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Alyssa Luck

Alyssa Luck

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Can L-Glutamine Cause Brain Fog? {Monday Musings}

Alyssa Luck · Dec 5, 2016 · 14 Comments

Welcome to Monday Musings! I don’t expect this to be a weekly thing, but I wanted a nifty little label to slap on posts where I’m basically just thinking out loud. Wouldn’t want to delude anyone into thinking I have all the answers, now would I?
Thanks for being here!

L-glutamine, once a lowly amino acid vying for attention among 19 siblings, has become a darling of functional medicine for its role in gut health and intestinal permeability. L-glutamine is an important fuel source for enterocytes, which are the cells lining the intestines, and there’s pretty solid evidence that L-glutamine can help strengthen the intestinal barrier.

That all sounds fantastic, right? I sure thought so, and I supplemented accordingly, on and off, for several years. But recently, some self-experimentation has led me to suspect L-glutamine of being a contributor to some pretty intense brain fog and other mental symptoms I’ve been experiencing. L-glutamine was low on my list of suspects, because I had such positive expectations of it, so it took me a while to notice an association. But the timing was there, so I decided to investigate.

Starting with a brief Google search, there were definitely a couple anecdotal reports of people not tolerating L-glutamine well, and several associations specifically with mental symptoms. There were also a few reports of L-glutamine improving brain function, though, so obviously nothing consistent. But the vast majority of both anecdotal reports and scientific papers were about the beneficial effects of L-glutamine on the gut.

However, one potential mechanism I saw mentioned for adverse effects of glutamine is its role in ammonia metabolism. Glutamate and ammonia can be combined to form glutamine, which functions as a (supposedly benign) carrier to transport ammonia to the liver to be detoxified. This process is especially important in the brain, so there’s a connection there. Obviously too much ammonia is bad, and can have adverse effects on brain function, but could supplemental glutamine somehow contribute to that?

I found a couple papers (1, 2) discussing the role of glutamine in ammonia-related neurotoxicity associated with hepatic encephalopathy, which is basically just brain dysfunction caused by liver disease. Some of the milder symptoms of chronic HE are pretty similar to what I’ve experienced, but I don’t have liver disease, so I’m not sure if it’s relevant. I do have a history of elevated liver enzymes, though, so my liver definitely isn’t in tip-top shape.

Anyway, these papers put forth the argument that glutamine itself can be toxic to the brain if levels are too high, while also being a contributor to hyperammonemia. Another paper seems to corroborate this as a possibility, but the evidence is ultimately sparse and conflicting. And said paper also asserts that a healthy liver should be able to keep blood ammonia levels in a safe range, regardless of glutamine supplementation. (What is a “healthy liver” though? Just non-cirrhotic? I don’t have liver disease, but judging by my liver enzymes and other symptoms, my liver could definitely be healthier.)

One problem with this potential mechanism is that it’s unclear how glutamine supplementation actually affects glutamine levels in the brain, if at all. It seems likely that unless you’re taking a TON of glutamine, or getting it through parenteral nutrition (which actually, many of these studies do consider glutamine supplementation in parenteral nutrition), any rise in blood levels of glutamine would be negligible once said glutamine makes it past your gut bacteria, then your intestinal border, then your liver.

The above paper also also mentions that the kidneys produce a lot of ammonia from glutamine, which goes directly into circulation and could thus affect the brain, but likewise, how would this excess glutamine from oral supplementation get to the kidneys? Seems highly unlikely.

I did come across one case report of oral glutamine supplementation contributing to hyperammonemia, but that was in a critically ill patient with extreme catabolism, mild liver dysfunction, and other stuff going on, and she was given 30 g of glutamine per day (which is a lot!). But this case report does also confirm that rising levels of glutamine itself, not necessarily ammonia, is related to neurotoxicity.

And just to throw another wrench into the works, some papers (like this one) suggest that glutamine supplementation actually protects against hyperammonemia. Have I mentioned the body is complicated? Because it’s really complicated.

A potentially more plausible mechanism is that L-glutamine supplements somehow alter the activity of intestinal bacteria, and this affects brain function either through direct by-products of bacterial glutamine metabolism (i.e. glutamate and ammonia), or through other by-products that result from increased bacterial activity in general. This would explain why many people tolerate glutamine just fine, while others don’t, since an individual’s reaction would be mediated by their unique bacterial profile.

One paper does support the idea that extra provision of glutamine increases the activity of small intestinal bacteria in the pig, and that pathogenic bacteria in particular are eager to metabolize glutamine.

