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 video, 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.
Look forward to more Masterclass with Masterjohn Energy Metabolism lessons on the D-lactate shuttle in the context of the related shuttles and the roles of L-lactate coming soon.
Read the written version for live links and references:
https://chrismasterjohnphd.substack.com/p/d-lactate-groundbreaking-research
00:00 Introduction
02:30 Summary
06:15 Will Probiotics Give You Brain Fog?
08:55 Methylglyoxal at the Origins of Glycolysis
16:35 My Doctoral Dissertation: Physiological Roles of Methylglyoxal
33:48 A Brief History of D-Lactate
48:15 Is D-Lactate Production “Minuscule”?
57:21 Why D-Lactate Is So Low in the Blood
1:03:15 Is D-Lactate Mainly Produced by the Microbiome?
1:06:10 D-Lactate in Diabetes
1:07:30 The Physiological Purpose of D-Lactate
1:19:40 Introducing the D-Lactate Shuttle
1:27:12 Glycolysis starts acidic and ends alkaline, made possible by L-lactate and the malate-aspartate and glycerol phosphate shuttles.
1:35:30 The D-Lactate Shuttle Is Superior for NAD+ Conservation
1:38:18 Pros and Cons of the Three Shuttles
1:40:08 D-Lactate, Gluconeogenesis and the Malate and 2-Oxoacid Antiporters
1:40:49 Does Glyoxalase-III Spare the Brain?
1:46:10 Practical Considerations
1:48:27 The Bottom Line
Read the written version for live links and references:
https://chrismasterjohnphd.substack.com/p/d-lactate-groundbreaking-research
11 Comments
Very interesting and informative video! Thank you for your work! 🌺💚
It's always a pleasure to watch your videos, they are so lively and informative! 🌺💚
Very interesting approach to the topic! Thank you for such an informative video! 🧡💖
Just delightful! Way to go! 😛💕
Ho cercato di sedurre il mio ragazzo con una poesia d'amore. Alla fine mi ha chiesto se stavo citando Shakespeare o se stavo cercando di scrivere il prossimo grande romanzo d'amore. Credo che mi limiterò alla prosa💞
Yo, that's cray-cray!
Hey Chris, great to see you!
my god do i feel like the dummy in the last seat in the back of the class!
please….JUST tell this idiot what to do, eat and drink!
make it short enough for the back of my t-shirt!!!!
Amazing, the way cross referencing research was so limited 70 years ago. The 1950s didn’t inform the 1970s very well lol Thankfully the web exists now. And this level of info on YouTube too for every dumb troglodyte like me 🤣
I pounded this at 2x on my run which was trippy lol. Kind of understood it, slightly. The analogies were funny too.
I’ve stopped taking Life Extension NAD+ and take an NMN instead from Time Health. Ive loved b vitamins my whole life, they’re my favorite. Never done drugs though and antibiotics only once or twice, (never in childhood) birth control for only a few months and rarely sick.
I think the bowel nosode Gaertner is helping me somewhat with this.
Speaking of pyruvate, do you have any deeper insights on pyruvate transport, like how does it actually get from the cytosol into mitochondria? As i understand, the MPC complex (mitochondrial pyruvate carrier) uses protons from intermembrane space to shuffle pyruvate into mitochondria, but is the MPC activity itself regulated by something else? For instance, we know that pyruvate dehydrogenase is allosterically regulated by NADH and acetyl-coa while pyruvate dehydrogenase phosphatase is regulated by calcium. So i wonder, does something similar like that happen with the MPC complex too? To me, this looks like another obvious bottleneck.