Bitter Orange Extract: What the Research Says

Bitter orange extract is one of the most common ingredients in “fat burner” and pre-workout supplements. It took off after the US banned ephedra in 2004, and it’s often sold as a gentler replacement. But does it actually help you lose weight, and is it safe for your heart? Here’s what the studies show.

In short: Bitter orange extract hasn’t been shown to help people lose weight: the best pooled analysis found no meaningful difference from a placebo (dummy pill). Its main active compound, synephrine, may raise blood pressure a little with regular use, and multi-ingredient products with caffeine may raise it more. It’s likely safe in the amounts found in food, but supplements are a different story, so check with your doctor first.

What is bitter orange extract?

Bitter orange (Citrus aurantium), also called Seville orange, sour orange or zhi shi, is a citrus tree native to Southeast Asia. The fruit is too sour to eat raw, but the fruit, peel and oil are used in cooking, to flavor drinks, and in perfumes [1].

Bitter orange extract is made from the unripe fruit or the peel [2]. It’s sold mainly for weight loss and sports performance [1]. The compound that gets most of the attention is p-synephrine (para-synephrine), a protoalkaloid, which is a plant compound related to the body’s own “fight or flight” chemicals such as adrenaline. Dried bitter orange extracts usually contain about 3–6% synephrine [2].

Synephrine comes in several chemical forms. The form found in bitter orange is mainly p-synephrine, while m-synephrine, the same compound as the decongestant phenylephrine, acts more strongly on blood vessels [2]. A 2005 lab analysis found that at least one supplement sold as bitter orange contained both forms, raising questions about what’s really in some products [3].

Is bitter orange extract the “new ephedra”?

The US Food and Drug Administration (FDA) banned ephedrine alkaloids (the stimulants in ephedra) from US dietary supplements in 2004, and bitter orange quickly became a popular alternative [1]. Ephedra use had been linked to heart attacks, high blood pressure and strokes [2]. (For one example, see our post on coronary thrombosis linked to ephedra extract.)

Synephrine looks a lot like ephedrine on paper, but it doesn’t act the same way in the body [1]. It’s less fat-soluble, so less of it gets into the brain [2]. In animal studies, it stimulates beta receptors (the “on switches” on fat cells that help release stored fat, a process called lipolysis), while its effects on blood vessels come partly from alpha receptors, the ones that make blood vessels tighten [2].

That fat-burning theory hasn’t held up well in human cells. A 2004 review noted that synephrine only boosted fat release in human fat cells at high doses [4]. So “a gentler ephedra” is partly true (it’s a weaker stimulant), but that doesn’t make it effective or risk-free.

Does bitter orange extract help with weight loss?

So far, the evidence says no, or at least not by any amount you’d notice.

• Early review (2004): A systematic review (a study that gathers all the relevant trials on a question) found only one eligible placebo-controlled trial. It followed 20 people for 6 weeks and found no statistically significant weight loss benefit (meaning any difference could easily have been due to chance) [5].
• Another review (2012): A review of more than 20 studies, written by the same group that later ran the Shara and Kaats studies described below, (including unpublished ones) reported “modest” weight loss over 6–12 weeks. But many of the products also contained caffeine or other ingredients, so the effect of bitter orange alone can’t be separated out [6].
• Best pooled analysis (2022): A meta-analysis (which combines the data from several trials) by researchers at the University of Szeged in Hungary pooled three placebo-controlled trials with 94 people who took 10–54 mg of synephrine a day for 6–8 weeks. All three included exercise, and two included a diet. Weight loss was no different from placebo (a difference of 0.6 kg, or about 1.3 lb, that wasn’t statistically significant), and there was no significant change in body fat or fat mass [2].

The US National Center for Complementary and Integrative Health (NCCIH) sums it up: bitter orange’s effects on body weight are unclear, the studies were small, often tested combination products, and had conflicting results [1].

If you’re comparing fat burners, the picture is similar for other popular ingredients, such as green coffee extract.

Bitter orange extract and exercise: more fat burned?

A group of Spanish researchers has tested whether synephrine changes the fuel your body burns during exercise, and several of their small, single-dose studies found more fat burned [7]. For example, in a double-blind (neither the volunteers nor the researchers knew who got what), placebo-controlled study of 18 healthy young adults, a single dose of 3 mg of synephrine per kilogram of body weight raised the highest rate of fat burning during a cycling test (0.40 vs 0.29 grams per minute), while total calories burned stayed the same [8]. That dose works out to around 210 mg for a 70 kg (154 lb) person, well above the 25–100 mg a day commonly used in supplements [2].

