Inflammation can play a massive role in our long-term health. Diabetes, cardiovascular diseases, allergies and asthma, arthritis, and joint diseases are all chronic inflammatory diseases and they are the most significant cause of death across the world (1). Unfortunately, the damage doesn’t stop there, as chronic inflammation can cause inflammation of the brain, leading to neurodegeneration in the form of neurological and mental health issues.
What is inflammation?
Inflammation is an immune system response to any type of foreign object or irritant, which can come in form of a pathogen (virus, bacteria, fungi), an injury (scrape, wound), a foreign object (splinter, thorn), a chemical, or even radiation (2). As soon as the body recognizes there is a threat, the immune system gets to work. Immune cells release various substances, called inflammatory mediators, which begin fighting the irritant (2). Two of these inflammatory mediators are histamine and bradykinin, which serve multiple purposes. They cause blood vessels to dilate, increasing blood flow and allowing more immune cells to enter the area (2). They also irritate nerves, which send pain signals to the brain (2). Each of these responses allows the body to do its job and heal, and alert your mind through many senses (pain, sight, and touch) that the area is injured and requires special care.
How can inflammation be bad for you?
While inflammation is a necessary and important response to harm and irritants, the body can at times mistake normal, healthy cells as foreign objects it needs to attack. This can be found in cases of chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and bowel diseases like Crohn’s disease and ulcerative colitis (2). However, widespread inflammation occurs concurrently in the most common conditions, such as diabetes, cardiovascular disease, obesity, depression, and dementia (3). Indeed, more studies are showing that chronic inflammation anywhere in the body can cause brain inflammation.
How can inflammation in one part of the body spread to the brain?
Chronic inflammation that begins in one area (from injury, illness, or microbiota disturbances, especially in the gut) can cause a breakdown in barriers, resulting in escaped pathogens or other harmful substances reaching the bloodstream (1, 4, 5). Once they reach the bloodstream, they can begin to disrupt the blood-brain barrier, increasing permeability and allowing substances that are toxic to enter the brain (1, 6). The immune system is then triggered, causing inflammation in the brain and potentially causing harm. For those with other types of conditions or disorders that cause inflammation, such as rheumatoid arthritis, system-wide inflammation can cause the same pro-inflammatory effect in the brain as well (1, 7, 8). Additionally, consistent levels of environmental toxins, stress, or even multiple episodes of acute inflammation from recurring infection or injury can also cause neuroinflammation (1).
What are the effects of brain inflammation?
While inflammation in any part of the body can cause harm, inflammation in the brain is especially worrisome. Inflammation can affect the physical structure of the brain, creating problems with brain metabolism and tissue structure and function (1). High levels of inflammatory markers can also disrupt or break down the blood-brain barrier. This may allow neurotoxins to enter the brain or lead to abnormal tissue structure, which can cause the immune system to continually respond and begin a cycle of chronic brain inflammation (1). This leads to problems with brain function, including (3, 5, 9, 10, 11):
General cognitive impairment
Memory decline and disorders, including dementia and Alzheimer’s Disease
Neurological disorders such as Parkinson’s Disease
Neuropsychiatric problems and disorders, including low mood, depression, and anxiety
What are the symptoms of chronic inflammation?
While the symptoms of neuroinflammation specifically will vary based on each person and may manifest as any of the disorders listed above, symptoms of chronic peripheral or neuro-inflammation may include (1):
General low mood, depression, anxiety, or other mood disorders
Gastrointestinal complications like diarrhea or constipation
Weight gain or loss
Frequent or recurring infections
If neuroinflammation is so often caused by peripheral inflammation, what are the most common causes of peripheral inflammation? There are four main categories to consider.
