Synephtrine
Also known as: p-synephrine, Bitter orange extract, Oxedrine, Citrus aurantium, Synephrine
Overview
Synephrine is a naturally occurring phenylethylamine alkaloid primarily found in the bitter orange (Citrus aurantium) fruit and its extract. It is structurally similar to ephedrine and is commonly used in dietary supplements marketed for weight loss, fat oxidation enhancement, and as an energy booster or appetite suppressant. Synephrine acts as a sympathomimetic agent, meaning it stimulates the sympathetic nervous system, which can lead to effects such as increased heart rate and blood pressure. While it has been extensively studied, research on synephrine's efficacy for weight loss and exercise performance has yielded mixed results, with many high-quality studies indicating no significant benefit for weight loss. Its safety profile is a significant concern due to its potential cardiovascular effects.
Benefits
Despite its widespread marketing, high-quality evidence, including meta-analyses of randomized controlled trials, indicates no significant effect of synephrine on weight loss or body composition after prolonged use. One meta-analysis of 18 placebo-controlled RCTs found no significant weight loss benefits. Acute intake, typically around 2–3 mg/kg body weight, may modestly enhance fat oxidation during exercise, but this effect has not been consistently linked to significant or clinically relevant weight loss. Some studies suggest a mild increase in metabolic rate, but the clinical relevance of this effect remains uncertain. Evidence does not strongly support benefits in overweight or obese populations for weight loss, and any observed effects are statistically non-significant and clinically negligible. The time course of benefits is limited to acute effects on fat oxidation during exercise, with no substantiated long-term weight loss.
How it works
Synephrine functions as a sympathomimetic agent, primarily by stimulating adrenergic receptors. Its main mechanism involves activating β3-adrenergic receptors, which are found in fat cells and can promote lipolysis (fat breakdown) and fat oxidation. However, synephrine also interacts with α1- and β1-adrenergic receptors, particularly in vascular and cardiac tissues. This interaction can lead to cardiovascular effects such as increased heart rate and blood pressure. In the metabolic system, synephrine may contribute to an increase in basal metabolic rate and fat oxidation. Oral bioavailability is moderate, and its metabolism and pharmacokinetics can vary among individuals, influencing its overall efficacy and safety profile.
Side effects
Synephrine's safety profile is a significant concern, as it tends to increase both systolic and diastolic blood pressure and heart rate, raising cardiovascular safety issues, especially with prolonged use. Common side effects include increased heart rate and elevated blood pressure. Less common side effects (1-5% frequency) may include headache, nervousness, or jitteriness. Rare side effects (<1%) such as palpitations and cardiac arrhythmias have been reported in case studies. Synephrine has potential additive cardiovascular effects when combined with other stimulants or monoamine oxidase inhibitors (MAOIs). It is contraindicated for individuals with pre-existing cardiovascular disease, hypertension, or known sensitivity to stimulants. Safety in special populations, including pregnant or breastfeeding women, children, and those with other pre-existing medical conditions, has not been established, and its use is not recommended in these groups.
Dosage
There is no established minimum effective dose for weight loss, as current evidence does not support this benefit. For acute effects on fat oxidation during exercise, doses around 2–3 mg/kg body weight have been studied. In dietary supplements, typical daily dosages range from 10–50 mg, but there is no consensus on an optimal dose for efficacy. A maximum safe dose has not been clearly established, and caution is advised due to its cardiovascular effects. If used, synephrine is often taken pre-exercise to potentially enhance fat oxidation. It is usually administered as bitter orange extract standardized to synephrine content. Food intake may affect absorption, and pharmacokinetics can vary individually. No specific cofactors are required for its action.
FAQs
Does synephrine cause weight loss?
Current high-quality evidence, including meta-analyses, consistently shows no significant weight loss benefit with synephrine supplementation, despite its marketing claims.
Is synephrine safe?
Synephrine can raise blood pressure and heart rate, posing cardiovascular risks, especially with prolonged use or in individuals susceptible to stimulant effects. Caution is advised.
When should synephrine be taken?
If used, synephrine is typically taken before exercise to potentially enhance fat oxidation, although the benefits are modest and not linked to significant weight loss.
How quickly do effects appear?
Acute metabolic effects, such as increased fat oxidation during exercise, may appear within hours. However, significant long-term weight loss effects are not substantiated.
Are there misconceptions?
Synephrine is often marketed as a safe alternative to ephedrine for weight loss, but evidence does not support significant efficacy and highlights notable cardiovascular risks.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/36235672/ – This systematic review and meta-analysis of 18 placebo-controlled RCTs found that synephrine significantly increased systolic and diastolic blood pressure, but showed no significant effect on weight loss or body composition. The study highlights cardiovascular safety concerns with synephrine supplementation.
- https://www.mdpi.com/2072-6643/13/1/233 – This narrative review on p-synephrine and exercise indicates that acute doses (2–3 mg/kg) may increase fat oxidation during exercise. However, it found no clear evidence of long-term weight loss benefits, suggesting that acute metabolic effects do not translate to significant body composition changes.
- https://onlinelibrary.wiley.com/doi/abs/10.1111/j.2042-7166.2011.01115.x – This systematic review of RCTs on Citrus aurantium and weight management concluded that there is insufficient evidence to support the efficacy of extracts containing synephrine for weight loss. The review also noted significant safety concerns, reinforcing the need for caution.
