Neuro-inflammation in the brain from a leaky blood-brain barrier can cause mental health problems

Do You Have a Leaky Brain?
Is a Leaky Blood-Brain Barrier part of your mental health problem?

© PeterSmithUK.com (#2)

The blood-brain barrier is a specialist membrane that surrounds the brain, it’s supposed to prevent toxins, bacteria and foreign proteins such as gluten from entering the brain. When the blood-brain barrier allows undesirable substances to enter the brain it can trigger inflammation that can damage key structures in the brain involved in depression, bipolar and other mental health problems; it can also cause a ‘foggy’ brain. In this section I’ll tell you how you can test the health of your blood-brain barrier and if it leaky how to fix it.

How to test the integrity of your blood-brain barrier

You can perform a basic test on your blood-brain barrier yourself at home, you can buy the neurotransmitter GABA as a supplement and take 1000 mg in the evening when you’re not going to go out or drive a car. When you take a GABA supplement and it is absorbed from the digestive system into the systemic blood it should not be able to get into across the blood-brain barrier and enter the brain; this is because the GABA molecule is very slightly too large to pass through a healthy blood-brain barrier.
 
When the blood-brain barrier (BBB) is excessively permeable or leaky however GABA from supplements can cross the BBB and will cause a rapid rise in GABA levels in the brain. Most people would experience this as a noticeable feeling of relaxation, sedation and a reduction in feelings of anxiety however paradoxically some people actually experience a temporary increase in anxiety or even a feeling of panic, this can be because their GABA synapses and pathways are already at the point of exhaustion and even a little bit of increased stimulation quickly leads to a temporary exhaustion and depletion. If you experience this paradoxical reaction because your GABA pathways are at the point of exhaustion you may initially respond badly to treatments aimed at increasing GABA activity in the brain, the solution is to aggressively reduce neuro-inflammation (inflammation in the brain) by treating any and every source of inflammation, see how to reduce neuro-information.
 
In terms of the GABA challenge test the important point is if feel any of the above effects it implies you have a leaky brain and you should fix it.
 
If you pass the test i.e. don’t feel anything on 1000 mg I would actually repeat the test the following night with 1500 mg just to be doubly sure. Do not engage in anything that you wouldn’t do if you were under the influence of alcohol or sleeping pills like drive a car during the test, ideally do the test in the evening just in case it produces a strong relaxation effect so that you have ample time to sleep it off overnight.
 
If you fail the GABA challenge test above you should not keep taking GABA because of the risk that repeatedly flooding the brain with GABA could desensitise your GABA synapses, the balanced way to increase GABA is to take substances like ashwagandha and theanine that readily pass the blood-brain barrier and stimulate the brain to make its own GABA and lithium orotate and passionflower that increase GABA sensitivity by increasing receptor sites within GABA synapses. See GABA Deficient Anxiety
 
A personal anecdote is I used to occasionally take GABA to sedate my brain counteract bipolar hypo-mania long before I knew that GABA should not be able to cross the BBB and that it could be used as a test the health of the blood-brain barrier. I found that GABA did work for me but was unpredictable, sometimes producing strong sedation and other times no noticeable effects at all. I now understand that this means the health of my blood-brain barrier was borderline and when the level of inflammation in my body was elevated my blood-brain barrier was leaky enough to allow GABA from supplements to enter my brain and other times my blood-brain barrier worked should; today GABA has no effect on me.
 

The importance of the blood-brain barrier in mental health

The blood-brain barrier is a protective membrane that separates the brain from the rest of the blood in the body, its job is to prevent unwanted substances from entering the brain. When healthy the blood-brain barrier blocks everything except nano-sized particles and a few desirable larger molecules are specifically allowed to pass through, even antibodies made by our own immune system are too big to pass through the blood-brain barrier, so the brain has its own separate immune system; furthermore the blood-brain barrier can make it difficult to administer medicines both pharmaceutical and natural to the brain, in my line of work I always have to ask the question does this medicinal substance cross the blood-brain barrier.
 
By and large the blood-brain barrier prevents viruses and bacteria from entering the brain, this is why infections in the brain are actually quite rare; some notable exceptions to this are the bacteria that cause meningitis, syphilis and Borrelia that causes Lyme disease, these smart pathogens release inflammatory chemicals called cytokines that cause inflammation and increased permeability in the blood-brain barrier to gain access to the brain.
 
The blood-brain barrier also prevents many toxins and pollutants from entering the brain it does not however do a good job of preventing toxic metals such as mercury[i], lead or cadmium from entering the brain.
 
