#002 Dr. George Brooks on Lactate Shuttle Theory, Relevance for Traumatic Brain Injury, and More

Dec 2, 2014 Episode Page ↗
Overview

Dr. George Brooks, an exercise physiology expert, discusses how lactate, once deemed a toxic byproduct, is a vital energy source for the heart, brain, and muscles, and a signaling molecule. He explains its role in exercise adaptations, brain health, traumatic brain injury recovery, and optimal daily activity levels.

At a Glance
8 Insights
1h Duration
13 Topics
6 Concepts

Deep Dive Analysis

Introduction to Lactate Research and Dr. Brooks' Background

Challenging the 'Lactic Acid' Misconception

Lactate Production, Use, and Muscle Fatigue

Exercise Adaptations: Mitochondria and Lactate Transporters

Lactate as a Signaling Molecule for Muscle Growth

Lactate Threshold Training for Athletes

Recommended Daily Exercise for Health and Weight Management

Lactate's Role in Brain Function and Cognition

Lactate for Traumatic Brain Injury Treatment

Glucose Sparing and Antioxidant Benefits of Lactate

Optimal Timing and Challenges for TBI Lactate Infusion

Distinguishing L-Lactate from Neurotoxic D-Lactate

Lactate's Potential in Neurodegenerative Diseases

Lactate Shuttle Theory

Proposed by Dr. Brooks, this theory explains how lactate, generated by muscles during exercise, is not a waste product but is actively used by various body tissues like the heart, liver, and brain as a preferred source of energy.

Lactic Acid vs. Lactate

Glycolysis actually produces lactate, not lactic acid. The acidosis associated with intense exercise and fatigue comes from the splitting of ATP (which liberates protons), not directly from 'lactic acid,' which is a strong acid that would be completely dissociated at physiological pH.

Lactate Transporters (MCTs)

These are specific monocarboxylate transporter proteins found in the plasma membranes and mitochondria of cells. They are crucial for moving lactate into cells where it can be oxidized for energy, and their number can double with physical training.

Mitochondrial Biogenesis

This is the process by which the mitochondrial network within cells increases in mass and branches out. Physical activity, particularly endurance training, can double the amount of mitochondria in muscle, and lactate itself acts as a signal to activate genes for this process.

Lactate as a Signaling Molecule

Beyond its role as an energy source, lactate acts as an upstream signal that upregulates over 600 genes related to muscle adaptation, mitochondrial biogenesis, and muscle protein synthesis, essentially mimicking many effects of exercise training.

Glucose Sparing

When lactate is supplied and utilized as a primary fuel source, it allows available glucose to be 'spared' for other critical metabolic pathways, such as the pentose phosphate pathway, which produces antioxidants like NADPH and glutathione, important for cellular protection.

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Is lactate a toxic waste product that causes muscle fatigue?

No, lactate is not inherently toxic. While high levels can accumulate during extreme exertion in oxygen-deprived conditions, it is primarily a vital fuel source and signaling molecule, and the acidosis associated with fatigue comes from other metabolic processes, not directly from 'lactic acid'.

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How does exercise training improve the body's ability to handle lactate?

Endurance training increases the mass of the mitochondrial network and doubles the number of lactate transporters in muscle cells, allowing the body to produce and clear lactate more efficiently, using it as fuel.

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What type of exercise is best for increasing mitochondrial mass and lactate transporters?

Endurance training is known to increase mitochondrial mass and transporter numbers. Coaches also use lactate threshold training, which involves exercising just below or occasionally above the lactate threshold, to optimize these adaptations.

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How much daily exercise is recommended for overall health and weight management?

While 30 minutes a day improves cardiovascular function and reduces disease risk, about an hour a day of moderate activity (like brisk walking) is generally needed to manage body weight and provide broader health benefits.

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How does lactate benefit brain health and cognitive function?

Lactate crosses the blood-brain barrier and is a preferred fuel source for the brain. It also acts as a signaling molecule, stimulating brain-derived neurotrophic factor (BDNF) and norepinephrine release, which can improve focus and attention.

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Why is lactate beneficial for traumatic brain injury (TBI) patients?

After TBI, the brain's ability to use glucose is often impaired. Lactate infusion bypasses this impairment, providing essential fuel to the starving brain and allowing available glucose to be spared for antioxidant production and other vital processes.

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What is the difference between L-lactate and D-lactate, and why does it matter?

L-lactate is the naturally occurring, beneficial form of lactate used by the body as fuel and a signaling molecule. D-lactate is its mirror image and is neurotoxic, though it doesn't share the same transporters as L-lactate.

