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  • Stimulates Metabolism
  • Boosts Mental and Physical Energy
  • Support for a Healthy Weight


Synephrine HCl is an energizing supplement extracted from the Bitter orange fruit. It is known for its ability to support and improve thermogenesis (production of heat through the burning of fat) as well as to provide an increase in physical energy. Studies have indicated that this supplement can be taken to promote healthy mental focus and attention.


The recommended serving size is around 50 – 100 mg daily, or taken 30 – 40 minutes prior to exercise. Increasing the serving size above what is recommended may result in adverse effects and may not improve your experience of this supplement. Unlike most other products used to increase thermogenesis, this product is not known to affect heart rate or blood pressure, when taken at the correct serving size. 


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Synephrine reviews



  • Synephrine HCL is a trace amine found in Bitter Orange or Citrus aurantium and has a long history of use in Chinese medicine.


  • The primary effect of synephrine is to increase the metabolism and thereby help with weight-loss.


  • Standard doses of synephrine HCL are 50-100mg daily or 30-40mins before a workout.


  • Side effects of synephrine may include increased heart rate and blood pressure when used in combination with other stimulants.




Synephrine HCl (P-hydroxy-α-{methylaminomethyl}benzylalcohol, P-Synephrine, para-Synephrine) is a trace amine found in some species of plants. It produces some interesting effects in the body, including increased thermogenesis, a boost in metabolism, and an improvement in mental focus and physical energy. The most common source of this compound is the Bitter orange fruit (Seville orange, Sour orange, Citrus auratium), which has a concentration of around 8.8% and is used in Traditional Chinese Medicine.[1]


Synephrine is often confused for a number of different compounds. It is important not to confuse this supplement with similar but markedly different extracts or compounds like Seville orange extract, Neo-Synephrine, Methylsynephrine, Adzantra Z, Ephedrine, and other Bitter orange extracts or Citrus auratium extracts. This supplement somewhat similar –  both in chemical structure and in its pharmacological profile – to the stimulant Ephedrine, but is less potent and has a lower potential to produce harmful side effects.[2]  Some important synonyms for this supplement include Oxedrine, Sympatol, Parasympatol, Sympaethamin, and Synephrin.


When people talk about Synephrine HCl, they are referring to the salt form (hydrochloride) of p-Synephrine, also known as para-Synephrine. The p- prefix refers to the orientation of the structure of this supplement, which is in contrast to similar compounds like m-Synephrine and o-Synephrine. The primary effect of this supplement is to boost the rate of metabolism and to increase thermogenesis (production of heat in the body). This means that it can it be used to promote a good metabolism and support a healthy weight while providing a boost in mental focus and physical energy.


business man with high energy after using Synephrine supplements


Synephrine Effects / Benefits


1.     Potent Metabolism Booster


This supplement can be used as a potent metabolism booster, through its effects on thermogenesis (heat production in the body by the burning of fat).


In a number of studies, researchers have pointed to the metabolism-boosting effects of this supplement. For example, an open-label study found that the 9 women who were participating lost an average of 2.40 kg, when the supplement was taken, and only 0.94 kg when placebo was used.[3] In another study, researchers focused on the effects of Synephrine-containing chew-tablets on heart rate, blood pressure, and appetite. Results pointed to a statistically significant decrease in appetite and with no changes in heart rate or blood pressure. [5]


A recent study, published in the International Journal for Medical Sciences, focused on the metabolic effects, both alone and in combination with other flavonoids. Researchers suggested that the mean resting metabolic rate was increased by an average value of 65 Kcal for subjects taking a baseline serving size of 65 mg. Importantly, the researchers found that, even when taken in combination with the flavonoids Naringin and Hesperidin, this supplement did not increase blood pressure or heart rate:


None of the treatment groups exhibited changes in heart rate or blood pressure relative to the control group, nor there were no differences in self-reported ratings of 10 symptoms between the treatment groups and the control group. This unusual finding of a thermogenic combination of ingredients that elevated metabolic rates without corresponding elevations in blood pressure and heart-rates warrants longer-term studies to assess its value as a weight control agent.” (G Kaats et al., 2011)[4]


Along with a few more recent studies, these results certainly suggest some interesting benefits relating to increases in metabolism and support for a healthy weight. Unlike most other supplements that increase metabolism rate, this supplement does not appear to have any effects on heart rate or blood pressure. [6]


2.     Increases Mental Energy and Focus 


The benefits for mental focus and alertness are mostly known as a result of reviews, as well as through an examination of effects on receptors in the brain and a synergistic relationship with Caffeine. Furthermore, scientific reviews looking into the safety and effects of this supplement have mentioned its ability to help promote mental focus and alertness. [7]


This supplement binds to Monoamine oxidase (MAO) enzymes in the brain – specifically to MAO-A type receptors. Although it does not inhibit the function of MAO enzymes, this supplement acts as a competitive ligand and binds to MAO receptors, preventing them from oxidizing the neurotransmitters that they would normally act on. [8] Compounds that act on monoamine oxidase enzymes are known for their ability to improve mental focus and alertness and are have been in a number of applications – often for the reduction of stress and to promote a healthy mental state.


