Despite numerous studies showing that bitter orange extracts are not stimulants, widespread controversy exists, and the NCAA has listed it as a banned substance.

Bitter orange may also interact with certain medications. Generally, bitter orange extracts in dietary supplements are safe to consume in doses of 50—98 mg per day 1 , One study showed that 40 mg of synephrine combined with mg of caffeine is a safe dose of these combined ingredients 3.

In another study, eating a whole bitter orange containing Still, people who are pregnant or breastfeeding should avoid bitter orange due to a lack of safety information 1. Bitter orange is likely safe in doses ranging from The juice of the bitter orange can be used as a marinade to flavor fish and meat.

Bitter orange has several other household uses outside of the kitchen. These include 2 :. Bitter orange is a citrus fruit with several household and industrial uses, ranging from food additives to perfumery.

You may want to avoid this fruit and its extracts if you have high blood pressure, an irregular heartbeat, or glaucoma. Likewise, bitter orange supplements are banned for NCAA athletes.

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Nutrition Evidence Based What Is Bitter Orange, and Does It Aid Weight Loss? Medically reviewed by Adrienne Seitz, MS, RD, LDN , Nutrition — By Amber Charles Alexis, MSPH, RDN on March 17, The fruit and its extracts. Compounds and nutrients. Does bitter orange aid weight loss?

Health benefits of bitter orange. Downsides and side effects of bitter orange. Dosage and safety information. Culinary uses of bitter orange. The bottom line. How we reviewed this article: History. Mar 17, Written By Amber Charles Alexis, MSPH, RDN.

Medically Reviewed By Adrienne Seitz, MS, RD, LDN. Share this article. Read this next. Can You Eat Orange Peels, and Should You? These natural compounds are extracted from the fruit and peel of bitter oranges for higher potency.

The primary proto-alkaloid, p-synephrine, is used in sports performance and weight loss supplements. Bitter orange extract contains p-synephrine, which increases thermogenesis and fat oxidation, especially when combined with exercise.

Several studies have shown that p-synephrine acts as a betaadrenoceptor, meaning it binds to the beta-3 receptors in fat cells. They then activate the beta-3s which promote the breakdown of fat cells, relaxation, and increased bladder capacity [ 3 ]. One study recorded the effects of taking a bitter orange extract for 12 weeks.

Some took the bitter orange extract alone, while others took that in combination with other ingredients.

The results showed that both groups saw significant increases in resting metabolic rate [ 4 ]. Other studies found that bitter orange is beneficial to people trying to up their fat utilization during exercise rather than carbohydrate stores [ 5 ].

Research has determined that doses from 49mg to 98mg are optimal to prevent adverse effects [ 6 ]. And many bitter orange supplements on the market reflect those numbers. Join tens of thousands of other customers for early access to new products, sales, and exclusive drops.

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In addition, p-synephrine is structurally similar to your flight-or-fight hormones, epinephrine and norepinephrine, which also increase your heart rate 1 , 4. P-synephrine is also found in other citrus fruits and their juices, such as mandarins and clementines 4 , 7.

Like other citrus fruits, bitter orange provides limonene — a compound shown to have anti-inflammatory and antiviral properties 10 , 11 , Population studies suggest that limonene may prevent certain cancers, namely colon cancer.

However, more rigorous human research is needed An ongoing study is also exploring the use of limonene as a treatment for COVID However, the results are not yet known.

Bear in mind that limonene cannot prevent or cure COVID Another protoalkaloid found in bitter orange is p-octopamine. However, little to no p-octopamine exists in bitter orange extracts.

The leaves of the bitter orange plant are rich in vitamin C , which acts as an antioxidant. Antioxidants are substances that may protect your body from disease by preventing cell damage.

They work by deactivating free radicals, which are unstable compounds that damage your cells, increasing inflammation and your disease risk 15 , Protoalkaloids are plant compounds found in bitter orange that have anti-inflammatory and antiviral properties.

They have been shown to be safe for consumption. Many weight loss supplements use bitter orange extracts in combination with other ingredients. However, scientific studies have not thoroughly examined the composition of these supplements to determine which ingredient, if any, supports weight loss.

Notably, p-synephrine has been shown to increase fat breakdown, raise energy expenditure, and mildly suppress appetite , all of which may contribute to reduced weight.

Yet, these effects occur at high doses that are discouraged due to the lack of safety information 4 , 8 , Bitter orange and its extracts are used in Traditional Chinese Medicine TCM to treat indigestion, diarrhea, dysentery, and constipation.