Another paper posits that ammonia produced by the bacterial metabolism of glutamine in the small intestine may play a significant role in the pathogenesis of hepatic encephalopathy. The effectiveness of Rifaximin in treating HE lends credence to this idea, because Rifaximin knocks back small intestinal bacterial growth and would decrease their by-products, ammonia being one of them. But again, it’s unclear whether this is relevant in people with non-cirrhotic livers.

A random extra thought related to this mechanism – could the high glutaminase activity of pathogenic bacteria be one mechanism by which bacterial overgrowth causes intestinal permeability? We know glutamine is important for enterocytes, so if bacteria are stealing and metabolizing all the glutamine, that kind of sucks for the intestines, right? A cursory Google Scholar search didn’t turn up any evidence along this line of reasoning, so maybe not.

Anyway, it seems that L-glutamine does cause adverse brain effects in some people (anecdotally), even if we have no idea how or why. But the good news is that the vast majority of scientific papers on the topic support L-glutamine as extremely beneficial for the intestines, so that’s awesome for the people it works for! Just be aware of your reactions and don’t be oblivious to any potential adverse reactions (like me).

 

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Comments

  1. Holly Oberholtzer says

    September 6, 2017 at 4:54 pm

    This is a wonderful blog. I learned quite a bit!

    Reply
    • Alyssa Luck says

      November 29, 2018 at 12:56 pm

      Thank you Holly!

      Reply
  2. andre says

    July 30, 2018 at 5:47 pm

    I felt the same

    Reply
    • Alyssa Luck says

      July 31, 2018 at 9:32 am

      Interesting! Glad it’s not just me!

      Reply
  3. Angelica says

    October 5, 2018 at 10:24 am

    I’ve been experiencing a massive brain fog after taking glutamine, I’ve beeb taking 5 mg and 10 mg doses on 1 scoop and sometimes it triggers the brain fog, sometimes it doesn’t. I take it with food and others on an empty stomach with water. I think my body handles it better when taken with food. It’s a sad situation cause I’ve read the tons of benefits for gut health and just now I’m just starting to feeling them 🙁

    Reply
    • Alyssa Luck says

      November 29, 2018 at 12:58 pm

      Hey Angelica! Somehow missed your comment before. That totally sucks! I mean, I’m glad to hear that you’re feeling the gut benefits, but with the brain fog, it’s a pretty tough trade-off to make. Hang in there, and good luck figuring everything out!

      Reply
  4. Jonathan says

    August 9, 2021 at 1:20 am

    I don’t have this problem but I am talking to a few people that do. I think it may be a bacteria in their gut that is producing glutamate from glutamine. Read how l-glutamine is commercially produced by I think it was a yeast. Anyways, I started a search for known bacteria that can convert l-glutamine into glutamate and quickly found one in sourdough… if you want to chat more let me know. Idk how people who have this problem can heal a leaky gut. The only other hint at what is going on would be to look at people who have an IV of l-glutamine vs ingesting it and knowing that ingesting it causes problems.

    Reply
    • Alyssa Luck says

      August 9, 2021 at 8:22 am

      Ah, very interesting that you know others who have the same problem! I agree that it would make sense for it to be mediated by gut bacteria, since that would explain the differences in how people react. Thanks for the comment Jonathan!

      Reply
      • Bogdan says

        August 13, 2021 at 5:34 am

        Just got directly to your blog googling brain fog and glutamine. Nice writing, thanks.
        I’m taking probiotics with l glutamin 2 g and I’m feeling dizzy and brain foggy.
        I stopped 3 days ago and I still have some brain fog. I have taken it for a week. Not sure how fast will dissapear.

        Reply
        • Alyssa Luck says

          August 13, 2021 at 1:44 pm

          Well thank you! Always very interesting hearing from folks who’ve had similar experiences. I hope your brain fog goes away soon!

  5. Katy says

    January 28, 2022 at 1:20 am

    Thanks for this post! I also found it through an “L-glutamine and brain fog” Google search as 5g daily supplementing has caused such pronounced neurological symptoms, it feels like I’ve suffered a concussion. Inflammation, sensory overstimulation, headache, brain fog as well as mental processing and memory problems. Would be interesting to see if there’s any research correlating SIBO with adverse l-glutamine reactions. I used to take glutamine years ago as a work out supplemt and never had problems but this is absolutely intolerable. Feels like I’m getting brain damage each time I dose.

