Changes of plasma amino acid levels and metabolic pathways in isotretinoin therapy: ınsights into managing acne vulgaris side effects

Acne vulgaris can be effectively treated with isotretinoin, however, there are several side effects both during and after the treatment. Preventing these side effects is important for continued treatment. This study focused on the relationship between the changes in the levels of plasma amino acids of patients with acne vulgaris after three months of isotretinoin treatment and the side effects. A pre- and post-treatment plasma sample of 35 patients was collected. Samples were analyzed by liquid chromatography-tandem mass spectrometry. After treatment, the plasma levels of 15 amino acids changed statistically. While L-arginine, taurine, L-asparagine, and L-proline levels decreased, L-serine, L-alanine, and L-cystine levels also increased. (p < 0.05) When the amino acid profiles of male and female patients before and after treatment were compared, the plasma levels of L-arginine (p = 0.0017), L-cystine (p = 0.0224) and L-histidine (p = 0.0167) were statistically different. Additionally, the correlation matrix analysis revealed a strong correlation (R > 0.8) between L-leucine, L-isoleucine, L-norvaline, and L-valine. The effect of isotretinoin treatment on eighteen metabolic pathways such as cysteine and methionine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism is strongly related to the treatment of therapeutic and side effects of isotretinoin. According to the results of the study, the use of L-arginine, L-asparagine, N-acetylcysteine and taurine supplements during isotretinoin treatment may help avoid side effects of skin dryness, blepharitis, nail fragility, and fatigue. As a result, the study provided useful information for enhancing the safety and efficacy of isotretinoin treatment, as well as lowering isotretinoin-related side effects. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.