George Brooks, PhD, on Lactate Shuttle Theory, Relevance for Traumatic Brain Injury, & More

Posted on December 3rd 2014 (almost 4 years)

George A. Brooks, PhD, is a professor in the Department of Integrative Biology at the University of California, Berkeley. He has spent more than four decades investigating energy substrate use in humans. His research has led to a greater understanding of the role and metabolic disposition of lactate and was instrumental in identifying the metabolic pathway known as the “lactate shuttle.”

Dr. Brooks’ current research is aimed at identifying treatments for individuals suffering from injuries and infections associated with lactic acidosis, such as traumatic brain injury, heart failure, inflammatory conditions, and HIV infection.

Dr. Brooks earned his master’s and doctorate degrees in exercise physiology at the University of Michigan. He has authored numerous peer-reviewed articles in the field of exercise physiology.

Debunking a long-held myth

Nearly 40 years ago, as a young, intercollegiate athlete, Dr. George Brooks sought answers to his questions about how to improve his athletic performance. That early interest spawned a lifelong career dedicated to debunking what is possibly one of the greatest misunderstandings in exercise physiology – the lactic acid myth.

This myth is based on the commonly held belief that lactate is a waste product formed by working muscles during intense exercise. According to this belief, lactate and its conjugate, lactic acid, build up in muscles, contributing to fatigue and subsequent performance losses. Much of the misunderstanding about lactate arose from early experiments in non-oxygenated frog muscles in which lactate concentrations rose markedly during stimulation. The myth was born, and it perpetuates today among coaches, athletes, and just about everyone else.

However, these dated ideas run counter to new evidence that suggests oral intake of lactate actively improves exercise performance. Other data demonstrate the role lactate plays as an energy substrate and point to uncertainty that proton accumulation, often associated with high lactate concentrations in blood, is a major cause of fatigue.

Another element of the myth centers around the difference between lactic acid and lactate. But this difference mostly serves to distract. What’s important to remember is that, at physiological pH, the majority of lactic acid is in the form of lactate, but the terms can be understood to be mostly interchangeable.

The lactate shuttle hypothesis

"Our unique contribution was to find that not only are [lactate transporters] in the plasma membranes of muscles and heart and other tissues, but they are also in the mitochondria." - Dr. George Brooks Click To Tweet

Lactate is a natural byproduct of glycolysis – the breakdown of sugar. It’s an essential fuel that cells in the heart, liver, and brain rely on. When produced during exercise (especially high intensity workouts like cycling, which shifts metabolism toward glycolysis to more quickly meet the high energetic demands), lactate switches on more than 600 genes involved in muscle adaptation, stimulates mitochondrial biogenesis – the process of making new mitochondria – and promotes protein synthesis, which is essential for muscle growth. The diverse nature of the signaling quality of lactate has led to Dr. Brooks’s coining of the term “lactormone.”

A key element in this process is a metabolic pathway called the lactate shuttle – initially posited by Dr. Brooks – which describes the movement of lactate within and between cells so it can be used. Moreover, more than merely cell to cell, this network of metabolic activity that includes the generation, transport, and consumption of lactate actually spans multiple organ systems: muscle to liver, muscle to brain, muscle to heart. When a person actively uses their muscles in exercise, we now know, transporters in distant tissues like the heart upregulate in direct proportion to the exertion as measured through muscular contraction – providing support for the idea that high heart-rate, lactate-threshold training provides a means of taking advantage of the lactate shuttle. This is the same sort of training you might expect to get from a professional coach, by the way.

Shuttling lactate to the brain

"I often talk to people about using the talk test. So, if we were on two treadmills here when we were having this conversation, and we got going faster and faster, we would get to the point where we couldn't talk anymore." - Dr. George Brooks Click To Tweet

But lactate appears to be even more complex – and essential – than first believed. Lactate serves as a signaling molecule in the brain, where it stimulates the production of neurotransmitters that promote focus and attention, as well as brain-derived neurotrophic factor, known for its role in supporting neurogenesis. And burgeoning research is pointing to the key role lactate may play in treating brain trauma, using lactate infusions that not only bypass the gut but also spare glucose for other immediate needs.

Providing nutrients – especially glucose – to an individual with a brain injury is a standard of care. However, as explained by Dr. Brooks in this episode, glycolysis is impaired in the injured brain. Without glycolysis, lactate production is halted, and the brain, which prefers lactate as a fuel, starves. Brooks and his colleagues are looking at ways to provide lactate to the injured brain to ameliorate the deleterious effects of trauma.

Read more about the diverse roles of lactate in Dr. Brooks seminal paper "The Science and Translation of Lactate Shuttle Theory."

Learn more about Dr. George A. Brooks

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