New research shows lactate just may be the answer to an exercise-induced energy shortage, especially in the brain.
The idea that this metabolite helps regenerate energy for sustaining exercise has replaced the common misconception of its role in muscle fatigue.
In fact, lactate is a fuel source for many cells, including neurons in the brain, under oxygen-deprived (hypoxic) conditions.
Lactate is Fuel
Lactate helps generate fuel as chemical energy (ATP) which powers every cell in the body. Apparently lactate also operates like a hormone due to its involvement in complex memory formation and neuroprotection.
Astrocytes release lactate in response to neuronal activation. Lactate synthesizes substrates, including acetyl-CoA for the Krebs cycle.
During exercise, ATP is generated mostly from free-flowing blood glucose and the retrieval and breakdown of muscle glycogen stores. To keep moving when the glucose supply is short, the body looks for other ways to regenerate glucose and ATP. With plenty of oxygen, consumption and regeneration flow in a relatively steady state.
A shortage of oxygen, however, causes more lactate production. Pyruvate, a byproduct of glycolysis (glycogen breakdown), can convert to lactate to regenerate the chemical compound NAD+, which is necessary to make ATP.
When produced this way, lactate is typically shuttled to the liver where it’s used to synthesize glucose through gluconeogenesis. Then the glucose is shuttled back to the muscles as a primary energy source in glycolysis.
Fat cells (adipocytes) produce lactate under anaerobic conditions as well. The amount produced depends on a person’s total fat mass.
Lactate and Neuron Metabolism
Researchers are investigating lactate’s ability to cross the blood-brain barrier and play a role in neuron metabolism.
Neuron cell death occurs with oxygen- and glucose-deprivation unless the cell receives lactate before the deprivation occurs. In fact, lactate, not glucose, is the necessary factor in neuron cell recovery from hypoxic conditions.
This process, called the astrocyte-neuron lactate shuttle (ANLS), is particularly active during excitatory neurotransmission and the conversion of neurotransmitters (such as glutamine from glutamate). ANLS both produces and consumes lactate.Researchers suggest lactate, not glucose, is the primary fuel source for brain neurons. Click To Tweet
Astrocytes are a type of glial cell in the brain which helps keep neurons healthy and function smoothly. Under resting conditions, apparently half of available glucose is used by the neurons and half by the astrocytes. Since astrocytes use only 10-15% of the brain’s total energy, researchers suggest lactate is the primary fuel source for neurons.
Is Lactate the Link to Improving Cognitive Function?
The ANLS pathway also may play a role in memory formation, causing researchers to question whether lactate could be the link between exercise and improved cognitive function.
In the hippocampus, the center of the brain where memories form, exercise induces an overflow of extracellular lactate. The lactate levels stay elevated for at least fifty minutes following exercise.
We need much more research to determine how lactate may correlate to memory formation and neuron plasticity, but these findings are progressive and promising.
Lactate and Physical Fitness
Under strenuous exercise conditions, the highest level of effort the body can physically sustain without accumulating lactate and hydrogen ions (H+) in the blood and muscles is called the lactate threshold.
The higher the lactate threshold, the greater the person’s physical fitness.
The point where lactate begins to accumulate in the blood stream creates the anaerobic threshold. Crossing the anaerobic threshold occurs when the body converts from primarily aerobic to anaerobic metabolism, shifting almost entirely from fat to carbohydrates as the primary fuel source.
Lactate, Muscle Fatigue, and DOMS
In this zone, hydrogen ion production accompanies lactate production. When glucose breaks down from the blood, the process releases two hydrogen ions. If glucose breaks down from muscle glycogen, it produces one ion.
The ions create an acidic environment, known as acidosis, which causes acute muscle fatigue, soreness, and delayed-onset muscle soreness (DOMS) twenty-four to forty-eight hours after exercise. Although lactate is not the direct source of H+ generation, it’s often blamed for muscle fatigue and soreness.
Lactic acid production, however, plays an essential role in chemical buffering to regenerate NAD+ and remove pyruvate from the cell to supply the next cycle of energy production. The blood can take lactic acid from resting or slowly working muscles. This is why muscles appear to recover during the rest periods of interval training occurring at, or above, the lactate threshold.
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Proia, P., Di Liegro, C. M., Schiera, G., Fricano, A., and Di Liegro, I. (2016). Lactate as a Metabolite and a Regulator in the Central Nervous System. International Journal of Molecular Sciences, 17(9), 1450. doi:10.3390/ijms17091450.