Dr. Datis Kharrazian’s GABA Challenge for a leaky blood brain barrier is a theory and we still have much to learn

I highly respect Dr. Datis Kharrazian and his work and had the pleasure of interviewing him last November on the Anxiety Summit 5: Gut-Brain Axis. During our preparations I asked if we could talk about his GABA challenge for a leaky blood brain barrier and he graciously agreed.

I wanted to address this topic in our interview because two of the most common questions I get asked are these:

• “How can GABA work if it can’t cross the blood brain barrier?” and
• “If GABA works does this mean I have a leaky blood brain barrier?”

We had such a great conversation on the topic I’ve decided to pull this part of the transcript into a blog so I can share it here with you and use the blog link to share it more widely as I’m asked these questions on social media and elsewhere.

You will learn how Dr. Kharrazian came up with the GABA Challenge, what his thoughts are today, his reservations with GABA and my excellent results with low doses of sublingual GABA. I also share some links to success stories, some of the research and how to figure out if GABA is for you.

Here it is, word for word.

Trudy: So while we’re talking about the leaky blood brain barrier, I want to just talk briefly about GABA and the GABA challenge that you have proposed as a tool for testing for a leaky blood brain barrier. And as you know, I use GABA extensively with clients with the low GABA physical type of anxiety.

I’ve always been a huge fan of you and your work but we do have a professional difference of opinion in this area. And I’ve never actually been a proponent of using the GABA challenge, and I’ve been pretty vocal about it. So I’m really glad that we had a discussion about this in the Facebook group of your neuroinflammation training, and you shared some insights because I was asking some questions about this.

I’d love you to just share some of what we talked about in that discussion. Because if we don’t talk about it, my community is going to say, “Hey, why didn’t you talk to Dr. Kharrazian about this?”

Dr. Kharrazian: Sure, no problem. I don’t think we have this big a disagreement. I think we just have different ways of looking at what’s out there and what we are observing as people working with people, patients who have anxiety.

So ultimately, we have a bunch of theory right now and a bunch of potential models, but we don’t have any clear studies to show what’s really happening. So, one of the things that I proposed in my book before… you understand, I was working with brain patients for over 20 years now….before we had S100 B readily available for many years, it was only in research; you couldn’t get it from conventional labs, even though research was showing it. And the blood brain permeability test was not available either. These have really become more available the past five years and prior to that, we didn’t really have a great test to evaluate if the blood brain barrier was breached.

In an effort to work with what’s out there, what we could do, one of the things that I was doing was doing a test that we called the GABA challenge test. It was really based on the lactulose mannitol test. So the lactulose mannitol test is a well-established test in gastroenterology where they measure leaky gut. So, in that test what the person does is they consume a monosaccharide and a disaccharide, lactulose and mannitol. Lactulose is a disaccharide, it’s very large, and mannitol is very small. And if mannitol doesn’t get absorbed, then there’s a malabsorption issue. And if lactose, which is very large; that should not get through the tight junctions of the gut, gets absorbed in a post urine test, after they drink it, then it shows they have leaky gut. So the whole premise of when you find particle sizes too large to cross, can be a clue to an indication of permeability.

So the GABA challenge that I write about in my book, Why Isn’t My Brain Working? (my Amazon link) was really a way for us to have patients consume GABA. If you look at the molecular weight of GABA, the Dalton size, it’s several hundred Daltons. Several hundred Daltons cannot cross the blood brain barrier. So the concept was, well if someone is taking GABA and they have an effect, then there’s a potential for it to cross the blood brain barrier. And it was kind of following the theory of the lactulose mannitol test. So there’s patients out there who take GABA and nothing happens and some patients take it and go, “It was amazing. Best thing ever. It finally helped me sleep,” or, “Helped reduce anxiety for me.” So, one of the theories was that maybe for some of these people, their blood brain barrier is breached.

Now I know we talked and there is actually the possibility of other pathways that can impact GABA, maybe directly to the gut itself, through the vagus, so I don’t discount those possibilities because we still don’t know. I mean, ultimately, there’d have to be a study designed where they look at it. And it would have to be an animal study, there’s no way you can get an IRB for human studies to check if it’s crossing the brain. It’s some really advanced isotope tracing techniques and I just don’t think the level of dyes they would have to consume to look at the gut and the brain is peripheral and separate… it wouldn’t be possible. So the real answer is, we don’t know.