But when the same team tested 18 healthy, active women, the same dose made no difference to fat burning or calories burned [9]. The researchers themselves say more research is needed to find out whether the effect lasts with regular use and whether it leads to any real fat loss [7]. Burning a bit more fat during a workout (while burning less carbohydrate) isn’t the same as losing body fat.

For sports performance in general, NCCIH says the studies were small and inconsistent, and most didn’t show a benefit [1].

Does bitter orange extract raise blood pressure?

This is where the research is most mixed. Blood pressure is given in mmHg (millimeters of mercury), and the top number (systolic) is the pressure when your heart beats.

• Haller 2005: In a crossover study of 10 healthy adults (everyone tried each product on different days), a bitter orange product with 46.9 mg of synephrine didn’t raise blood pressure, though heart rate was about 11 beats per minute higher than placebo after 6 hours. A multi-ingredient “ephedra-free” product with only 5.5 mg of synephrine, plus caffeine and other stimulants, raised blood pressure by about 9–10 mmHg. The authors concluded the blood pressure rise may have come from the caffeine and other stimulants rather than bitter orange alone [10].
• Bui 2006: In 15 healthy young adults, a single 900 mg capsule of bitter orange extract (6% synephrine, so about 54 mg) raised systolic blood pressure by up to 7.3 mmHg and heart rate by up to 4.2 beats per minute compared with placebo, for up to 5 hours [11].
• Shara 2016: In 18 healthy adults, a single dose of bitter orange extract with 49 mg of synephrine caused no significant changes in heart rate, systolic blood pressure or heart tracings (ECGs) [12].
• Kaats 2013: In a 60-day study with 25 people per group, about 49 mg of synephrine twice a day didn’t change blood pressure [13].

The 2022 meta-analysis found that single doses didn’t significantly change blood pressure or heart rate. But in two 8-week trials with 75 people, taking 10–49 mg of synephrine a day raised systolic blood pressure by about 6.4 mmHg and diastolic (bottom number) by about 4.3 mmHg compared with placebo [2]. These pooled trials may include the Kaats study, which found no change by its own analysis; the meta-analysis compared end-of-study readings between groups, which can give a different answer. That’s a small number of people, but it’s enough for the authors to say synephrine “may not be a safe alternative to ephedrine” for people with existing health problems [2].

Not everyone agrees. Reviews by pharmacologist Sidney Stohs, who co-authored the Shara and Kaats studies above and lists a consulting company among his affiliations, conclude that bitter orange extract doesn’t act as a stimulant or affect the heart at commonly used doses [6, 14]. NCCIH calls the evidence on heart effects inconclusive [1].

Bitter orange extract safety and side effects

NCCIH says bitter orange is likely safe in the amounts found in foods, but there are “serious concerns” about supplements [1].

Case reports of heart problems

Abnormal heart rhythms, heart attacks and strokes have been reported in people taking bitter orange supplements. Most of these products contained several ingredients, though, so bitter orange’s role isn’t clear [1]. Examples include:

• A healthy 24-year-old man who had a heart attack within hours of taking a synephrine-containing fat burner [15].
• A previously healthy 22-year-old man who had a heart attack after 3 weeks of taking a bitter orange supplement together with a pre-workout containing DMAA (1,3-dimethylamylamine, another stimulant) before exercise [16].
• A middle-aged man who developed variant angina (chest pain caused by a spasm in a heart artery) linked to a bitter orange supplement [17].

Case reports can’t prove that a supplement caused the problem, but they’re a reason for caution, especially with multi-ingredient products.

Caffeine and other stimulants

Bitter orange is often sold alongside caffeine. France’s food safety agency (ANSES) has advised keeping synephrine from supplements below 20 mg a day, not combining it with caffeine, and not using it during exercise [2]. If you already use a caffeine-containing pre-workout, adding bitter orange stacks stimulants.

What’s on the label may not be what’s in the bottle

When FDA researchers analyzed 59 bitter orange supplements, only 5 of the 23 products that listed a synephrine amount were within 80–120% of the labeled dose. Six products contained synthetic stimulants (methylsynephrine or isopropyloctopamine) that aren’t legal dietary ingredients in the US [1].

Medicine interactions

Like grapefruit, bitter orange contains compounds (such as 6′,7′-dihydroxybergamottin and bergapten) that block CYP3A, a liver and gut enzyme that breaks down many medicines. That could raise blood levels of those drugs [4]. (We’ve written more about 6′,7′-dihydroxybergamottin.) If you take any regular medicine, talk to your doctor or pharmacist first [1].

