Amino acid supplementation confers protection to red blood cells prior to Plasmodium falciparum bystander stress

• Intracellular reactive oxygen species (ROS) is acquired in red blood cells (RBCs) incubated with Plasmodium falciparum conditioned media

• Glutamine, cysteine, and glycine amino acid supplementation led to increased glutathione biosynthesis and reduced ROS within stressed RBCs

Malaria is a highly oxidative parasitic disease in which anemia is the most common clinical symptom. A major contributor to malarial anemia pathogenesis is the destruction of bystander, uninfected red blood cells (RBCs). Metabolic fluctuations are known to occur in the plasma of individuals with acute malaria, emphasizing the role of metabolic changes in disease progression and severity. Here, we report that conditioned media from Plasmodium falciparum culture induces oxidative stress in uninfected, catalase-depleted RBCs. As cell permeable precursors to glutathione, we show a benefit of pre-exposure to exogenous glutamine, cysteine, and glycine (QCG) amino acids for RBCs and that this pre-treatment intrinsically prepares RBCs to mitigate oxidative stress.