In other regions, the fruit is used to treat anxiety and epilepsy 3. Another study noted that the bitter orange compound p-synephrine may improve athletic performance though by increasing total reps and volume load, or your ability to train harder A stimulant is a substance that increases your heart rate and blood pressure 1.

Several sports organizations, such as the National Collegiate Athletic Association NCAA , list synephrine as a stimulant. Furthermore, one study determined that bitter orange juice contains furanocoumarin, a compound that may cause the same medication interactions as grapefruit juice Therefore, people taking decongestants or those who have high blood pressure, an irregular heartbeat, or glaucoma should avoid the juice and fruit of bitter oranges.

Despite numerous studies showing that bitter orange extracts are not stimulants, widespread controversy exists, and the NCAA has listed it as a banned substance.

Bitter orange may also interact with certain medications. Generally, bitter orange extracts in dietary supplements are safe to consume in doses of 50—98 mg per day 1 , One study showed that 40 mg of synephrine combined with mg of caffeine is a safe dose of these combined ingredients 3.

In another study, eating a whole bitter orange containing Still, people who are pregnant or breastfeeding should avoid bitter orange due to a lack of safety information 1. Bitter orange is likely safe in doses ranging from The juice of the bitter orange can be used as a marinade to flavor fish and meat.

Bitter orange has several other household uses outside of the kitchen. These include 2 :. Bitter orange is a citrus fruit with several household and industrial uses, ranging from food additives to perfumery.

You may want to avoid this fruit and its extracts if you have high blood pressure, an irregular heartbeat, or glaucoma. Likewise, bitter orange supplements are banned for NCAA athletes. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

Some argue that orange peels contain important nutrients and should be eaten rather than thrown away. This article reviews whether orange peels are a…. Orange juice is the most popular fruit juice worldwide but opinions differ on whether it's healthy. This article looks at orange juice and whether….

Blood oranges are known for their great taste and vitamin C, but that's just the beginning. Here are 7 health benefits, along with a few tips on…. Here are 7 reasons to eat citrus fruits. Subjects received either the placebo or the product and were followed for seven hours or exercised on a treadmill for 60 min.

The product had no effect on ATP utilization under resting or exercise conditions relative to control. Fatty acid oxidation to ATP decreased while plasma levels of fatty acids increased in response to the product.

The product had no effect on resting heart rate or blood pressure. Gougeon et al. No other ingredients were present in the product. The thermic effect of food on a 1. Five capsules of the C. aurantium extract provided 26 mg p -synephrine, and 4 mg or less each of other phenethylamines Advantra Z ®.

The thermic effect of food was determined on an initial 30 subjects. A subset of 11 men and 11 women were additionally studied after ingestion of the bitter orange extract in conjunction with the protein meal, while a another subset of 12 women and 8 men were studied a third time following ingestion of the C.

aurantium -containing capsules alone. 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. No significant changes occurred in systolic and diastolic blood pressures or pulse rates when compared with base line values following exposure to the bitter orange extract.

Hoffman et al. aurantium extract, Garcinia cambogia and chromium JavaFit TM over a three hour period of time in a randomized, double blind study which involved 10 healthy, physically active subjects Table 1.

The enriched coffee product contained mg caffeine, Significant increases were observed in responders with respect to resting metabolic rate and respiratory exchange ratio.

No significant differences were observed in average heart rate or diastolic blood pressure while a 3 mm Hg increase was observed in the systolic blood pressure. The modest effect on blood pressure is not surprising based on the amount of caffeine in the product. Talbott et al. aurantium extract product Advantra Z ® while the other half of the subjects received the placebo Table 2.

Heart rate and blood pressures were determined at the start of the study and after six weeks. No significant differences were observed between the treated and placebo control groups at the conclusion of the study with respect to these cardiovascular parameters.

No effects on body weight were reported. This study represents the highest dose of p -synephrine for the longest period of time that has been reported. The study was presented at a scientific meeting but never published. The product Ripped Fuel Extreme Cut TM contained 21 mg p -synephrine and mg caffeine, as well as other ingredients including herbal extracts of green tea, ginger root, cocoa seed, willow bark, and wasabi.

The product or placebo was taken one hour prior to 30 min of moderately intense exercise. No significant treatment-related differences in systolic blood pressure, heart rate or body temperature were observed.

Product-related increases in diastolic blood pressure 8. Exercise was perceived as being less strenuous after consumption of the product. Due to the poly-alkaloidal and protoalkaloidal nature of this product, the factor or factors responsible for the effects on blood glucose and diastolic blood pressure cannot be determined.

