Do you need to take the Leaky Brain Challenge? Read on to find out.

The most disturbing thing I see in regards to Hashimoto’s is that although people’s TSH may be managed with thyroid hormones, their immune dysregulation goes unchecked. This leaves other areas of the body vulnerable to attack, the most profound being the brain.

There are three ways Hashimoto’s can affect the brain. First, many people with Hashimoto’s also have an autoimmune attack against their nervous system. On a blood test this can be identified by positive antibodies to neurological tissue.  Second, unrelated to an autoimmune attack against the nervous system, the inflammatory response generated by Hashimoto’s can activate the brain’s immune system, hence promoting inflammation in the brain. Third, Hashimoto’s can lead to low thyroid hormones, which are necessary to dampen the brain inflammation caused by the previous two factors.

Depression, fatigue, and brain fog

It’s important to know that we all experience brain degeneration on an ongoing basis. A more common term for accelerated brain degeneration is simply known as aging. The trick is to prevent the brain from degenerating any faster than it has to.

Unfortunately, it is very common to see advanced brain degeneration in long-term, unresolved Hashimoto’s cases, with the most common symptoms being depression (from decreased firing of the frontal cortex), fatigue (from brain fatigue due to neurodegeneration), and brain fog (from brain inflammation).

True, these are also symptoms of hypothyroidism, but in some cases, particularly when the condition is long standing or still persistent despite successful management of thyroid levels, the impact of an unresolved thyroid condition on the brain should be investigated.

How Hashimoto’s affects the brain’s immune system

The brain is made up of two types of cells: neurons and microglia cells. Neurons are responsible for communication within the brain and everything we associate with brain activity, such as our intelligence, emotions, and the ability to automatically breathe, digest or maintain a heartbeat.

The microglia cells are the brain’s immune cells. It’s their job to react to foreign invaders, clean up debris and plaque, and dissolve dead neurons. The microgia are necessary for optimal neuronal communication and healthy brain function.

Although microglial cells function as the brain’s immune system, they are unlike the immune system in the rest of the body. When a virus or bacteria invades your body, the body’s immune system orchestrates a comlex and multi-faceted response, as described briefly in Chapter Three of my book. For instance, once an antigen (a foreign invader) is successfully dispatched, the immune system’s T-suppressor cells call off the attack and send the troops home.

Not so with the brain’s immune system. If an antigen makes its way into the brain, there is no complex orchestration, but rather an all-out assault by the brain’s microglial cells on the invader and, as a consequence, inflammation and degeneration of surrounding brain tissue. What’s worse is that there are no T-suppressor cells to call off the attack, and the glial cells, in their unrestrained assault, create brain inflammation and chew up brain tissue in a degenerative cascade.

Hashimoto’s is a double whammy for the brain

Unfortunately, Hashimoto’s activates microglia cells in two ways.  First, thyroid hormones are integral to brain health, and Hashimoto’s can lead to low thyroid hormone status. Thyroid hormones dampen overactivity of the microglial cells, thus preventing or slowing down this cascade that causes inflammation and degeneration in the brain.(1-8)

Second, the inflammatory response caused by Hashimoto’s increases the activity of the brain’s microglia cells, hence promoting brain inflammation.(9)

So failing to address the autoimmune attacks of Hashimoto’s is a double whammy on the brain — the inflammation caused by Hashimoto’s increases microglial activity, while low thyroid hormone status fails to adequately dampen the microglial cells.

The effect of Hashimoto’s on the blood-brain barrier

The microglia cells not only make up more than half of the total mass of the brain, but they also make up the blood-brain barrier, a thin barrier that lines the brain and allows necessary, nano-sized substances to pass through. The blood-brain barrier is important for keeping antigens (foreign invaders, such as viruses or bacteria) and environmental toxins out of the brain.

Unfortunately, the blood-brain barrier can develop “leaks” for a variety of reasons, including poor blood-sugar stability (particularly insulin resistance),(10) chronic stress,(11) chronic inflammation,(12) poor gut health, poor diet with unhealthy fats,(13) and unchecked autoimmune activity, such as Hashimoto’s disease (alcohol and high homocysteine are other recognized factors(14-16)). If you are familiar with leaky gut, as discussed in the book, then you’ll understand leaky brain, as both the gut and the brain are immune barriers vulnerable to the same problems.