For me, I still am always suspicious if someone takes GABA and they have a reaction. I always want to go and check the blood brain barrier. And it’s not 100%, I mean, I can tell you without question, there’s people who take GABA, you do a blood brain barrier test, they feel benefit from it, but their blood brain barrier doesn’t have any markers to show permeability.

So it’s not hard for me to consider the possibility that there’s some exogenous pathways too. But at the same time, it’s also really hard to look at the molecular weight of GABA and look at what can cross a healthy blood brain barrier. This Dalton size, we’re talking nanoparticles to a huge, huge particle. So I don’t know but I think we’ll just have to see what happens. And ultimately, if you feel better with GABA, that’s great. If it’s not harmful to you, and if you feel like taking it, that’s great.

I like to also use things like Valerian root, passion flower, and hops because those compounds cross the blood brain barrier. They cross the blood brain barrier and they bind to GABA receptors.

So, the other thing too with actually using GABA you always have the potential for your neurotransmitter receptor sites to down regulate. And this is seen all the time too, patients take GABA and they feel great and then they have to increase their dose and they don’t get the effect as they first did. And they increase the dose and finally, they just don’t get much of an effect from it. And that’s potentially due to receptor site down regulation, which is not as common if you take agonists like Valerian root or passion flower, or hops. These things bind to GABA receptors. So I did a review in my book, where I went over all the literature of the different GABA compounds, which have been published in the literature.

But I’m not going to deny the possibility that there is a potential exogenous source but I also can’t let go the possibility that the blood brain barrier is permeable. So I’m still waiting.

Trudy: Yes, I think it’s great because the fact that you write about that and you taught about that, and you teach about it. It got me looking into the research further and it got me more curious; and it’s good, it’s good to have a healthy discussion and a healthy debate, and be open to possibilities. I’m very open to having my mind changed if something comes up.

I just see GABA works so well with my clients and we use very, very small amounts. I know with your GABA challenge, it’s… what is the amount, its 1,500 milligrams, I think or 1,500 to 2,000? So I’ll start my clients on 125 milligrams of GABA sublingually and get results. I have not noticed the effect that they need more and more, and more. So that’s interesting that you say that. But yeah, it’s good, I’m glad that we’ve had this discussion.

And the other thing that you did say in the online discussion, you said, if someone has a response to taking oral GABA, in other words, taking a GABA supplement does help them, you would want to test for the blood brain barrier permeability, just to see what’s going on. And I like that you say we can track. I’ve actually been in discussions with Cyrex and said, “Hey, why don’t we monitor people who are doing the Cyrex test and have a response to GABA, either therapeutically for the anxiety or with your challenge?” We may start to see some patterns, which I think would be very interesting.

Dr. Kharrazian: Yes, the best we can do with the data in that scenario is just the correlation statistical analysis. But it still wouldn’t answer it.

Trudy: No, I know. But maybe that will trigger someone to want to do a study. So, the good news is we’re seeing more and more research on GABA in the literature. So, it’s exciting. Well, thank you for discussing that with me.

You can read more from our very enlightening interview here: Fix the Brain to Fix the Gut. Dr Kharrazian covers the impact of brain injury and impaired vagal activity (as well as motility and breakdown of the blood brain barrier), how to activate your neurons, using polyphenols for neuroinflammation and butyrate for leaky gut/brain.

These blogs have additional information on GABA and some of the many possible mechanisms:

• GABA and theanine for easing anxiety, improving sleep and supporting immunity
• Oral GABA supplementation allows better prioritizing of planned actions
• GABA helps with inhibition of unwanted thoughts
• Pharma-GABA: study participants with an irrational fear of heights are relaxed and less anxious when crossing a swaying suspension bridge

Here are some blogs with feedback from folks who have benefited from using sublingual GABA for dental anxiety, ADHD/focus issues and Lyme anxiety:

• GABA, Rescue Remedy & essential oils for eliminating dental anxiety
• GABA for children: ADHD, focus issues, irritability, anxiety and tantrums
• GABA helps with Lyme anxiety (while addressing the underlying disease)

The best way for you to figure out if you will benefit from GABA is to use the trial method. Do the low GABA questionnaire and do a trial of GABA (used sublingually), starting low and increasing until you find the right amount to ease anxiety and improve sleep. You can find the GABA products I recommend on my supplements blog.

Please do share if you’ve benefited from using GABA or if you use it with success with your clients or patients.