The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis

Abstract

Synephrine has been used to promote weight loss; however, its safety and efficacy have not been fully established. The goals of our study were to give an overview of the safety and efficacy of p-synephrine, to systematically evaluate its efficacy regarding weight loss and to assess its safety, focusing on its cardiovascular side effects in a meta-analysis. PubMed, the Cochrane Library, Web of Science and Embase were searched for relevant studies. Only placebo-controlled, human clinical trials with synephrine intervention were included in the meta-analysis. The meta-analysis was reported according to the PRISMA guidelines using the PICOS format and taking into account the CONSORT recommendations. Altogether, 18 articles were included in the meta-analysis. Both systolic and diastolic blood pressure (DBP) increased significantly after prolonged use (6.37 mmHg, 95% CI: 1.02–11.72, p = 0.02 and 4.33 mmHg, 95% CI: 0.48–8.18, p = 0.03, respectively). The weight loss in the synephrine group was non-significant after prolonged treatment, and it did not influence body composition parameters. Based on the analyzed clinical studies, synephrine tends to raise blood pressure and heart rate, and there is no evidence that synephrine can facilitate weight loss. Further studies are needed to confirm evidence of its safety and efficacy.

Citrus p-Synephrine Improves Energy Homeostasis by Regulating Amino Acid Metabolism in HFD-Induced Mice

“…p -Synephrine with purity greater than 95% was purchased from Macklin Co., Ltd. (Shanghai, China). Ten-week-old male C57BL/6J mice (20 mice, 20–25 g, SPF) were obtained from Hunan Slake Jingda Experimental Animal Co., Ltd. (Changsha, China) After 1 week of adaptive feeding, all mice were randomly divided into three groups ( n = 6–7 mice per group): (1) Control group (CON)—gavage with 200 μL sterile normal saline for 8 weeks; (2) HFD group (HFD)—HFD containing 60% kcal% fat (D12492) was given [ 9 ] and 200 μL sterile normal saline was intragastrically administered for 8 weeks; and (3) Citrus p -synephrine intervention group (HFD+PSY)—HFD was given and p -synephrine was diurnally intragastrically administered (30 mg/kg body weight) [ 10 , 11 ]. Body weight and food intake were recorded weekly during the intervention period.…”

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology

“…The presence of these components is likely to influence the properties of C. aurantium -based products, making hard a true assessment of the toxicological effects. In addition, these dietary products usually contain stimulants such as caffeine or, sometimes, they are adulterated with synthetic compounds that might trigger severe adverse effects per se or enhance the toxicological properties of the natural product [ 89 , 90 , 91 ].…”

Evaluation of medicinal plant-based products used for weight loss

“…The extract of bitter orange (Citrus × aurantium L.) and its active constituent p-synephrine is also a common ingredient in weight loss and pre-workout supplements, and it is frequently used to replace ephedrine. 88 Chitosan may help with weight management by reducing dietary fat and cholesterol absorption. 89,90 Additionally, it may increase fat excretion, which would result in weight loss without changes in diet.…”

“…187 The health of consumers may also be at risk from variations in the amount of some substances, whether they are below minimum or over maximum, as in the case of synephrine, which is particularly dangerous when combined with a high caffeine dosage. 88 Another relevant factor is that a person's nutritional requirements vary depending on their energy requirements (based on weight, height, etc. ), and other physiological conditions (development stage, pregnancy and lactating).…”