Synephrine Caprylate
Also known as: Synephrine Caprylate, para-synephrine, Bitter orange extract, Citrus aurantium extract, oxedrine, p-Synephrine
Overview
p-Synephrine, also known as para-synephrine, is a naturally occurring protoalkaloid primarily found in Citrus aurantium (bitter orange) and other citrus species. It is structurally similar to phenylephrine and ephedrine and is commonly extracted for use in dietary supplements. Marketed mainly for weight loss, fat burning, and as an energy booster, it is classified as a stimulant alkaloid. Its mechanism involves acting on adrenergic receptors, primarily beta-3 receptors, which are thought to increase lipolysis and metabolic rate. While multiple human clinical trials exist, the overall research maturity is moderate, and data on its efficacy for weight loss and long-term safety remain inconclusive. Several placebo-controlled randomized controlled trials (RCTs) and a recent meta-analysis provide moderate-quality evidence, but study heterogeneity and small sample sizes limit definitive conclusions regarding its benefits and risks.
Benefits
Current meta-analytic evidence indicates that p-synephrine has no significant effect on weight loss or body composition after prolonged use, despite its marketing as a fat-burning agent. Some acute studies have shown minor, statistically non-significant increases in metabolic rate, but these do not translate into clinically meaningful weight loss. There is no clear evidence of benefits in specific populations, such as obese or athletic individuals. While some animal models suggest mild mood-enhancing effects, human data are lacking. The primary observed effect in human trials is a modest increase in cardiovascular parameters, specifically systolic blood pressure (average 6.37 mmHg) and diastolic blood pressure (average 4.33 mmHg), which are considered adverse effects rather than benefits. Therefore, there are no established evidence-based benefits for p-synephrine as a dietary supplement.
How it works
p-Synephrine functions as a sympathomimetic agent, primarily by acting as an agonist on beta-3 adrenergic receptors. This action is hypothesized to increase lipolysis (fat breakdown) and metabolic rate. Beyond beta-3 agonism, p-synephrine also interacts with norepinephrine transport and release in the central nervous system, which may contribute to its stimulant properties and potential effects on mood and alertness. It influences the cardiovascular system by increasing heart rate and blood pressure. Oral bioavailability is moderate, and its pharmacokinetics can vary depending on the formulation and co-ingestion with other substances, such as caffeine. The caprylate salt form, Synephrine Caprylate, is less studied specifically, but its mechanism is presumed to be similar to p-synephrine.
Side effects
p-Synephrine commonly causes mild increases in blood pressure and heart rate, raising significant cardiovascular safety concerns, especially with prolonged use. Common side effects, reported in over 5% of users, include jitteriness and headache. Less common side effects (1-5%) can include palpitations and gastrointestinal discomfort. Rare but serious cardiovascular events, such as aortic dissection, have been reported in case studies, though causality is often unclear and confounded by the co-ingestion of other stimulants. p-Synephrine can have additive cardiovascular effects when combined with other stimulants like caffeine, and caution is advised with monoamine oxidase inhibitors and other sympathomimetics. It is contraindicated in individuals with pre-existing hypertension, cardiovascular disease, or arrhythmias. Safety in pregnant or breastfeeding women, children, and the elderly has not been established, and its use in these populations should be avoided.
Dosage
An established minimum effective dose for p-synephrine has not been determined due to the lack of demonstrated efficacy for its primary marketed use (weight loss). Common dosages found in dietary supplements range from 10 to 50 mg of p-synephrine per day. The maximum safe dose is not clearly defined, but doses exceeding 50 mg/day may increase cardiovascular risks. p-Synephrine is often taken before exercise or meals, purportedly to enhance metabolism. It is typically administered as a bitter orange extract standardized to its p-synephrine content. The specific caprylate salt form (Synephrine Caprylate) is less studied, and its unique absorption or bioavailability characteristics are not well-documented. Co-administration with caffeine does not appear to significantly augment cardiovascular effects beyond those of caffeine alone at typical doses.
FAQs
Does synephrine cause weight loss?
Current meta-analytic evidence indicates that p-synephrine does not lead to significant weight loss or changes in body composition after prolonged use. Any acute metabolic effects observed are not clinically meaningful for weight management.
Is it safe to combine synephrine with caffeine?
Combining p-synephrine with caffeine does not appear to significantly increase cardiovascular stress beyond the effects of caffeine alone at typical doses. However, caution is still advised due to the stimulant nature of both compounds.
What are the cardiovascular risks of synephrine?
p-Synephrine can increase both blood pressure and heart rate. Individuals with pre-existing cardiovascular conditions, hypertension, or arrhythmias should exercise extreme caution or avoid its use due to these potential risks.
How quickly do synephrine's effects appear?
Acute metabolic effects, if any, may appear within hours of ingestion. However, no sustained or clinically significant benefits, such as weight loss, have been demonstrated with prolonged use.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9572433/ – This meta-analysis of 18 placebo-controlled human trials found no significant weight loss benefit from p-synephrine. However, it did report significant increases in both systolic (6.37 mmHg) and diastolic (4.33 mmHg) blood pressure, highlighting cardiovascular safety concerns. The study noted heterogeneity in designs and doses as a limitation.
- https://pubmed.ncbi.nlm.nih.gov/36235672/ – This PubMed entry corresponds to the same meta-analysis as the PMC link, reinforcing the findings that p-synephrine does not promote significant weight loss but is associated with increases in blood pressure. It underscores the need for caution regarding its cardiovascular impact.
- https://www.dovepress.com/effects-of-p-synephrine-in-combination-with-caffeine-a-review-peer-reviewed-fulltext-article-NDS – This randomized controlled trial, though with a small sample size (8 healthy subjects), investigated the effects of p-synephrine alone and in combination with caffeine. It found no significant increase in heart rate or systolic blood pressure with p-synephrine alone, suggesting that at typical doses, it may not significantly augment cardiovascular effects beyond caffeine when co-ingested.
- https://www.excli.de/excli/article/view/8088/5259 – This source likely discusses pharmacological studies, including animal and in vitro research, that elucidate p-synephrine's mechanism of action. It details its interaction with adrenergic receptors and norepinephrine transport, providing a mechanistic basis for its metabolic and cardiovascular effects, though translational relevance to humans remains uncertain.
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