding to β-3 adrenergic receptors in adipose tissues. These same β-3 adrenergic receptors are also associated with cardiovascular tissues, and their activation results in a down-regulation of cardiovascular stimulation. (1)

Thus, p-synephrine stimulation of β-3 adrenoreceptors in the cardiovascular system does not result in an increase in blood pressure or heart rate but may exhibit a modulating rather than a stimulatory effect. This cardiovascular receptor response may explain why an increase in heart rate or blood pressure is not seen in most cases when p-synephrine is used alone. The results indicate that Bitter Orange extract and p-synephrine increase metabolism and energy expenditure. (1)

Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the widespread consumption of p-synephrine in the form of dietary supplements. (2)

Most review articles regarding p-synephrine and Bitter Orange extract assume that because of the structural similarities, p-synephrine, m-synephrine, ephedrine, norepinephrine, epinephrine, and amphetamine all exert similar properties and fail to consider or discuss the receptor binding studies that have been conducted. For more detail on this see reference (2)

Synephrine

Bitter Orange – Scientific Evidence

A total of 23 published and unpublished studies involving a total of approximately 450 total human subjects were reviewed. Of these total subjects, approximately 360 consumed Bitter Orange/p-synephrine containing products, with 247 subjects involved in published studies and 113 subjects involved in studies that have not been published to date. (1)

Weight loss

In one study after six weeks, the treated group lost small but significant amounts of body weight (1.4 kg) and body fat (2.9%). No significant changes in blood pressure, heart rate, electrocardiographic findings, serum chemistry or urinalysis were noted and no significant changes were observed in the results of the Profile of Mood States Questionnaire for fatigue or vigor. The treated group also experienced a significant increase in basal metabolic rate as compared to the placebo group. (1)

In another ten-week study a 32 person group consuming the product-only lost an average of 4.63 kg, the group on the diet and exercise regime lost 3.45 kg, and the group taking the product plus diet and exercise lost 6.59 kg. (1)

A product containing extracts of Bitter Orange, guarana, and green tea as well as 7-oxo-dehydroandrostenedione (DHEA), conjugated linoleic acid and chromium picolinate. The daily consumption of Bitter Orange extract was 200 mg. At the completion of the 8-week study, the treated group lost an average of 2.9 kg body weight, while the placebo group lost 1.5 kg body weight. (1) Thermogenik (120 capsules) contains virtually all of these ingredients.

Metabolic rate

In 10 Healthy human subjects consuming synephrine capsules, at the two and three hour time points after ingestion of synephrine, 13.4 %, and 8.9% increases, respectively, were observed in the basal metabolic rate. No significant differences in heart rate or blood pressure were observed in response to the product relative to baseline and control values. (1)

Another study with 40 people showed at 75 minutes after ingestion of 50mg of synephrine a 6.9 % increase in resting metabolic rate was observed in response to the p-synephrine relative to the placebo-control group. (1)

Thermogenic

A study involving 30 subjects demonstrated that the thermic effect of food was 20% lower in women than men following a meal. An increase in the thermic effect of food was seen only in women, increasing by 29%, when the Bitter Orange extract was used in conjunction with the protein meal. The thermic effect of the Bitter Orange extract was greater in men than women in the absence of a meal. A significant increase in the respiratory quotient occurred in both sexes in response to the Bitter Orange extract alone. (1)

Adverse effects

Uncertainty has existed concerning the safety of Bitter Orange extract and p-synephrine. In general, both the lay public and scientific communities have failed to differentiate between p-synephrine which is a phenylethylamine derivative that has the hydroxy group in the para position on the benzene ring and the synthetic m-synephrine (phenylephrine) which has a hydroxyl group in the meta position on the benzene ring). m-Synephrine exhibits cardiovascular effects but is not a constituent of Bitter Orange. Properties possessed by m-synephrine are inappropriately attributed to Bitter Orange extract and p-synephrine, and clinical case study reports and reviews involving Bitter Orange extract frequently make inappropriate references to m-synephrine. (1)

The issue of safety and efficacy is further clouded and complicated by the structural similarity of p-synephrine to ephedrine and other biogenic amines, in spite of the fact that the pharmacokinetics of these compounds and their receptor-binding specificities are vastly different due to significant structural and stereochemical differences. (1)

There are multiple reports of adverse effects found online after consuming Bitter Orange extract (synephrine) in complex weight loss formulations containing other stimulants such as caffeine. What these fail to consider is the Millions of individuals ingest p-synephrine and Bitter Orange-containing food products as Orange juices and marmalades as well as dietary supplements on a daily basis. Therefore, although these case reports should raise the level of awareness with regard to the use of complex weight management products, it is not possible to extrapolate the cause of these adverse effects to the p-synephrine which may have been present in the products.

Conclusion

There is a strong body of evidence for the use of Bitter Orange extract in a weight loss program and there seems to be very little concern around safety.

Adding Oranges to your daily smoothie including the skin could be a good way to get the extra Bitter Orange extract.

You can also find Synephrine 50mg per capsule/sachet in the following products.

• Thermogenik 120 capsules
• The Ultimate Herbal SLIM 480 capsules
• Ultimate BodiTune Drink 32 Sachets