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What Causes Leaky Brain?
Repairing the Blood Brain Barrier

It is valuable to discuss the different aspects of a Leaky Brain and how to make the blood-brain barrier whole

Inside the Blood-Brain Barrier

The brain, with its numerous functions critical to life, is protected from potentially harmful substances in the bloodstream by a fence-like structure called the Blood-Brain Barrier.

The Blood-Brain Barrier, or BBB, is a single-layered lattice of cells joined together by tight junctions that keep most substances out and allow few substances into the brain.

Toxic substances typically kept out include heavy metals, pesticides, pcbs as well as damaging proteins while substances allowed in are oxygen, hormones, and nutrients.

What is a Leaky Brain?

A brain is considered leaky when the Blood-Brain Barrier has been compromised in some way. . If the tight junctions become loose or broken, the BBB becomes more permeable and harmful substances can leak in. Harmful chemicals and proteins can damage the brain leading to inflammation; in other words, a Leaky Brain is an Inflamed Brain.

What Causes Leaky Brain?

The profound connection between the brain and the gut cannot be underestimated as research repeatedly confirms that microbes living in the gut affect the brain both positively and negatively.

In fact, the stomach and small intestine contain a lining similar to the blood-brain barrier which also keeps harmful substances from entering the gut.

Therefore, many of the same factors that cause a leaky gut—poor gut health, unhealthy diet, food intolerances, food sensitivities, toxins and infections—can also create a leaky brain.

Studies from Harvard³ show that wheat creates leaky gut in everyone as a protein called gliadin, found in wheat and gluten, increases another protein, zonulin. Zonulin weakens the tight junctions of the gut lining and BBB thereby contributing to leaky gut and leaky brain.

Five causes of Leaky Brain

  1. Gut Dysbiosis (infections)
  2. Leaky Gut
  3. Autoimmune Disease
  4. Mental Health Conditions
  5. Stress & Vagus Nerve Dysfunction

All five of these categories have inflammation as a basis for the problem, yet they become even more problematic in the following disease states:

  • Bacterial infections deteriorate the BBB allowing bacteria into the brain where they do not belong
  • CIRS and Mold toxins trigger inflammation, promote oxidative damage in the brain, and disrupt the BBB
  • Excess glutamate overstimulates nerves causing the BBB to breakdown increasing permeability to potentially harmful agents
  • Free radicals benefit inflammatory as well as aging processes further damaging the BBB
  • High blood sugar and diabetes represent dramatic changes in blood sugar which produce oxidative stress and inflammation
  • Elevated homocysteine, seen in individuals living with heart disease, autoimmune disease, cancer, and neurodegenerative disease or those who survive a stroke, changes tight junction function and prevents the BBB from functioning properly
  • High-fat, high-calorie diets and obesity increase oxidative damage and deprive the brain of oxygen
  • Hypoxia places the body in a condition of insufficient oxygen supply thereby further damaging the BBB’s tight junctions
  • Liver damage releases a signal called MMP9 into the bloodstream that increases BBB permeability
  • Low quality sleep interrupts the sleep-wake cycle interrupting the uptake of nutrients and offload of toxins while increasing inflammation

Mental Health Conditions and Leaky Brain

Whilst it is more obvious that leaky brain causes inflammation which then drives mental health conditions, it is less known that mental health conditions can also drive inflammation and leaky brain.  The contributing factors could be:

  • Toxins 
  • Stress Hormones
  • Neurotransmitters
  • Stress

The Brain-Gut Axis: The Vagus Nerve Connection

The brainstem connects to the vagus nerve, which in turn connects to all the digestive organs. The brain sends signals through the vagus nerve to the organs. The organs also send signals through the vagus nerve to the brain.

The vagus nerve initiates many important digestive functions such as stomach acid secretion, enzyme production, gallbladder function and intestinal motility.

If there is poor brain communication to the vagus nerve there can be many negative effects including:

  • Chronic inflammation
  • Poor digestion
  • Leaky gut,
  • Inflamed brain
  • Depression and related mental health conditions

Gut–brain axis. Leaky BrainWhat are the Signs and Symptoms of a Leaky Brain?

Leaky Brain manifests as multiple signs and symptoms, so pay attention to these as opposed to ignoring them:

  • ADD/ADHD/Autism spectrum disorders
  • Brain fog or difficulty concentrating
  • Chronic fatigue that does not improve with rest or sleep
  • Headaches or migraines that come on suddenly become worse with standing, and grow more severe as the day progresses
  • Memory loss or another cognitive decline which may lead to dementia and Alzheimer’s disease
  • Mood disorders, particularly anxiety, depression, and schizophrenia
  • Peripheral neuropathy or muscular sclerosis
  • Seizures

It is important not to ignore these signs and symptoms because those living with Leaky Brain are at an increased risk of developing neurological or psychiatric conditions. Many of these conditions are considered signs and symptoms of Leaky Brain, but they may also be counted among the causes of Leaky Brain.

