The latest research reviewed all the data available on synephrine and bitter orange for fat loss, weight loss, and side effects. Synephrine was not beneficial for long-term weight loss or fat loss. Synephrine was not found to boost fat metabolism. Synephrine was found to increase blood pressure long term.


  • Bitter Orange supplements/ Synephrine was not beneficial for long-term weight loss or fat loss.

  • Synephrine was not found to boost fat metabolism.

  • Synephrine was found to increase blood pressure long-term.

Synephrine supplementation was supposed to be the next “big thing” for fat loss and increased stamina. When the FDA pulled ephedrine from the market, many looked for an alternative stimulant in pre-workouts and fat burners.


Bitter orange, or citrus aurantium, traditionally utilized in Chinese medicine, now features prominently in numerous sports supplements, also known as Seville orange, orange marmalade, and sour orange.

Advantra Z®, a patented extract of Citrus Aurantium (Bitter Orange), has piqued interest due to the discovery of a compound called p-synephrine in bitter orange fruits (Andrade et al., 2009; Fugh-Berman & Myers, 2004). This compound, structurally akin to ephedrine, impacts the heart rate less significantly (Stohs, Preuss, Keith, et al., 2011). Those who have experienced ephedrine might recall the sensation of a racing heart. However, studies on animals and humans reveal that short-term use of synephrine can elevate metabolic rate and fat oxidation, proving beneficial for weight loss (Stohs, Preuss, & Shara, 2011) (Colker et al., 1999; Kalman et al., 2000).

Consequently, many companies incorporate synephrine HCl and bitter orange into fat burners and pre-workouts to amplify energy, facilitate fat burning, and boost performance


Typical pre-workout supplements contain synephrine with a combination of caffeine and other amino acids, such as beta-alanine. A single dose of 50mg p-synephrine in healthy subjects resulted in an increase in calories burned (i.e., 65 kcals) in a rested state.(Stohs, Preuss, Keith, et al., 2011)

No long-term studies have been conducted on synephrine’s health benefits or adverse effects. Synephrine is structurally similar to your adrenal hormones, epinephrine and norepinephrine, which can increase heart rate. (Stohs & Badmaev, 2016)

Some studies have found positive benefits with bitter orange supplements, and others have found no benefits. The safety and effects of synephrine for weight loss and improving body composition are unclear.

New Study

In this month’s journal of Nutrients, researchers collected all the studies available on synephrine to date. 18 randomized controlled studies consisting of 341 men and women were examined. They looked at how synephrine affected cardiovascular responses, weight loss, muscle mass, and fat metabolism. The dosages of synephrine ranged from 6 to 214 mg in the studies.

The most commonly used dosage of synephrine for weight loss is 25-100 mg. (Stohs, Preuss, & Shara, 2011; Stohs et al., 2020; Suntar et al., 2018) When the researchers analyzed all the data, here are the results:

bitter orange bitter orange supplement bitter orange benefits synephrine benefits synephrine weight loss bitter orange weight loss stimulants in pre workout bitter orange dosage for weight loss synephrine hcl benefits

Synephrine was not found to reduce weight, fat loss, or muscle mass.


·      Synephrine did not raise systolic blood pressure short-term, but long-term use did raise systolic blood pressure (+6.4 mmHg). Similarly, diastolic blood pressure followed similar responses (+4.3 mmHg).

·      Acute synephrine resulted in small increases in heart rate.

·      Synephrine was not found to reduce weight, fat loss, or muscle mass.

·      Synephrine did not affect fat metabolism (i.e., fat burning)

The review was interesting because synephrine is found in many fat burners and pre-workout, but there were no changes in body composition. The long-term increases in blood pressure mean synephrine is not without side effects.

Many supplement companies advocate synephrine as a fat burner. Still, the authors suggested that the lack of changes in fat metabolism means that the fat-burning effects of fat burners are more related to caffeine than synephrine.

The study reported that 6-103 mg of synephrine did not increase fat metabolism. The most widely cited studies found synephrine increased fat metabolism with caffeine combined with synephrine. (Kalman et al., 2000; Seifert et al., 2011)

Researchers, as per the study by Koncz et al. (2022), concluded that while synephrine does affect blood pressure and heart rate, it doesn’t yield significant results in weight loss and body composition; hence, its usage isn’t recommended for health promotion.

Conclusions and Recommendations

Given the findings, lifters might consider opting for synephrine-free pre-workout supplements until the completion of more extensive, long-term studies. The elevation in blood pressure due to synephrine results in the vasoconstriction of blood vessels, subsequently impeding the enhancement of blood flow to the muscles.

Synephrine will reduce muscle pumps. Additionally, it has been found that synephrine can cause you to test positive in a drug-tested competition. Synephrine is on the WADA-banned list. This study is similar to the most recent review finding that fat burners are ineffective for weight loss.


Andrade, A. S., Schmitt, G. C., Rossato, L. G., Russowsky, D., & Limberger, R. P. (2009). Gas Chromatographic Method for Analysis of p-Synephrine in Citrus aurantium L. Products. Chromatographia, 69(2), 225-229.

Colker, C. M., Kaiman, D. S., Torina, G. C., Perlis, T., & Street, C. (1999). Effects of Citrus aurantium extract, caffeine, and St. John’s Wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Current Therapeutic Research, 60(3), 145-153.

Fugh-Berman, A., & Myers, A. (2004). Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood), 229(8), 698-704.

Kalman, D. S., Colker, C. M., Shi, Q., & Swain, M. A. (2000). Effects of a weight-loss aid in healthy overweight adults: double-blind, placebo-controlled clinical trial. Current Therapeutic Research, 61(4), 199-205.


Koncz, D., Tóth, B., Bahar, M. A., Roza, O., & Csupor, D. (2022). The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients, 14(19).

Seifert, J. G., Nelson, A., Devonish, J., Burke, E. R., & Stohs, S. J. (2011). Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans. Int J Med Sci, 8(3), 192-197.

Stohs, S. J., & Badmaev, V. (2016). A Review of Natural Stimulant and Non-stimulant Thermogenic Agents. Phytother Res, 30(5), 732-740.

Stohs, S. J., Preuss, H. G., Keith, S. C., Keith, P. L., Miller, H., & Kaats, G. R. (2011). Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med Sci, 8(4), 295-301.

Stohs, S. J., Preuss, H. G., & Shara, M. (2011). The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine. Phytother Res, 25(10), 1421-1428.

Stohs, S. J., Shara, M., & Ray, S. D. (2020). p-Synephrine, ephedrine, p-octopamine and m-synephrine: Comparative mechanistic, physiological and pharmacological properties. Phytother Res, 34(8), 1838-1846.

Suntar, I., Khan, H., Patel, S., Celano, R., & Rastrelli, L. (2018). An Overview on Citrus aurantium L.: Its Functions as Food Ingredient and Therapeutic Agent. Oxid Med Cell Longev, 2018, 7864269.

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