Mercury is a highly penetrating substance, a dentist that specialises in safe amalgam filling removal once told me that the mercury vapours released when you drill an amalgam filling can penetrate a man-made rubber dam during the drilling process, inhaled and absorbed, which led to the development of new safer extraction techniques.
 
Besides obvious things such as bacteria and viruses the blood-brain barrier should keep toxins, pollutants and large half-digested food molecules such as gluten from wheat out of the brain. Our digestive system attempts to break down large protein molecules into individual amino acids (the building blocks of proteins), we then absorb the amino acids and build up into human shaped proteins but the process of breaking down foreign proteins into amino acids is never hundred percent complete or successful resulting in half-digestive protein molecules and strings of amino acids. Ideally the walls of our digestive tract should not allow these half digestive protein molecules to enter the bloodstream but when the walls of the digestive tract are excessively permeable then half-digested proteins pass through into the blood, this is sometimes called leaky gut syndrome. If the blood-brain barrier is also leaky then the half-digested proteins can make it all the way from digestive system into the brain and trigger the brains immune system and inflammatory response. Generally treating a leaky blood-brain barrier should go hand-in-hand with treating a leaky gut.
 

The role of hidden neuro-inflammation in mental health

There’s a growing understanding that mental health problems including depression, bipolar syndrome, OCD and anxiety are caused by diminished function in specific parts of the brain that control mood and mental health. In the affected areas there is literally a loss of synaptic connections and inflammation is thought to be the primary factor that causes this; a loss of serotonin carrying synapses in the limbic system that controls our mood for example result in depression. This is the new BDNF hypothesis of what causes mental health problems.
 
It can be very upsetting to hear that you may have a loss of synapses in your brain, so let me immediately reassure you that the brain is constantly remodelling itself losing and growing new connections this is called neuroplasticity and it can be stimulated and increased so you can regrow and repair the function in the affected parts of your brain. To learn how to do that see: How to regenerate your broken brain
One of the key goals to achieve to increase neuroplasticity and overcome a mental health problem is to eliminate neuro-inflammation.
 
A leaky blood-brain barrier is not the only thing that can cause neuro-inflammation, other things that can independently cause neuro- inflammation include a pro-inflammatory diet, elevated cortisol production from overactive stress responses (a common finding in people with mental health problems), elevated blood sugar/insulin levels, drug and alcohol use although the latter also weakens the blood-brain barrier causing it to become leaky. Furthermore when a leaky blood-brain barrier is combined with leaky gut syndrome and an unhealthy bowel flora it increases the ability of the latter to cause neuro-inflammation.
 
In my practice a big part of my treatments is to eliminate neuro-inflammation by working on everything just mentioned.
 

Understanding inflammation

It’s common to think of inflammation is a bad thing but a short appropriate burst of inflammation is part of a healthy immune response, inflammation helps the affected body part to fight infection, clear toxins and repair itself.
 
Inflammation can exist in an extreme form with tell-tale signs including swelling, fever, pain and clinical markers such as elevated CRP in the blood; in the brain extreme inflammation is extremely dangerous and should be treated immediately with aggressive anti-inflammatory drug therapy such as steroids.
 
Alternatively inflammation can exist in a low-level in the background without producing any obvious signs this can be referred to as hidden inflammation; one of the big problems with low-level background inflammation is that it hidden and so may persist unnoticed for years chipping away at the health of your brain. When hidden inflammation persists over a long period of time it can damage key parts of the brain that control mood and cause at least contributes to mental health problems. Hidden inflammation can also be a central component of degenerative diseases including dementia and Alzheimer’s disease.
For more information inflammation see: How to Reduce Neuro Inflammation to Treat Depression and Mental Health Problems
 

The brain has a separate hyper-sensitive immune system

Two important things to note about the brains immune/inflammatory response are firstly because the brain is so important it’s defensive immune/inflammatory responses are very easily provoked and secondly once provoked they remain active for a very long time. The combination of features is why a leaky blood-brain barrier can be so detrimental, for example just a small seemingly benign provocation from the entry of gluten into the brain can provoke neuro-inflammation that could last for days; gluten is notorious for being able to provoke a particularly aggressive immune/inflammatory response. I recently treated a patient who identified wheat is a clear trigger for her bipolar mania.
 
When we have a leaky blood-brain barrier and leaky gut syndrome the immune/inflammatory response may switched on literally every time we eat from half-digested foreign proteins entering the brain; the result would be continuous persistent neuro-inflammation wreaking havoc on delicate brain structures.
 
