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Archives for January 2025

Exploring the Therapeutic Potential of Gamma-Aminobutyric Acid (GABA) in Stress and Depressive Disorders through the Gut–Brain Axis

January 31, 2025 By Trudy Scott 4 Comments

gaba and stress disorder

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition.

Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. GABA is readily available and approved as a food supplement in many countries.

Although there is substantial evidence indicating that orally ingested GABA may affect GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain.

Emerging evidence highlights that oral GABA intake may exert beneficial effects on the brain and psyche through the gut–brain axis. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking.

Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

This is the abstract from a recently published review paper: Exploring the Therapeutic Potential of Gamma-Aminobutyric Acid in Stress and Depressive Disorders through the Gut–Brain Axis

Does GABA exert calming and mood benefits via the gut-brain axis or is it really just a placebo effect? This paper discusses both possibilities. I’m excited by the former (and share more about this below) but I do not agree with the latter. Based on my clinical and personal experience, the calming effects of the amino acid GABA, used as a supplement (when you have low GABA symptoms/levels and used in a very specific way), is not a placebo effect. I also discuss this and share some cases that clearly confirm there is no placebo effect. Read on to be enlightened and encouraged about the power of GABA.

GABA and the microbiota-gut-brain axis

The authors describe the microbiome-gut-brain axis as “the bidirectional communication between the gastrointestinal tract, including its resident microbiota and the brain, linking emotional and cognitive centers of the brain with peripheral intestinal functions.”

They acknowledge that while we don’t quite understand the exact mechanisms of this bidirectional communication, “the vagus nerve, the endocrine and immune system, and the synthesis and metabolism of metabolites and neurotransmitters in the gut are critically involved.” This is exciting given what we know about the blood brain barrier.

If you are new to this concept of the gut-brain axis or want to read some of the latest updates, I encourage you to read the paper and learn about the benefits of probiotics (such as Lactobacillus and Bifidobacterium, and Lactococcus, Enterococcus, Streptococcus, and Leuconostoc) and prebiotics i.e. psychobiotics; and fermented foods – for mood improvement and stress reduction.

You’ll read this about GABA (both as a metabolite produced by the microbiome and as a supplement):

  • found in the enteric nervous system it contributes significantly to gut-brain axis functions and related disorders, including depression, anxiety, inflammatory, and cardiovascular disorders (they refer to GABA as a crucial ‘postbiotic’ i.e. a metabolite produced by the microbiome)
  • while GABA may not directly cross the blood-brain barrier in humans, an indirect influence through the enteric nervous system could potentially provide a viable pathway for the impact of GABA dietary supplements
  • although the connection between oral GABA administration i.e. GABA supplementation, the vagal nerve, and GABA levels in the brain has not been firmly established, considering the existing evidence, it represents a promising avenue for future research.

The last two bullets are worth emphasizing because one of the most common myths is that “GABA supplements don’t work because GABA is too big a molecule to get across the blood brain barrier.”  It really doesn’t need to get through the blood brain barrier in order to be calming.

I share more about this in a blog I published in 2023 – you can read it here.

GABA is a lifesaver and helps with mycotoxin-induced anxiety

Joie has Sjogren’s, Hashimoto’s, fibromyalgia & collagenous colitis (all diagnosed after severe mold exposure) and shares how GABA

has been a life saver for me (for my anxiety), and I share this with all I know who experience anxiety. I also use L-theanine at night because of insomnia. The 5-HTP has helped somewhat for sleep. L-tryptophan didn’t seem to make a difference. However the 5-HTP has made a significant difference in lessening my daily pain levels, which I am most grateful for.

Micki Contini, MS CNC, a board-certified holistic health and nutrition consultant, is a friend and colleague whose life was hugely impacted by mold toxicity. She shares this about how GABA helped her:

As they started tearing my house apart for remediation, I started eating GABA Calm like candy. At the beginning I had to have a lot more than I do now. GABA Calm takes me down a notch and I feel my shoulder coming away from my ears and I get closer to relaxing.

Here are a few other blogs that illustrate just how calming GABA can be when used as a supplement:

  • GABA Calm is a game changer for husband’s sound and tactile hypersensitivity, significant coordination problems and his anxiety
  • Her mum just passed away and although she is sad, GABA allows her to sit with a feeling of peace and calm most of the time
  • GABA worked amazingly for 18-year-old during a MCAS/histamine flare, helping with OCD, anxiety, rage and skin issues

If GABA works it’s a placebo effect?!

