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

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.

A Systematic Review of the European Rapid Alert System for Food and Feed: Tendencies in Illegal Food Supplements for Weight Loss.

Background: Slimming products represent a dynamically growing group of food supplements worldwide. The efficacy of safely usable natural ingredients is usually below consumers' expectations. Certain manufacturers add unauthorized or prohibited ingredients to weight loss supplements in order to increase their efficacy. Hence, many of these products are adulterated and may pose a risk to the consumers' health. Aims: The aim of our work was to give an overview on natural ingredients used in slimming products, to summarize the frequently used synthetic adulterants and also to assess the trends of adulterated and illegal food supplements in the European Union based on the warnings of the Rapid Alert System for Food and Feed (RASFF) in the time period of 1988-2019. Methods: Reports between 1988-2019 were extracted from the RASFF portal on January 1, 2020. Each entry was individually reviewed. Results: 2,559 records of food supplements with quality problems were identified in the RASFF, several of which [319 (12,5%)] were marketed to facilitate weight loss. 202 (63,3%) contained unapproved, synthetic drug ingredients. The major adulterant (113 of 319, 35.4%) was DNP (2,4-dinitrophenol), whereas sibutramine was the second most frequent adulterant agent (69 products, 21,6%) between 1988 and 2019. Conclusion: The number of approved medicines for the indication of weight loss is relatively low and their efficacy (and also that of the natural ingredients) is limited. Therefore, a significant number of weight loss supplements is adulterated to satisfy patients' expectations. Hence, these products may cause serious adverse effects in sensitive patients.