Seifert et al. The product contained 13 mg p -synephrine as Advantra Z ® , mg caffeine as guarana , and The study involved 14 females and 9 males in a placebo-controlled, crossover design. Subjects ingested one capsule with each of three meals on day one of treatment, and one more capsule on the morning of the second day.

Data were collected 60 min after the last administration of the product. No differences were observed in heart rate or blood pressure following treatment. This was an acute study which did not provide information on long-term effects, but did demonstrate an increase in energy expenditure.

Stohs et al. The study was a randomized, placebo-controlled, double blind design with the vehicle for the p -synephrine being one ounce of tomato juice. The amount of p -synephrine in the product was verified by independent analysis. Measurements were taken at baseline prior to consuming the product and at 75 min.

At this time point, a 6. No significant effects were observed with respect to blood pressure or heart rate, nor were there any significant differences in responses to a 10 item self-report questionnaire which addressed such issues as nervousness, tension, anxiety, hunger, energy, headache, general discomfort, and sleepiness.

Longer term safety and efficacy studies involving p -synephrine alone are warranted. The amount of p- synephrine in the capsules was determined by high pressure liquid chromatographic analysis.

Electrocardiograms, blood pressures, heart rates, blood chemistries and blood cell counts with differentials were determined at baseline, 30 min, 60 min, 90 min, 2 hours, 4 hours, 6 hours and 8 hours, as well as after 5, 10 and 15 days. Blood samples were drawn after 2 hours after the first dose as well as at 5, 10 and 15 days to measure p -synephrine levels to ensure compliance.

p -Synephrine had no significant effect on heart rate, blood pressure, blood chemistries, or blood cell counts, and caused no cardiovascular abnormalities.

Bloomer et al. Methyl-synephrine is purported to occur in nature, does not occur in bitter orange extract, and is of synthetic origin in this product and other products that have been marketed. For the sake of completeness, the results of these studies will be summarized, but these results will not be incorporated into the general discussion of bitter orange extract and p -synephrine provided below.

Both studies examined the effects of the product on metabolic rate, and plasma free fatty acids, glycerol, norepinephrine and epinephrine levels. The initial study [ 38 ] measured changes over a 90 min time frame in 10 healthy male subjects.

The second study [ 39 ] measured the same parameters over a six hour time frame in 10 healthy male and 10 healthy female subjects. Increases in each of the parameters were observed, with a It is also important to note that significant increases in heart rate as well as systolic and diastolic blood pressure occurred in both studies in response to the consumption of the product.

The authors note that the product may be useful in healthy, normotensive, closely monitored individuals. However, it is not a product that should be recommended to the general public.

In a study similar to those reported by Bloomer et al. Over a three hour time period following ingestion of the product significant increases in resting oxygen uptake and caloric expenditure were occurred. However, increases in heart rate, systolic blood pressure, tension and confusion were also observed, confirming the highly undesirable properties of this synthetic product.

Stohs [ 41 ] has reviewed and assessed the 22 FDA adverse event reports AERs from April through October associated with bitter orange C. aurantium -containing products, as well as 10 clinical case reports published during this time interval regarding the possible involvement of bitter orange-containing weight management products with cardiovascular incidents and other adverse events.

In all reported AERs and case cases, the products involved were poly-herbal, poly-alkaloidal and poly-protoalkaloidal. Adverse events that have been purported in conjunction with the published clinical case reports included: acute lateral-wall myocardial infarction, exercise-induced syncope associated with QT prolongation, ischemic stroke, ischemic colitis, vasospasm and stroke, variant angina, coronary vasospasm and thrombosis, exercise induced rhabdomyolysis, ST segment myocardial infarction, and ventricular fibrillation [ 41 ].

In one case report it was suggested that a bitter orange-containing dietary supplement may have masked bradycardia and hypotension while exacerbating weight loss in an individual with anorexia nervosa, although no evidence was provided that an adverse event had actually occurred.

Although the products consumed were all multi-ingredient, in each case reference was specifically made to C. aurantium, bitter orange or p -synephrine as the most likely causative agent.

A more probable culprit for at least some of these effects may have been the high caffeine intake associated with the products in question.

Another factor to be considered is the occurrence of up to mg p -synephrine per quarter liter of various Citrus juices [ 42 , 43 ] which are widely consumed without the report of adverse events.

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.

No evidence showing a direct link between bitter orange extract and the adverse events is provided [ 41 ]. A total of 23 published and unpublished studies involving a total of approximately total human subjects were reviewed.

The authors located information regarding the unpublished studies through presentations at scientific meetings and availability of research reports on the internet, as well as information from the investigators involved in the studies.