I find this statement in the conclusion of the review to be confusing given all that the authors share about the gut-brain axis, vagus nerve and bidirectional communication:

The dietary supplement form of GABA is readily accessible to consumers. While many individuals assert that they derive advantages from using these products, it remains uncertain whether these supplements provide benefits beyond what could be attributed to a placebo effect.

Their argument about conflict of interest and small sample sizes when it comes to studies doesn’t hold water with me.

As I mentioned above, based on my clinical experience, the calming effects of the amino acid GABA, used as a supplement when you have low GABA levels (and used in a very specific way), is not a placebo effect.

The following two cases clearly confirm there is no placebo effect (and these are just a few of many which I plan to share with the authors).

My 6 year old was having panic attacks getting out of the car for Kindergarten

My 6 year old son was having panic attacks getting out of the car going to Kindergarten and taking two GABA Calm has completely relieved him of his fears. He has been going for 3 straight weeks in a row.

I thought it may be low serotonin since this happened last winter as well but I gave him 5-HTP for a couple months and it didn’t seem to affect him and his anxiety. We had to have him repeat Kinder this year.

But wow, the GABA has been fabulous and Kindergarten is in full swing because of your help.

Lisa, a mom in the community, shared these wonderful results about her son. This is most definitely not a placebo effect.

You can read the entire story on the blog here. The school is actually in shock at how well carpooling is going for him.

GABA lessens anxiety, agitation and defiance in 98 year old mother who has been “sundowning” for a couple of years

My mother is 98 and has been “sundowning” for a couple of years. It starts around 3pm, sometimes earlier. Some days it’s no big deal. It is on those other days when she starts and then it goes to anxiety, agitation, then she can get sort of defiant which is so not her. She is a gentle soul, friendly, and kind so this is difficult on her as well as our family.

I just started to use my pestle and mortar to crush up a 125 mg GABA CALM supplement (Source Naturals) and I mix a little into her flavored yogurt when I start to see her having difficulty. I give it to her throughout the day. She only gets the 125 mg amount so I feel safe with that.

I believe that I do notice it lessens her anxiety. I pray that this will be helpful for her because that anxiety can be really draining for her. I have not noticed any adverse reactions.

This is another heartwarming success story shared by Marsha who used GABA Calm with her mother. It’s yet another one that is not a placebo effect either. You can read the entire blog post here.

My personal GABA results are also not a placebo effect

I can also share from first-hand experience that GABA was a life-saver for me in my late 30s when I had no idea what a panic attack was and knew very little about GABA other than the fact it calmed me down very quickly!

I still use GABA in various situations to this day: to help with back spasms after a fall, to help with rectal spasms, to help with throat spasms/pain caused by crying (after the loss of my darling mom), to help me sleep solidly and before doing an on-stage presentation, and much more.

GABA is effective and safe when used in a very specific way

Many people use GABA and report it didn’t work or that they had a strange or uncomfortable reaction to their GABA supplement (such as tingles or flush or feeling dizzy). I’m on a mission to educate folks how GABA is effective and safe when used in a very specific way:

  • Only if you have low GABA levels and symptoms of physical tension, overwhelm, fears, anxiousness, stiff and tense muscles, stress eating, drinking to calm down or fit in socially (you can see all the symptoms here)
  • Starting with a low dose of around 125mg (and less if you’re sensitive)
  • Only using it as a sublingual, powder or capsule opened on to the tongue, liposomal or GABA cream (to see results in 1-10 mins and to bypass the digestive system)
  • Titrating up (and sometimes back down) to find the ideal dose for your unique needs
  • Being open to trialing different products and forms and sometimes combining GABA with theanine
  • Understanding that there can be nuances to using GABA, making one change at a time and not giving up too soon
  • Tracking carefully and course-correcting as needed

I educate anxious individuals about all of the above and offer guidance and encouragement in the GABA Quickstart 2.0 online group 5 week program.

I hope this summary, the review paper and the cases leave you feeling enlightened and encouraged about the power of calming GABA.

Additional resources when you are new to using GABA and other amino acids as supplements

As always, I use the symptoms questionnaire to figure out if low GABA or other neurotransmitter imbalances may be an issue.