    Reply
    • Alyssa Luck says

      January 28, 2022 at 9:40 am

      Hi Katy – thanks for commenting! That’s super interesting that you’ve experienced the same thing. Good thought on SIBO potentially being a factor – someday I’ll look into this issue more. It’s definitely an interesting one considering how popular L-glutamine is for gut issues!

      Reply
    • TDR says

      February 18, 2023 at 7:29 am

      Same! I have been working on writing a doc for the past few weeks. Yesterday, I felt as though my brain was short-circuiting. I can’t really explain it, I just know it’s even worse than brain fog (which I had when I had Covid over a year ago, also not fun). It’s as though I feel this wall, where I can’t process anything behind it, even if I wanted to. And the only thing I’ve done different is take a supplement from Pure Therapeutics called “Leaky Gut Defense” in the morning. The “fog” was so pronounced that I started googling, and also stumbled across your post. Kind of scary that there isn’t a lot of information out there regarding this. I could barely write a cohesive sentence, and felt useless all day. I initially wondered if this was perhaps part of the “detox” process but for me, it’s not worth it. Hopefully I’ll be back to normal in a few days.

      Reply
      • Alyssa Luck says

        February 18, 2023 at 12:39 pm

        That’s wild! Your “wall” description is good – I know exactly the feeling you’re talking about. Hope this resolves quickly for you! And thanks for sharing. We’re conducting a little bit of citizen science here in this comment section 🙂

        Reply

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Hi! I’m Alyssa. I like thunderstorms and cats, hate wearing shoes, and enjoy devising extensive research projects for myself in my free time. This is me in Bali with a monkey on my shoulder. And this is my blog, where I muse about health-related topics and document my relentless self-guinea pigging. If you want to know more about me, click here!

alyssa.luck

alyssa.luck
Photo dump from the last year. Thanks to everyone Photo dump from the last year. Thanks to everyone who made 28 the best yet - excited for 29🥰

(PS. In case anyone wants to know what it’s like in my head, I was going to write something like “year 28” or “my 28th year” but then I realized that the year between your 28th and 29th birthdays is not your 28th year of life, it’s your 29th year. I am turning 29 because I have been alive for 29 years. So then I had a whole thing about how to word it without being inaccurate and ended up going with what you see above which is vague and weird but the point is it was a good year and I love all the people in my life dearly)
Biology of Belief (2005) was written by Bruce Lipt Biology of Belief (2005) was written by Bruce Lipton, who earned a PhD in developmental biology in 1971 and was an anatomy professor and academic researcher in the 70s and 80s. Despite the book's presentation and Lipton's background, this is not a science book. It is an exposition of an ideology, supported by haphazard and poorly contextualized nuggets of evidence, rhetorical leaps, and a mind-boggling overuse of analogies. 

The book largely failed to deliver on its promised content. What it does is argue for the primacy of the environment over DNA in controlling life; propose that the cell membrane rather than the nucleus is the "brain" of the cell; invoke quantum physics to explain why modern medicine fails; explain that our behavior is largely controlled by our subconscious mind; inform parents that they therefore have a great deal of control over the destiny of their children; and conclude that humans must become nonviolent protectors of the environment and of humanity because Everything Is Connected.

It’s not that these points aren’t relevant to the topic at hand - they are. But they were not connected in a coherent way that would explain how “belief” actually works (like…biologically), and the treatment of scientific concepts throughout was careless, or perhaps disingenuous.

I think he's correct about many things, some of them being common knowledge. For instance, the "new" science of epigenetics is now old news, as is the critical role of parenting and early environment in shaping a child’s future. But however important these and attendant concepts may be, the book did not do a good job explaining, supporting, or connecting them. 

As far as practical guidance, he refers the reader to a list of resources on his website, which is fine, but I expected some scientific insight into how/why those modalities work. None was given. 

On the plus side, the book was quite thought-provoking, and I came away with loads of references and topics to follow up on. My favorite line? "There cannot be exceptions to a theory; exceptions simply mean that a theory is not fully correct."
Friedrich Nietzsche, The Gay Science (section 382) Friedrich Nietzsche, The Gay Science (section 382), as quoted in the introduction to Thus Spoke Zarathustra because I like the translation better.
This paper totally changed the way I think about e This paper totally changed the way I think about early nervous system development and the relationship between physiology and sociality. 

The authors propose that newborn babies are not inherently social, and have just one goal in life: physiological homeostasis. I.e. staying alive. This means nutrients, warmth, and regulation of breath and heart rate, i.e. autonomic arousal (it’s well-accepted that newborns sync their breathing and heart rate with caregivers through skin to skin contact). 

