Synephrine

Synephrine is a naturally occurring alkaloid found in certain plants, most notably in the bitter orange (Citrus aurantium). It has gained popularity in recent years due to its potential benefits in weight loss and athletic performance.

Sources of Synephrine

Synephrine is primarily extracted from the bitter orange, a fruit that has been used in traditional medicine for centuries. The bitter orange tree is native to Southeast Asia but is now cultivated in various parts of the world, including the Mediterranean region and the United States. The fruit, peel, and flowers of the bitter orange are used to produce synephrine supplements.

Mechanisms of Action

Synephrine is structurally similar to ephedrine, a compound known for its stimulant effects. However, synephrine is considered to be less potent and has a different mechanism of action. It primarily works by stimulating the adrenergic receptors, specifically the beta-3 receptors, which are involved in the regulation of fat breakdown and thermogenesis (heat production). This stimulation can lead to increased metabolic rate and energy expenditure, making synephrine a popular ingredient in weight loss supplements.

Benefits of Synephrine

Weight Loss

One of the most well-known benefits of synephrine is its potential to aid in weight loss. By increasing the metabolic rate and promoting fat breakdown, synephrine can help individuals burn more calories and reduce body fat. Several studies have shown that synephrine can increase resting metabolic rate by up to 65 calories per day, which can contribute to gradual weight loss over time.

Appetite Suppression

Synephrine may also help suppress appetite, making it easier for individuals to adhere to a calorie-restricted diet. This effect is believed to be due to its influence on certain neurotransmitters that regulate hunger and satiety.

Enhanced Athletic Performance

Athletes and fitness enthusiasts often use synephrine to enhance their performance. The compound can increase energy levels, improve focus, and reduce fatigue, allowing for more intense and prolonged workouts. Additionally, synephrine's ability to promote fat oxidation can help athletes maintain a leaner physique.

Potential Side Effects

While synephrine is generally considered safe when used in moderate amounts, it can cause side effects, especially when taken in high doses or combined with other stimulants. Some of the potential side effects include:

• Increased heart rate
• Elevated blood pressure
• Insomnia
• Nervousness
• Headaches

Individuals with pre-existing medical conditions, such as cardiovascular disease or hypertension, should exercise caution when using synephrine and consult with a healthcare professional before starting any supplement regimen.

Regulatory Status

The regulatory status of synephrine varies by country. In the United States, synephrine is classified as a dietary supplement and is widely available over-the-counter. However, the Food and Drug Administration (FDA) has issued warnings about the potential risks associated with high doses of synephrine, particularly when combined with other stimulants like caffeine.

In contrast, some countries have stricter regulations regarding synephrine. For example, Canada has banned the sale of products containing synephrine due to safety concerns. It is important for consumers to be aware of the regulations in their respective countries and to purchase supplements from reputable sources.

Articles/Studies

• Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?
• Synephrine and phenylephrine act as α‐amylase, α‐glycosidase, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase enzymes inhibitors
• Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors
• Effects of synephrine and β-phenethylamine on human α-adrenoceptor subtypes
• The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p‐Synephrine
• Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine
• Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine
• p‐Synephrine, ephedrine, p‐octopamine and m‐synephrine: Comparative mechanistic, physiological and pharmacological properties
• A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects
• The isolation and identification of l-synephrine in the leaves and fruit of citrus
• Stereochemical and pharmacological differences between naturally occurring p-synephrine and synthetic p-synephrine
• Synephrine content of juice from Satsuma mandarins (Citrus unshiu Marcovitch)

Cardiovascular

• Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood …
• Cardiovascular Safety of Oral p‐Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo‐Controlled Cross‐over Clinical Trial
• Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults

Cautions

• Safety evaluation of p‐synephrine following 15 days of oral administration to healthy subjects: A clinical study
• Ventricular fibrillation associated with use of synephrine containing dietary supplement
• Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions
• Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine
• Subchronic toxicity of Citrus aurantium L.(Rutaceae) extract and p-synephrine in mice

Depression

• Characterization of antidepressant-like effects of p-synephrine stereoisomers
• Antidepressant-like effects of p-synephrine in mouse models of immobility tests

Weight Loss

• Isopropylnorsynephrine is a stronger lipolytic agent in human adipocytes than synephrine and other amines present in Citrus aurantium
• Acute p‐synephrine ingestion increases fat oxidation rate during exercise
• Synephrine: from trace concentrations to massive consumption in weight-loss
• Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update

Other Effects

• The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance
• p-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells
• Effects of Citrus aurantium (bitter orange) fruit extracts and p-synephrine on metabolic fluxes in the rat liver
• Effects of p-Synephrine during Exercise: A Brief Narrative Review