There’s also growing evidence that the toxins produced by an unhealthy bacterial colony in our intestines can be a significant contribution to neuro-inflammation if they are allowed to enter the brain, there are often so many supplements to take when you’re using natural therapies to improve a mental health condition that is easy to overlook the health of the bowel flora but it can have a significant effect and it’s worth taking probiotic supplements.
 
A personal anecdote is that for many years I used to eat wheat once a week, if I ate it twice a week I would get a pressure headache at the back of my head feel very slightly depressed and very grumpy; at that time I didn’t understand the significance of this and for over a decade enjoyed my one sandwich a week. I now understand that that one serving of wheat provoked inflammation in my brain that lasted several days and if I had a second serving of wheat before the inflammation from the previous serving had completely subsided the inflammatory effects were combined and compounded on top of each other to produced sufficient neuro-inflammation to give me a headache and psychological symptoms. Looking back I regret provoking low-grade hidden inflammation in my brain for several days each week. Today I avoid wheat and use rye/spelt bread made with sourdough rather than modern yeast which as far as I can tell does not produce any neuro-inflammation, I follow an anti-inflammatory diet and I have improved the health of both my digestive tract and blood-brain barrier.
 

What makes the blood-brain barrier become leaky?

The main thing that makes the blood-brain barrier become too permeable or leaky is inflammation in the blood-brain barrier itself. Just to be clear inflammation in the blood-brain barrier causes the blood-brain barrier to become too permeable or leaky which then allows undesirable substances to enter the brain which then triggers the brains defensive immune/inflammatory response and this results in increased neuro-inflammation.
 
The blood-brain barrier is just another part of the body and when there is widespread systemic-inflammation in the body in general it can inflame the blood-brain barrier and therefore from a practical treatment point of view to heal a leaky blood-brain barrier we have to eliminate systemic-inflammation throughout our whole system. Systemic-inflammation can be caused by a poor pro-inflammatory diet, over-active stress responses, pollution, toxins from and friendly bacteria in the intestines, leaky gut syndrome, allergies, autoimmunity, et cetera.
 

Alcohol and yeast overgrowth (Candida)

Excessive consumption of alcohol specifically weakens the blood-brain barrier because one of the breakdown products of alcohol is acetaldehyde and this specifically damages the blood-brain barrier. Acetaldehyde is also produced from yeast (Candida) overgrowth, the worst thing in the diet to promote the overgrowth of yeast is sugar.
I have a question if anyone can answer this for me: does yeast overgrowth produce acetaldehyde by fermenting sugar in the blood into alcohol and then the alcohol breaks down into acetaldehyde or is the acetaldehyde produced independently of alcohol production and breakdown?
 
The clinical significance here is that if you have abused alcohol and or you have a yeast/candida overgrowth you should suspect you have a leaky blood-brain barrier and treated just in case.
 

How to heal a leaky blood-brain barrier

As just mentioned above systemic-inflammation in the body is a primary cause of a leaky blood-brain barrier, the practical implication of this is that the key thing to do to heal a leaky blood-brain barrier is reduce systemic-inflammation.
 
Two really big things to do to reduce systemic-inflammation are:-
  • Follow the anti-inflammatory diet and
  • Dampen down overactivity in the HPA axis.

 Additional measures to reduce systemic-inflammation and heal the BBB include:-

  • Drink no alcohol for the duration treatment.
  • Eliminate leaky gut syndrome by following the anti-inflammatory diet and if necessary treating and eliminate SIBO (small intestine bacterial overgrowth) and intestinal yeast (Candida) overgrowth
  •  Improve the condition of your intestinal microbiota (the bacteria) primarily with a diet containing a large amount of diverse polyphenols and fibre, if necessary thoroughly cleanse the bowels first then repopulate with friendly bacteria.
  • Consume copious amounts of chicken stock, this promote regeneration of both the blood-brain barrier and the intestinal wall. See How to Make a Healing Chicken Stock
  • Remove amalgam fillings from your teeth and detoxify heavy metals
  • Eat organic foods because they contain less pesticide residues.
  • Improve the quality of your sleep, because sleep deprivation particularly inadequate the rapid eye movement sleep that occurs in the second half of the night when we dream and learn new memories has been shown to degrade the integrity of the BBB[ii][iii]. For techniques on how to improve your sleep see my book: Sleep Better with Natural Therapies by Peter Smith available from Amazon.
  • Improve your oral hygiene, particularly your gum health with regular flossing and if necessary the use of the new oral pro/friendly bacteria lozenges. Believe it or not oral bacteria can be a significant source of inflammation in the body, if you have poor gum health consult with an oral hygienist before embarking upon the use of dental floss to avoid initially releasing dangerous bacteria into your bloodstream.
 