When the blood-brain barrier develops leaks, bad guys get in, the microglial cells go nuts, and a whole lot of brain tissue gets chewed up. This creates inflammation, which in felt in some as “brain fog,” and leads to accelerated brain degeneration.

The Leaky Brain Challenge

How do you know if your blood-brain barrier is leaky? A simple and easy way to find out is to do Blood-Brain Barrier Challenge. To do this, simply take 1000 mg of straight GABA (not GABA precursors such as theanine).

GABA is a neurotransmitter synthesized in the brain and is responsible for calming or inhibiting over activity. Although some companies sell GABA supplements, the reality is the GABA molecule is too large to pass through an intact blood-brain barrier. The fact that this supplement sells so well is a testament to the integrity of the average American’s blood-brain barrier.

So, if several hours after taking 1000 mg of GABA, you feel calm, relaxed or sleepy, you know that GABA, a molecule too large to pass through the blood-brain barrier, has nevertheless made it into your brain and is performing its calming duties. This means your blood-brain barrier has become compromised and your brain is highly susceptible to the immune rampages I discussed above.

Some people, instead of feeling relaxed, will find GABA makes them feel more anxious or jittery. There are other reasons for this that will be discussed in my next book, however any reaction at all indicates a leaky brain barrier.

If you felt no change after taking GABA, that is a good sign that your blood-brain barrier is intact and functioning well. (For accurate results, be sure to take this test during the day and not at bedtime.)

What to do about a leaky brain barrier

Addressing the areas that helped cause a permeable blood-brain barrier is the best place to start if you want to restore integrity. First make sure your diet is strictly void of gluten. Then do an Elimination/Provocation diet, as explained in my book, to determine whether other foods, such as dairy or eggs, are also provoking the immune system.

Continue on with the other strategies explained in the book: Balancing blood sugar, addressing gut health and gut infections, and supporting adrenal health so your adrenal hormones are neither too high or too low. All of these will help quench inflammation, a notorious saboteur of brain health. Also, ask your practitioner about the supplements I have created specifically for blood-brain barrier integrity, brain inflammation and increased blood flow to the brain (which will be discussed in my next book). Other strategies include enhancing the liver’s methylation pathway (Chapter Eight of the thyroid book) and supplementing with alpha-lipoic acid.

Modulating your autoimmune disease is a vital step to protecting the integrity of your blood-brain barrier and the health of your brain. The longer Hashimoto’s or any autoimmune disease goes on unchecked, the more vulnerable your brain is to autoimmune disease, degeneration, and inflammation.


1 Pumirat J. Prog Neurobiol. 1992;39:281-294.

2 Limr FRS, et al. J Endocrinol. 1997;154:161-175.

3 Gomes FCA, et al. Adv Exp Med Biol. 1997;429:99-108.

4 Mallet M, et al. Adv Exp Med Biol. 1997;429:99-108.

5 Dobbertin A, et al. J Neuroscie. 1997;17:5305-5315.

6 Bernal J, et al. Thyroid hormones and brain development. Eur J Endocrinol;133:390-398.

7 Calza L, et al. Thyroid hormone-induced plasticity in the adult rat brain.  Brain Res Bull. 1997;44(4):549-57.

8 Flavin RSL, et al. Regulation of microglial development: A novel role for thyroid hormones. The Journal of Neuroscience. 2001;21(6):2028-2038.

9 Flavin RSL, et al. Regulation of microglial development: A novel role for thyroid hormones. The Journal of Neuroscience. 2001;21(6):2028-2038

10 Kamada H et al. Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats. Stroke. 2007;38:1022-1049.

11 Espositie, P, et al. Acute stress increases permeability of the blood-brain barrier through activation of brain mast cells. Brain Research. 2001;888(1):117-127.

12 Haroh J, et al. Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction. J neurochem. 2007;22(1).

13 Jali C, et al. Cyclooxygenase inhibition limits blood-brain barrier diruption following intracerebral injection of tumor necrosis factor-alpha in the rat. JPET. 2007;323(2):488-498.