Seven of the studies were not published in peer reviewed journals [ 17 - 20 , 25 , 33 , 37 ] Table 2. However, six of these studies were presented at national meetings [ 18 - 20 , 25 , 33 , 37 ], and one of these six studies is in the process of being submitted for consideration for publication [ 37 ].

As noted in the references, information including presentations and final reports are available on the internet regarding these unpublished studies. The results associated with these unpublished studies Table 2 in general are consistent with the results of the published studies Table 1.

Five published studies [ 6 , 24 , 27 , 31 , 36 ] and two unpublished studies [ 33 , 37 ] reported no cardiovascular effects when using p -synephrine bitter orange only containing products. The published studies involved a total of subjects with a total of 31 subjects in the two unpublished studies.

However, in one of these studies [ 24 ] consisting of 12 subjects it is not clear that effects on heart rate and blood pressure were specifically examined, with the authors simply reporting that no adverse effects were observed.

Five published studies [ 15 , 21 , 22 , 26 , 30 , 35 ] using p -synephrine in combination with other ingredients reported no cardiovascular effects. A total of 88 subjects were involved in these studies. Small cardiovascular effects were reported by Bui et al.

Small cardiovascular effects were reported for three studies that involved subjects consuming p -synephrine plus caffeine [ 28 , 32 , 34 ]. reported an increase in heart rate [ 28 ] and diastolic blood pressure [ 34 ] 10 subjects. Upon careful review, the study of Haller et al.

p -Synephrine Advantra Z ® alone had no effect on systolic or diastolic blood pressure. The authors reported an increase in heart rate six hours after treatment. The half-life of p -synephrine is two to three hours [ 28 , 34 , 45 ]. As a consequence, an increase in heart rate after two to three half-lives when the p- synephrine blood levels will have dropped to one-fourth to one-eighth the peak blood levels would not be expected.

Furthermore, a major complicating factor is that all subjects consumed a meal three hours after ingesting the p -synephrine The cardiovascular and thermic effects of food are well known [ 31 ], and an increase in heart rate in the control group was also observed.

Thus, it is not plausible to attribute the increase in heart rate to p -synephrine, or an increase in heart rate and blood pressure to a product that contained very little p -synephrine 5.

This study did show that the commercial product Xenadrine EFX® which contained only 5. This product was reported to also contain 5. aurantium extracts are either devoid of octopamine or contain only trace amounts [ 3 ], thus the product being used [ 28 ] appears to have been adulterated.

Hansen et al. These doses represent over 13 times the usual daily dose for p -synephrine and the equivalent of the caffeine in about three cups of coffee given together as a single bolus dose to these animals. When caffeine was added, increases in heart rate and blood pressure were observed [ 46 ].

These studies indicate that in rats at very high doses of p -synephrine the combination with caffeine may result in cardiovascular effects. However, due to the highly inequivalent dosing between this study in rats and typical dosing in humans, the results of this study in rats cannot be directly extrapolated to humans.

A dose of 3. Various studies indicate that the lipolytic activity of p -synephrine is due to binding to β-3 adrenergic receptors in adipose tissues [ 10 ]. These same β-3 adrenergic receptors are also associated with cardiovascular tissues, and their activation results in a down-regulation of cardiovascular stimulation [ 48 , 49 ].

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 or in combination with caffeine in dietary supplements, in spite of the fact that caffeine alone may produce modest increases in these parameters under some conditions [ 50 , 51 ].

Approximately half of the clinical studies involved the use of commercial products. In only one case [ 28 ] was the actual amount of p -synephrine and other protoalkaloids determined, while in the remaining studies involving commercial products the reported amounts of p -synephrine and caffeine were simply based on label claim.

The amount of p -synephrine was independently determined in two studies in which bitter orange extract was used as a single ingredient product [ 36 , 37 ]. Various studies have shown that there are not always good correlations between the label claim of marketed products or the product data sheet and the amount of p -synephrine shown to be present by independent analysis [ 52 - 56 ].

Therefore, the actual amount of p -synephrine consumed in the majority of the studies was not verified. Finally, nine studies involving the administration of bitter orange extract alone or in combination with other constituents have demonstrated an increase in metabolic rate without an increase in heart rate or blood pressure [ 18 - 20 , 26 , 30 - 32 , 35 , 36 ].

These results suggest that bitter orange extract and p -synephrine may be beneficial in weight management. The results involving both published and unpublished clinical studies indicate that p -synephrine alone or in combination with caffeine does not appear to produce significant adverse cardiovascular effects or pose a risk to human health at doses commonly ingested orally.

