Unveiling the Brain’s Workout: Lactate, Angiogenesis, and Cognitive Fitness

Jacqueline K. Morris, Ph.D. – 


Suffice it to say that for your brain to function optimally, it requires a generous supply of both oxygen and glucose. These essential nutrients are transported through the extensive network of vessels and capillaries that circulate blood to the brain. It is crucial to note that as we age, there is a decline in the volume of blood vessels within the brain, which is correlated with a decrease in cognitive function. Nevertheless, regardless of age, the brain has the capacity for new vessel growth, a phenomenon known as angiogenesis. Scientists provide compelling evidence that lactate, produced during exercise, plays a crucial role as a key regulator in angiogenesis within our brains (Wu et al., 2023).


The initiation of new blood vessel growth in the brain is facilitated by small proteins known as growth factors. These proteins are usually secreted by cells within the body, which then stimulate responses like angiogenesis. One pivotal growth factor in inducing angiogenesis is VEGF, short for vascular endothelial growth factor (Apte et al., 2019). While angiogenesis is beneficial in improving cognition and memory, it can also pose risks, as blood vessels provide energy and oxygen to tumors, allowing them to thrive (Apte et al., 2019). Moreover, age-related eye diseases, such as age-related macular degeneration, can be linked to an overgrowth of blood vessels that obstruct vision (Penn et al., 2008). Suffice it to say, balance is key. 


VEGF, a protein with two similar parts, is secreted by cells and binds to receptors in the membranes of cells. Mammals have multiple VEGF proteins and various VEGF receptors, with specific proteins being critical for stimulating angiogenesis in different tissues or at different stages of an organism’s life. When VEGF binds to its receptor, it induces cells to divide, migrate, or survive. The critical role of VEGF is evident in the development of a new organism and the growth of all vessels within an organism. Functional mutations of VEGF can result in the non-viability of an embryo (Apte et al., 2019).


Cells within the brain usually release VEGF, either inducing angiogenesis or collaborating with other factors. One collaborator is IGF-1 and is released into the blood during exercise (Sujkowski et al., 2021), has a direct impact on memory and cognition, as observed in various cognitive tests conducted on rodents (Han et al., 2023). One potential pathway is that IGF-1 regulates the release of VEGF in the hippocampus, leading to increased neuronal survival and health (Morland et al., 2017). Another benefit of exercise for the brain is the increase in BDNF or brain-derived neurotrophic factor. BDNF directly contributes to neuronal protection and the growth of dendritic spines, which are regions forming connections or synapses with other neurons in our brains (Lin et al., 2018).


Our brains, the orchestrators of our thoughts and actions, consist of diverse cell types, with neurons taking the spotlight and glia providing crucial support. Among these supporting cells, astrocytes play a vital role in maintaining a barrier between the brain and blood, shuttling energy sources like glucose to neurons (Maddock et al., 2011). While glucose is the primary fuel, the often-overlooked lactate has recently emerged as a key player in brain health, with exercise-induced lactate may have profound effects on cognitive function (Maddock et al., 2011).


Astrocytes, with their faster glucose metabolism, support energy-demanding neurons that control vital functions such as heart rate and breathing. Neurons, unable to store glucose, rely on astrocytes as reservoirs, especially during low glucose levels or high lactate conditions, like those induced by exercise or injury (Wu et al., 2023).


During rest, our blood lactate levels are low, spiking during exercise or heightened neuronal activity. Elevated lactate in the spinal fluid may even serve as a marker for neurodegenerative diseases, highlighting its potential significance in brain health (Sujkowski et al., 2022).


Lactate isn’t just a bystander; it actively supports neuronal activity and neuroprotection. Microglia cells are resident immune cells in the brain that are activated during injury, stroke, or infection (Han et al., 2023). Recent studies indicate that lactate expedites microglia’s transition to a neuroprotective stage, preventing prolonged clean-up phases that might harm sensitive neurons (Han et al., 2023). Moreover, lactate appears to regulate genes essential for neuron health leading to increased cognitive functions (Wu et all, 2023).


As we age, the volume of blood vessels in our brains decreases, correlating with cognitive decline. Enter angiogenesis – the growth of new blood vessels. Lactate, produced during exercise, emerges as a key regulator in this process, influencing cognition and memory positively (Liu et al., 2018). 


During exercise, our muscles need energy to function, and they primarily rely on a process called glycolysis. This is like a quick energy source where glucose, a form of sugar, gets broken down. Sometimes, when oxygen is scarce, glycolysis produces lactate as a byproduct. It might sound counterintuitive, but lactate isn’t the culprit for muscle fatigue – it actually helps in the energy production process (Wu et al., 2023). As exercise intensity increases, our muscles produce more lactate. While once thought to be a cause of muscle soreness, lactate is now understood as a valuable fuel source for working muscles, contributing to our ability to sustain physical activity (Maddock et al., 2011).


