p-Synephrine is a compound derived from citrus aurantium (aka bitter orange, Zhi Shi or sour orange), which are small citrus plants. Synephrine gained popularity as a fat-burning agent following the ephedra ban as both share a similar chemical structure. Though they share chemical similarities, synephrine has many differing biological properties, the most intriguing of which is that it elevates metabolism without increasing blood pressure and heart rate. Synephrine binds to β-3 receptors on fat cells that enhance fat release and fat burning. As well, it has stimulant effects similar to that of caffeine, thus increasing focus, energy and appetite suppression.
The latest research published in the British Journal of Clinical Pharmacology indicates that taking a single high dose (3 mg/kg body weight) of synerphrine preworkout can immediately boost your peak rate of fat burning (during cardio) by almost 40%. Interestingly, resting metabolic rate was unchanged with acute synerphrine supplementation, as was total caloric expenditure during exercise. Instead, synephrine promoted a significant shift in metabolism— from carbohydrate utilization to fat burning—with maximum fat burning occurring at low to moderate exercise intensity (50% VO2max).
ACTION POINT: This study and others used single 3 mg/kg synephrine dosing without adverse health consequences; however, the authors reported no change in blood pressure or heart rate despite using a dose that is about 10x what is normally promoted. A study published in 2013 evaluated the safety of synerphrine supplementation and reported that 98 mg of synephrine daily produced no safety concerns. So, it seems that this stuff is safe at higher doses than traditionally recommended.
In an effort to maximize fat burning, especially if you are a proponent of low to moderate intensity fat burning cardio sessions, we recommend a single daily (starting) dose of 30-60 mg, taken 30-60 minutes before or doing cardio. If you feel the need (and based on tolerance), slowly build your dose to 3 mg/kg over the course of several weeks.
Gutiérrez-Hellín J, Coso JD. Acute p-synephrine ingestion increases fat oxidation rate during exercise. Br J Clin Pharmacol. 2016 Apr 1. doi: 10.1111/bcp.12952. [Epub ahead of print]
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 May;55:358-62.