bitter orange
© 2018 Steven Foster

A bitter orange monograph for the home

Latin Name: Citrus aurantium

Common Names: bitter orange, Seville orange, sour orange, zhi shi

This bitter orange monograph provides basic information about bitter orange—common names, usefulness and safety, and resources for more information.


Bitter Orange Basics

  • Native to eastern Africa and tropical Asia, bitter orange now is grown throughout the Mediterranean region and elsewhere, including California and Florida.
  • Bitter orange has been used in traditional Chinese medicine and by indigenous people of the Amazon rainforest for constipation. Amazonian natives also used it for nausea and indigestion.
  • Today, people use various bitter orange products as a dietary supplement for heartburn, loss of appetite, nasal congestion, and weight loss. It is also applied to the skin for pain, bruises, and bed sores.
  • Bitter orange, used in some weight-loss products, contains synephrine, which is similar to the main chemical in the herb ephedra. Ephedra is banned by the U.S. Food and Drug Administration because it raises blood pressure and is linked to heart attack and stroke.
  • The National Collegiate Athletic Association (NCAA) placed synephrine (bitter orange) on its current list of banned drugs.
  • The fruit, peel, flower, and oil are used and can be taken by mouth in tablets and capsules. Bitter orange oil can be applied to the skin.

Bitter Orange in Health Research

  • Only a few studies have investigated the usefulness of bitter orange as a dietary supplement for health purposes in people.

Bitter Orange Research Summary

  • Applying bitter orange oil to the skin may help with ringworm, jock itch, and athlete’s foot infections.
  • There’s not enough scientific evidence to support the use of bitter orange for other health purposes.

Bitter Orange Safety

  • There are case reports of healthy people experiencing fainting, heart attack, and stroke after taking bitter orange alone or with caffeine. However, evidence regarding the effects of bitter orange (alone or combined with other substances, such as caffeine and green tea) on the heart and cardiovascular system are inconclusive.
  • Because products that contain bitter orange may be unsafe, pregnant women and nursing mothers should avoid them.

Bitter Orange References

PubMed Articles About Citrus aurantium

Source: National Center for Biotechnology Information (NCBI)[Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; [1988] – [cited 2018 Apr 5]. Available from:

Search query:(Citrus aurantium AND diabetes AND (( Clinical Trial[ptyp] OR systematic[sb] ) AND Humans[Mesh]))

Al-Aubaidy, HA., Dayan, A., Deseo, MA., Itsiopoulos, C., Jamil, D., Hadi, NR., Thomas, CJ., (2021) Twelve-Week Mediterranean Diet Intervention Increases Citrus Bioflavonoid Levels and Reduces Inflammation in People with Type 2 Diabetes Mellitus.

The benefits of a Mediterranean Diet (MedDiet) in the management of diabetes have been reported, but the contribution of polyphenol-rich citrus fruit has not been studied widely. Here, we report the sub-study findings of a previously conducted MedDiet intervention clinical trial in patients with type 2 diabetes mellitus (T2DM), where we aimed to measure the diet intervention effects on plasma citrus bioflavonoids levels and biomarkers of inflammation and oxidative stress. We analysed plasma samples from 19 (of original 27) participants with T2DM who were randomly assigned to consume the MedDiet intervention or their usual diet for 12 weeks and then crossed over to the alternate diet. Compared with baseline, MedDiet significantly increased levels of the citrus bioflavonoids naringin, hesperitin and hesperidin (by 60%, 58% and 39%, respectively, < 0.05) and reduced plasma levels of the pro-inflammatory cytokine IL-6 (by 49%, = 0.016). Oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased by 32.4% ( = 0.128). Usual diet did not induce these beneficial changes. The reduced inflammatory profile of T2DM participants may, in part, be attributed to the anti-inflammatory actions of citrus bioflavonoids. Together with indications of improved oxidative stress, these findings add to the scientific evidence base for beneficial consumption of citrus fruit in the MedDiet pattern.

Gandhi, GR., Vasconcelos, ABS., Wu, DT., Li, HB., Antony, PJ., Li, H., Geng, F., Gurgel, RQ., Narain, N., Gan, RY., (2021) Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies.