Lactate secretion by muscles typically occurs during high-intensity or anaerobic exercise. Activities that demand a rapid and intense energy output, such as sprinting, weightlifting, or high-intensity interval training (HIIT), can trigger glycolysis and the subsequent production of lactate. In these scenarios, the oxygen supply to the muscles may become limited, leading to the conversion of glucose to lactate for quick energy. Endurance exercises, on the other hand, often involve a more sustained and aerobic energy production process, where lactate levels remain relatively lower (Wu et al., 2023).


Lactate is indeed secreted into the bloodstream during exercise. As muscles produce lactate through glycolysis, some of it diffuses into the blood and is transported to other tissues, including the liver, where it can be converted back into energy. This process is part of the body’s intricate energy management system, allowing lactate to serve as a valuable resource for various tissues during physical activity. So, both muscle and bloodstream play roles in the distribution and utilization of lactate during exercise (Wu et al., 2023).


In the brain of rats undergoing high intensity interval exercises, scientists measured  a 40% increase in vascularization in a crucial region of the brain involved in memory and spatial navigation called the dentate gyrus (Moreland, et al. 2017). While the vasculature in the cortex which is associated with the senses, control of muscles, and decision making increased by 10-20% (Moreland et al., 2017).


Exercise training has been shown to enhance learning and memory abilities in both young and old mice, according to a study using mice of different ages (4, 15, and 20 months). Older mice exhibited lower learning and memory function, but after 8 weeks of running exercise, improvements were observed, suggesting that exercise may positively impact cognitive function, even with aging (Han et al., 2023). 


In summary, understanding the intricate relationship between lactate, exercise, and brain health unveils a fascinating interplay that goes beyond muscle soreness. As we acknowledge the vital role of lactate in neuroprotection, angiogenesis, and cognitive function, the importance of regular exercise becomes even more evident. So, lace up those sneakers, embrace the sweat, and fuel not just your body but also your brain for a healthier, more resilient mind.


Before starting any exercise program, it is important to consult with a qualified healthcare professional or physician to ensure that it is safe for you to do so, especially if you have any pre-existing medical conditions, injuries, or concerns about your health.


About the author: 

Dr. Morris trained as a cell biologist while earning her doctorate from Baylor College of Medicine. She subsequently conducted research on glial cells at esteemed institutions such as the Salk Institute and the Cleveland Clinic. For over 18 years, she facilitated undergraduate neuroscience research at Baldwin Wallace University, where she also served as Director of the Neuroscience program for 5 years. Currently, she provides support to researchers with their imaging needs as a field application scientist. Jacqueline has maintained a keen focus on the interplay of exercise, nutrition, and health throughout her research and teaching endeavors. For inquiries, Jacqueline can be reached at or connected with via LinkedIn at https://www.linkedin.com/in/jacquelinemorrisphd.


Works Cited

Apte, R. S., et al. (2019). VEGF in signaling and disease: Beyond Discovery and Development. Cell, 176(6), pp. 1248–1264. https://doi.org/10.1016/j.cell.2019.01.021.

Han, H., et al. (2023). Exercise improves cognitive dysfunction and neuroinflammation in mice through histone H3 acetylation in microglia. Immunity & Ageing, 20(1). https://doi.org/10.1186/s12979-023-00390-4.

Lin, T. W., et al. (2018). Physical exercise enhances neuroplasticity and delays Alzheimer’s disease. Brain Plasticity, 4(1), pp. 95–110. https://doi.org/10.3233/bpl-180073.

Liu, J., et al. (2023). The effect of exercise on cerebral blood flow and executive function among young adults: A double-blinded randomized controlled trial. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-33063-9.

Maddock, R. J., Casazza, G. A., Buonocore, M. H., & Tanase, C. (2011). Vigorous exercise increases brain lactate and Glx (glutamate+ glutamine): a dynamic 1H-MRS study. Neuroimage, 57(4), pp. 1324-133.

Morland, C., et al. (2017). Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nature Communications, 8(1). https://doi.org/10.1038/ncomms15557.

Penn, J. S., et al. (2008). Vascular endothelial growth factor in eye disease. Progress in Retinal and Eye Research, 27(4), pp. 331–371. https://doi.org/10.1016/j.preteyeres.2008.05.001.

Sujkowski, A., et al. (2022). The protective role of exercise against age-related neurodegeneration. Ageing Research Reviews, 74. https://doi.org/10.1016/j.arr.2021.101543

Wu, A., et al. (2023). Lactate metabolism, signaling, and function in brain development, synaptic plasticity, angiogenesis, and neurodegenerative diseases. International Journal of Molecular Sciences, 24(17), p. 13398. https://doi.org/10.3390/ijms241713398.