Oxygen Radical Absorbance Capacity (ORAC) is a water-based method commonly used to determine the antioxidant capacity of bioactive compounds such as polyphenols. However, some antioxidants are lipophilic molecules and the inability to achieve high concentrations has encouraged the use of cyclodextrins as solubility enhancers. Carotenoids, tea catechins, essential oils, stilbenes, mangiferin and flavonols are some examples of lipophilic antioxidants whose activity has been measured by the cyclodextrin-modified ORAC method.
Despite the beneficial improvement in solubility, the use of these oligosaccharides has resulted in variation in fluorescent readings in some studies. The discrepancy in the conclusions of several authors using this modified method has led the team of Prof. José Manuel López Nicolás of The University of Murcia (Spain) to question the role of cyclodextrins in the ORAC method.
By means of a physicochemical and computational approach , the influence of cyclodextrins in the ORAC method is challenged. The researchers found that different types of cyclodextrins interfere in a dose-dependent manner generating a deviation in the antioxidant measurement. The encapsulation of the other reagents in the medium was proposed as the main cause of the interference.
 Navarro-Orcajada, S., Conesa, I., Matencio, A., Rodríguez-Bonilla, P., García-Carmona, F., & López-Nicolás, J. M. (2022). The use of cyclodextrins as solubility enhancers in the ORAC method may cause interference in the measurement of antioxidant activity. Talanta, 243:123336. https://doi.org/10.1016/j.talanta.2022.123336