Like the gut barrier, the blood-brain barrier is lined with one layer of cells that separate the blood from the brain. It only allows a few substances like oxygen, hormones, and certain cytokines in, while blocking out others.
When this protective layer is compromised, the brain is vulnerable to damage from chemicals, inflammatory cytokines, and immune cells. This causes brain fog (cognitive dysfunction), chronic fatigue, anxiety/depression, neurodegenerative diseases, and other neurological conditions.
In this post, we cover ways to protect the blood-brain barrier and repair it if you already suffer from a leaky brain.
How to Fix Leaky Brain at the Root Causes
1) Anti-Inflammatory Diet
Avoid Inflammatory Substances
The lectin avoidance diet is an elimination diet that helps you reduce inflammation and avoid substances that trigger your immune system. By reducing inflammation from foods, you reduce inflammation throughout the body, including the cytokines that disrupt the blood-brain barrier.
Avoiding inflammation from foods is especially important if you have a traumatic brain injury because brain injuries can directly cause leaky gut.
Avoid High-Calorie and High-Fat Diets
High calorie and high-fat diets increase leaky gut, which causes LPS (a bacterial toxin) to enter the bloodstream .
2) Normalize Blood Sugar
3) Deal with Infections and Toxins
Infections and toxins damage the blood-brain barrier. It is therefore important to kill off and clear these infections accordingly.
4) Reduce Stress
Stress induces leaky gut and induces overall inflammation .
In addition, acute stress activates brain mast cells that secrete proinflammatory cytokines that disrupt the BBB .
5) Sleep and Circadian Rhythm
Chronic sleep loss decreases glucose transport across the BBB, increases inflammation, and impairs BBB permeability .
6) Healthy Brain Circulation
Poor brain circulation reduces the amount of oxygen and nutrients available to the brain. This increases oxidative stress. When oxidative stress is increased in glial cells and pericytes, it damages the blood-brain barrier and the tight junctions [10, 11].
7) Reduce Homocysteine
High levels of homocysteine disrupt tight junction function and cause BBB dysfunction .
Read this post to learn more about testing for and lowering homocysteine levels.
8) Reduce Glutamate Levels
In the brain, glutamate is present in balance with GABA. Defects in the enzymes (GAD) that convert glutamate to GABA, such as from autoimmune attacks, increase glutamate levels.
Read this post to learn more about these enzymes and how to optimize them.
Reduce Dietary Glutamate
Typically, glutamate in the blood does not cross the blood-brain barrier. However, many people with a leaky blood-brain barrier may have brain symptoms in reaction to dietary free glutamate.
With the exception of monosodium glutamate, most foods that are high in glutamate are also high in histamine-like substances, so it is unclear whether the reaction comes from the glutamate or the histamine-like substances.
Blocking Glutamate Receptors
Substances that block glutamate receptors, such as memantine, are used as a treatment for neurological diseases that also involve high glutamate levels and leaky blood-brain barriers . These include Alzheimer’s, vascular dementia, and Parkinson’s disease.
9) Lose Weight (If Obese)
Obesity-induced inflammation also causes problems in the blood-brain barrier (BBB) .
It is, therefore, important to lose weight to repair the leaky blood-brain barrier.
Supplements That May Help Repair the Blood-Brain Barrier
There are several supplements that may be connected to repairing the blood-brain barrier:
1) Acetyl L-Carnitine
When mitochondria are damaged, dangerous oxygen types leak out into the cells and destroy them. ALCAR helps repair the BBB by reversing the mitochondria decay caused by the oxidative damage .
2) Alpha-Lipoic Acid
In rats, treatment with GPC in the dose of 150/kg per day partially reverses the changes in BBB caused by damage to brain vessels .
4) Angelica (Dong Quai) Extracts
In rats with a severe form of brain stroke that involves brain bleeding, treatment with a component extracted from Angelica sinensis, Z-ligustilide, reduced brain swelling and strengthened BBB .
Astragalus is often used in Chinese herbal remedies. Researchers have found injecting an astragalus extract through IV to rats that have suffered stroke strengthened the blood-brain barrier when compared to the control group of animals .