Leaky Brain Can Cause:

  • Reduced mental ability, difficulty concentrating or multitasking, short and long-term memory loss, collectively referred to as brain fog, via prolonged activation of mast cells
  • An increase in VCAM-1 adhesion molecules which allow beta-amyloid peptides to accumulate in the brain forming plaques around nerve cells interrupting their function and blocking their nutrient supply, a process more commonly known as Alzheimer’s disease.
  • Changes in the transport of molecules between the brain and bloodstream which allow Huntington Disease to progress and decrease the number of proteins available to form tight junctions within the BBB.
  • Brain inflammation and oxidative damage, increasing the risk for schizophrenia, by destroying BBB-supporting, astroglial cells and triggering the release of toxic inflammatory agents further breaking down the BBB.
  • Insufficient blood flow to the brain as well as abnormal brain activity, as seen in patients living with depression, because extended periods of brain inflammation disable adequate nerve function similar to schizophrenia.

Diseases that Contribute to Leaky Brain include:

  • Multiple Sclerosis – People with this disease have high levels of MMP9 which damages nerves along with significant albumin in the brain which promotes inflammation and makes nerves more susceptible to glutamate toxicity.
  • Autism – More of a reciprocal relationship, Autism can cause Leaky Brain and vice versa; BBB permeability is higher in people diagnosed on the Autism spectrum thereby tolerating mast cell activation and inflammation.
  • Seizures & Epilepsy – Seizures interrupt BBB function, and prolonged seizures permit inflammation and albumin to rise in the brain increasing BBB permeability which can lead to chronic epilepsy.

Are there Diagnostic Tests for a Leaky Brain?

With the assistance of an Integrative Health Practitioner, individuals can screen for their overall risk of Leaky Brain with one or more of the following tests:

  • GABA-EEG
    Gamma-aminobutyric acid, or GABA, is a neurotransmitter that inhibits neural impulses. Once believed not to cross the BBB at all, recent research indicates that GABA crosses the BBB in small quantities. So, with the assistance of an EEG, the amount of GABA crossing the BBB (or the rate at which it crosses) can reveal the overall leakiness of the BBB
  • Spectrophotometry and Optical Imaging
    Albumin, a prominent protein that circulates in the blood, cannot cross the BBB under healthy conditions. A dye called Evans Blue which only binds and dyes albumin can be injected into the bloodstream. Then, spectrophotometry reveals the amount of Evans Blue dye accumulated in the brain, if any. To assess the full amount of BBB leakage, optical imaging is preferred following the dyeing process
  • MMP9 Level Evaluation
    Matrix metalloproteinases, or MMPs, are enzymes that break down the peptide bonds that hold proteins together. They contribute to BBB damage by breaking the tight junctions that maintain BBB integrity. MMP levels elevate following tissue damage in the liver or brain (i.e., stroke, traumatic brain injury). Testing for high MMP in the blood can disclose a patient’s likelihood of Leaky Brain. As a preliminary treatment, the patient can begin taking an MMP inhibitor to limit BBB damage
  • Genetic Testing
    Genetic testing can reveal if someone is innately inclined to develop a Leaky Brain. Alterations in any of the genes that express tight junction proteins, control oxidative stress, regulate inflammation, or fight autoimmunity can cause Leaky Brain. Knowing such altered genes are present can even further direct an individual’s treatment options and choices
  • Occludin and Zonulin
    Occludin and zonulin are two proteins that help determine both gut lining and blood-brain barrier permeability. Elevated antibodies against occludin and zonulin are another way to gauge leaky brain syndrome.

Additional diagnostic measures that can be explored involve testing with horseradish peroxidase (HRP), radiolabeled markers with sucrose or inulin, other blood proteins (fibrinogen and immunoglobulin), sodium fluorescein, and dextran. An Integrative Health Practitioner can provide more information on all these tests.

How to Reverse and Heal a Leaky Brain – Stop, Start, and Seek

Treating a leaky brain starts by healing a leaky gut. This involves eliminating all the causative factors of leaky gut and leaky brain and then adding dietary and lifestyle factors that support brain health.

Following these steps will lower inflammation in the body and brain, maximize the transport of oxygen, glucose, and other nutrients into the brain, facilitate better removal of toxins out of the brain, reduce oxidative stress, and help rebuild tight junctions to restore the integrity of the BBB.