Who should avoid it

• Pregnant or breastfeeding women: it may not be safe, and animal data suggest it may reduce milk supply [1].
• People with high blood pressure or heart conditions, given the possible blood pressure rise with regular use [2].
• Children and teens, and anyone taking medicines that interact with it: ANSES advises these groups not to use synephrine [2].
• Competitive athletes: the National Collegiate Athletic Association (NCAA) lists synephrine (bitter orange) as a banned stimulant [1], and it has been on the World Anti-Doping Agency’s monitoring program [2].

Bitter orange isn’t the only “ephedra-free” herb with a misleading weight loss reputation. See our review of rauwolfia serpentina, which has also been sold as a fat burner.

The bottom line on bitter orange extract

Bitter orange extract is a weaker stimulant than ephedra, but that doesn’t make it a good weight loss tool. Pooled trials show no real weight loss compared with a placebo. The extra fat burning seen during exercise in several small, single-dose studies by one research group didn’t show up in a study of women, and no study has shown it leads to fat loss. Regular use may nudge blood pressure up, and many products mix it with caffeine and other stimulants or don’t contain what the label says.

Bitter orange used in cooking, in normal food amounts, is likely safe [1]. If you’re thinking about a bitter orange extract supplement, especially if you have high blood pressure, a heart condition or take medicines, talk to your doctor first.

This article is for general information only and isn’t medical advice. Talk to your doctor or another qualified health professional before starting a new supplement. See our medical disclaimer.

References

1. National Center for Complementary and Integrative Health (NCCIH). Bitter Orange: Usefulness and Safety. Last updated November 2024. https://www.nccih.nih.gov/health/bitter-orange
2. Koncz D, Tóth B, Bahar MA, Roza O, Csupor D. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients. 2022;14(19):4019. doi:10.3390/nu14194019
3. Allison DB, Cutter G, Poehlman ET, Moore DR, Barnes S. Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain? Int J Obes (Lond). 2005;29(4):443-446. doi:10.1038/sj.ijo.0802879
4. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 2004;229(8):698-704. doi:10.1177/153537020422900802
5. Bent S, Padula A, Neuhaus J. Safety and efficacy of citrus aurantium for weight loss. Am J Cardiol. 2004;94(10):1359-1361. doi:10.1016/j.amjcard.2004.07.137
6. Stohs SJ, Preuss HG, Shara M. A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine. Int J Med Sci. 2012;9(7):527-538. doi:10.7150/ijms.4446
7. Ruiz-Moreno C, Del Coso J, Giráldez-Costas V, González-García J, Gutiérrez-Hellín J. Effects of p-Synephrine during Exercise: A Brief Narrative Review. Nutrients. 2021;13(1):233. doi:10.3390/nu13010233
8. Gutiérrez-Hellín J, Del Coso J. Acute p-synephrine ingestion increases fat oxidation rate during exercise. Br J Clin Pharmacol. 2016;82(2):362-368. doi:10.1111/bcp.12952
9. Gutiérrez-Hellín J, Aguilar-Navarro M, Ruiz-Moreno C, et al. Effect of p-Synephrine on Fat Oxidation Rate during Exercise of Increasing Intensity in Healthy Active Women. Nutrients. 2022;14(20):4352. doi:10.3390/nu14204352
10. Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med. 2005;118(9):998-1003. doi:10.1016/j.amjmed.2005.02.034
11. Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother. 2006;40(1):53-57. doi:10.1345/aph.1G488
12. Shara M, Stohs SJ, Mukattash TL. Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial. Phytother Res. 2016;30(5):842-847. doi:10.1002/ptr.5590
13. Kaats GR, Miller H, Preuss HG, Stohs SJ. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362. doi:10.1016/j.fct.2013.01.013
14. Stohs SJ. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytother Res. 2017;31(10):1463-1474. doi:10.1002/ptr.5879
15. Thomas JE, Munir JA, McIntyre PZ, Ferguson MA. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex Heart Inst J. 2009;36(6):586-590. PubMed 20069086 (PMCID PMC2801940)
16. Smith TB, Staub BA, Natarajan GM, Lasorda DM, Poornima IG. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. Tex Heart Inst J. 2014;41(1):70-72. doi:10.14503/THIJ-12-2870
17. Gange CA, Madias C, Felix-Getzik EM, Weintraub AR, Estes NA 3rd. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin Proc. 2006;81(4):545-548. doi:10.4065/81.4.545