Drive Podcast Lecture Notes

Hosts and Guests

• Host: Peter
• Guest: George, a researcher on lactate metabolism

Introduction

• Discussion focus: Lactic acid and its role in muscle metabolism.
• Common misconception: The body produces lactate, not lactic acid.

Historical Context

• Otto Myhoff's Discovery (100 years ago):
  • Experiment with frog muscles in anaerobic conditions.
  • Glycogen in muscles degrades into lactate.
  • Misinterpretation led to belief in lactic acidosis and anaerobic threshold.
• Warburg Effect (Cancer Metabolism):
  • Cancer cells produce lactate in presence of oxygen.
  • Originally thought to indicate defective mitochondria.

Glycolysis and Lactate

• Glucose Metabolism:
  • Glucose enters cells via Transporters, crucial for glycolysis.
  • Glucose splits into two 3-carbon molecules, resulting in lactate production.
  • Glycolysis is pH neutral but can be alkalizing.
• Mitochondrial Role:
  • Discovery of mitochondrial lactate oxidation complex.
  • Lactate enters mitochondria, contradicting traditional glycolysis teachings.

Exercise Physiology

• Mitochondrial Function:
  • Trained athletes have more mitochondrial mass.
  • MCTs (Monocarboxylate Transporters) increase with training, aiding lactate transport.
• Lactate Shuttles in Muscle Fibers:
  • Type I (red) fibers use lactate produced by Type II (white) fibers.
  • Exercise enhances lactate clearance, preventing metabolic diseases.

Clinical Implications

• Traumatic Brain Injury (TBI):
  • Lactate as a preferred fuel for injured brains.
  • Potential therapy: Lactate infusion to aid brain function post-injury.
• Sepsis and Lactate Measurement:
  • High lactate in sepsis may not indicate tissue hypoxia.
  • Potential involvement of gut microbe-produced D-lactate.

Disease and Metabolism

• Type 2 Diabetes and Lactate:
  • Elevated lactate due to impaired disposal, not just production.
• Cancer Metabolism:
  • Lactate production linked to cancer cell metabolism.
  • Exercise could improve lactate clearance, potentially reducing cancer risk.

Brain Health and Aging

• Exercise and Cognitive Function:
  • Lactate may stimulate neurogenesis and improve cognitive function.
  • Protective role against Alzheimer’s and dementia.

Future Research Directions

• Metabolic Flux Studies:
  • Need for detailed studies on lactate flux and mass balance.
• Impact of Metformin:
  • Investigating how Metformin alters lactate and glucose metabolism.

Conclusion

• Lactate plays a crucial role in metabolism beyond being a stress marker.
• Exercise is essential for maintaining metabolic health and clearance of lactate.
• Further research required to unravel the complete role of lactate in various health conditions.