1. High Levels of Stress
Stress is something that all of us are familiar with and, especially in our modern world, suffering from chronic stress is almost a given. While it may be easy to write it off as normal, elevated stress levels can be incredibly harmful to the body and brain. Too much chronic stress is a precursor to the development of the most common inflammatory diseases, as well as all of the effects on brain function listed above, because it is directly linked to both peripheral inflammation and neuroinflammation (5, 12). Stress and inflammation are being more commonly recognized as playing a role in the risk for and development of mood and neurodegenerative disorders (12).
2. Arthritis, Gout, and Other Autoimmune Diseases
An autoimmune disease is, as its most basic, an overreaction of the immune system resulting in the body mistakenly attacking its own cells and causing inflammation. Gout, rheumatoid arthritis (RA), and lupus are three such autoimmune diseases that are also directly tied to neurological inflammation and changes (7, 13, 14). Rheumatoid arthritis activates pro-inflammatory pathways in the body that lead to both joint and general peripheral inflammation and can also inflame the brain (7). One therapy for RA is actually so successful at reducing neuroinflammation that it is also protective for Alzheimer’s disease (7).
Gout is another type of arthritis that is caused by too much uric acid in the body (13). Uric acid can trigger the release of pro-inflammatory proteins in joints and in the brain as well. Thus, gout is related to an increase in the risk of neurological disorders such as Alzheimer’s, Parkinson’s, Huntington’s, and other inflammatory diseases. Similarly, common symptoms of lupus, another inflammation-causing autoimmune disease, include cognitive decline, mood disturbances, and mood disorders (14).
3. Allergic Reactions to Environmental Factors
Allergies are chronic inflammatory conditions that affect 20-30% of the world’s population and can occur alongside other conditions such as asthma, sleep disturbances, and sleep apnea (15). They are also associated with neuroinflammation, especially when the reaction is caused by exposure to toxic environmental factors such as smoke, exhaust fumes, environmental compounds, and other chemicals commonly found in thousands of our everyday products (16). The allergic reaction that occurs when the body encounters these allergens is also associated with a release of pro-inflammatory proteins in the brain. As a result, there is an association with dementia and Alzheimer’s disease, as well as mood disorders such as anxiety and depression (15, 17).
4. Poor Diet and Unhealthy Gut Microbiome
An unhealthy gut microbiome can cause something called leaky gut, which occurs when the lining of the intestine doesn’t function properly and allows substances to leak through (4). Bacteria and other particles that are able to escape can cause inflammation locally and, if they enter the bloodstream, create an immune response in the brain as well. This can create a ‘leaky brain’, which can lead to neuroinflammation and, unfortunately, a number of neurodegenerative and neuropsychiatric disorders (more information on leaky gut and brain here) (4).
Similarly, a poor diet that is high in sugar, salt, and processed foods can cause inflammation in the brain and also reduce levels of brain-derived neurotrophic factor, both of which can lead to the same symptoms and neurodegenerative diseases (see this article for more information) (18, 19).
So, how can I reduce inflammation?
Reducing inflammation in the body as a whole, as well as addressing neuroinflammation specifically, is a different journey for everyone, based on their unique environment, body, and habits. A great first step is to identify any allergies, toxin exposures, or inflammatory diseases you may have or be at risk for. Another important step is to focus on the 5 pillars of health: quality sleep, regular exercise, healthy diet, well-managed stress, and strong relationships. (Read this article for more info on how focusing on the 5 pillars of health can improve brain health).
If you have any concerns about the symptoms, conditions, or information above, please give us a call! We would love to discuss you and your family’s health and determine the best ways to work together toward healing, prevention, and a healthy body and brain. Happy New Year!
Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.
Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functional Medicine.
Pahwa R, Goyal A, Bansal P, et al. Chronic Inflammation. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493173/
InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. What is an inflammation? 2010 Nov 23 [Updated 2018 Feb 22]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279298/
Rosano, C., Marsland, A. L., & Gianaros, P. J. (2012). Maintaining brain health by monitoring inflammatory processes: a mechanism to promote successful aging. Aging and disease, 3(1), 16–33.