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Can lactate supplementation help with neurodegenerative diseases like Parkinson's?

Emerging research suggests that lactate can improve mitochondrial function and cell viability in Parkinson's models (worms and mice). Exercise-induced lactate may also fuel neurons and stimulate BDNF, potentially aiding in neurodegeneration.

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Does lactate compete with ketone bodies for transport into cells and the brain?

Yes, lactate will out-compete ketone bodies for transport via monocarboxylate transporters because its configuration fits the transporter better.

1. Daily Activity for Health

Engage in approximately one hour of physical activity daily, equivalent to brisk walking, to manage body weight and improve overall health. This level of activity builds bone and muscle mass, enhances cardiovascular and endocrine function, fuels the brain, and may reduce cancer risk.

2. Exercise for Brain Function

Incorporate regular exercise into your routine to improve focus and attention. Physical activity increases lactate in the brain, which stimulates the release of norepinephrine, a neurotransmitter crucial for focus and attention.

3. Optimize Exercise Training Adaptations

To optimize muscle adaptations, including doubling mitochondrial mass and lactate transporters, engage in endurance training. Coaches also recommend training below the lactate threshold for mitochondrial biogenesis and occasionally above it for harder exercise.

4. Monitor Exercise Intensity

Track your exercise intensity using heart rate monitors, lactate measuring devices, or the ’talk test.’ If you can no longer talk during exercise, your lactate levels are likely very high, indicating you’ve reached an acidotic state.

5. Lactate Infusion for TBI

For individuals with traumatic brain injury, consider lactate infusions (salts and esters) as early as possible. This approach can mitigate swelling, provide essential fuel to the brain by bypassing impaired glucose metabolism, and manage acidosis, potentially improving long-term outcomes.

6. Avoid D-Lactate Consumption

Be mindful of D-lactate, as it is neurotoxic and does not share beneficial transporters with L-lactate. When choosing fermented products or probiotics, opt for those that primarily contain L-lactate.

7. Sodium Lactate for Energy

Consume sodium lactate (e.g., in sports drinks like Cytomax) for quick energy and improved gut health. It is taken up much faster by the intestinal tract than glucose due to sodium-mediated transporters, and it can also alkalize the blood.

8. Ketotic Diet Post-TBI

For individuals recovering from traumatic brain injury, a ketotic diet may help supplement energy supply to the brain. Ketone bodies are transported into cells via the same monocarboxylate transporters as lactate, potentially aiding recovery when combined with other interventions.

Why is the fire department always there at a fire? Is lactate the cause of the problem, or is it there to mitigate the problem, just like the fire department?

Dr. George Brooks

You can actually double the amount of mitochondria you have in your muscle by training. That's really one of the most incredible adaptations we know about.

Dr. George Brooks

Lactate, in addition to being used as an energy source to produce energy for the cell, it also is a signaling molecule that seems to regulate, maybe even on an epigenetic level where it's upregulating, meaning increasing the transcription of a variety of genes that are related to mitochondrial function and muscle adaptation...

Dr. Rhonda Patrick

Physical activity, I say, works from the tip of your toes to the top of your head.

Dr. George Brooks

Get out and move. Get some exercise. You know, it seems like the best medicine you can possibly have.

Dr. Rhonda Patrick

The body is a thief.

Dr. George Brooks

Lactate Threshold Training (Coaches' Empirical Method)

Dr. George Brooks
  1. Train below the lactate threshold for significant mitochondrial biogenesis.
  2. Occasionally exercise above the threshold for harder training (not daily).
  3. Track training by measuring heart rate, lactate levels, or using the 'talk test' (if you can't talk, you're likely acidotic and lactate is high).
Over 600
Genes upregulated by lactate All genes basically of muscle adaptation.
Can double
Mitochondrial increase with training In muscle by training.
Can double
Lactate transporter increase with training In muscle by training.
About an hour a day
Recommended daily activity for weight control Equivalent of brisk walking, for healthy, lean, freely living people.
30 minutes a day
Recommended daily activity for cardiovascular benefits Improves cardiovascular function, reduces risk of heart disease and diabetes.
5 minutes
Lactate uptake time in breath After consuming Cytomax, isotopically labeled lactate is taken up by the intestinal tract and burned, appearing in breath.
At least half an hour
Glucose uptake time to peak After consuming Cytomax, isotopically labeled glucose takes this long to reach a peak.
About 3
PK of lactic acid At physiological pH, lactic acid would be completely dissociated.
43 years
Dr. Brooks' tenure at UC Berkeley As a professor.