Furthermore, this supplement has been shown to have a synergistic relationship with Caffeine. Studies have shown that the two compounds work well together to boost mental focus and alertness, as well as wakefulness and mental energy. As one study (published in the International Journal of Medical Sciences) found, many Synephrine-containing supplements and products also contain Caffeine because of their well known synergistic relationship. Using Caffeine may help to enhance the cognitive effects of this supplement. [9]


3.     Increases Physical Energy and Performance


This supplement also has clear and significant effects on exercise performance, a few of which have been confirmed in recent human studies. It has the potential to increase exercise performance and endurance, as well as to boost physical energy levels and thermogenesis.


In one study, researchers focussed on the effects of this supplement on exercise performance, both alone and in combination with Caffeine. Results showed a significant increase in mean power, endurance, and exercise performance for the test groups. Synephrine can be used to increase physical energy and performance either when taken alone or when used in combination with Caffeine. [10]


In another study, researchers found that p-Synephrine supplements, when taken at a serving size of around 2-3 mg/kg, significantly improved fat oxidation (fat burning and the subsequent generation of energy, also known as thermogenesis) in people who were performing exercise of increasing intensity. Interestingly, in both the placebo and the test groups, the highest level of fat oxidation with seen to occur at around 38-42% of VO2 max, for each person. [11]


Finally, in a third and more recent study (published in 2016), researchers investigate the effects of this supplement on fat metabolism and energy expenditure. Synephrine did not affect energy consumption or fat oxidation at rest, but had significant effects on these markers during exercise. Researchers suggest that the supplement increases the fat oxidation rate – producing more energy and helping to maintain a healthy weight – without affecting the exercise intensity for optimum fat oxidation (around 50% of VO2 max in this study). [12]


Synephrine HCl Recommended Usage


The recommended serving size for this supplement is around 50 – 150 mg, once to twice daily. Some studies have indicated that the optimum dosage for fat burning and energy production is around 2 – 3 mg/kg body weight. It is not recommended to exceed the serving size for this product. It may be beneficial to use this supplement in cycles.


Some people use this supplement with Caffeine because of the synergistic relationship between the two compounds. If you use these compounds together, please ensure that you use lower than usual servings, since both supplements are strongly energizing.[13]


bitter orange fruit, a source of synephrine hcl


Synephrine Side Effects and Warnings


Importantly, p-Synephrine is considered highly safe, due to its ability to increase energy and metabolism without affecting heart rate or blood pressure.


There is some confusion about the safety of this supplement, as a result of the use of poorly-designed stacks that contain Synephrine along with a number of additional energizing/metabolism-boosting compounds, some of which are known to produce unwanted side effects. Many ‘supplement stacks’ contain this product along with other compounds found in the Bitter orange/ Citrus aurantium – including the now-banned Ephedrine. In the past, people who used these stacks suffered from adverse effects and this created some confusion about the safety of Synephrine HCl. A recent review of literature looked into the safety of Synephrine supplements for humans. Researchers pointed out the fact that this supplement has a very wide safety margin, and does not produce any cardiovascular effects at serving sizes of up to 100 mg. [14]


The mechanism of action for this powerful supplement involves interactions with β‐3 adrenergic receptors (whose role is to regulate fat and carbohydrate metabolism), NMUR2s, and AMP‐activated protein kinases, cAMP, and Ca(2+)‐dependent channels. This supplement produces few binding effects at α‐1, α‐2, β‐1, and β‐2 adrenergic receptors, which allows improved energy levels without producing effects on heart rate or blood pressure. [15] 

Side effects from larger servings may include headaches, nausea, and restlessness. If you have any underlying medical conditions or are taking any medication, please speak to your doctor before using this supplement. There is not yet sufficient research regarding the safety of this supplement for breastfeeding and pregnant women.


Similar Compounds and Synephrine Derivatives


1. Methylsynephrine (Oxilofrine):

An amphetamine-like compound with powerful stimulant and wakefulness-promoting effects. It is sometimes included in ‘pre-workout’ supplement stacks and is a banned substance by the WADA.[16]


2. Neo-synephrine (Phenylephrine):

Sometimes prescribed for medical use as a vasopressor to maintain blood pressure. It has potent decongestant effects and can be bought through prescription as a nasal spray for the treatment of stuffiness and congestion in the nose due to hay fever or allergies.[17


3. Advantra Z:

A patented supplement stack containing a number of active compounds from the Bitter Orange extract.