Mu, Q., Kirby, J., Reilly, C. M., & Luo, X. M. (2017, May 23). Leaky Gut As a Danger Signal for Autoimmune Diseases. Frontiers in immunology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/.
Gerwyn Morris, B. S. F. Leaky brain in neurological and psychiatric disorders: Drivers and consequences - Gerwyn Morris, Brisa S Fernandes, Basant K Puri, Adam J Walker, Andre F Carvalho, Michael Berk, 2018. SAGE Journals. https://journals.sagepub.com/doi/10.1177/0004867418796955.
Obrenovich, M. E. M. (2018, October 18). Leaky Gut, Leaky Brain? Microorganisms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313445/.
Fuggle, N. R., Howe, F. A., Allen, R. L., & Sofat, N. (2014). New insights into the impact of neuro-inflammation in rheumatoid arthritis. Frontiers in neuroscience, 8, 357. https://doi.org/10.3389/fnins.2014.00357
Chaurasia, N., Singh, A., Singh, I. L., Singh, T., & Tiwari, T. (2020). Cognitive dysfunction in patients of rheumatoid arthritis. Journal of family medicine and primary care, 9(5), 2219–2225. https://doi.org/10.4103/jfmpc.jfmpc_307_20
Houser, M. C., & Tansey, M. G. (2017). The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?. NPJ Parkinson's disease, 3, 3. https://doi.org/10.1038/s41531-016-0002-0
Bested, A. C., Logan, A. C., & Selhub, E. M. (2013). Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II - contemporary contextual research. Gut pathogens, 5(1), 3. https://doi.org/10.1186/1757-4749-5-3
Li, Z., Zhu, H., Zhang, L., & Qin, C. (2018, September 25). The intestinal microbiome and Alzheimer's disease: A review. Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1002/ame2.12033.
Liu, Y. Z., Wang, Y. X., & Jiang, C. L. (2017). Inflammation: The Common Pathway of Stress-Related Diseases. Frontiers in human neuroscience, 11, 316. https://doi.org/10.3389/fnhum.2017.00316
Fang, P., Li, X., Luo, J. J., Wang, H., & Yang, X. F. (2013). A Double-edged Sword: Uric Acid and Neurological Disorders. Brain disorders & therapy, 2(2), 109. https://doi.org/10.4172/2168-975X.1000109
Kayser, M. S., & Dalmau, J. (2011). The emerging link between autoimmune disorders and neuropsychiatric disease. The Journal of neuropsychiatry and clinical neurosciences, 23(1), 90–97. https://doi.org/10.1176/jnp.23.1.jnp90
Amritwar, A. U., Lowry, C. A., Brenner, L. A., Hoisington, A. J., Hamilton, R., Stiller, J. W., & Postolache, T. T. (2017). Mental Health in Allergic Rhinitis: Depression and Suicidal Behavior. Current treatment options in allergy, 4(1), 71–97. https://doi.org/10.1007/s40521-017-0110-z
Yang, S. N., Hsieh, C. C., Kuo, H. F., Lee, M. S., Huang, M. Y., Kuo, C. H., & Hung, C. H. (2014). The effects of environmental toxins on allergic inflammation. Allergy, asthma & immunology research, 6(6), 478–484. https://doi.org/10.4168/aair.2014.6.6.478
Sarlus, H., Höglund, C. O., Karshikoff, B., Wang, X., Lekander, M., Schultzberg, M., & Oprica, M. (2012). Allergy influences the inflammatory status of the brain and enhances tau-phosphorylation. Journal of cellular and molecular medicine, 16(10), 2401–2412. https://doi.org/10.1111/j.1582-4934.2012.01556.x
Beilharz, J. E., Maniam, J., & Morris, M. J. (2016, March 10). Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation. Behavioural Brain Research. https://www.sciencedirect.com/science/article/pii/S0166432816301437?via=ihub.
Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., & Gómez-Pinilla, F. (2002, June 21). A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience. https://www.sciencedirect.com/science/article/abs/pii/S0306452202001239?via=ihub.