Astragalus, combined with ligustrazine, increased the level of proteins responsible for BBB strength, such as occludin and claudin, and decreased MMP9 .
It was shown that astaxanthin decreased inflammatory molecules and protected the BBB in rats that had brain bleeding .
Apigenin is a color compound naturally found in plants. Administration of apigenin in the dosage of 20 mg/kg in rats suffering from brain injury and bleeding in the brain blocked inflammatory proteins (TLR4 and cytokines) and increased tight junction proteins .
8) B12-B6-Folate Mix
11) Bitter Melon
Bitter melon (Momordica charantia) extract protects the blood-brain barrier (BBB) against disruption caused by a high-fat diet .
In mice that were fed a diet with a lot of fats, bitter melon extract prevented leaks in the brain and excessive activity of brain immune cells and decreased the concentration of inflammatory proteins .
Butyrate is often produced by bacteria in the gut .
In healthy mice, the lack of necessary butyrate-producing bacteria in the gut weakened the blood-brain barrier .
If germ-free mice (healthy mice that previously had no bacteria at the gut at all) are given those bacteria afterward, their BBB becomes stronger .
13) Chlorogenic Acid
Injection with 3 to 30 mg/kg of chlorogenic acid in rats with experimental stroke decreased the level of MMP-2 and MMP-9 .
Injection of 400 mg/ kg of citicoline into mice with traumatic brain injury strengthened the BBB and partially reduced brain swelling .
Collagen (type IV) is known to be important for BBB structure and function of the cell that forms it .
Curcumin in a nanoparticle format was reported to improve the state of the BBB better than traditional curcumin .
17) Vitamin D3
Vitamin D3 protects the BBB by increasing the level of BBB proteins occludin, claudin-5 ZO-1, and by blocking MMP9 .
Vitamin D supplementation appears to be protective in cases where the blood-brain barrier is disrupted because of inflammation from a high-fat and high-calorie diet .
However, personally, I’m more in favor of getting sun and calcitriol rather than supplementing with vitamin D3. Read this post to learn why.
18) Ellagic Acid
Ellagic acid decreased BBB permeability in rats with traumatic brain injury .
19) Fish Oil
Chemicals obtained from ginseng were also able to support the development of new nerve cells after stroke in rats .
21) Goji Fruit
In mice, pre-treatment with Goji fruit extract (10 mg/kg/day) before they experienced stroke prevented the leaks in the BBB and reduced glial cell inflammation .
In animals treated with hydrogen-rich water, fewer leaks from the brain were observed, and MMP 9 concentration was lower, which indicates improvement in the state of the BBB .
It also blocked a protein HMGB1, which is thought to drive traumatic damage in the body .
It also restores the proper function of the BBB in rats with experimental diabetes .
It also made the BBB stronger in pregnant rats that had high blood pressure .
In a cell-based study, melatonin pre-treatment protected rat brain blood vessel cells taken from inflammatory molecules .
It is known that melatonin is anti-inflammatory, and it is widely used to treat brain disorders .
28) Methylene Blue
29) Olive Leaf Extract
In a rat model of brain bleeding, oxaloacetate protected the BBB through blocking glutamate from damaging the BBB and brain .
31) Parthenolide (Feverfew)
In rats with brain artery blockage, a chemical parthenolide protected the BBB by lowering the content of inflammatory protein and increased the level of the BBB protein claudin – 5 .
Treatment of mice after stroke with pterostilbene in the dosage of 10 mg/kg protected against the BBB damage and brain swelling by decreasing the concentration of dangerous oxygen types .
Resveratrol is an antioxidant .
It stabilizes the BBB and protects it from damage .
In rats that have Alzheimer’s disease, resveratrol blocked MMP9 activities and increased the level of claudin-5, strengthening the BBB and protecting it from destruction .
35) Rosmarinic Acid
Rosmarinic acid protected against blood-brain barrier damage permeability in diabetic rats after stroke by lowering inflammation .
If Sulforaphane is given to rats before induction of a stroke, it prevents the destruction of brain blood vessels and the BBB by increasing the level of the antioxidant proteins Nrf2 and HO-1 [71, 72, 73].
Sulforaphane also reduced BBB dysfunction by decreasing inflammation proteins .
