Lactate Is A Key Signal Enhancing Brain Adaptatio
Lactate is a bi-product constantly produced in the body during normal metabolism and exercise, and research suggests it is a key driver of brain adaptations. In this article Dr. Paul Henning investigates to learn more about the effects of lactate on the brain.More
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Physical inactivity is the fourth leading cause of death worldwide, and it is also a major cause of non-communicable diseases worldwide. Strong evidence indicates that physical inactivity increases the risk of many adverse health conditions, including coronary heart disease, type 2 diabetes, and breast and colon cancer, and leads to reduced life expectancy(1). Not only that, but studies have also reported that about 10% of all non-communicable disease deaths worldwide are attributable to physical inactivity, and some diseases are even higher(1).
This is a significant public health problem worthy of attention.
It is clear from research that physical exercise is beneficial to health, including the brain. In the general population, exercise can enhance attention, processing speed, memory, and executive function(2). Apart from these, numerous studies have demonstrated that different exercise regimes can significantly enhance various brain functions, including regulating cerebrovascular function, enhancing neuroplasticity, inhibiting neuroinflammation, and preventing neurodegenerative diseases(3). Recently, research has focused on the protective effects of physical exercise on neurodegenerative diseases and cerebrovascular diseases. A very interesting finding is that lactate, a substance that was considered a metabolic waste for a long time in the past, has gradually been proved to play an essential role in exercise-mediated benefits in brain functions.
Lactate is a bi-product constantly produced in the body during normal metabolism and exercise.
It doesn't increase in concentration in the bloodstream until the rate of lactate production exceeds the rate of lactate removal which is governed by a number of factors.Since the initial discovery of lactate in 1780, scholars’ views on it have been continuously changing. Historically, it was believed that lactate was a useless glycolysis product and was the leading cause of muscle fatigue during exercise. However, in the past few decades, new evidence indicates that lactate is an important energy source and plays many critical roles in the body. For example, astrocyte-neuron lactate transport is necessary for long-term memory formation. Besides, lactate can also ameliorate depression symptoms, potentiate angiogenesis and neurogenesis, and may be involved in exercise-induced cerebrovascular changes and the release of brain-derived neurotrophic factor (BDNF)(4). In this article, I will elucidate the relationship between lactate- and exercise-induced benefits in brain functions.
Exercise, Neuroplasticity, and Cerebrovascular Plasticity
“Neuroplasticity” refers to the capacity of the nervous system to adapt and optimize its limited resources in response to physiological changes, injuries, new environmental demands, and sensory experiences. The historical consensus is that in the early stages of an individual’s development, the nervous system has tremendous potential for inherent plasticity that gradually fades over time. However, in recent decades, convincing evidence indicates that stimulation, such as environmental changes, physical exercise, or cognitive training, reactivates the adult neocortex’s plasticity, alters cortical circuit activity, and changes the structure or function of the brain, suggesting that brain plasticity may be lifelong(5). It should be highlighted that exercise, a cost-effective method, has great potential in activating neuroplasticity. Specifically, exercise can induce a cascade of molecular and cellular processes that support brain plasticity, thus contributing to cognitive function and resisting the brain function decline caused by aging or nervous system diseases. In addition, exercise could improve neuroplasticity and positively affects cerebrovascular function(6).
The Effects of Lactate on the Brain
Overall, from the waste product of glycolysis to important energy substrates and signaling molecules in the body, research is not clear that the role of lactate is much more important than we thought in the past.For example, recent evidence indicates that during learning tasks in rats, hippocampal astrocytes released a large amount of lactate into extracellular space, accompanied by a significant increase in the expression of monocarboxylic acid transporter (MCT1).
Essentially, this was necessary to maintain long-term potentiation (LTP), a neuronal signal enhancement phenomenon that constitutes the basis of learning and memory(7).
It is postulated that learning triggers a series of events in the brain that lead to short-term and long-term memory. In contrast, long-term memory formation is accompanied by the activation of neural networks and higher metabolic demands, thus causing astrocytes to release lactate to supply active neurons. In addition, astrocyte-derived lactate is also crucial for maintaining brain function during exhaustive exercise. Exhaustive exercise can greatly reduce glycogen levels in muscles and the hippocampus and elevate MCT2 and lactate in the brain.Interestingly, lactate may also be a potential novel antidepressant. In different animal models of depression, peripheral administration of L-lactate, especially long-term administration, could reduce depression-like behaviors similarly to antidepressants, thus partially restoring social avoidance behavior(4).
Essentially, research indicates that lactate exhibits many effects in the brain.
These studies show that lactate may be a molecular signal used by specific neurotrophic factors via certain mechanisms to activate neurogenesis or cerebrovascular plasticity. The potential mechanisms of lactate and exercise-induced effects on the brain are shown in the figure below.
Fig: The possible mechanisms of lactate in exercise-induced positive effects on neuroplasticity and cerebrovascular plasticity. Exercise causes muscles to produce lactate, which is then released into the blood and passes through the BBB through different MCTs into the brain parenchyma(8).
Summary
In today’s rapidly aging society, age-related memory decline and neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, may become more prevalent. In some highly stressed groups, the incidence of depression cannot be ignored.
Research has proved that exercise can effectively prevent or combat these diseases, highlighting the importance of exercise.
Recent evidence indicates lactate is likely to be a key signal molecule that regulates beneficial adaptation of the brain caused by exercise. However, how lactate mediates this effect is still unknown and more research is needed. The establishment of the molecular pathways responsible will facilitate the application of lactate to clinical treatment. Current evidence suggests that high-intensity interval training (HIIT) induces higher BDNF levels and beneficial cerebrovascular changes compared to moderate- or high-intensity continuous exercise. There are people that cannot participate in HIIT due to physical reasons. If lactate therapy can be developed into a pill that partially mimics the benefits of exercise; this treatment could help more people to maintain the physical and brain health effects of exercise with a low-cost means.
In addition to exercise, another powerful addition to your daily routine that has incredible brain benefits is creatine. Creatine has many benefits on the brain and body. Whether you get it from food or you get it from supplements the key is to make sure you get it every day.
If you're looking to support your cognitive function there is no better combination than the Ultimate Brain Stack.
The Ultimate Brain Stack contains ATP-Fusion (5,000 mg of creatine and 220 mg of sodium) and FOCUSED-AF (our world-class nootropic comprised of 10 powerful brain-boosting ingredients) to provide a full range of nutrients to support a high-performance brain.
References: 1. Lee IM, Shiroma EJ, Lobelo F, et al: Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 380:219-29, 2012 2. Wu C, Yang L, Li Y, et al: Effects of Exercise Training on Anxious-Depressive-like Behavior in Alzheimer Rat. Med Sci Sports Exerc 52:1456-1469, 2020 3. Guadagni V, Drogos LL, Tyndall AV, et al: Aerobic exercise improves cognition and cerebrovascular regulation in older adults. Neurology 94:e2245-e2257, 2020 4. Karnib N, El-Ghandour R, El Hayek L, et al: Lactate is an antidepressant that mediates resilience to stress by modulating the hippocampal levels and activity of histone deacetylases. Neuropsychopharmacology 44:1152-1162, 2019 5. Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, et al: Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease. Nat Med 25:554-560, 2019 6. Joris PJ, Mensink RP, Adam TC, et al: Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise. Nutrients 10, 2018 7. Suzuki A, Stern SA, Bozdagi O, et al: Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810-23, 2011 8. Huang Z, Zhang Y, Zhou R, et al: Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity. Frontiers in Physiology 12, 2021
