D-lactate is commonly stated to be exclusively a microbial metabolite. This is found in assumptions within the medical literature for decades even when it was long-known to be false. While D-lactate is indeed made by bacteria, D-lactate is also inarguably and irrefutably produced by human enzymes. In this podcast, moreover, I will argue the following: Microbial contribution to D-lactate in humans under normal circumstances is negligible. I coin the term "the D-lactate shuttle" to describe a role for D-lactate that should eventually make its way into biochemistry textbooks alongside the malate-aspartate shuttle and the glycerol phosphate shuttle. The D-lactate shuttle operates alongside these other shuttles to balance the priorities of conserving cytosolic NAD+, reducing cytosolic acidity, bypassing complex I, or generating ATP. It is uniquely useful as a shuttle when there is an absolute deficit of niacin or NAD(H). D-lactate is an important contributor to gluconeogenesis that could account for up to 11% of it and rival an individual amino acid. While D-lactate concentrations in human plasma are infinitesimal, when the downstream metabolism of D-lactate and L-lactate are blocked by genetic disorders, the concentrations of the two forms are similar in plasma. This contrasts wildly with the common claim that flux through D-lactate is "minuscule." Most likely D-lactate is produced in considerable quantities in liver and kidney but is rarely secreted into plasma because doing so would risk neurotoxicity. D-lactate should be taken seriously for its potential role in Parkinson's and in neurological problems generally, for its role in diabetes, and for its extremely underappreciated roles in glycolysis, gluconeogenesis, and the respiratory chain. Oxalate powerfully impairs D-lactate clearance, so D-lactate should be investigated as a potential link between oxalate and autism, and oxalate-lowering strategies should be seen as a way to improve D-lactate clearance and reduce its potential role in diabetes and neurological disorders. See the sections on riboflavin, zinc manganese, and glutathione in Testing Nutritional Status: The Ultimate Cheat Sheet, as well as Does CoQ10 Deserve a Spot on Your Longevity Plan? and the How to Detox Manganese guide for managing the relevant nutrients. Read the written version for live links and references: https://chrismasterjohnphd.substack.com/p/d-lactate-groundbreaking-research Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome .
