Synephrine is a naturally occurring chemical often sought after by those looking to aid fat loss. Found at high levels in the peels of citrus plants, extracts from fruits or peels have been used in traditional Chinese medicine to treat various ailments for hundreds of years [1].
Synephrine is structurally similar to ephedrine, a cult-favourite weight loss drug -ephedrine – banned in 2014 due to its adverse effects on human health. Touted to encourage weight loss by increasing the basal metabolic rate, stimulating fat breakdown and suppressing appetite, synephrine is now increasingly being used as a substitute for ephedrine to promote weight loss.
Classed as a banned substance by almost every major sports commission, supplementing with synephrine is not without controversy.
There is much confusion over whether or not it is safe and the effects it has on the body. It’s often confused with other substances including bitter orange, phenylephrine and ephedrine itself, and scientific evidence is lacking. Below, we take an unbiased look at the evidence, the potential side effects and the dosage of this fairly new drug.
Reported Effects of Synephrine
1. Encourage Weight Loss
Synephrine is similar in structure to ephedrine, which was banned as a dietary supplement in 2014 due to its associated side effects [2]. Touted to encourage weight loss by increasing the basal metabolic rate, stimulating fat breakdown and suppressing appetite, it’s gathered popularity as a weight-loss supplement in recent years.
In animal and cell studies, the drug increased the breakdown of glucose and glycogen in the liver and inhibited α-amylase and α-glucosidase, enzymes that digest complex starches. This is likely to prevent post-meal blood sugar spikes, and contribute to appetite suppression [3].
At the moment, scientific results don’t line up with the theory. Though research has shown that synephrine increases the numbers of calories burned, the effect on weight loss is inconclusive [4].
Synephrine is often combined with other compounds, such as caffeine, in weight loss supplements, it’s difficult to interpret its effectiveness. A single dose of 50mg of synephrine was found to induce an increase of 65kcal in 75 minutes versus control subjects [5]. This was supported in a review of 23 studies that concluded that 20–35 mg per day increased metabolic rate and had a modest impact on weight loss.
However, some of the studies resulted in no weight loss or even weight gain after treatment with synephrine [6]. Early research is promising, but it’s exactly that, early. More work is needed to confirm the long-term applications for weight management.
2. A Mild Stimulant
More recently, synephrine has become prevalent in pre-workout supplements. Like caffeine, it stimulates the central nervous system, but without the unwanted side effects.
Synephrine weakly activates alpha-1 and alpha-2 adrenoreceptors, which respond to adrenaline and increase heart rate and blood pressure. Despite the stimulatory actions, it is not likely to cause elevations in blood pressure or heart rate [7], making it a great option for those with caffeine sensitivity.
Synephrine also stimulates neuromedin U2 receptors, found in the hypothalamus. These molecules are responsible for controlling sleep, and therefore the stimulatory action can increase wakefulness [8].
3. Anti-Inflammatory Properties
Synephrine also exhibits anti-inflammatory properties.
It’s suggested to inhibit the activation of NF-kB, a substance key in inflammatory ailments such as asthma, inflammatory bowel disease and psoriasis [9].
Although not yet backed with human studies, in cell studies synephrine was also found to block acetylcholinesterase and butyryl cholinesterase, enzymes that harmful in Alzheimer’s disease [10].
Common Supplements that Contain Synephrine
Synephrine is found in various supplements, but is not quite as readily available over the counter as it once was. It can still be found as a stand-alone supplement, normally in capsule form.
Although once a prevalent ingredient in fat burner supplements, uncertainty around interactions with other common ingredients such as caffeine, green tea extract and guarana have saw it become less common.
Side Effects of Synephrine Supplementation
Synephrine, when taken in both isolation and moderation, is a relatively safe supplement. No adverse side effects have been recorded, but mild side effects that may be experienced by some individuals are:
- Migraine
- Cluster headaches
- Excessive sweating
Synephrine, particularly when taken with stimulants such as caffeine or caffeine-containing herbs, increases the risk for high blood pressure, heart attack, stroke and other severe side effects. When used in conjunction with caffeine, the two have similar properties to ephedrine. On that note, some European government agencies have ordered the removal of supplements with a combination of the two supplements from the market.
Higher doses have also produced worse adverse effects in safety studies. A study of mice showed high rates of serious side effects, including gasping and reduced motor function.
Synephrine Dosage
There is no recommended safe and effective dose of synephrine as it is not yet recommended by the FDA for medical purposes.
As standard, studies used clinical doses ranging between 35-50mg per day.
A review of 30 human studies involving over 600 subjects concluded that dosages up to 100mg did not adversely affect the heart, liver or kidneys. This upper limit should be lowered when combined with other stimulatory drugs, such as caffeine.
When taken In combination with up to 320 mg of caffeine, the studies did not use more than 40 mg of synephrine per day [11].
References
- Fang YS, Shan DM, Liu JW, et al. Effect of constituents from Fructus Aurantii Immaturus and Radix Paeoniae Alba on gastrointestinal movement. Planta Med. 2009;75(1):24-31.
- Stohs SJ. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytother Res. 2017;31(10):1463-1474.
- Taslimi P, Akıncıoglu H, Gülçin İ. p-synephrine and phenylephrine act as α-amylase, α-glycosidase, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase enzymes inhibitors. J Biochem Mol Toxicol. 2017;31(11):10.1002/jbt.21973.
- Stohs SJ, Preuss HG, Shara M. The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine. Phytother Res. 2011;25(10):1421-1428.
- Stohs SJ, Preuss HG, Keith SC, Keith PL, Miller H, Kaats GR. 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. Published 2011 Apr 28.
- 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.
- Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects. Oxid Med Cell Longev. 2011;2011:482973.
- Zheng X, Guo L, Wang D, Deng X. p-Synephrine: a novel agonist for neuromedin U2 receptor. Biol Pharm Bull. 2014;37(5):764-770.
- Wu Q, Li R, Soromou LW, et al. p-Synephrine suppresses lipopolysaccharide-induced acute lung injury by inhibition of the NF-κB signaling pathway. Inflamm Res. 2014;63(6):429-439.
- Taslimi P, Akıncıoglu H, Gülçin İ. Synephrine and phenylephrine act as α-amylase, α-glycosidase, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase enzymes inhibitors. J Biochem Mol Toxicol. 2017;31(11):10.1002/jbt.21973.
- Stohs SJ. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytother Res. 2017;31(10):1463-1474.