14 Haorah J, et al. Alcohol0induced oxidative stress in brain endothelial cells causes blood-brain barrier dysfunction. Journal of Leukocyte Biology. 2005;78:1223-1232.

15 Atul F, et al. Elevated levels of homocysteine compromise blood-brain barrier integrity in mice. Blood. 2005.

16 Homocysteine attenuates blood-brain barrier function by inducing oxidative stress and the junctional proteins. FASEB. 2008;22:734-7.


  • Carol Boudreaux February 21, 2010 at 5:18 pm

    I very much enjoyed this article.

    Is there a way to get the supplements or supplement list for blood-brain integrity now, rather than having to wait for another book to be published!? In the past, I’ve had huge reactions to GABA – like I’m on a major narcotic – even though I tested low in it, and thought I needed it. By far, my biggest sx is brain fog/diminished consciousness/lightheadedness/confusion. (I was dx’d with Hashimoto’s many years ago, but have had years without antibodies. Also adrenal, sex hormone issues, low vasopressin, etc.) Thanks much.

    • admin February 21, 2010 at 8:49 pm

      The best approaches to restoring blood-brain barrier integrity are listed in article. It is a multifaceted approach more so than a simple nutritional deficiency, athough a strict gluten-free diet is essential.

      Brain fog is often associated with brain inflammation and nutrients that have been shown to help with that include catechin (from green tea), curcumin, rutin, baicalein, resveratrol, apigenin and luteolin.

      Increasing blood flow to the brain is also helpful and nutrients that have been shown to help with that include feverfew extract, butcher’s broom extract, Ginkgo Biloba, capsaicin, and vinpocetine.

      If you can work with a practitioner who is practiced in both thyroid and brain health, as those who have taken the seminars are, this can simplify the process.

  • april king March 27, 2010 at 7:15 pm

    desperately seeking help and answers related to my daughter’s Hashimoto’s and cognitive decline. She is now in Special Ed. Her TSH was over 1,200 upon initial testing.

  • Carol Makuta April 15, 2010 at 3:30 pm

    Dear Dr.Karrazzian,
    First ,I want to Thank-you for bringing this cutting edge information and technology to the forefront of Endocrinology.
    This is of course is a huge step for all Hashimotos and Thyroid Sufferers all over the world. I myself am very grateful…That being said .
    I can’t help but wonder why we as patients are to be charge thousands of dollars to get this help that we so desperately need. Some of us have lost our husbands , some lost their wives, some have lost jobs and more due to this dreadful disease. We’ve already spent thousands of dollars on Meds, Doctors, tests, Hospitals, and now were told …Well we can help you! But
    you have to pay this much to get the care that you need…Doesn’t matter if you have health Ins… Doesn’t matter if your in “The network”..Your Insurance won’t cover it….Alot of people can’t afford to pay a couple to 6,000.00 for getting healthy. Why Once again, do we as Thyroid Auto-Immune
    Sufferers have to pay for this! I would love to be able to be healthy again.
    But I and like alot of other people I know, Can Not afford to pay this kind of money….I really thought you were a Godsend .

  • Yolanda Loafer April 26, 2010 at 10:24 am

    I am sorry to read about your frustration regarding being stuck in a ‘sick care’ system with doctors who are in a symptom-based model of care. Dr. Kharrazian’s work is a god-send to many, many people and practitioners all over the world.
    He cannot control how other providers charge for their care. There are some doctors who study & have adopted his teachings in practice who will help people without the $6,000.00 price tag. You shouldn’t give up, just keep looking!

  • LIN STEV May 17, 2010 at 3:15 pm


  • linda dutre May 18, 2010 at 11:31 am

    Try the Evergreene Herbal products for thyroid dis-ease/ They are on the internet. They are a group of chinese Doctors that speciallize in very ancient chinese herbal concoctions..one of which is for Thyroid problems
    They have a hypo product and a hyper product. check them out on the internet. Evergreen Herbal Products California. I tried the throdex
    combination and it helped a great deal with hyperthyroidsim.Diet is very important…Yes it is difficult without enough money to treat any thyroid problem. Stress and anxiety is very bad for thyroid problems of all kinds.
    Put on the music and sing and get rid of all strewss and anger. It helps.
    Good luck…it is difficult.I believe that stress and worry and anger and sadness causes all thtroid problems.