The consumption of plant-based food is important for health promotion, especially concerning the prevention and management of chronic diseases. Flavonoids are the main bioactive compounds in citrus fruits, with multiple beneficial effects, especially antidiabetic effects. We systematically review the potential antidiabetic action and molecular mechanisms of citrus flavonoids based on in vitro and in vivo studies. A search of the PubMed, EMBASE, Scopus, and Web of Science Core Collection databases for articles published since 2010 was carried out using the keywords citrus, flavonoid, and diabetes. All articles identified were analyzed, and data were extracted using a standardized form. The search identified 38 articles, which reported that 19 citrus flavonoids, including 8-prenylnaringenin, cosmosiin, didymin, diosmin, hesperetin, hesperidin, isosiennsetin, naringenin, naringin, neohesperidin, nobiletin, poncirin, quercetin, rhoifolin, rutin, sineesytin, sudachitin, tangeretin, and xanthohumol, have antidiabetic potential. These flavonoids regulated biomarkers of glycemic control, lipid profiles, renal function, hepatic enzymes, and antioxidant enzymes, and modulated signaling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications. Citrus flavonoids, therefore, are promising antidiabetic candidates, while their antidiabetic effects remain to be verified in forthcoming human studies.

Egbuna, C., Awuchi, CG., Kushwaha, G., Rudrapal, M., Patrick-Iwuanyanwu, KC., Singh, O., Odoh, UE., Khan, J., Jeevanandam, J., Kumarasamy, S., Chukwube, VO., Narayanan, M., Palai, S., Găman, MA., Uche, CZ., Ogaji, DS., Ezeofor, NJ., Mtewa, AG., Patrick-Iwuanyanwu, CC., Kesh, SS., Shivamallu, C., Saravanan, K., Tijjani, H., Akram, M., Ifemeje, JC., Olisah, MC., Chikwendu, CJ., (2021) Bioactive Compounds Effective Against Type 2 Diabetes Mellitus: A Systematic Review.

Type 2 diabetes (adult onset diabetes) is the most common type of diabetes, accounting for around 90% of all diabetes cases with insulin resistance and insulin secretion defect. The key goal of anti-diabetic therapy is to increase the development of insulin, immunity and/or decrease the amount of blood glucose. While many synthetic compounds have been produced as antidiabetic agents, due to their side effects and limited effectiveness, their usefulness has been hindered.

Mollace, V., Scicchitano, M., Paone, S., Casale, F., Calandruccio, C., Gliozzi, M., Musolino, V., Carresi, C., Maiuolo, J., Nucera, S., Riva, A., Allegrini, P., Ronchi, M., Petrangolini, G., Bombardelli, E., (2019) Hypoglycemic and Hypolipemic Effects of a New Lecithin Formulation of Bergamot Polyphenolic Fraction: A Double Blind, Randomized, Placebo- Controlled Study.

Hyperlipemia represents an independent risk factor in the development of atherosclerosis in patients undergoing type 2 diabetes mellitus (DM). Moreover, the pharmacological treatment of dyslipemia in patients undergoing type 2 DM (e.g. by means of statins), is accompanied by relevant side effects and oral supplementation with natural antioxidants, such as Citrus polyphenols, has recently been suggested to improve cardioprotection in such patients. However, due to the poor gastrointestinal absorption of polyphenols, novel formulations have recently been developed for getting a better bioavailability of polyphenolic rich fractions of citrus species extract rich in polyphenols.

Agulló, V., García-Viguera, C., Domínguez-Perles, R., (2021) Beverages Based on Second Quality Citrus Fruits and Maqui Berry, a Source of Bioactive (Poly)phenols: Sorting Out Urine Metabolites upon a Longitudinal Study.

The intake of sugar-sweetened beverages has been associated with an augmented prevalence of metabolic diseases, namely, obesity, type II diabetes, and metabolic syndrome. On the other hand, nowadays, it is broadly accepted that foods and beverages rich in (poly)phenols could contribute to reducing the incidence of these pathologies. In this sense, the objective of the work was to revalue second quality citrus fruits for the development of new beverages, rich in anthocyanins and flavanones (maqui berry and second qualities citrus-based), and evaluate the influence of alternative sweeteners (sucralose, sucrose, or stevia), regarding the bioaccessibility and bioavailability of these bioactive compounds in the frame of a chronic (longitudinal) intervention. To fulfill this objective, a longitudinal study of the urinary excretion of anthocyanins and flavanones, after 2-months of ingestion of the developed maqui-citrus beverage, by 138 volunteers ( = 46 per beverage) and the analysis of the resulting phenolic metabolites by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-ESI-QqQ-MS/MS) was carried out. As major results, the bioavailable metabolites of caffeic acid (CA), catechol (CAT), 3,4-di-hydroxyphenylacetic acid (DHPAA), eriodictyol (E), homoeriodictyol (HE), hippuric acid (HA), naringenin (N), trans-ferulic acid (TFA), 2,4,6-tri-hydroxybenzaldehyde (THBA), trans-isoferulic acid (TIFA), and vanillic acid (VA) were detected. Accordingly, significantly different bioavailability was dependent on the sweetener used, allowing proposing stevia and, to a lower extent, sucralose, as valuable alternatives to sucrose.