39) Ursolic Acid
Supplements That May Disrupt the Brain Barrier in Some Circumstances
L-Arginine can force the blood-brain barrier to open up .
Nicotine makes the BBB less strong by re-shuffling blood-brain barrier proteins responsible for keeping it together .
Do You Have a Genetic Susceptibility to Have a Leaky Brain?
Sometimes blood barrier issues are caused by infections, while other times a combination of genetics and your environment can be the issue.
The key genes that influence the blood-brain barrier include:
- Matrix metalloproteinases (MMPs)
- Tissue Inhibitors of Metalloproteinases (TIMPs)
- Tight junction proteins
- Genes that control oxidative stress
- Genes that control inflammation and susceptibility to autoimmunity
There might not be a direct study that tests the effects of each gene, SNPs, or mutations on the strength of the blood-brain barrier. However, we can infer the significance of these SNPs from the gene functions and their association with worsened brain disease/injury outcomes in humans.
Tight Junction Proteins
Claudin-5 is a tight junction structural protein. It is important for BBB strength. Variants in this gene are linked to risks of various diseases.
For instance, it was hypothesized that variants of CLDN5 inherited together with the HLA-DQB1 gene (the celiac disease gene) lead to schizophrenia .
This was corroborated by another study carried out among the Chinese population. It was shown that an SNP of CLDN5, rs10314, is associated with an increased risk of schizophrenia .
Another blood-brain barrier protein, P-glycoprotein, transports necessary chemicals through the BBB and protects it from unwanted molecules because it is selective .
Oxidative Stress Genes
In newborns, NOS3 in the cells that line the blood vessel in the brain can mitigate nerve damage due to a lack of oxygen during birth (hypoxic-ischemic encephalopathy) .
This is a disease of the disrupted blood-brain barrier.
rs1800779 and rs1799983 are not associated with the difference in hypoxic-ischemic encephalopathy.
Mutations in SOD1 are linked to familial ALS .
In addition, mice that have defective SOD1 function have the same leaky blood-brain barrier, blood-spinal cord barriers, and neurovascular units as ALS patients .
This variant is associated with leukoaraiosis (white matter lesions) after stroke, which may be linked to the worsened leaky brain after stroke .
Genes That Control Inflammation and Susceptibility to Autoimmunity
ApoE4 activates an inflammatory pathway in pericytes that disrupt the tight junctions, while ApoE2 and ApoE3 suppress this pathway .
Not surprisingly, ApoE4 is also linked to Alzheimer’s disease .
Alpha 2-Macroglobulin (A2M)
In addition, it is also linked to increased risk of complication following tissue plasminogen activator treatment .
This also predicts the outcome of post-ischemic stroke .
Drugs That Help Protect and Repair the Blood-Brain Barrier
Currently, the only conventional therapy to help improve the blood-brain barrier integrity is glucocorticoids (synthetic cortisone) treatments .
Glucocorticoids are generally the treatment for autoimmune disorders.
GM6001, also known as Ilomastat or galardin, is a broad-spectrum inhibitor of matrix metalloproteinases .
In mice with experimental autoimmune encephalomyelitis (EAE) (a multiple sclerosis model), 4 mg of GM6001 stopped the development of the disease .
Another group of synthetic MMP inhibitors, BB-1101 and BB-94, also helped repair the damage to BBB in mice that had their BBB damaged by lipopolysaccharide (a bacterial toxin) .
In rats with an injury to brain blood vessels, treatment with a protein involved in blood vessel activity, angiotensin Ang(1-7) protected their BBB .
Ang(1-7) blocked MMP9 and increased the concentration of TIMP-1 in the rats with brain injury and protected BBB from more damage .
Leaky Brain – Part Three of a Three-Part Series
You can read about the introduction to the blood-brain barrier and causes of the leaky brain in Parts 1 and 2.
- Part 1: Introduction to the Blood-Brain Barrier, Causes of Leaky Brain, and Resulting Diseases
- Part 2: Factors and Disease States That Cause Leaky Brain
- Part 3: How to Repair a Leaky Blood-Brain Barrier
Want More Targeted Ways to Combat Inflammation?
If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.
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