No adverse effects have been directly attributable to bitter orange extract or p- synephrine. The results indicate that bitter orange extract and p -synephrine increase metabolism and energy expenditure.

The data accumulated to date do not support hypothesized concerns regarding potential adverse effects of p -synephrine particularly with respect to the cardiovascular system due to a paucity of binding to α-, β-1 and β-2 adrenergic receptors while exhibiting modest binding to β-3 adrenergic receptors.

All authors have served as consultants for Nutratech, Inc. Nutratech Inc. provided some of the unpublished research reports. Chen JK, Chen TT. Zhi Shi Fructus Aurantii Immaturus. Chinese Medical Herbology and Pharmacology. City of Industry, CA USA: Art of Medicine Press. Stohs SJ, Shara M. A review of the safety and efficacy of Citrus aurantium in weight management.

In: ed. Bagchi D, Preuss HG. Obesity: Epidemiology, Pathophysiology, and Prevention. Boca Raton, FL, USA: CRC Press.

Pellati F, Benvenuti S. Chromatographic and electrophoretic methods for the analysis of phenethylamine alkaloids in Citrus aurantium. J Chromatog A. Sander LC, Putzbach K, Nelson BC. et al. Certification of standard reference materials containing bitter orange. Analyt Bioanalyt Chem. Evans RL, Pho AN, Roman MC, Betz JM.

Penzak SR, Jann MW, Cold JA. Seville sour orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol. Bent S, Padula A, Neuhaus J.

Safety and efficacy of Citrus aurantium for weight loss. Amer J Cardiol. Nasir JM, Durning SJ. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine.

Mayo Clinic Proceed. Stephensen TA, Sarlay JrR. Ventricular fibrillation associated with use of a synephrine containing dietary supplement. Military Med. Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p -synephrine as related to its pharmacological effects.

Oxid Med Cell Long. Stohs SJ, Preuss HG. Stereochemical and pharmacological differences between naturally occurring p -synephrine and synthetic p -synephrine. J Funct Foods. McGuffin M. Media spins numbers on bitter orange AERs based on erroneous information from FDA.

The Safety of bitter orange Citrus aurantium and its primary protoalkaloid p -synephrine. The safety of Citrus aurantium bitter orange and its primary protoalkaloid p -synephrine. Phytother Res. Colker CM, Kalman DS, Torina GC, Perlis T, Street C.

Effects of Citrus aurantium extract, caffeine, and St. John's wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Therap Res. Dulloo AG, Duret C, Rohrer D. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing h energy expenditure and fat oxidation in humans.

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Presented at the annual meeting of the American College of Nutrition, Abstract No. J Amer Coll Nutr. Kalman DS, Rubin S, Martinez T, Schwartz HI. Presented at a meeting of NIH-National Institute of Diabetes and Digestive and Kidney Diseases. Kalman DS, Rubin S, Schwartz HI.

An acute clinical trial to evaluate the safety and efficacy of a popular commercial weight loss supplement when used with exercise. Presented at Federation of American Societies of Experimental Biology. Kalman DS, Colker CM, Shi Q, Swain MA.

Effects of a weight-loss aid in healthy overweight adults: double-blind, placebo-controlled clinical study. Curr Ther Res. Kalman DS, Incledon T, Gaunaurd I. An acute clinical trial evaluating the cardiovascular effects of an herbal ephedra-caffeine weight loss product in healthy overweight adults.

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Clin Pharmacol Therap. Zenk JL, Kuskowski MA. Zenk JL, Leikam SA, Kassen LJ, Kuskowski MA. Effect of Lean System 7 on metabolic rate and body composition. Min B, Cios D, Kluger J, White CM. Absence of QTc interval- prolonging or hemodynamic effects of a single dose of bitter orange extract in healthy subjects.

Haller CA, Benowitz N, Peyton J III. Hemodynamic effects of ephedra-free weight loss supplements in humans. Amer J Med.

Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate affects following a single dose of bitter orange. Ann Pharmacodyn. Sale C, Harris RC, Delves S, Corbett J.

Metabolic and physiological effects of ingesting extracts of bitter orange, green tea and guarana at rest and during treadmill walking in overweight males. Int J Obesity. Gougeon R, Harrigan K, Tremblay JF.

Increase in the thermic effect of food in women by adrenergic amines extracted from Citrus aurantium. Obesity Res. Hoffman JR, Kang J, Ratamess A.

Thermogenic effect from nutritionally enriched coffee consumption. J Int Soc Sports Nutr. Citrus aurantium extract has no effect on blood pressure or heart rate in healthy adults.