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.
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.