Gender differences in biochemical markers and oxidative stress of rats after 28 days oral exposure to a mixture used for weight loss containing p-synephrine, ephedrine, salicin, and caffeine

Gabriela Cristina Schmitt,Renata Pereira Limberger,Andréia Louise Lorensi,Marcelo Dutra Arbo,Eliane Dallegrave,Sabrina Nunes Do Nascimento,Kristiane De Cássia Mariotti,Mirna Bainy Leal,Solange Cristina Garcia,Ana Laura Bemvenuti Jacques

doi:10.1590/s1984-82502016000100007

Abstract

ABSTRACT The association of p-synephrine, ephedrine, salicin, and caffeine in dietary supplements and weight loss products is very common worldwide, even though ephedrine has been prohibited in many countries. The aim of this study was to evaluate a 28-day oral exposure toxicity profile of p-synephrine, ephedrine, salicin, and caffeine mixture (10:4:6:80 w/w respectively) in male and female Wistar rats. Body weight and signs of toxicity, morbidity, and mortality were observed daily. After 28 days, animals were euthanized and blood collected for hematological, biochemical, and oxidative stress evaluation. No clinical signs of toxicity, significant weight loss or deaths occurred, nor were there any significant alterations in hematological parameters. Biochemical and oxidative stress biomarkers showed lipid peroxidation, and hepatic and renal damage (p < 0.05; ANOVA/Bonferroni) in male rats (100 and 150 mg/kg) and a reduction (p < 0.05; ANOVA/Bonferroni) in glutathione (GSH) levels in all male groups. Female groups displayed no indications of oxidative stress or biochemical alterations. The different toxicity profile displayed by male and female rats suggests a hormonal influence on mixture effects. Results demonstrated that the tested mixture can alter oxidative status and promote renal and hepatic damages.

Highlights

Overweight and obesity are highly prevalent worldwide
There are a large number of products being marketed for weight loss, most usually containing a mixture of ingredients including p-synephrine (Citrus aurantium L.), ephedrine (Ma Huang, Ephedra sinica, Ephedra sp.), salicin (Salix sp.) and caffeine (Paullinia cupana, Cola nitida, Cola acuminata, Camellia sinensis), as well as vitamins, minerals, and other herbs (Arbo et al, 2008, 2009a, 2009b)
According to Lewis et al (2002), some factors can be useful in differentiating between a significant change from control values and a treatment-related effect. This difference is less likely to be an effect of treatment if: there is no obvious dose response; it is due to findings in one or more animals that could be considered outliers; or it is normal biological variation. In this experimental work we evaluated a 28-day period of oral exposure to a mixture of p-synephrine, ephedrine, salicin, and caffeine, which has been used in weight loss formulations

Summary

Introduction

Overweight and obesity are highly prevalent worldwide. Many consumers are seeking strategies for reducing weight to healthier levels, including the use of dietary supplements and weight loss products. The use of p-synephrine, a biogenic amine found in Citrus aurantium, became very popular after the banning of ephedrine-containing dietary supplements by the Food and Drug Administration (FDA) due to the occurrence of significant adverse effects, mainly related to the cardiovascular system (Bouchard et al, 2005). It quickly replaced ephedrine in supplements called “ephedra-free” due to their structural similarity (Fugh-Berman, Myers, 2004; Jordan et al, 2004; Grollman, 2005)

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