STOP:

  • Consuming gluten and foods that the individual cannot tolerate
  • Including sugar and processed foods in meals
  • Ignoring stress
  • Allowing bacterial and viral infections to fester before getting treatment
  • Drinking alcohol in excess
  • Exposure to environmental toxins in air, water and food

START:

  • Detoxifying the body of pesticides,  and heavy metals
  • Taking in probiotic foods to keep the gut balanced
  • Eating essential fatty acids, which are vital for the brain, including avocado, coconut oil, flaxseed, hemp seed, oily fish, pumpkin seeds, and walnuts
  • Reducing inflammation through the diet – see our article Understanding Leaky Gut Syndrome
  • Making quality sleep a priority
  • Reducing psychological and emotional stress through exercise, meditation, chanting/song

SEEK:

  • Supplements that help repair the BBB, (do seek the support of an integrative health practitioner) including:
    • Acetyl L-Carnitine, Alpha-Lipoic Acid, Alpha-GPC
    • Angelica (Dong Quai) Extracts, Astragalus, Astaxanthin, Apigenin
    • B12-B6-Folate Mix, Berberine, Bitter Melon, Butyrate
    • Catechins, Chlorogenic-Acid, Citicoline, Collagen, Curcumin
    • Vitamin D3, Ellagic Acid, Fish Oil, Ginseng, Goji Fruit
    • Hydrogen, Licorice, Luteolin, Lycopene
    • Myoinositol, Magnesium, Melatonin, Methylene Blue
    • Olive Leaf Extract, Oxaloacetate, Parthenolide (Feverfew)
    • Progesterone, Pterostilbene, Resveratrol, Rosmarinic Acid
    • Shilajit, Selenium, Sulforaphane, Ursolic Acid
  • Therapeutic medications that repair the BBB, like:
    • Glucocorticoids which increase anti-inflammatory proteins in the brain
    • MMP Inhibitors which inhibit MMP function and help rebuild the BBB
    • Angiotensin which blocks MMP9 increases anti-inflammatory proteins and protects the BBB from further damage

Special Treatment for People with Multiple Sclerosis

Steroid hormone treatments, such as methylprednisolone, have proven helpful in reducing MMP9 levels in the central nervous system. Such therapies also prevent BBB leakage, demonstrate BBB strengthening effects, and decrease brain inflammation by lowering the number of circulating immune cells.

Special Treatment for People with Seizures and Epilepsy

Anti-epileptic, anticonvulsant drugs, microRNA treatments, and mTOR inhibitors are potential forms of treatment exclusively for their ability to prevent or limit seizure activity. While more research is needed, in theory reducing seizure events will limit the spread of inflammation as well as albumin leakage into the brain allowing BBB tight junctions time to repair.

It is never too early to take measures to prevent Leaky Brain nor too late to take steps to fight Leaky Brain.

The sooner diet and lifestyle align to support gut health as well as brain health, the sooner the Blood-Brain Barrier will regain it’s full protective function and prevent Leaky Brain.

References

  1. Anyia, A. (2018). Leaky brain: Signs, symptoms, causes, treatments and more. Retrieved from Consumer Health Digest at https://www.consumerhealthdigest.com/brain-health/leaky-brain.html
  2. Ball, K. (2018). Could your leaky gut be causing a leaky brain? Retrieved from Mr Vitamins at https://www.mrvitamins.com.au/news/digestion/could-your-leaky-gut-be-causing-a-leaky-brain/
  3. Fasano, A. Zonulin, regulation of tight junctions, and autoimmune diseases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384703/
  4. Cohen, J. (2017, October). What is the blood-brain barrier? Causes and tests for a leaky brain. Retrieved from Self-Hacked at https://www.selfhacked.com/blog/blood-brain-barrier-causes-tests-leaky-brain/
  5. Kent, J. (n.d.) 7 Tips for reversing leaky brain syndrome. Retrieved from Mind Body Network at https://mindbodynetwork.com/article/7-tips-for-reversing-leaky-brain-syndrome
  6. Lopez-Ramirez, M. A., Wu, D., Pryce G.,…Romero, I. A. (2014). MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. The FASEB Journal, DOI: 10.1096/fj.13-248880
  7. Perlmutter, D. (2018). What on earth is a leaky brain? [Video file]. Retrieved from https://www.drperlmutter.com/leaky-brain/
  8. What is the Gut-Brain Axis? Retrieved from https://empoweredsustenance.com/gut-brain-axis/
  9. Signs you might have a leaky brain. https://www.mindbodygreen.com/0-20800/signs-you-might-have-a-leaky-brain-what-to-do-about-it.html