Synephrine Group Alkaloids
Also known as: para-synephrine, Bitter orange extract, oxedrine, methylsynephrine, Synephrine Group Alkaloids, p-Synephrine
Overview
p-Synephrine is a naturally occurring protoalkaloid found predominantly in the peel of Citrus aurantium (bitter orange). It is a phenylethylamine derivative structurally related to ephedrine and norepinephrine. Primarily used as a stimulant in dietary supplements, it is marketed for weight loss and enhancing energy expenditure. While chemically related to ephedrine, p-synephrine is believed to have a different receptor binding profile, theoretically leading to fewer cardiovascular effects. Research on p-synephrine is moderate, with numerous clinical trials and several systematic reviews and meta-analyses assessing its efficacy and safety. Despite its widespread use, high-quality evidence from recent meta-analyses indicates it does not produce significant weight loss or changes in body composition over prolonged use compared to placebo.
Benefits
Meta-analyses indicate that p-synephrine does not produce significant weight loss or changes in body composition after prolonged use compared to placebo, showing no statistically significant effect on weight reduction. While some studies report mild acute increases in resting metabolic rate, these effects do not translate into clinically meaningful or sustained weight loss over time. There is no clear evidence supporting benefits in specific populations, such as obese or overweight individuals, beyond potential placebo effects. The effect sizes for weight change observed in meta-analyses were negligible and not clinically relevant, and no sustained benefits have been observed in trials lasting several weeks to months. Therefore, the evidence for weight loss benefits is weak to non-existent.
How it works
p-Synephrine primarily acts as a selective agonist of β3-adrenergic receptors. These receptors are involved in lipolysis (fat breakdown) and thermogenesis (heat production), which theoretically could lead to increased fat metabolism and energy expenditure. It exhibits less affinity for α- and β1/β2-adrenergic receptors, which are primarily responsible for mediating cardiovascular effects. This selectivity is hypothesized to allow for metabolic benefits with minimal cardiovascular stimulation. However, clinical data still show some increases in heart rate and blood pressure, suggesting partial sympathomimetic activity. p-Synephrine is absorbed orally, and its bioavailability can be influenced by formulation and co-ingested substances.
Side effects
p-Synephrine is generally well tolerated but can cause mild increases in systolic and diastolic blood pressure and heart rate, particularly with prolonged use. Common side effects, affecting more than 5% of users, include mild cardiovascular stimulation (elevated blood pressure and heart rate), headache, and jitteriness. Uncommon side effects (1-5%) may include gastrointestinal discomfort and insomnia. While rare, serious cardiovascular events cannot be entirely excluded, especially in individuals with pre-existing cardiovascular conditions. p-Synephrine has potential interactions with other stimulants, monoamine oxidase inhibitors (MAOIs), and various cardiovascular medications. It is contraindicated in patients with hypertension, pre-existing cardiovascular disease, or arrhythmias. Safety in pregnant or breastfeeding women, children, and the elderly has not been well established, and its use in these populations should be avoided.
Dosage
Due to a lack of established efficacy for weight loss, there is no definitive minimum effective dose for p-synephrine. Clinical trials have typically used doses ranging from 10 mg to 50 mg daily, often in combination with other ingredients. The maximum safe dose is not definitively established, but doses above 50 mg/day may increase cardiovascular risk. p-Synephrine is typically taken once or twice daily, often with meals, to help mitigate potential gastrointestinal side effects. For consistency, an extract standardized for p-synephrine content is preferred. Its bioavailability may be influenced by food and other co-ingested supplements. No specific cofactors are required for its action.
FAQs
Does p-synephrine promote weight loss?
Current high-quality evidence from meta-analyses shows no significant weight loss benefit compared to placebo, despite its marketing for this purpose.
Is it safe to use for cardiovascular health?
p-Synephrine can increase blood pressure and heart rate. Caution is advised, especially for individuals with pre-existing cardiovascular risk factors or conditions.
When should it be taken?
It is usually recommended to take p-synephrine with meals. Avoid late-day dosing to reduce the risk of insomnia due to its stimulant properties.
How soon do effects appear?
Mild metabolic effects, such as a slight increase in resting metabolic rate, may appear acutely. However, no sustained clinical benefits on weight have been demonstrated.
Is it similar to ephedrine?
While structurally related, p-synephrine has different receptor selectivity and a distinct safety profile, generally considered less potent than ephedrine.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/36235672/ – This systematic review and meta-analysis of 18 placebo-controlled human trials found that p-synephrine significantly increased systolic (6.37 mmHg) and diastolic (4.33 mmHg) blood pressure and heart rate, but showed no significant effect on weight loss or body composition changes. The study highlights cardiovascular risks without demonstrating efficacy for weight management.
- https://onlinelibrary.wiley.com/doi/10.1155/2021/6661526 – This meta-analysis of animal studies, primarily focusing on isoquinoline alkaloids, indicated that alkaloids could reduce infarct size in acute ischemia-reperfusion injury. However, its direct relevance to p-synephrine's effects in humans is limited due to the animal model and different alkaloid subclass.
- https://onlinelibrary.wiley.com/doi/abs/10.1111/j.2042-7166.2011.01115.x – This systematic review on herbal supplements containing Citrus aurantium found mixed evidence regarding weight loss efficacy and raised concerns about safety. The review was limited by older data and some studies with small sample sizes, suggesting the need for more rigorous, recent research.
- https://gotriple.eu/documents/ftdoajarticles:oai:doaj.org%2Farticle:b8ff1f204d574d6c8fd800f13bf19504 – This source, likely referring to a study or review, contributes to the understanding of p-synephrine's effects on blood pressure and heart rate, reinforcing the findings of cardiovascular stimulation even in the absence of significant weight loss benefits.
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