About a decade ago, a very controversial study came out, which claimed to demonstrate that the amino acid glycine is pro-cancer, and that glycine restriction may be therapeutic. Subsequent in-vivo studies repeatedly demonstrated that glycine addition to the diet was actually therapeutic in cancer and in many cases halted tumor growth, but the damage the original study did was already done and even now many prominent dietitians and even doctors advise against supplementing with gelatin/glycine due to its pro-cancer effects. The study below is yet another one to demonstrate that glycine deficiency actively drives tumor growth and aggressiveness by increasing the stemness of cancer cells. Metabolically, this effects seems to be mediated by the increased fatty acid oxidation resulting from the glycine (or serine) deficiency. Thus, once again, we have evidence that cancer is metabolically driven and that its reliance on fat for fuel is a fundamental growth factor, and simultaneously a therapeutic target. Since glycine supplementation is known to shift the macronutrient preference in favor of glucose, it seems that Peat’s statements have once again been confirmed correct. Namely, glycine deficiency strongly promotes cancer growth, while glycine supplementation is oncostatic, and this effect is once again manifested through the “controversial” Randle Cycle.
https://doi.org/10.1186/s40170-026-00457-y
Serine and Glycine Scarcity Drives Pancreatic Cancer Cells Toward Stem-like, Invasive Behavior
“…The team then examined how PDAC cells adapt to long-term limited extracellular serine and/or glycine availability. The resistant cultures acquired increased mitochondrial respiratory flexibility, characterized by higher maximal respiration, greater spare respiratory capacity and resistance to the complex I inhibitor rotenone. At the same time, their mitochondria became less efficient, showing increased proton leak and a lower mitochondrial transmembrane potential. Adaptation to deprivation of a single amino acid was associated with features consistent with increased fatty acid utilization…”
“…Functionally, the deprivation-resistant cultures showed increased CSC frequency, migration and invasion, and greater in vivo tumorigenicity. The authors conclude that these findings reveal a functional link between serine/glycine availability, mitochondrial plasticity and PaCSC behavior. Adaptation to serine and/or glycine deprivation promotes metabolic rewiring that enhances the stemness potential of PDAC cells, supporting the idea that amino acid metabolic flexibility contributes to the persistence of pancreatic cancer stem cells under nutrient-limited conditions.”
