Summary
In this follow-up conversation, Simon Hill and Dr. Inigo San Millan take a deep dive into lactate -- debunking the long-held myth that it is a toxic waste product and revealing it as one of the body's most powerful signaling molecules, a preferred fuel source, and the best available biomarker of mitochondrial function. Dr. San Millan explains how George Brooks' 54 years of research at UC Berkeley established that lactate has hormone-like signaling properties, enters mitochondria directly without needing to be broken down, and is preferred over glucose by the brain, heart, and kidneys. The episode presents compelling new research from San Millan's lab showing that healthy sedentary individuals already have 30 to 50 percent reductions in key mitochondrial components like the mitochondrial pyruvate carrier, electron transport chain complexes, and fatty acid transporters -- even while their standard blood glucose and insulin levels appear normal. This suggests that mitochondrial dysfunction begins years or decades before clinical diabetes manifests, and that lactate testing during graded exercise can detect it early. Dr. San Millan shares clinical evidence of reversing pre-diabetes through individualized zone 2 exercise prescription, discusses why resistance training alone leaves mitochondrial function resembling that of sedentary individuals, and explains why ketogenic diets likely produce measurement artifacts in fat oxidation testing rather than genuine improvements in mitochondrial capacity.
Key Points
- Lactate is a signaling molecule, a fuel source, and the best biomarker of mitochondrial function -- not a toxic waste product as historically believed
- The burning sensation during intense exercise is caused by muscle acidosis from ATP hydrolysis, not by lactate; lactate actually acts as a mild buffer during glycolysis
- Lactate enters mitochondria directly through its transporter and is metabolized faster than glucose, making it the body's preferred fuel source for the brain, heart, and kidneys
- Healthy sedentary individuals already show 30 to 50 percent reductions in mitochondrial pyruvate carriers and electron transport chain complexes, even with normal blood glucose and insulin
- Lactate testing during graded exercise can detect mitochondrial dysfunction 10 to 20 years before clinical diabetes appears, analogous to cardiac stress testing
- A pre-diabetic patient reversed her metabolic dysfunction in six to seven months through an individualized zone 2 exercise prescription based on lactate testing
- People who only do resistance training can present with metabolic profiles similar to sedentary individuals; cardiovascular training is essential for mitochondrial function
- Zone 2 training targets 200 to 300 minutes per week, with high-intensity bursts to stimulate MCT4 transporters and glycolytic enzymes
Key Moments
Lactate as the best biomarker of mitochondrial function
Dr. San Millan explains that lactate is not just a biomarker but a signaling molecule with hormone-like properties. It enters mitochondria directly as the most direct fuel source available.
"And I think that it's been, as you said, a big, you know, like it hasn't been understood. And it's going to be a major biomarker in the next years and going forward. But yeah, it is a major biomarker of mitochondrial function. And it's probably right now the best biomarker that we have to see what's your mitochondrial function in the I mean, it's everywhere, it's ubiquitous to every pretty much every single reaction in the body, and its presence across the body is as ubiquitous as the presence of oxygen or CO2."
Debunking the lactic acid burn myth
Dr. San Millan debunks the widespread belief that lactic acid causes the burning sensation during intense exercise. The real cause is muscle acidosis from ATP hydrolysis, and lactate actually serves as a mild buffer during glycolysis.
"People might say, that's a kind of lactic acid burn post-exercise. Is that a myth? Absolutely. It's a myth. And the thing is that what really causes that burning sensations that we all have felt is muscle acidosis."
Sedentary individuals show 30-50% reduced mitochondrial function
Research from San Millan's lab reveals that healthy sedentary individuals already show significant reductions in mitochondrial pyruvate carriers and electron transport chain complexes -- even while their glucose transporters remain normal.
"And it's very clear that sedentary individuals have a significant decreased in mitochondrial function already. And we can see that also without the need of doing muscle biopsy by looking at lactate during incremental tests. So this is what we wanted to also correlate, what we see in the muscle biopsy."
Pre-diabetic patient reversed through zone 2 exercise
Dr. San Millan recalls the first patient he treated with individualized zone 2 exercise prescription. A pre-diabetic woman returned to normal metabolic function within six to seven months.
"And after just, I think it was like six, seven months, she came back to normal. So we were able to reverse that metabolic dysfunction."