4. Ephedrine:

A phytochemical that is similar in action to Synephrine, but is more potent and has some serious side effects at higher doses. Ephedrine is found in the Ephedra herb and is banned as a dietary supplement. [18]


5. N-Methyltyramine (4-hydroxy-N-methylphenethylamine):

A compound found in several plant species, including the Bitter orange, with powerful vasopressor effects (increases blood pressure and heart rate). Increases norepinephrine levels and stimulates the production of gastrin.[19


6. Hordenine:

An energizing compound also found in the Bitter orange. It is a powerful norepinephrine re-uptake inhibitor and and MAO-B substrate that can be taken to boost cognition and to increase mood and energy.


7. Octopamine:

The immediate metabolite of Synephrine, Octopamine is produced in the body after taking Bitter orange extract supplements. Octopamine is banned by the WADA. Importantly, using Synephrine supplements does not increase octopamine levels in urine.[20]




In summary, this supplement is extracted from the Bitter orange (Citrus aurantium) and is known for its ability to increase thermogenesis and metabolism rate. It should not be confused with compounds like Ephedrine, Hordenine, or extracts from the Seville orange or sour orange which contain a number of different phytochemicals.


People who take this supplement often talk about its ability to promote increased mental energy and focus, alongside its benefits in increasing physical endurance and exercise performance. Studies have pointed to this supplement’s capacity to increase fat metabolism without affecting heart rate or blood pressure, making it much safer than most other energizing and metabolism-boosting products available today. 

supplement can be used for a healthy metabolism


Medical Disclaimer: 

Not intended to treat, diagnose, or cure any disease or ailment. Please read and fully understand potential adverse effects before using this product. These statements have not been reviewed by the FDA and are not written by a medical professional. Please consult your doctor before using any supplements, especially if you have any medical conditions.




[1]Synephrine”,, available online from [Accessed February 20, 2018]

[2]Synephrine”, PubChem, Open Chemistry Database, US National Library of Medicine, available online from

[3] Preuss HG, DiFerdinando D, Bagchi M, Bagchi, D. “Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview.”. J Med. 2002;33(1-4):247-64.

[4] Sidney J. Stohs, Harry G Preus Samuel C. Keith, Patti L. Keith, Howard Miller, Gilbert R. Kaats,  “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  2011; 8(4):295-301. doi:10.7150/ijms.8.295

[5] Kaats, Gilbert & Leckie, Robert & Mrvichin, Nate & Stohs, Sidney. (2017). “Increased eating control and energy levels associated with consumption of bitter orange (p-synephrine) extract: a randomized placebo-controlled study.” Nutrition and Dietary Supplements. Volume 9. 29-35. 10.2147/NDS.S136756.

[6] Haaz S, Fontaine KR, Cutter G, Limdi N, Perumean-Chaney S, Allison DB. “Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update.” Obes Rev. 2006 Feb;7(1):79-88.

[7] Stohs SJ, Preuss HG, Shara M. “A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects.” Oxidative Medicine and Cellular Longevity. 2011;2011:482973.

[8] Suzuki O, Matsumoto T, Oya M, Katsumata Y. “Oxidation of synephrine by type A and type B monoamine oxidase.” Experientia. 1979 Oct 15;35(10):1283-4.

[9] 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.” International Journal of Medical Sciences. 2012;9(7):527-538.

[10] Ratamess NA, Bush JA, Kang J, Kraemer WJ, Stohs SJ, Nocera VG, Leise MD, Diamond KB, Faigenbaum AD. “The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance.” J Int Soc Sports Nutr. 2015 Sep 17;12:35

[11] Gutiérrez-Hellín J, Del Coso J. “Dose-Response Effects of p-Synephrine on Fat Oxidation Rate During Exercise of Increasing Intensity.” Phytother Res. 2018 Feb;32(2):370-374.

[12] Gutiérrez-Hellín J, Del Coso J. “Acute p-synephrine ingestion increases fat oxidation rate during exercise.” Br J Clin Pharmacol. 2016 Aug;82(2):362-8.

[13]  “SYNEPHRINE: Is Chih-shih (Zhishi) Toxic?” by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon. Available online from

[14] Stohs SJ. “Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine.” Phytotherapy Research. 2017;31(10):1463-1474.

[15] Stohs SJ, Preuss HG, Shara M. “A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects.” Oxidative Medicine and Cellular Longevity. 2011;2011:482973.

[16]List of Prohibited Substances” (2018) World Anti-Doping Agency (WADA). Available online from”

[17]Neo-Synephrine (Injection).” Available online from

[18]Ephedrine.”, available online from

[19] “N-Methyltyramine”. PubChem, Open Chemistry Database, US National Library of Medicine, available online from

[20] Thevis M, Koch A, Sigmund G, Thomas A, Schänzer W. “Analysis of octopamine in human doping control samples.” Biomed Chromatogr. 2012 May;26(5):610-5.