If you suspect low levels of any of the neurotransmitters and do not yet have my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and using amino acids on your own so you are knowledgeable. And be sure to share it with the practitioner/health team you or your loved one is working with.

There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control (this is covered in an entire chapter too), sugar cravings, anxiety and mood issues.

The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the amino acids that I use with my individual clients and those in my group programs.

If, after reading this blog and my book, you don’t feel comfortable figuring things out on your own (i.e. doing the symptoms questionnaire and respective amino acids trials), a good place to get help is the GABA QuickStart Program (if you have low GABA symptoms). This is a paid online/virtual group program where you get my guidance and community support.

If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids.

Wrapping up and your feedback

Have you experienced the benefits of GABA for stress and/or low mood? Do you believe it’s more than a placebo effect?

And are you excited to understand the possible mechanisms and read the research? Or do you just want to know how GABA could help you and how to use it?

Have you tried GABA without success or only had limited success? Feel free to share and I’ll provide my feedback.

Feel free to ask your questions below.

Filed Under: Anxiety, Depression, GABA Tagged With: amino acid, anxiety, anxiousness, calming, depressive disorder, drinking, fears, GABA, GABA Quickstart, gamma-aminobutyric acid, gut-brain axis, inhibitory neurotransmitter, low mood, neurotransmitter, overwhelm, physical-tension, placebo effect, sleep, stiff and tense muscles, stress, stress-eating, vagus nerve

Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis (for pain, anxiety, sleep issues and more)

January 3, 2025 By Trudy Scott 2 Comments

GABAergic system and its potential role in rheumatoid arthritis

This is a great question posed by a woman in my GABA/anxiety online group program:

Can GABA be good for rheumatoid arthritis, and in its early stages? If so, in what ways would someone see signs of improvement with GABA?

When I looked into some of the recent research on GABA and rheumatoid arthritis I was fascinated. A 2023 review paper, Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis, discusses the relationship between rheumatoid arthritis (RA), an autoimmune condition, and GABA (gamma-amino butyric acid), a calming neurotransmitter.

The authors discuss “a new mechanism of action in RA” and the fact that “bidirectional communication occurs between the brain and immune system…and neuroinflammatory responses in the brain.”

The paper discusses GABA and neurosignalling, immunomodulatory effects and inflammation, stating that the:

GABAergic system may modulate the abnormal pain response in RA patients.

So to answer her question, if she has low GABA levels we would expect to see some reduction in her RA pain.

As always, we look for the signs and symptoms of low GABA regardless of the diagnosis or possible diagnosis. So if someone has low GABA symptoms of physical tension, overwhelm, fears, anxiousness, stiff and tense muscles, focus issues, pain, stress eating or drinking to calm down, and poor sleep, we consider a trial of the amino acid GABA, and could expect improvements in all or some of the above symptoms.

I would also recommend that she tracks markers of inflammation (like hs CRP, IL-6, IL-1β, and TNF-α) and RA markers to see if they shift in a positive direction with her use of GABA too.

I share more below about the incidence of anxiety and sleep issues in rheumatoid arthritis and some of the mechanisms covered in the review paper. Also, there are lab tests to track and there are other nutritional approaches for supporting an autoimmune condition such as RA.

Some of the mechanisms covered in the review paper

This image from the paper and the explanation provides some insights on the mechanisms at play.

  • Glutamate interacts with glutamate decarboxylase (GAD65 and GAD67) to produce gamma-aminobutyric acid (GABA).
  • Binding of GABA to GABA-A receptors inhibits macrophage activation and decreases the release of inflammatory factors such as IL-6, IL-1β, and TNF-α. Antigen presentation by antigen-presenting cells, however, is impaired, inhibiting CD4+ T cell proliferation and differentiation and reducing the expression of inflammatory factors such as IL-6, IL-1β, and TNF-α.
  • Pain signaling activates the P38/MAPK pathway, whereas GABA binding to GABA-A receptors inhibits P38/MAPK. The P38/MAPK signaling pathway contributes to inflammation and is involved in the activation of myocardin-related transcription factor A (MRTFA), myocardin-related transcription factor B (MRTFB), and serum response factor (SRF) that played key roles in fibroblast activation.
gaba and rheumatoid arthritis
Figure 1. Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis

The authors don’t mention the use of the amino acid GABA as a supplement for RA but do list a number of clinical trials (mostly diabetes patients) where GABA has been used with success. It’s a start and I look forward to future research in this area.

