Dietary serine supplementation: Friend or foe?

Serine lies at a critical node in biological processes involved in supplying intermediates for redox homeostasis, nucleotide, or lipid biosynthesis and one-carbon metabolism-coupled methyl donor production. Recently, dietary serine supplementation has been reported to modulate cellular serine levels and ameliorate neurological abnormalities induced by serine deficiency. Moreover, growing evidence showed that serine supplementation also alleviates fatty liver, encephalopathy, diabetes mellitus, and related complications, indicating the possibility of serine supplementation as a complementary therapeutic option. However, considering the serine addiction observed in tumorigenesis and tumor development, limitations may exist regarding the application of dietary serine supplementation in patients with cancer. Here, we assess recent research toward the mechanistic understanding of serine supplementation in various diseases to improve our cognition on modulating serine levels in different patients.