Chema Moya

As requested by many, here is a post trying to explain the differences between Exercise-drived lactate and Cancer-derived lactate. Exercise-Derived Lactate: During high-intensity exercise, lactate is produced as skeletal muscles rely more heavily on glycolysis. However, lactate is eventually cleared and oxidized by mitochondria—both within active muscle fibers and in distant tissues like the heart, liver, and brain. This dynamic lactate shuttling fuels oxidative metabolism acting probably as the preferred fuel for cells. In addition to being a fuel, lactate functions as a signaling molecule and “exerkine”, activating beneficial pathways like PGC-1α, AMPK, and BDNF, which promote mitochondrial biogenesis, neuroplasticity, angiogenesis, and anti-inflammatory effects. Exercise-derived lactate communicates across organ systems to enhance metabolic flexibility, homeostasis and systemic health. Once exercise activity ceases, lactate is cleared by mitochondria in active muscle and the rest of the body. Cancer-Derived Lactate: A key player in carcinogenesis In contrast, cancer cells produce large amounts of lactate (Warburg effect), even in the presence of oxygen. Unlike during exercise, this lactate is not effectively cleared and although it is also used as a fuel, lactate accumulates chronically and as a signaling molecule, it elicits multiple deleterious effects key for carcinogenesis. According to our “lactagenesis hypothesis” (pubmed.ncbi.nlm.nih.gov/2799…), cancer-derived lactate functions as a central regulator of carcinogenesis. We and others have recently shown that lactate modulates cancer’s gene expression through transcriptional activation andepigenetic mechanisms like histone lactylation. Lactate promotes angiogenesis, immune escape, metastasis, and metabolic self-sufficiency, also responsible for the acidosis of tumor microenvironment which makes it a further niche for carcinogenesis. A decreased mitochondrial function capacity (probably due to genetic mutations) along with increased glycolytic flux result in excessive lactate production which as we propose through our "lactagenesis hypothesis", is the purpose and the explanation of the Warburg Effect.

While it is great that finally the Warburg Effect is viewed by the scientific community as a key piece of the cancer puzzle, it has brought some significant misunderstanding and misinformation to the general population. Such as intellectually cheap and “lazy” concepts like “sugar causes cancer” which is a very wrong way to understand the Warburg Effect. Also, thinking that Cancer is purely a Metabolic Disease is not correctly framed.