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.

Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.

Steady-state population pharmacokinetics of a noncommercial immediate-release metformin (hydrochloride) drug product were characterized in 28 severely obese children with insulin resistance. The concentration-time profiles with double peaks were well described by a 1-compartment model with 2 absorption sites. Mean population apparent clearance (CL/F) was 68.1 L/h, and mean apparent volume of distribution (V/F) was 28.8 L. Body weight was a covariate of CL/F and V/F. Estimated glomerular filtration rate was a significant covariate of CL/F (P < .001). SLC22A1 genotype did not significantly affect metformin pharmacokinetics. The response to 6 months of metformin treatment (HbA1c , homeostasis model assessment for insulin resistance, fasting insulin, and glucose changes) did not differ between SLC22A1 wild-type subjects and carriers of presumably low-activity SLC22A1 alleles. However, SLC22A1 variant carriers had smaller reductions in percentage of total trunk fat after metformin therapy, although the percentage reduction in trunk fat was small. The median % change in trunk fat was -2.20% (-9.00% to 0.900%) and -1.20% (-2.40% to 7.30%) for the SLC22A1 wild-type subjects and variant carriers, respectively. Future study is needed to evaluate the effects of SLC22A1 polymorphisms on metformin-mediated weight reduction in obese children.

Flavonoids from Cyclopia genistoides and Their Xanthine Oxidase Inhibitory Activity.

The present paper reports the chemical analysis of the methanolic extracts of fermented and non-fermented Cyclopia genistoides herbs and an investigation of the xanthine oxidase inhibitory activity of the isolated constituents. Chemical analysis of the leaves and stems of C. genistoides yielded the isolation and identification of two benzophenone glucosides, iriflophenone 2-O-ß-glucopyranoside (1) and iriflophenone 3-C-ß-glucopyranoside (2), two pterocarpans, (6aR,11aR)-(-)-2-methoxymaackiain (5) and (6aR,11aR)-(-)-maackiain (6), along with the flavanones liquiritigenin (9) and hesperetin (10), the flavone diosmetin (11), the isoflavones afrormosin (7) and formononetin (8), piceol (3), and 4-hydroxybenzaldehid (4). Among the eleven compounds, nine are reported for the first time from this species, and six from the genus Cyclopia. These compounds, together with previously isolated secondary metabolites of this species, were tested for xanthine oxidase inhibitory activity. The 5,7-dihydroxyflavones luteolin and diosmetin significantly inhibited the enzyme in vitro, while hesperetin (10) and 5,7,3',5'-tetrahydroxyflavone exerted weak activity.

Chemical composition of essential oils of Grindelia squarrosa and G. hirsutula.

The essential oils of Grindelia squarrosa (Pursh) Dunal and G. hirsutula Hook. & Am. cultivated in Romania were isolated by hydrodistillation. The essential oils were analyzed by a combination of GC-FID and GC-MS. The identification of the constituents was achieved from their retention indices and comparison of their MS data with computer library database and literature data. The fifty-six identified constituents accounted for 72.1-81.3% of the oils. The oils were found to contain a-pinene, beta-pinene, limonene, borneol, bornyl acetate and germacrene D as main constituents. The oils obtained from the two species showed small differences in chemical composition. However, menthol, menthone and pulegone were detected only in the essential oil of G. hirsutula.

Sympathomimetic activity of a Hoodia gordonii product: a possible mechanism of cardiovascular side effects.

Hoodia gordonii, a popular appetite suppressant, is widely used as an ingredient in many food supplements despite the fact that supporting scientific evidence is scarce. Recently alarming side effects of H. gordonii products (increased blood pressure and elevated pulse rate) have been reported. The aim of our study was to elucidate the underlying mechanism of these symptoms. A H. gordonii-containing product was tested for sympathomimetic activity. Isolated organ experiments on rat uterine rings revealed smooth muscle relaxant effect with a substantial component mediated through ß -adrenergic receptors. Chromatographic comparison of the analyzed product and authentic plant material confirmed that the herbal product contained Hoodia spp. extract, and its cardiovascular effects may be linked to the compounds of the plant.