Oxedrine
Also known as: Oxedrine, bitter orange extract, synephrine, p-synephrine
Overview
p-Synephrine, commonly known as Oxedrine, is a naturally occurring protoalkaloid found predominantly in *Citrus aurantium* (bitter orange). Structurally, it is a phenylethanolamine derivative, sharing similarities with ephedrine and other adrenergic amines. It is widely used in dietary supplements marketed for weight loss, increased energy expenditure, and potential ergogenic effects. While it acts as a sympathomimetic agent, influencing cardiovascular parameters and metabolism by primarily targeting beta-3 adrenergic receptors, its stimulant effects are generally considered milder than ephedrine. Research on p-synephrine's efficacy and safety is moderate, with several human clinical trials and meta-analyses yielding mixed results, particularly regarding its weight loss benefits.
Benefits
Despite its widespread use in weight loss supplements, high-quality evidence indicates that p-synephrine alone does not significantly promote weight loss or improve body composition. A meta-analysis of 18 placebo-controlled randomized controlled trials (RCTs) found no meaningful changes in body weight or fat mass compared to placebo. Some studies have reported mild increases in resting metabolic rate and fat oxidation, but these effects are often inconsistent and frequently observed when p-synephrine is co-administered with other stimulants like caffeine, making it difficult to attribute the benefits solely to p-synephrine. The clinical relevance of these minor metabolic changes remains unclear, and no specific population subgroup has shown clear efficacy. While statistically significant, observed increases in systolic blood pressure (~6 mmHg) and diastolic blood pressure (~4 mmHg) are modest and do not translate to a beneficial outcome for weight management.
How it works
p-Synephrine functions as a sympathomimetic agent, primarily interacting with adrenergic receptors. Its main mechanism involves stimulating beta-3 adrenergic receptors, which are known to play a role in lipolysis (fat breakdown) and thermogenesis (heat production), potentially leading to increased energy expenditure. Compared to ephedrine, p-synephrine has weaker effects on alpha and beta-1/2 adrenergic receptors. This interaction with the sympathetic nervous system also affects the cardiovascular system, leading to mild increases in heart rate and blood pressure. Oral bioavailability is moderate, but detailed human pharmacokinetic data are limited.
Side effects
At typical supplement doses (50-100 mg/day), p-synephrine is generally well tolerated, but cardiovascular stimulation is a primary concern. Common side effects, reported in over 5% of users, include mild increases in heart rate and blood pressure, as well as occasional headaches, dizziness, and palpitations. Less common side effects (1-5%) can include nervousness, irritability, hyperventilation, and blurred vision. Serious adverse events have not been consistently linked to p-synephrine alone in controlled trials. However, potential additive cardiovascular effects exist when combined with other stimulants (e.g., caffeine) or sympathomimetic drugs. It is contraindicated in individuals with cardiovascular disease, hypertension, or during pregnancy. Caution is advised for those on antihypertensive or cardiac medications, and its safety in children, the elderly, or pregnant women has not been established.
Dosage
There is no established minimum effective dose for weight loss, as current evidence does not support its efficacy for this purpose. Typical supplement doses range from 25 to 100 mg/day of p-synephrine. Clinical studies frequently use doses around 50-100 mg/day. Higher doses are not recommended as they increase cardiovascular risk without providing clear additional efficacy benefits. The maximum safe dose has not been definitively established, but doses exceeding 100 mg/day may elevate the risk of adverse effects. p-Synephrine is usually administered in divided doses, often before meals or exercise. It is commonly delivered as a bitter orange extract standardized for its p-synephrine content. Co-administration with flavonoids like hesperidin and naringin may influence its cardiovascular effects.
FAQs
Does oxedrine cause weight loss?
Current high-quality research, including meta-analyses, indicates that p-synephrine supplementation alone does not lead to significant weight loss or improvements in body composition.
Is it safe to combine with caffeine?
Combining p-synephrine with caffeine or other stimulants is not recommended without medical supervision due to an increased risk of adverse cardiovascular effects.
How quickly do effects appear?
Cardiovascular effects, such as mild increases in heart rate and blood pressure, can occur within hours of dosing. However, weight loss effects are not reliably observed even after weeks or months of use.
Are side effects common?
Mild cardiovascular side effects like increased heart rate and blood pressure are relatively common. Serious adverse events are rare when p-synephrine is used alone in controlled settings.
Is it legal and regulated?
Yes, p-synephrine is generally legal as a dietary supplement, but its regulatory status can vary by country. Some regulatory bodies have issued warnings regarding its cardiovascular risks.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/36235672/ – This meta-analysis of 18 RCTs found that p-synephrine significantly increased systolic and diastolic blood pressure but showed no significant benefit for weight loss or body composition changes. The study highlights the cardiovascular risks without evidence of efficacy for its primary marketed use.
- https://www.foodstandards.gov.au/sites/default/files/publications/Documents/Risk%20assessment%20scheduled%20pharmaceuticals%20in%20foods.pdf – This animal toxicology study in rats found no mortality or major toxicity from p-synephrine at doses up to 50 mg/kg, though it did note an increase in systolic blood pressure. It provides preclinical safety data but acknowledges the limitations of translating animal doses to humans.
- https://www.rivm.nl/bibliotheek/rapporten/2017-0069.pdf – This review of human RCTs noted a small increase in heart rate when p-synephrine was combined with flavonoids, but no significant adverse events were observed with p-synephrine alone. The report contributes to risk assessment but points out limitations due to small sample sizes and lack of long-term data.
- https://onlinelibrary.wiley.com/doi/abs/10.1111/j.2042-7166.2011.01115.x – This source discusses the influence of co-administered flavonoids (hesperidin, naringin) on the cardiovascular effects of p-synephrine. It suggests that these interactions can modify the physiological responses to p-synephrine, which is relevant for understanding its overall safety profile in complex supplement formulations.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9572433/ – This article discusses the inconsistent findings regarding p-synephrine's effects on energy expenditure and fat oxidation, often noting that these effects are confounded by co-administration with caffeine or other stimulants. It underscores the difficulty in isolating p-synephrine's independent benefits.