All these things are traditionally provided by a loving caregiver. So what the baby experiences during the first weeks of life, over and over, is a shift from physiological perturbation to homeostasis (a highly rewarding event inherently) REPEATEDLY PAIRED with things like the sound of a caregiver’s voice and seeing their face. Thus, over time, the face/voice stimuli become rewarding as well. 

The authors argue that THIS is the beginning of humans’ wiring for sociality, and may explain why loving social interactions can have such a profound regulating effect on physiology throughout life: because the brain was trained for it at an early age. 

This framework holds all kinds of fascinating implications for what happens if that initial “training” isn’t so ideal. What if the return to nutritional homeostasis via feeding is paired with negative expressions and vocalizations rather than loving ones, perhaps as could occur with PPD? What happens if the caregiver has poor autonomic regulation, such that social stimuli become paired with cardiorespiratory overexcitement in the baby? Could that have potential for influencing later introversion vs extroversion? (Because if social interaction is paired with autonomic overexcitement, that could lead to social interaction literally being more energetically draining, which is what introverts experience. Thoughts?)

For my energy metabolism enthusiasts: Table 1 in the paper draws a link between metabolic rate and sociality across species. Swipe for a screenshot. 

Anyway, check out the paper! It’s free, just google “growing a social brain pdf.”
I’ll be under general anesthesia in a couple day I’ll be under general anesthesia in a couple days to have two tooth implants placed, and I think I’ll take the opportunity to have a little heart-to-heart with my subconscious mind. A bit of medically-assisted self-hypnosis, if you will. 

I randomly stumbled upon these papers a couple months ago - an RCT showing reduced post-op pain in patients who listened to recorded positive messages while under general anesthesia, plus a post-hoc analysis of the same data that found reduced post-op nausea and vomiting in a subset of high-risk patients. 

The full review paper from the first slide is unfortunately in German, but it has long been recognized that even when unconscious, the patient is listening (for better or for worse). 

It boggles my mind that it isn’t standard of care to have patients listen to recordings like this while under sedation, considering that almost nothing could be easier, safer, or cheaper, and we have at least some evidence of significant efficacy. I mean c’mon, what more could you want from an intervention? 

(Yeah, I know. Profit. If anyone still thinks that our medical system operates with patient well-being as the foremost goal, you’re deluding yourself.)

“There should be a fundamental change in the way patients are treated in the operating room and intensive care unit, and background noise and careless conversations should be eliminated.”

“Perhaps it is now time to finally heed this call and to use communication with unconscious patients that goes beyond the most necessary announcement of interventions and is therapeutically effective through positive suggestions. When in doubt, assume that the patient is listening.”
If you've seen "vagus nerve exercises" that have y If you've seen "vagus nerve exercises" that have you moving your eyes or tilting your head, you've probably encountered the work of Stanley Rosenberg. The exercises he created and introduced in his 2017 book now appear in instructional videos all over the internet. 
 
The book itself has much to recommend it: it's accessible, it's practical, it's inspiring. But it has one major flaw: the solid practical and informational content regarding the cranial nerves is framed in terms of the scientifically dubious polyvagal theory. 
 
I particularly enjoyed the book as an introduction to the therapeutic arena of bodywork, of which Rosenberg is a skilled practitioner. His book is full of case reports that demonstrate how immensely powerful extremely subtle movements and physical manipulations can be. These do need to be kept in perspective: it's a small sample size of the most remarkable cases, and the results were achieved within the supportive clinical environment of a skilled practitioner. You can tell from his descriptions how refined his technique is. But nevertheless, it was a paradigm-shifting read for me, and the exercises give you something concrete to play around with. 
 
The book also brought the cranial nerves and the concept of “social engagement” to the fore as arbiters of health. Rosenberg has a solid background in cranial nerve anatomy and shares many interesting tidbits and considerations that you don’t typically hear; for instance, the potential impact of dental and orthodontic work on cranial nerve function.
 
So, is it worth reading? If any of the above piques your interest, go for it! Just read my post on polyvagal theory first – you can use the book to practice separating the wheat (solid informational content) from the chaff (pseudoscientific framing). If nothing else, the book is a nice reminder that genuine healers who get lasting results for their patients do exist.

But if you just want to try the exercises, you can easily find them all on YouTube. 

“You learn techniques to understand principles. When you understand the principles, you will create your own techniques.” -Stanley Rosenberg
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