When You Fire Up Those Muscles, You May Be Accomplishing More Than Muscle Fatigue and Burn: The Role of Exercise Metabolite Lactate in Brain Function and Mental Health

Today, our approach to medicine is shifting, and the realization that physical activity can be a powerful medicine is undeniable. Years ago, before the burgeoning fields of information and systems biology, we did not understand the body’s signaling communication channels and often viewed problematic medical conditions as occurring within isolated areas within the body.  Research in physical activity, a primary health pillar, provides a greater understanding of the deeper cellular and molecular reasons why a sedentary lifestyle is harmful to health and overall longevity (1). 

Evidence-based benefits of exercise are quickly expanding our knowledge in understanding the body’s vital communication pathways and relationship axes. One such example pertains to lactate, a known by-product of physical activity involved in the crosstalk between muscles and the brain. Entering the blood and crossing the blood-brain barrier at the level of brain capillaries, lactate produced from exercise-induced skeletal muscles serves as an anti-inflammatory, antidepressant, and agent in new blood vessel formation within the brain. Modifying such transmissions in various brain regions, lactate now can be viewed in a new light in comparison to the experience of undesirable muscular burn upon exercise exertion (1). 

In an oxygen shortage, lactate can serve as fuel for cells, including neurons. The microvessels of the brain are lined with lactate-sensing receptors.  Upon activation, these receptors can escalate the growth and sprouting of new capillaries from existing vessels, thereby increasing capillary density, a process known as angiogenesis (1)(2). An increase in lactate triggers an associated receptor that escalates growth factor levels in the vessel lining. This growth factor directly enhances both synaptic function (speed) and the generation of new neurons (neurogenesis) (3). Elevated vascular density is one mechanism by which exercise improves cognitive function. 

Exercise-induced lactate production promotes memory formation, protects blood flow-related stress, and provides antidepressant effects (4). In animal studies, lactate was found to mediate stress resilience. By controlling specific proteins in a particular brain area involved in learning and memory known as the hippocampus, lactate acts as a signaling molecule (4). Other animal study results revealed improved social interaction and mitigation of anxiety and depression  (4)(5). In addition, lactate provides the required starting materials for bioenergetic reactions within neurons, ultimately restoring vital brain cell formation (neurogenesis) in the hippocampus (5).

Lastly, lactate has been shown to have anti-inflammatory effects in the body (6). This metabolite aids in the downregulation of proteins modulating inflammation in the gut (7). In combination with other metabolites, lactate reduces liver inflammation, especially in acute conditions (6). 

Within a nature-centric health model, four primary pillars contribute to a solid health foundation. These include mobility, nutrition, mindset, and relationships (self, others, and world). It is essential to address these pillars to attain the complete healthscape we desire. Every day, research provides novel insights evolving science-based practices to serve us better and deepen the understanding of how our bodies genuinely function. 

Health science points to the interconnectedness of our bodies and elucidates the vast influence of our surroundings. Everything is information to the body, and the body is constantly sensing, signaling, and adapting based on this sensory input. The processes of neuroception and interoception allow the body to signal appropriate cellular responses. Movement provides encoded information not only to the skeletal muscles but also to the nervous system (brain). Our physiology reflects our need to move through synergistic relationships within the body.  

KEY POINTS and CALL-TO-ACTION

1. Physical activity can aid cognitive function and brain health.

2. Lactate, a byproduct of skeletal muscle exertion, has anti-inflammatory, antidepressant, and capillary-promoting properties.

3. Enhanced vascular density in the brain equals increased brain function.

4. Physical activity is a primary pillar of health due to its systemic benefits.

5. In as little as 5 minutes a day, you can make strength gains to support your health. Check out Dr. Rangan Chatterjee’s 5 Minute Kitchen Workout (8). 

6. Health is the intersection of multiple elements. Engaging in activities, environments, and behaviors that support your health is an act of self-care and compassion (9). 

7. Physical activity can be more fun and engaging when performed with others. Find friends who want to support and join you in this process.

REFERENCE

1. Di Liegro CM, Schiera G, Proia P, Di Liegro I. Physical Activity and Brain Health. Genes (Basel). 2019;10(9):720. Published 2019 Sep 17. doi:10.3390/genes10090720. https://pubmed.ncbi.nlm.nih.gov/31533339/

2. Adair TH, Montani JP. Angiogenesis. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Chapter 1, Overview of Angiogenesis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53238/. 

3. Morland C, Andersson KA, Haugen ØP, et al. Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nat Commun. 2017;8:15557. Published 2017 May 23. doi:10.1038/ncomms15557. https://pubmed.ncbi.nlm.nih.gov/28534495/

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. 2019;44(6):1152-1162. doi:10.1038/s41386-019-0313-z

5. Carrard A, Cassé F, Carron C, et al. Role of adult hippocampal neurogenesis in the antidepressant actions of lactate. Mol Psychiatry. 2021;26(11):6723-6735. doi:10.1038/s41380-021-01122-0

6. Hazem SH, Hamed MF, Saad MA, Gameil NM. Comparison of lactate and β-hydroxybutyrate in the treatment of concanavalin-A induced hepatitis. Int Immunopharmacol. 2018;61:376-384. doi:10.1016/j.intimp.2018.06.026

7. Iraporda C, Errea A, Romanin DE, et al. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology. 2015;220(10):1161-1169. doi:10.1016/j.imbio.2015.06.004

8. Chatterjee, R. The 5 Minute Kitchen Workout:  A step by step guide. YouTube: March 2018.

1. Jastremski, H. Bright Heart Wellness Newsletter, 2022. “Learning From Those Who Have Lived the Longest and  Healthiest.”

Learning From Those Who Have Lived the Longest and Healthiest

*Please share this newsletter with others who may benefit. We can change our collective health by assisting others.

**As always, please consult your physician before making changes to your health regimen. The information provided is for educational and informative purposes only and is not intended for treatment or diagnosis.

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