  • Melanie Smithson May 24, 2010 at 8:53 am

    Smithson Clinic in Denver, Colorado has adopted the teachings of Dr. K and has very reasonable rates.

  • Alice McDonnell May 30, 2010 at 6:53 am

    My Doctor, Dr. Geronimo in Poway, CA is trained with Dr. Kharazian and I do phone consults with him since i’m in CT and there are no other trained drs. in my areas. this has worked out really well and he’s on top of any messages I send him via fb or e-mail. Most Drs. don’t even personlly return calls but he does! : ) he’s on Dr. K’s referral list but here’s his weblink….

  • LIN STEV June 30, 2010 at 5:51 pm

    Where are people blogging about how their treatment is going? Is this website going to activate the areas that are not usable yet? Seems like nothing new has been added here since May? Is this cause for concern?

  • Dr. Stan Guberman October 10, 2010 at 9:51 pm

    We practice Dr. K’s thyroid protocols in South Florida

  • savanna November 27, 2010 at 2:26 pm

    Hi i was diag. with hashmoto’s disease finally after going to so many doc’s.My primary m.D. finally sent me to a rheum.arthrities specialist. I was hurting so bad in my neck,shoulders,mid back, lower back pain chronic.He found out i had Rheum., arthries along with Hashimoto’s all this was found about 5month’s ago.Theirs no telling how long i’ve had this, i’ve been suffering from memory loss for along time and pain. I’m trying to get on disabilitie pray that they see this for what it is a disease like any other that people are getting help for.I’m glad i ran across your website it’s given me more insite of the disease.Pray for all of us that has any kind of autoimmune disease it’s going to be a long journey. Love you all and i’ll be praying for you.

  • Forrest Basini January 8, 2011 at 11:09 pm

    Thanks for this nice article it had been simply what i was searching for today! I even have my very blog on hypothyroidism furthermore and if you have got the prospect please take the time to check it out as I even have some very interesting info on these topic’s.

  • Sherry March 25, 2011 at 5:07 pm

    Would Hashimoto’s and its resultant damage to the blood-brain barrier be a cause for MSG sensitivity?

  • narayan September 15, 2011 at 7:40 am

    Many current students are studying Dr. Kharrazians work, they are at all kinds of schools, form chiropractic, to nutrition and chinese medicine. Check out these types of schools in your area and ask if any one knows about and has taken his seminars. They are all learning but of course have access to the same support as practicing doctors. Check it out ! Some time you just need a teammate in dealing with these sort of issues. All schools have very reasonable rates to see their interns.

  • Brian Smith September 15, 2011 at 8:46 am

    How to become a tutor in creative writing for Further education and or teach English as a second language?

  • ruth Jaenchen February 21, 2013 at 11:38 am

    I can’t remember what I just typed, but I forgot the image at the bottom so I lost my text. Shortened version, does anybody out there have symptoms that accompany brain confusion like, dizziness, “hot head” with headache, bizzare vision disturbances, slurred speech, word loss, etc. My symptoms mimic MS almost to a T. I don’t have the diagnosis of Hashimoto’s Encepholapathy yet, only confirmed Hashimoto’s by surgery. I don’t know what to do or where to go & how to deal with this. It’s really shutting me down on a regular basis these days. Any ideas or confirmation of symptoms?

  • Theresa June 14, 2013 at 6:48 am

    Can the degeneration of brain tissue be reversed? I am almost unable to drive, remember, concentrate at this point. If I find a practitioner who can guide me, can I undo the damage that years of undiagnosed Hashimoto’s has caused? What if I just start of the recommended supplements? I bought this book and am reading it – as I can – at present.

    Thank you.

  • Debbie Whitt March 25, 2014 at 7:14 pm

    Why does a server error come up when I click on this link? I am extremely interested in information related to Hashimoto’s possibly being misdiagnoses as bipolar disorder!

    Thank you!

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