In the first half of the 20th century lactate had a largely negative reputation in medical circles and was viewed as something far from being a benign (let alone beneficial) byproduct of cellular metabolism. The people studying cancer knew very well of lactate’s nefarious role in that disease and Nobel Prize winner who have the “Warburg Effect” its name was firmly of the opinion that lactate is intimately connected to not just cancer, but also to most other chronic diseases. After medicine took a decisive turn towards fascism/authoritarianism since the 1950s those original studies and opinions on lactate were largely (and conveniently) forgotten and now lactate is even given to critically ill people in the hospital under the form of the (in)famous Ringer Lactate solution. The rationale is that lactate serves as a fuel for cells and it “beneficial” in critical illness. Somehow, it escapes even emergency medicine that about half of the patients who present to the ER are already in lactic acidosis, so giving them extra lactate is perhaps the worst possible intervention and likely ensures their demise since the organic lactic acidosis alone has a mortality rate of about 40%. One can easily imagine the mortality rate following additional lactate infusions.
Well, the study below adds to the evidence that lactate is directly harmful to cells, and this harm is mediated mostly by lactate causing mitochondrial damage/fragmentation as well as increased generation of reactive oxygen species (ROS), with the latter being a likely result of the former. Over time, the combination of these effects led to the development of “idiopathic” pulmonary fibrosis (IPF) in the animals used in the study. IPF also exists in humans and is progressive, and invariably lethal. Big Pharma companies such as Pfizer have been running trials quietly with serotonin antagonists such as terguride (an ergot derivative almost identical to lisuride), which suggests that lactate promotes either synthesis/release of serotonin, its action, or both. Yet another reason to keep lactate levels under control. Interestingly, preventing the formation of ROS ameliorated IPF, which suggests something as simple as vitamin E may be able to put the brakes on this progressive and lethal condition, currently considered by medicine to be incurable. Now, I did put the “pulmonary” in the title in parenthesis. Why? Well, because the mechanisms through lactate caused fibrosis in the lungs are general enough to be applicable to all organs, and not just the lungs. Thus, lactate is likely a universal pro-fibrotic agent and it may be turn out that preventing/reversing many fibrotic conditions may be as simple as keeping lactate at bay with substances such as vitamin B1, B2, B3, B7, methylene blue, etc.
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05289-2
“…Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung diseases, which mainly existed in middle-aged and elderly people. The accumulation of reactive oxygen species (ROS) is a common characteristic of IPF. Previous research also shown that lactate levels can be abnormally elevated in IPF patients. Emerging evidence suggested a relationship between lactate and ROS in IPF which needs further elucidation. In this article, we utilized a mouse model of BLM-induced pulmonary fibrosis to detect alterations in ROS levels and other indicators associated with fibrosis. Lactate could induce mitochondrial fragmentation by modulating expression and activity of DRP1 and ERK. Moreover, Increased ROS promoted P65 translocation into nucleus, leading to expression of lung fibrotic markers. Finally, Ulixertinib, Mdivi-1 and Mito-TEMPO, which were inhibitor activity of ERK, DRP1 and mtROS, respectively, could effectively prevented mitochondrial damage and production of ROS and eventually alleviate pulmonary fibrosis. Taken together, these findings suggested that lactate could promote lung fibrosis by increasing mitochondrial fission-derived ROS via ERK/DRP1 signaling, which may provide novel therapeutic solutions for IPF.”
