Most textbooks portray lactate as a byproduct of glycogen metabolism and have blamed it for causing sore muscles during workouts. But researcher George Brooks, a professor of integrative biology at UC Berkeley, wants to change the way people think of the molecule. Brooks has been researching lactate since the 1970s, and has recently published a review on lactate in Cell Metabolism. The heart and brain run more efficiently when they’re powered by lactate instead of glucose, Brooks found. He's convinced that it is far from waste; it acts as a normal fuel.
"It's a historic mistake," Brooks said. "It was thought that lactate is made in muscles when there is not enough oxygen. It has been thought to be a fatigue agent, a metabolic waste product, a metabolic poison. But the classic mistake was to note that when a cell was under stress, there was a lot of lactate, then blame it on lactate. The proper interpretation is that lactate production is a strain response, it's there to compensate for metabolic stress. It is the way cells push back on deficits in metabolism."
High lactate levels in the blood have been observed after injury and illness by clinicians and researchers. Now some are wondering if it’s a crucial part of a repair mechanism. "After injury, adrenaline will activate the sympathetic nervous system, and that will give rise to lactate production," Brooks explained. "It is like gassing up the car before a race." Brooks hypothesized that lactate has several critical roles: it’s a fuel, it plays a role in blood sugar, and helps adapt metabolism in response to stress. It may also help recovery after injury.
"The reason I wrote the review is that people in all these different disciplines are seeing different effects of lactate, and I am pulling it all together," noted Brooks. "Lactate formulations have been used for decades to fuel athletes during prolonged exertions; it's been used widely for resuscitation after injury and to treat acidosis. Now, in clinical experiments and trials, lactate is being used to help control blood sugar after injury, to fuel the brain after brain injury, to treat inflammation and swelling, for resuscitation in pancreatitis, hepatitis and dengue infection, to fuel the heart after myocardial infarction and to manage sepsis."
Brooks coined the phrase lactate shuttle to describe the movement of lactate in various processes throughout the body's organs and tissues (which he discusses in the video). When the body needs energy, it can utilize fatty acids from adipose tissue, and glycogen, from food intake and muscles. After glycogen is metabolized, creating lactate and glucose, and fatty acids are made from fat cells, the chemicals are all released into the blood. Brooks and colleagues have found that lactate is then used as the preferred source of energy.
It was thought for nearly a century that lactate was made only after cells lacked oxygen, But with isotope tracers, Brooks showed it is made, and used, under normal conditions. It turns out that glucose and glycogen are not broken down into pyruvate, as was thought. Other researchers have since confirmed the findings with other techniques.
In the presence of lactate, cells’ energy powerhouses, mitochondria, will opt to use it instead of fatty acids or glucose. Again with tracers, Brooks’ team found that the muscles and brain also opt for lactate, using it more efficiently. Lactate can also be a signal that halts the breakdown of fat.
In Brooks’ review, he proposes several roles for lactate: it is a primary source of energy, and because it is a precursor for glucose production in the liver, it supports blood sugar, and is a signaling molecule that can interact with tissues and affect gene expression. Lactate’s versatility can be a liability, however. Cancer cells can also use it for energy. Brooks noted in his review that lactate shuttles might be a good drug target in cancer therapeutic development.
"It's like the VISA of energetics; lactate is accepted by consumer cells everywhere it goes,” he said. “Lactate is the key to what is happening with metabolism. That is the revolution."
Sources: Phys.org via University of California, Berkeley, Journal of Experimental Biology, Cell Metabolism