Predicting Antioxidant Synergism via Artificial Intelligence and Benchtop Data

Lipid oxidation is a major issue affecting products containing unsaturated fatty acids as ingredients or components, leading to the formation of low molecular weight species with diverse functional groups that impart off-odors and off-flavors. Aiming to control this process, antioxidants are commonly added to these products, often deployed as combinations of two or more compounds, a strategy that allows for lowering the amount used while boosting the total antioxidant capacity of the formulation. While this approach allows for minimizing the potential organoleptic and toxic effects of these compounds, predicting how these mixtures of antioxidants will behave has traditionally been one of the most challenging tasks, often leading to simple additive, antagonistic, or synergistic effects. Approaches to understanding these interactions have been predominantly empirically driven but thus far, inefficient and unable to account for the complexity and multifaceted nature of antioxidant responses. To address this current gap in knowledge, we describe the use of an artificial intelligence model based on deep learning architecture to predict the type of interaction (synergistic, additive, and antagonistic) of antioxidant combinations. Here, each mixture was associated with a combination index value (CI) and used as input for our model, which was challenged against a test (n = 140) data set. Despite the encouraging preliminary results, this algorithm failed to provide accurate predictions of oxidation experiments performed in-house using binary mixtures of phenolic antioxidants and a lard sample. To overcome this problem, the AI algorithm was then enhanced with various amounts of experimental data (antioxidant power data assessed by the TBARS assay), demonstrating the importance of having chemically relevant experimental data to enhance the model's performance and provide suitable predictions with statistical relevance. We believe the proposed method could be used as an auxiliary tool in benchmark analysis routines, offering a novel strategy to enable broader and more rational predictions related to the behavior of antioxidant mixtures.

Automated summary

Lipid oxidation is a major issue in products containing unsaturated fatty acids. Antioxidants are commonly added to control this process, but predicting the interactions of antioxidant mixtures has been challenging. In this study, an artificial intelligence model based on deep learning was used to predict the interaction types of antioxidant combinations. The addition of chemically relevant experimental data improved the model's performance and provided accurate predictions.