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#312 - A masterclass in lactate: Its critical role as metabolic fuel, implications for diseases, and therapeutic potential from cancer to brain health and beyond | George A. Brooks, Ph.D.

Aug 5, 2024 2h 6m 16 insights
<p><a href="https://peterattiamd.com/georgebrooks/?utm_source=podcast-feed&amp;utm_medium=referral&amp;utm_campaign=240804-pod-georgebrooks&amp;utm_content=240804-pod-georgebrooks-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&amp;utm_medium=referral&amp;utm_campaign=240804-pod-georgebrooks&amp;utm_content=240804-pod-georgebrooks-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&amp;utm_medium=referral&amp;utm_campaign=240804-pod-georgebrooks&amp;utm_content=240804-pod-georgebrooks-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>George A. Brooks is a renowned professor of integrative biology at UC Berkeley. Known for his groundbreaking "lactate shuttle" theory proposed in the 1980s, George revolutionized our understanding of lactate as a crucial fuel source rather than just a byproduct of exercise. In this episode, George clarifies common misconceptions between lactate and lactic acid, delves into historical perspectives, and explains how lactate serves as a fuel for the brain and muscles. He explores the metabolic differences in exceptional athletes and how training impacts lactate flux and utilization. Furthermore, George reveals the significance of lactate in type 2 diabetes, cancer, and brain injuries, highlighting its therapeutic potential. This in-depth conversation discusses everything from the fundamentals of metabolism to the latest research on lactate's role in gene expression and therapeutic applications.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>Our historical understanding of lactate and muscle metabolism: early misconceptions and key discoveries [3:30];</li> <li>Fundamentals of metabolism: how glucose is metabolized to produce ATP and fuel our bodies [16:15];</li> <li>The critical role of lactate in energy production within muscles [24:00];</li> <li>Lactate as a preferred fuel during high-energy demands: impact on fat oxidation, implications for type 2 diabetes, and more [30:45];</li> <li>How the infusion of lactate could aid recovery from traumatic brain injuries (TBI) [43:00];</li> <li>The effects of exercise-induced lactate [49:30];</li> <li>Metabolic differences between highly-trained athletes and insulin-resistant individuals [52:00];</li> <li>How training enhances lactate utilization and facilitates lactate shuttling between fast-twitch and slow-twitch muscle fibers [58:45];</li> <li>The growing recognition of lactate and monocarboxylate transporters (MCT) [1:06:00];</li> <li>The intricate pathways of lactate metabolism: isotope tracer studies, how exceptional athletes are able to utilize more lactate, and more [1:09:00];</li> <li>The role of lactate in cancer [1:23:15];</li> <li>The role of lactate in the pathophysiology of various diseases, and how exercise could mitigate lactate's carcinogenic effects and support brain health [1:29:45];</li> <li>George's current research interests involving lactate [1:37:00];</li> <li>Questions that remain about lactate: role in gene expression, therapeutic potential, difference between endogenous and exogenous lactate, and more [1:50:45]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights

1. Double Mitochondrial Mass via Training

Engage in consistent training over several weeks to months, as this can double mitochondrial mass in muscle, enhancing the body’s energy delivery system and improving metabolic capacity.

2. Exercise to Suppress Appetite

Engage in exercise intense enough to raise lactate levels to around 3-4 millimolar, as this can cross the blood-brain barrier, inhibit ghrelin secretion, and suppress appetite for several hours post-exercise.

3. Increase MCT Density with Training

Train consistently to increase the abundance of monocarboxylate transporters (MCTs) in muscle cells, which facilitates both the export of lactate and its uptake into mitochondria for oxidation.

4. Enhance Lactate Clearance for Cancer

Increase your body’s lactate clearance capacity through regular exercise, as effective removal of lactate may lessen the chance for carcinogenesis if lactate is indeed carcinogenic.

5. Generate Endogenous Lactate for Biogenesis

To stimulate mitochondrial biogenesis, focus on generating high levels of endogenous lactate through exercise, as this appears to be a more effective signal than simply infusing exogenous lactate.

6. Exercise for Brain Health, Neurogenesis

Engage in physical exercise to promote brain health, as it can stimulate neurogenesis in the dentate gyrus and improve brain blood flow and substrate delivery, contributing to the development of new brain cells.

7. Exercise Boosts Cognition

Engage in exercise that raises lactate levels, as this can temporarily improve scores on cognitive tests and fuel the brain, suggesting a direct link between physical activity and enhanced executive function.

8. Administer Lactate for TBI

For brain-injured individuals, consider intravenous lactate infusion, as early clinical trials suggest it may serve as a preferred fuel source for injured neurons and could lead to better outcomes.

9. Use ‘Lactate,’ Not ‘Lactic Acid’

Refer to the molecule as ’lactate’ rather than ’lactic acid,’ as the body produces lactate, and this distinction corrects a century-old historical mistake in understanding its role.

10. Recognize Lactate as Fuel

Understand that lactate is an integral participant in powering muscle and all cells, serving as a crucial fuel source rather than merely an unfortunate byproduct or waste product of exercise.

11. Metformin’s Lactate: A Good Thing

If taking metformin, understand that the associated rise in lactate levels may be a beneficial outcome, as the drug could be encouraging enterocytes to produce lactate as a valuable carbohydrate energy form.

12. Distinguish Lactate from pH in Sepsis

In septic patients, differentiate between elevated lactate and low pH; while a low pH requires intervention, a high lactate level in the absence of a significant pH change may not warrant aggressive treatment for acidosis.

13. Recognize Enteric Glycolysis

Understand that enteric glycolysis, occurring in the gut, is an initial and rapid process of carbohydrate energy distribution, producing lactate that appears in arterial blood even before glucose levels significantly rise after a meal.

14. Liver Sequestering Glucose Load

Understand that the liver plays a key role in glucose disposal, sequestering approximately 80% of an oral glucose load and gradually releasing it over time, rather than immediate muscle uptake.

15. Lactate Signals Gene Expression

Recognize that lactate is a potent signaling molecule that can directly bind to genes (lactylation) and affect gene expression, potentially influencing mitochondrial biogenesis and other physiological adaptations.

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