Supplements to heal a leaky blood-brain barrier

Only a few supplements are known to specifically improve the health of the BBB they include acetyl-L-carnitine, a specific form of B5 called pantethine and melatonin.
 
Acetyl-L-carnitine boosts the production of antioxidant enzymes that protect and heal the BBB[iv]. Unfortunately there some studies have suggested that if carnitine is regularly consumed it feeds and builds up a particular bacteria in the intestines and these bacteria produce a chemical from the carnitine that damages our arteries; the suggestion is that the inherently high level of carnitine found in meat may actually be the mechanism whereby meat consumption increases the risk of heart disease. The evidence that this is the case still limited furthermore in the animal studies the form of carnitine look at was specifically L carnitine as opposed to acetyl-L-carnitine which can help heal the BBB, nevertheless I don’t recommend consuming something that could cause arterial damage and contribute to heart disease which is the leading cause of death in developed countries especially at high doses. I hope that further studies will show that acetyl-L-carnitine is not harmful to arterial health because carnitine is useful for depression, cellular energy, weight loss and healing the BBB.
 
Pantethine boosts the production of the key enzyme that clears acetaldehyde from the brain and therapeutic use of pantethine has been shown to strengthen the BBB so significantly it was able to prevent malaria from entering the brain (you can easily find references to this online).
 
Therapeutic doses start at 1000 mg twice a day with meals.
 
Melatonin besides being a potent free radical scavenger and inherently anti-inflammatory, melatonin has been shown to protect the integrity of the BBB, however the dosage used in the animal studies was enormous way beyond any human would supplement [v]. I’ve accumulated quite a lot of both personal and professional experience with the use of melatonin supplements, I have observed that at high doses above 2-3 mg many people experience a significant increase in the intensity their dreams even to disturbing levels and by personal experimentation one can work out a dosage that enhances and prolongs the rapid eye movement dreaming sleep phase.
 
Resveratrol is an antioxidant/polyphenols naturally occurring in foods such as red grapes, red wine and raspberries that has numerous health benefits especially the health of the brain, it has also appears to restore the integrity of the BBB and reduce neuro inflammation[vi].
 
High strength resveratrol is expensive, a good value for money resveratrol containing product I take myself and regularly prescribed Doctor’s Best French Red Wine Grape Extract 2 to 4 capsules a day, the same company also make quite good value resveratrol, if you are not limited by the expense Life Extension make very high quality resveratrol supplements; you can find all these products on iherb.com
 
Remember alcohol specifically weakens the blood-brain barrier so abstain from alcohol while you are treating a leaky BBB.
 
In addition to the above remedies I would recommend simultaneously taking high doses of antioxidants supplements that reduce systemic-inflammation to help create the conditions in the body conducive to repairing the blood-brain barrier.
 
My recommended combination:-
Rutin Now Foods one capsule twice a day
Ascorbyl palmitate 1000 mg twice a day
Curcumin plus piperine (there are lots of curcumin products available but only very few deliver significant levels of curcumin to the brain) I recommend Super Bio Curcumin from Life Extension with a separate piperine.
Vitamin E (gamma E) 400 IUs twice a day
Alpha lipoic acid 150 to 600 mg twice a day
NAC cysteine 1200 mg once or twice a day.

REFERENCES:

[i] American Chemical Society. "Mercury Can Jump Barrier That Keeps Toxins Out Of Brain." ScienceDaily. ScienceDaily, 9 September 1999. <www.sciencedaily.com/releases/1999/09/990909080318.htm>.
[ii] J Immunol Res. 2016;2016:4576012. Epub 2016 Sep 21. Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link. Hurtado-Alvarado G1, et.al. PMID: 27738642 PMCID:  PMC5050358 DOI:10.1155/2016/4576012
[iii] Sleep Restriction in Pairs Blood-Brain Barrier Function PMID:  25355222 PMCID:  PMC4212067 DOI:  10.1523/JNEUROSCI.2111-14.2014
[iv] Haorah J, Knipe B, Persidsky Y. Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: Novel protective approach. Free Radic Biol Med.  2011 June
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA.
[v] PLoS One. 2016; 11(5): e0154427. Published online 2016 May 6. doi:  10.1371/journal.pone.0154427
PMCID: PMC4859489 Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition Himakarnika Alluri, Rickesha L. Wilson, et al
[vi] Georgetown University Medical Center. "Resveratrol appears to restore blood-brain barrier integrity in Alzheimer's disease ScienceDaily 27 July 2016.
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Hi my name is Peter Smith I specialise in treating and coaching people how to live well with mental health problems, digestive health problems/IBS, sleep problems and type II diabetes using natural therapies.
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