Anxiety, depression, insomnia, cognitive issues and stress-eating in RA

This paper, Psychiatric aspects of rheumatoid arthritis: Review of literature, reports that

Among the major psychiatric disorders found in RA, the anxiety and depressive disorders are prevalent (13 to 48% of patients), as well as suicide, insomnia and tiredness. The impairment of quality of life is markedly after age 65.

This paper, A 30-Day Adjunct Wellness Intervention for the Management of Extra-Articular Symptoms of Rheumatoid Arthritis: A Formative Study, also mentions “cognitive and physical dysfunction” and “stress-related eating” in addition to anxiety, depression and insomnia in RA patients.

Doing a trial of GABA (and other amino acids such as tryptophan and d-phenylalanine/ DPA), will confirm which symptoms are related to which neurotransmitter deficiencies. It’s exciting to consider a very possible role of GABA and other amino acids given the fact that “individuals with rheumatoid arthritis (RA) continually fall short of treatment targets using standard drug therapies alone”

Looking further than GABA and other amino acids: a gluten-free diet and other root causes

With RA we obviously want to address more than just GABA (and other amino acids). Gluten removal is recommended but I do want to mention that the research is surprisingly mixed. This paper, Efficacy of gluten-free diet in patients with rheumatoid arthritis states that

Gluten seems to be a glycoprotein with a clinically relevant inflammatory effect. Several observational studies and anecdotal cases reported a correlation between gluten and various diseases, including autoimmune diseases, such as rheumatoid arthritis. This study aimed to evaluate whether gluten-free diet could be effective in controlling inflammation and ongoing rheumatoid arthritis symptoms.

We report 4 cases of patients with long-standing rheumatoid arthritis with no response to several conventional and biotechnological drugs, treated with a gluten-free diet concurrently with the drug therapy. Our patients presented different degrees of response to the diet, in terms of disease remission and improvement of symptoms. Our cases confirm that a gluten-free diet may improve symptoms of rheumatoid arthritis, even in patients resistant to conventional drug therapies.

Many other papers dismiss the role of gluten and inflammatory diets. This one is an example of a number of similar papers.

The benefits of addressing neurotransmitter imbalances with GABA and other amino acids means the addiction is stopped and quitting bread and cookies now no longer requires willpower,

Here are some autoimmune recipe resources:

  • The Autoimmune Solution Cookbook by Amy Myers MD
  • The Autoimmune Fix by Dr. Tom O’Bryan: gluteomorphins, casomorphins and withdrawal
  • Hashimoto’s Food Pharmacology, a new recipe book by Dr. Izabella Wentz

In addition to dietary changes, a full functional medicine approach is warranted as there is much research supporting the benefits of the following for RA: omega-3 fatty acids, olive oil, low vitamin B6, addressing heavy metals such as mercury and much much more.

I cover 60+ root causes of anxiety here – I’d be carefully assessing each of these root causes for RA too.

Additional resources when you are new to using GABA and other amino acids as supplements

As always, I use the symptoms questionnaire to figure out if low serotonin or low GABA or other neurotransmitter imbalances may be an issue.

If you suspect low levels of any of the neurotransmitters and do not yet have my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and using amino acids on your own so you are knowledgeable. And be sure to share it with the practitioner/health team you or your loved one is working with.

There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control (this is covered in an entire chapter too), sugar cravings, anxiety and mood issues.

The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the amino acids that I use with my individual clients and those in my group programs.

If, after reading this blog and my book, you don’t feel comfortable figuring things out on your own (i.e. doing the symptoms questionnaire and respective amino acids trials), a good place to get help is the GABA QuickStart Program (if you have low GABA symptoms). This is a paid online/virtual group program where you get my guidance and community support, and is where this question was asked of me during one of the live Q&A calls.

If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids.

Wrapping up and your feedback

Do you have rheumatoid arthritis (RA) or another autoimmune condition and has GABA helped?

Were you aware of these possible connections?

What about dietary and nutritional approaches?

Feel free to share your feedback and ask your questions below.

Filed Under: Anxiety, GABA, Pain Tagged With: amino acids, anxiety, anxious, anxiousness, autoimmune, calming, drinking, fears, focus, GABA, GABA Quickstart, GABAergic system, Inflammation, neurotransmitter, overwhelm, pain, physical-tension, rheumatoid arthritis, sleep issues, stiff and tense muscles, stress-eating

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