Brain fog is much more than an annoyance or inconvenience; it can be downright debilitating. You know the feeling – an inability to focus and multitask, lacking sharpness and mental speed, memory loss, or just feeling like you want to sleep. It’s something many individuals experience at some point and often dismiss with excuses of lack of sleep, too much stress, age, or poor diet. While these factors can certainly impact brain function, brain fog may also be a sign of a bigger problem; namely, inflammation in the brain.

Brain fog is associated with numerous health conditions that have an inflammatory component to their pathology. Autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as “minimal cognitive impairment,” an early clinical presentation of Alzheimer's disease (AD) are all examples of common health problems that include brain fog. Mast cell activation syndromes are becoming far more prevalent and moderate to severe brain fog characterizes these conditions in over 90 percent of the individuals diagnosed. Mold exposure, biotoxins, and histamine release are related conditions resulting in significant brain fog. Nearly all neuroimmune, neurodegenerative, and psychiatric conditions have brain fog as a clinical presentation.

Lyme disease is a condition with brain fog as a primary, but often overlooked, clinical outcome. In fact, in many patients treated for Lyme disease, fatigue and brain fog lingers long after the treatment is completed. The condition has been dubbed post-treatment Lyme disease syndrome (PTLDS). Brain scans of people with PTLDS show widespread brain inflammation compared to healthy controls.

Conditions rooted in systemic inflammation are also linked to brain fog and psychiatric manifestations as the inflammatory markers reach brain tissue. For example, rheumatoid arthritis (RA) – a chronic inflammatory arthritis – is now being linked to neuropsychiatric conditions such as anxiety and depression. In one study, published in 2019, over 80 percent of patients with RA had depression, while 52 percent showed clinical anxiety. Psychiatric symptoms were strongly correlated with the severity of the disease. Other studies presented in a systematic review have shown a link between RA and the development of cognitive impairment such as Alzheimer’s disease and dementia, both of which involve brain inflammation. Structural and functional changes in the brain, leading to these conditions, were suggested to arise from chronic inflammation, affecting the brain.

The Role of Mast Cells in Brain Fog

In many of these conditions, the expression of pro-inflammatory genes is heightened in brain tissue, but this is coupled with immune activation from various compounds. For example, mast cells are an integral part of allergic reactions and immunity. They are capable of exerting significant immunomodulatory actions. Being present in the brain, they regulate the permeability of the blood brain barrier (BBB) and, therefore, brain function. When mast cells are activated by an allergen, biotoxin, or other compounds, they will secrete numerous vasoactive, neurosensitizing and pro-inflammatory mediators including histamine, serotonin, kinins, proteases and tumor necrosis factor (TNF), leukotrienes, prostaglandins, chemokines, cytokines, and vascular endothelial growth factor (VEGF), which increase BBB permeability. In this way, mast cells can initiate neuroinflammation and brain fog. Mast cells have been involved in the etiology of many of the aforementioned conditions including ASDs, celiac disease, chronic fatigue syndrome, and others. Mast cells are located close to brain neurons and the hypothalamus and play a role in the clinical manifestations of various neuropsychiatric conditions, including brain fog.

Flavonoids to the Rescue

Flavonoids have been shown to counteract brain inflammation at various junctions and may be helpful for counteracting brain fog. Not only do flavonoids inhibit mast cell degranulation (which results in the release of a flood of inflammatory compounds such as histamine, serotonin, and proteases), but flavonoids also inhibit T-cell activation, the release of interleukins, and IgE-stimulated histamine release. According to a review published in 2015 in the Frontiers of Neuroscience, flavonoids protected against inflammatory activation, but they also supported brain function by protecting against mitochondrial damage and neurotoxicity, possessed neuroprotective activities, and improved memory and attention. Flavonoids are compounds found in numerous fruits, herbs, root, stems, bark, flowers, grains, tea, and wine; their powerful anti-inflammatory properties help fight brain inflammation and brain fog.

The next time brain fog threatens to overwhelm your day, don’t just brush it aside as a lack of sleep, dehydration, or too much stress. While these things can certainly exacerbate brain fog, take a deeper look and make sure inflammation isn’t at the core.